Fasting For Longevity With Valter Longo, Ph.D.

When it comes to longevity, the goal isn’t just to live as long as possible. The true objective is to live as vibrantly and energetically as possible for as long as possible. So how exactly do we do this? Valter Longo, Ph. D. has devoted his life to answering this question. Along the way, his groundbreaking discoveries hold the potential to change your life in truly dramatic fashion. One of the world's leading scientific authorities on the subject of longevity, Dr. Longo is an expert in gerontology and biological science as well as the Director of the USC Longevity Institute and the Program on Longevity and Cancer at IFOM in Milan, both of which focus on developing a better scientific understanding of the fundamental mechanisms of aging, disease and, of course, longevity. In addition, Dr. Longo is the author of an extraordinary new book entitled, The Longevity Diet*. The culmination of 25 years of research on aging, nutrition and disease across the globe, it provides an easy-to-understand, accessible and implementable road map to living to living well longer through improved nutrition. What differentiates Dr. Longo from many of his peers is that his focus is not purely academic, but practical. From his exhaustive research on aging in both mice and humans, he has created specific diet and lifestyle protocols scientifically proven to active stem cells; promote organ regeneration and rejuvenation; reduce the risk for diabetes, cancer, Alzheimer’s and heart disease; and ultimately extend that which we all seek: lifespan. As discussed at length over the course of our almost 2-hour exchange, Dr. Longo's specific longevity prescription entails a daily diet regimen based on a studied group of centenarians (think Blue Zones). He then combines this with a periodic 5-day fasting protocol called the Fasting Mimicking Diet (undertaken 3-4 times per year), designed to reap the benefits of a true calorie free fast while still nourishing the body daily. This is a powerful conversation the explores all of the foregoing. It's about what promotes longevity and what undermines it. Separating truth from misconception, it's exploration of the benefits of fasting and the science that supports it. And it's a primer on the optimal lifestyle protocols you can employ in your every day life to live well and long. Break out pen and paper because you're going to want to take notes on this one. It's an honor and a privilege to share Dr. Longo's experience with you — one of my most important podcasts to date. I sincerely hope you not only enjoy the exchange, but employ his wisdom for your long-term well-being. Because we all deserve to live our best life. For the visually inclined, you can watch our conversation on YouTube at: http://bit.ly/richandvalter If you are enjoying the video versions of the show, do me a favor and subscribe! I sincerely hope you enjoy the exchange. 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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• 0:44Rich Roll?

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• 1:06Valter Longo?

  I think that for sure, these five meals a day is a bad idea. It's accompanied this obesity epidemic in the United States and around the world. When you have 70% of people in the US that are either obese or overweight, and you still recommend eating five times a day, it's entertaining to me that they don't understand that if you tell somebody to eat five times a day, then what happens is that they start eating more, and they eat for 15, 16 hours a day.

• 1:33Rich Roll?

  That's Dr. Valter Longo, and this is the Rich Roll Podcast. The Rich Roll Podcast.

• 1:52Rich Roll?

  When it comes to the subject of longevity, I think we can agree that the goal isn't just to live as long as possible. The goal is actually to live as vibrantly, as actively, as energetically as possible for as long as possible. So, how exactly do we do this? Well, this is the question that today's guest has devoted his entire life to answering. And I think it's fair to say that what he has discovered is truly life-changing stuff. My name is Rich Roll. I am your host on this podcast adventure. And let me say this, there's been a lot of hype, there's been a lot of excitement and anticipation about today's conversation with one of, if not the, leading scientific authorities on the

• 2:36Rich Roll?

  subject of longevity, Dr. Valter Longo. An expert in gerontology and biological science, Dr. Longo is the director of something called the USC Longevity Institute, which focuses on developing a better understanding of the fundamental mechanisms of aging. He's also the author of a new book entitled The Longevity Diet, which you may recall was a popular topic of conversation in my recent podcast with Dr. Joel Kahn, and which is really the culmination of 25 years of research on aging, on nutrition, and disease across the globe. It's a fascinating read, and I think it's fair to say a groundbreaking book.

• 3:16Rich Roll?

  And I'm just thrilled to share Dr. Longo's important wisdom on these subjects with you guys today. Before we launch in, though, another thing I think we can all agree on is that staying fit and active is important if we want to live long and live well. Dr. Valter Longo. You know what's really interesting about Dr. Longo and his work is that it's not just academic or theoretical, it's actually practical. What he

• 3:50Rich Roll?

  And his team have done is that they have taken all of this research, all these research findings, for example, discoveries found in both mice and humans that demonstrate that certain types of microfasts lead to reduced disease risk and greater longevity by activating stem cells and promoting organ rejuvenation. And then they've translated all of these findings into scientific fasting diet and lifestyle protocols specifically designed to improve longevity. The diet aspect of this, the diet component derives from that of a studied group of centenarians, people who live longer than 100 years. Think about the blue zones. And he combines this with a periodic and scientifically determined five-day fasting

• 4:33Rich Roll?

  protocol called the fasting mimicking diet, FMD, which he advises that people undertake a couple of times, maybe three or four times a year, and which you can learn more about on prolonfmd.com. That's the website, the company that he founded that provides products and support for this FMD. And I might add that the profits of which, or I should say the profits, Dr. Longo's profits of which are funneled right back into longevity research, which I really love. So this is a conversation that explores these very topics, longevity, what promotes it as well as what undermines it. It's an exploration of the world of fasting, both the truths and the misconceptions behind

• 5:16Rich Roll?

  it, and the optimal lifestyle protocols that support longevity. I think you're going to want to take notes on this one, people. It's a fascinating exchange, and I really appreciate Dr. Longo taking the time to share his wisdom with us today. So, let's do it.

• 5:37Rich Roll?

  Dr. Longo, it's a pleasure to meet you. Thank you for making the trip out here. I'm excited to talk to you.

• 5:42Valter Longo?

  Well, great to talk to you, Rich.

• 5:44Rich Roll?

  I had our mutual friend Joel Kahn on the show a couple of months ago. He was out here and he was singing your praises. I was familiar with your work, but he just went on and on and on. And that created quite an impact with the audience. So there's been a lot of anticipation and excitement about you sharing your wisdom with us.

• 6:04Valter Longo?

  Yeah, he's an excellent actor.

• 6:06Rich Roll?

  Yeah, he's very cool. So so many things to talk about. I think probably the best way to approach this is sort of to bifurcate it between a discussion about longevity and then we can get into the fasting mimicking diet protocol that you talk about. But to kind of contextualize this, it would probably be good to hear a little bit about your background and what got you interested in aging and longevity to begin with.

• 6:35Valter Longo?

  Yeah, so I started actually very early. I was a music major back in college. So my second year, I think I always wanted to do aging, do research on aging because as soon as I had an opportunity to change, I was immediately sure I wanted to study aging. And so I switched to the biochemistry department and that's all I've ever done since then. And that was 30 years ago.

• 7:00Rich Roll?

  Yeah, had something to do with having to lead, lead the band, like the marching band or something that just crushed the rock star dream?

• 7:08Valter Longo?

  Yeah, so they asked me to, to direct a marching band and I said, there's no way I'm gonna do that. And they say, well, you know, this is the program. If you don't do that, you gotta find something else. And so within a couple of days, I was in biochemistry and I think it was a good switch. And yeah, so.

• 7:25Rich Roll?

  Why, what, but what was the empathy, like what, where did that interest in longevity come from? Is that from growing up where you grew up in Italy?

• 7:33Valter Longo?

  Yeah, you know, I'm not sure. I speculate that maybe I was five years old when I, my father, my grandfather died, but I was in the room when he died, you know? Usually you keep five years old away from, from the actual moment where somebody dies. And, and maybe, you know, I acted very grown up at the time, but maybe that's, that's stuck in my head that people die and, you know, and, and so that was very early in my life that I had to face that. And yeah, maybe I always wanted to look for the opportunity to start studying aging.

• 8:07Rich Roll?

  Right. How could I prevent this from happening?

• 8:09Valter Longo?

  Yes, yes. And of course, then I started probably thinking about me and my parents and all of that. And so, yeah, I suspect maybe had nothing to do with it, but the fact that I was so sure that I had to study aging, I suspect it had more to do than just a topic in college.

• 8:26Rich Roll?

  Yeah, it's interesting because most people might find themselves attracted to science or biochemistry or becoming a doctor, but you were very specific in what it is that you wanted to explore.

• 8:38Valter Longo?

  Yes, specific. And also, I picked biochemistry because at the time, nineteen years old, I just thought biology and chemistry, that's probably going to be good to know both, to address the problem of aging. And but also, I think that, I mean, it's hard to remember what I thought at that time, but certainly, the potential for medicine to me was also pretty obvious. I just had spent a few years in Chicago with my relatives. There, I came from Italy. But then, in Chicago, I started seeing all this cardiovascular disease and diabetes in my relatives, which are a hundred percent genetically from Southern Italy. And I never saw that in Southern Italy. I mean, I saw it, but not like that.

• 9:23Valter Longo?

  It was very obvious, very early in the 50s and 60s. And so that, I think, also was a factor in my head. And so in Texas, the diet was also very poor, you know, this Tex-Mex. So I guess it went from bad to worse, Chicago and Dallas. And then, you know, then eventually, LA, with Roy Walford, who was one of the guru of nutritional longevity, I had the opportunity to go back to this ideal, or at least understanding of what diet, which diet is good and which is bad. And he certainly was, his lab was certainly the place to do that.

• 10:07Rich Roll?

  Was your intention in going from, it was North Texas University, that's where you did your undergrad, coming out to UCLA, were you intentional about seeking out Walford as a mentor? Like, did you know about him and that's what attracted you to come to UCLA?

• 10:22Valter Longo?

  Oh, absolutely. So there were two people in Los Angeles. They were essentially I think, at least in my view at the time and the view of many, the two leading people in the world for aging research. And LA always had this for some reason. I'm not sure if it's Hollywood or what it is.

• 10:41Rich Roll?

  Everyone wants to be perennially young.

• 10:43Valter Longo?

  Yes. And so interestingly, the scientists that were attracted to LA were also attracted to be leaders in this field. And so Roy Walfer was one, and the other one was Caleb Finch at USC. So I visited both, I applied to both programs, and eventually I chose to go to UCLA. But, and you know, at USC, that's where I still am, already for decades, had a comprehensive aging center, which is unbelievable if you think about that. This building called the Andrews Gerontology Center was built in the 70s, and the center was actually established in the 60s.

• 11:26Rich Roll?

  Yeah, that's quite traumatic, because, you know, what people probably don't know, I mean, there's so much interest around what you do now, but there were many years where you struggled to get your work published, and just people were not keen on hearing what you had to say. So, you know, what was the status of, you know, academia with respect to aging research, longevity research then? Like, what was Walfer doing versus like what's happening now?

• 11:54Valter Longo?

  Yeah, so when I thought about Walfer now, everybody, all the journalists and everybody says, oh, he's a hero. And back then, people made fun of Walfer.

• 12:04Rich Roll?

  He was like a whack job.

• 12:06Valter Longo?

  He was viewed by his own colleagues at UCLA as out there. I remember when I was in the biochemistry department, the comment when I said, I'm gonna go to pathology and work with Walfer, and they said, we don't even know what they do out there, out there.

• 12:21Rich Roll?

  Also, he's doing the experiments on himself, too. That's always a red flag.

• 12:26Valter Longo?

  Yeah, Walfer was doing the experiment on himself. And in fact, that experiment on himself might have cost him his life, because he went for two years in this place in Arizona called Biosphere 2. Him and the other seven people, that's when I joined his lab, that's where he was. He was locked up in this sealed environment in the middle of the desert. And and many of us suspect that, you know, and in in that place, he started the first human color restriction experiment on himself and these other seven people. And we suspect that that might have cost him his life. He developed Lou Gehrig's disease and which is a motor neuron disease. And I mean, nobody knows for sure.

• 13:10Valter Longo?

  He may have developed it for some other reason, but there were some harsh conditions in that in that biosphere too, between diet and oxygen being low. It is very possible those those conditions led to his motor neuron disease.

• 13:26Rich Roll?

  Yeah, but like all pioneers, they have to test the outer limits. Right. They gotta they gotta push that envelope to see what's possible.

• 13:33Valter Longo?

  Absolutely. And and Wolford, I think, I think when he came out, he was in bad shape. But and he was having doubts because at the time, even that operation was not really viewed as, is this a good idea? Was a stupid idea? Now, I think most people view that view it as a, you know, pioneering operation or event. And so I think if I think by the time he died, he was proud of what he had done. I'm not sure that he was that sure when he came out in nineteen ninety two.

• 14:11Rich Roll?

  So before we kind of get into what you've discovered through all of your research into into this field, perhaps we should define our terms a little bit like what? What is aging? What causes it? What exacerbates it? And what have you discovered can perhaps slow it down?

• 14:31Valter Longo?

  Yes, so aging is actually, I started the book by talking about that aging is actually not a bad thing, right? I mean, violins age and they get better, right? And marathon runners, they get better, at least for a while, as they age. And then, you know, maybe the peak performance for a marathon runner peaks around thirty-two to thirty-five, which is very different from other athletes. Senescence is really the word that deals with changes that are detrimental. So accumulation of damage and other dysregulation that leads to dysfunction, right? So that's the word senescence. Usually, we use aging because

• 15:15Valter Longo?

  people, everybody understands that word better. So it's fine to use aging. But yeah, so as time goes by, systems become, accumulate damage, and they start becoming dysfunctional.

• 15:29Rich Roll?

  Why does the body suddenly become less adept at repairing that damage?

• 15:35Valter Longo?

  Well, I mean, there are a lot of theories of aging, and a lot of people, most people are focused on the aging part itself. I come up with a term which I call juventology or juventology. And the difference is that I focus on what is the program that keeps you young versus what is the process that makes you old, right? So it's very different.

• 16:01Rich Roll?

  Right. Gerontology versus juventology is sort of like the study in science of health versus the study in science of disease, which is really the model of Western medicine.

• 16:12Valter Longo?

  Yes, yes. In a sense, I think so. Because if you're studying things going wrong, aging, right, then you focus on the deterioration. So for example, if you think of a car, and that's one of the pillars that I talk about in the book, you can study the tires, and you can say, okay, I'm gonna learn everything about the rubber, how the rubber gets older and older, and how to make it not get older and older. But I can come around with juventology and say, why are you worried about that? Just change. Do tires, do 50,000 miles and put a new set of tires on. Now all of a sudden, all their research, you can see how it's pointless, right? You just have to find out how to replace the tires.

• 16:52Rich Roll?

  Right, so you got to figure out how the body can produce new tires, right? Which gets into this stem cell regeneration work that you do. Super interesting. What do you, before we even get into the, into the next thing I want to talk about, it just occurred to me like, what, what do you think of this trend amongst the new kind of billionaire elite to like, try to live forever? And you know, the things that Peter Thiel is looking into and funding, you know, whether it's cryotherapy type science or, or other?

• 17:25Valter Longo?

  Yes, I mean, I don't know for sure, but I've been told that Wolford was on the list to be cryopreserved.

• 17:34Rich Roll?

  Oh, wow.

• 17:34Valter Longo?

  And, and I was also told that eventually he removed himself from the list, right? So I think it's very meaningful, this, this decision. And I mean, I think all of us went through a period of, of thinking about immortality. I think, you know, when I was 20, I was probably thinking the same way. And then eventually you start realizing that that's probably not why we're here. And there is something fundamentally, you know, just impossible about it, right? You just, it's not consistent with life on, on earth.

• 18:10Rich Roll?

  Right.

• 18:10Valter Longo?

  And so, and I'm not sure that, and I think that's probably what Wolford thought that would he want to wake up, you know, in 20,000 years or 2,000 years and find himself in the middle of God knows what?

• 18:25Rich Roll?

  Uh huh. Do you think about the implications of your work as it sort of exponentially develops? That that could be a possibility for human life?

• 18:36Valter Longo?

  Yes, but I think, you know, first of all, we really been focusing, even though, you know, we did extend the lifespan of a yeast by tenfold. So certainly, we could move in that direction much more and continue and say, well, if we were able with a microorganism to extend the lifespan by tenfold, couldn't we do it with humans? But we, I decided a long time ago that I didn't want to do that anymore. That I was much more interested in getting everybody to be 110 healthy. You know, like Salvatore Caruso, who's from the same town as my grandfather, was this little town in southern Italy that has record longevity.

• 19:18Valter Longo?

  They usually have, you know, between two and four centenarians out of 2,000 people. So it's one of the highest in the world. And Salvatore Caruso made it to 110 healthy. And then I also followed Emma Morano in northern Italy up to a few months ago. Emma was the oldest person in the world and the oldest in the history of Italy. And she was 117 and still eating on her own. And, you know, she wasn't completely independent, but mostly independent or mostly, you know, able to operate and do almost everything within in the house. So I think that that's really what we're what we're studying now. That's, I think, that would be a much greater achievement than than try to make people live 10 times longer.

• 20:02Rich Roll?

  So your your research begins with yeast cells. It moves on to mice and then ultimately to humans. What is your approach and what do you begin to learn?

• 20:15Valter Longo?

  Yeah, so with Walfer,

• 20:19Valter Longo?

  we were doing a lot of comparative biology. So you take a mouse that you starve and I mean, you calorie restrict them one day you don't, one old, one young. And then after a while, I thought, I'm never gonna get anywhere with this. Uh, we're just gonna have a lot, a lot of differences, but we don't know what they mean. We don't know what to do with it. Uh, so that's when I went to back to the genetics. Uh, and me and maybe a group of, of 10 scientists in the United, mostly in the United States, a few in Europe. They decided, let's go to fruit flies, yeast, worms. And, uh, and they're so simple that we're bound to figure out the age fairly quickly. Get, uh, identify genes that regulate their aging quickly. And then if we're lucky, we move back to, to mice and humans.

• 21:03Valter Longo?

  And, uh, and people thought it was a joke, right? People thought it was a stupid, I mean, some famous scientists in the field thought it was the stupidest idea they've ever heard. You know, that, that you could work in a yeast, a unicellular organism. And that will somehow tell you, um, our human age, right? In fact, a lot of people still think it's a joke, but most people don't know.

• 21:23Rich Roll?

  It's funny that people think that though, because it's a fundamental question that we all would like the answer to.

• 21:29Valter Longo?

  Yeah, it's a fundamental question, but also you think about yeast as some kind of ancient organism. But these organisms have evolved for as many billions of years as we have, right? I mean, you know, we are the result of the same evolution process and, and their ancestors are our ancestors. Um, so they're quite sophisticated and they obey the same rules as human being. I mean, like, um, the force of natural selection. So this process that keeps an organism young for a certain period of time, um, is very, is the same. It acts in a different way in a, with a different period than a yeast. So in a yeast, you just in six days.

• 22:11Valter Longo?

  In six days, you basically can reproduce enough time to get out of the way. And for, for us, it's more like 50 years. Um, and, uh, but the rules are the same. And, and in fact, it turned out that the genes that we and, and others identified in, in these simple organisms. Uh, were the ones, the same ones that control aging in, in mice are very, very similar. And we now have, you know, from our own work, evidence from, uh, genetic mutations in humans.

• 22:42Valter Longo?

  Suggesting that

• 22:43Rich Roll?

  Right.

• 22:44Valter Longo?

  The humans have certain similar genes to the ones that we identified in yeast deleted. They they're protected from aging.

• 22:53Rich Roll?

  Right. So what is the structure that you set up to try to determine what keeps a cell young or what can sort of increase its longevity?

• 23:02Valter Longo?

  Yeah, so the the beginning it was use this simple organism and use genetic tools. They at the time were only available for yeast, for baker's yeast, right? So for example, we are for one of our first studies that we published in Science, in the Science Journal, was let's delete every single gene in the genome, which is about 6,000 genes, and see which one is becomes most protected against toxins, right? Multiple toxins. And then the the hypothesis was if something is super protected against damage, it's going to be protected against aging. And that worked out very well, and that led to the identification was probably now

• 23:43Valter Longo?

  recognized as the most important pro-aging pathway is the tor sciss kinase pathway. And and and so there was one strategy, use the tools, genetic tools that we had. And the other one was because I was in a Wall for Lab, and we had some people, lots of people working on the on the molecular biology of aging and the molecular biology of yeast, not aging, nobody cared about aging at that time. But for example, upstairs, I had somebody called Fuyu Tamanoy, and he was working on on RAS. And we, the field had described our RAS reacted or was activated by sugar, right?

• 24:24Valter Longo?

  So then I started, I came out of the Wall for Lab, I say if sugar activates RAS and calorie restriction extends the lifespan of all these organisms, it must be that if I delete RAS, the yeast are going to live longer. So this is a biased approach versus what I said earlier, which is completely unbiased. And sure enough, you know, now they live a lot longer, they live two or three times longer just by deleting this sugar gene. So now the tor sciss kinase is the protein pathway, and the RAS PKA is the sugar pathway.

• 24:57Rich Roll?

  Right.

• 24:57Valter Longo?

  You delete both of them, you get tenfold lifespan extension.

• 25:00Rich Roll?

  Wow. And then you then step it up and and apply this to a rat population?

• 25:06Valter Longo?

  Yeah, then you apply it to, in our case, a mouse population, also knowing the data from Cynthia Canyon, Gary Ravkin and others in worms and flies, right, which was matching. So everything was starting to make sense. That was all aligned. So TOR was causing aging in all these organisms. If you activate it and if you did protein restriction, the organism will live longer, right? So just protein restriction. So, yeah, so then you do the work in mice. And then, of course, you do the work with nutrition and say, well, if deleting the protein gene and the sugar gene makes the organism live longer,

• 25:51Valter Longo?

  what if I just remove sugar and proteins? And then you go in proteins and you say, well, do I need to remove all proteins? Maybe not. Maybe just certain amino acids that are contained in proteins. So we remove serine, trionine and valine, three amino acids, and show that those were the ones, the major ones that control the TOR gene, right? So, yeah, so then we started really having a much more sophisticated understanding of all the network that controls aging in yeast and mice, but also understanding of the nutrients within food that controls the genes that control aging.

• 26:27Rich Roll?

  Right. And then, so then with this population of mice, these studies that you were conducting, how much longer were they living?

• 26:34Valter Longo?

  So the mouse work was originally done by Andrei Barky and John Kapchik. And these mice remarkably lived up to twice as long. So it's very remarkable for a two and a half year mouse to live five years now.

• 26:47Rich Roll?

  Right.

• 26:48Valter Longo?

  And

• 26:49Rich Roll?

  And that would be the equivalent in a human of how much longer?

• 26:52Valter Longo?

  Well, this would be equivalent to humans living an average to 165 years of age. And so this was obtained by a combination of mutation and nutrition. So restriction of protein, restriction of sugars, and the mutation in the growth hormone in this master gene that controls both TOR and PKA.

• 27:12Rich Roll?

  Right, right, right.

• 27:13Valter Longo?

  And so then, eventually, we knew about the yeast tenfold longer, the mouse twice as long, lived twice as long. And then we eventually start studying this population in Ecuador that was lacking the same gene, the growth hormone receptor, that the mice, made the mice having this record longevity.

• 27:35Valter Longo?

  And sure enough, you know, they had a terrible diet, by the way.

• 27:40Rich Roll?

  How did you figure out that they had that same genealogy?

• 27:44Valter Longo?

  Well, there was an endocrinologist, Jaime Guevara, down in Ecuador that had been following them because they have a small stature phenotype. They're small, they're about three and a half feet tall. And so he was studying them because of that, right? The growth, he was trying to get them to be taller.

• 28:03Rich Roll?

  Right.

• 28:04Valter Longo?

  And so he was following a hundred of them. And to me, it was just an incredible opportunity. So I remember when Hossi Kohane and Yusei Alai told me, "You gotta call this Jaime Guevara because he's following a hundred of these subjects and he knows each one of them by name." So I immediately invited him at USC to give a talk. And then I went down there and then eventually it took us five years. He always complains that it took us too long. But it took us five years to publish the first paper in Science, Translation of Medicine, showing protection from diabetes and cancer in this population.

• 28:42Rich Roll?

  But they were eating a terrible diet. And then you went down and like, what was the protocol that you that you applied to that population?

• 28:50Valter Longo?

  Yeah, we didn't apply any protocol. The task was to, in a way, without affecting anything that they do, randomize them in a sense, right? So having relatives against them, right? They live in the same houses, eat the same food. What are the relatives dying of? And at what age? And what are the this group that are, it's called GHRD, growth hormone receptor deficient? What do they die of and at what age? And so it looked like, at least in 2011, there wasn't a single cancer death.

• 29:30Valter Longo?

  That we could find either in these hundred subjects in Ecuador, nor in the 250 subjects that Zvilarone had been following in Europe and the Middle East. Out of 350 people in 50 years of observation, not a single cancer died. Now, that happened later, probably due to this terrible diet. You know, at a certain point, these genes are not able to create immunity against cancer. But and thus far, there's been three cases of diabetes, again, out of the 350 or so subjects, which is another extremely low prevalence of diabetes, considering that they have a terrible diet, a lot of them are obese and overweight.

• 30:11Valter Longo?

  So, yeah, so then then this mutation in humans seems to be very much behaving like the the mouse mutation, which makes them protected from diabetes, protected from cancer, the mice, and also very long live. Now, the longevity, we don't see a big effect on longevity. There's probably a small effect on longevity. But we suspect, as we know for mice, that by having a terrible diet, this may be not removing the protection against diseases, but removing this record longevity that.

• 30:44Rich Roll?

  Right, right, right. So you deduce from that what? And how does that inform like the next chapter?

• 30:51Valter Longo?

  Well, from that, we deduce that it works, right? It's not a mouse or a yeast finding. This is going after cellular protection, multi-system cellular protection across the board. So then these mice that could get to 50% longer life, but have healthy cancers and protection of diabetes, protection for inflammation, protection from cognitive decline, their brain work better, longer. And we also show that for the humans. So now, all of this is possible. You're starting to say, well. We don't have to be this, you know, Western world of living long, very sick now.

• 31:36Valter Longo?

  You know, we used to live a little bit shorter, healthier. Now we live longer, sicker. And we can live longer, healthier. So the opposite of what we are obtaining now. So now we're keeping people alive with lots of drugs, lots of intervention.

• 31:50Rich Roll?

  Yeah, the idea that extending longevity will only extend the period of time in which you're sick is the paradigm you're trying to upend.

• 31:58Valter Longo?

  Yeah, we want to turn it completely around. So not only we don't go to higher, because of course, as soon as you start saying, we want to make people live 20 years longer to 110, I say 30 years longer than now, right? People are going to say, no, absolutely not, because they think of all the people that they know, they're all sick.

• 32:16Rich Roll?

  Right, you're just being in an old folks home the whole time, you know, unable to walk.

• 32:19Valter Longo?

  Yeah, so but if you look at Emma Morano, who at 112 could still live in her house alone, right? I mean, she didn't live alone, but she could have if she wanted to. I mean, she had people that came. But I think until 105, 106, she was alone, living alone. And yeah, and also if you saw Salvatore Caruso at 110, you'd think, that's pretty good.

• 32:40Rich Roll?

  Right.

• 32:41Valter Longo?

  I want that. I mean, Salvatore, you know, in the latest years, you know, television used to come, National Geographic came and they did a cover story on him, and not just him, but Santander's. And he loved it, you know? He was so happy that.

• 33:01Rich Roll?

  He's getting so much attention.

• 33:02Valter Longo?

  He's getting attention, but he was healthy, you know? He could come out and walk and walk with the television crews. And so, yeah, he was healthy enough to really enjoy all this attention.

• 33:20Rich Roll?

  So Dan Buettner is a friend of mine. He's been in here a couple of times. So we've talked extensively on the podcast about the work that he's done on the Blue Zones. And your work really intersects with his work, you know, in a very beautiful way. You're looking at the same or similar populations of people, evaluating what is contributing to their health and their longevity. And you know, when you talk to Dan, it's a, it's a, it's confounding factors. It's, it's diet, it's lifestyle, it's community, it's making the healthy choice, the convenient, the easy choice. It's, you know, continual sort of movement throughout the day, but nothing too crazy. Nobody's on treadmills or going to the gym. They're just active throughout their day.

• 34:02Rich Roll?

  They're engaged with their relatives and, you know, their, their sort of neighbors in a way that we're not, the way that we live here. A lot of these communities, you know, have a strong faith component to them. So you kind of surveying all of this and thinking about what you're doing in the lab, where do you start to look at, all right, well, I can, I can sort of deconstruct all of these factors. But it's really the nutrition piece that you zero in on and you can kind of extrapolate from the essentially Mediterranean diet that most of these people are eating, very low protein, not very much meat, lots of legumes and nuts and seeds and vegetables and the like.

• 34:46Rich Roll?

  Does that like, where does that, where does Dan's work intersect with yours and like, where do you then kind of take it further?

• 34:52Valter Longo?

  Yeah, so Dan is a friend of mine also, and I think he's done great work. And, and we see the blue zones and other areas of the world that are, they have record longevity as one of the major pillars. So in the book, I talk about five pillars and that's one of them, right? So the centenaires are one, but there are other four pillars. And, and, and why is this important? For example, one of the other pillars is epidemiology. Why is it important? Well, epidemiology is really looking at large population and saying, okay, what if you had low protein versus high protein, low fat versus high fat? Who does better, right? So a few years ago, we published a paper, they got a lot of attention where we said,

• 35:36Valter Longo?

  we went against the idea of a high protein diet, but we went against it and we went for it at the same time, right? And this is where the sophistication of the multi-pillar strategy comes in. Meaning that up to age sixty five, the low protein, plant-based diet seemed to be ideal. After age sixty five, that was not the case anymore.

• 35:55Rich Roll?

  Yeah, your protein needs become more important.

• 35:58Valter Longo?

  Yeah, and we also show why, because we had mouse and human data in the same paper. And if you took a mouse, a young mouse, and you give extremely low protein, take four percent of the calories coming from protein. The young mice did perfectly well. Then you took old mice and you give four percent protein and they started dropping weight very rapidly, right? That's where the the science, and this is just one of the four four extra pillars of science that that we use. This is why it's so important. Now, if you look at, you know, for example, Colin Campbell has always talked about low protein diet, right? But he's always talked about two problems, you know, and and I really think he's been a pioneer in the low protein. But you cannot have, and this also happened with the calorie restriction field, good and bad.

• 36:42Valter Longo?

  You give something that is good and it's bad at the same time. If the end, it neutralizes, it's a neutral effect. So what's the problem with saying eat low protein, go with the only population studies? The problem is that you don't see, for example, that you can make somebody so weak that their immune system shuts off when they're eighty two, because they thought the protein is always bad. Another thing that is not bad, for example, and there is different phases of life, is weight. If you're overweight when you're fifty, it's clearly bad, right? Or obese. If you're overweight when you're eighty two, it's actually protective, right? So a slight, now obese, but certainly in the twenty five, twenty six BMI, that's actually a good thing, right?

• 37:27Valter Longo?

  So low protein, high, moderate protein, low protein up to age sixty five, moderate protein. Vegan, let's say up to age sixty five, or pescatarian, fish plus vegan, plus vegetable up to age sixty five. And then maybe expand a little bit. These are all tricks that come from really putting all these pillars together. You may not see by just going to Italy. For example, Italy, very few people, Italy, and I'm assuming Greece, are very frail populations when they're old, right? Very few people know this. So these these Italians that live so long in Sardinia and Calabria and other areas are actually very frail, flayer than the people in Northern Europe, right?

• 38:09Valter Longo?

  And that comes probably from this continuing this low protein diet and continuing this.

• 38:16Valter Longo?

  Narrow diet, that is so helpful when you're younger and now it becomes detrimental. It makes you weak when you're older, right? So it gets

• 38:23Rich Roll?

  Yeah, I got you. I got you. Yeah, I mean, basically, like, like everything, it's more nuanced and complicated than we want to believe. You know, we want to reduce it down to one core principle that's applicable to everybody, no matter what age or how they, where they find themselves in life. Is there a difference between, so on this, on this idea that when you hit 65 and as you start to, you know, move in that direction where your protein needs become more important, has there been any work done on the differences between animal protein and, and plant protein? I mean, you certainly don't want to be taking in a lot of IGF-1 when you're older, right? You're going to be more susceptible to cancers and the like.

• 39:04Valter Longo?

  Not necessarily, because now, and that's we've shown in the paper, the IGF-1 is so low because of age that eating high protein or low protein made no difference in IGF-1. So the people that had over 20% of the carries from protein and the people that had less than 10% at the same levels of IGF-1. So, so yeah, so I think that it gets much trickier than, than we want to appreciate. Another issue, for example, that I under-discuss in my book, but I think it should be much more discussed is autoimmunities and immunities and allergies, right? So you can have a vegetable-based diet, but then whether it's gluten or it's lactams

• 39:46Valter Longo?

  or it is some pro-inflammatory vegetables to a percentage, which could be a significant percentage, if you think about autoimmunities are increasing at a rate of 17% in the world every year, right? It's a huge increase. So, so this exposure to a lot of this potentially or apparently healthy foods to some people, and it could be quite a big number, can be detrimental, right? So this is why in the book I start talking about gluten and talking about lactose, but I say really got to pay attention because you may think something is super healthy for you. And that something may be killing you. So you, you, you need to find out, are you autoimmune, allergic, intolerant to something?

• 40:27Valter Longo?

  And, and that something may be 20 different foods, which are all vegetable, by the way, right? So, so if you don't remove it, you're gonna have a problem and you're gonna suffer. And, and a clear case, I always talk about Italy in, in the lactose years. I used to go to Italy and I said, this is really incredible. And because 90% of the Sicilians are lactose intolerant. And yet, for until five years ago, I never seen a, a, a coffee shop in Sicily that serves soy milk or, or almond milk. They had the regular milk. So I said, you know, everybody that is drinking this must be suffering. And, and so you have a whole, you had a whole country that was getting the macchiato, the lattes. And they were all cow milk.

• 41:10Valter Longo?

  And they must, this must contributed to an epidemic of gastrointestinal disorders. They were very obvious because on paper, we knew that they were lactose intolerant. And yet, nobody, nothing was done for decades.

• 41:25Rich Roll?

  He was doing anything about it. Yeah, that's pretty funny. All right. So on this idea of the five pillars, you know, let's talk about what we can extract from the research that you've done and what you've learned, you know, into some principles that can kind of guide us in the direction of promoting longevity in our own lives. Like what's most important?

• 41:47Rich Roll?

  I'm asking you to be reductionist after my, my, my speech about how we shouldn't be reductionist.

• 41:53Valter Longo?

  Yeah, yeah. So, I mean, so you're asking about the most important?

• 41:56Rich Roll?

  Well, yeah, I, I just want to kind of move into this area of, of, you know, what people should be aware of and some habits and some practices that they can adopt and also things to avoid so that people can be more mindful of, you know, how to practice, you know, these principles that you speak about for their own well-being.

• 42:15Valter Longo?

  Yes. Yeah. So then number one, I think is a pescatarian diet. Why is that? Well, if you are vegan, lots of times you hear people saying, oh, I ate 30 grams of carbons of beans or chickpeas. There should be enough proteins. It's not, right? You need about 10 times as much as that.

• 42:33Rich Roll?

  I've been vegan for 11 years.

• 42:35Valter Longo?

  No, no, no. Sure. You can be vegan and do very well, but most people out there are not you. That's why, that's my point, right?

• 42:43Rich Roll?

  Everybody always tells me I'm an outlier. I'm not convinced about that, Volta.

• 42:47Valter Longo?

  No, no, no. I'm not, I'm saying vegan is perfectly fine. I'm just saying that being vegan and healthy is much harder than people think, right? Because, for example, it takes about 400 grams of chickpeas to have enough proteins, right? And a lot of times, forget you, let's say, we pick 10 vegans out there, right? At random, we pick the first time we can find, and we start asking questions. I do this all the time, and you'd be surprised how many times you've say, well, you haven't had B12 in a while, and you haven't had enough proteins in three or four days, and a, you know, problem, problem, problem, problem. So I'm just saying, if you're gonna be vegan, great, but you gotta pay attention.

• 43:26Rich Roll?

  Yeah, I don't know. I mean, I think, look, I take a B12 supplement like, I don't know, once a week at most. I have my blood work done, it's fine. I go out and I do these crazy ultra endurance races. I'm able to compete, I'm 51, I feel good. I've never had any problems building lean muscle mass or recovering in between workouts. So I think there's a lot of misconception out there about protein, and I think one thing we can agree on is that most people are eating too much protein. There's plenty of plant foods that meet my amino acid needs. I'm not eating buckets full of garbanzo beans, but, you know, I'm mindful about it. I think I would concede to you that it's easier and easier to eat a very nutrient-poor vegan diet, especially with all the analog products that are coming out,

• 44:10Rich Roll?

  and people moving further and further away from, you know, sort of nutrient-dense, whole, whole plant foods.

• 44:18Valter Longo?

  I mean, you know, we're in the, on the same choir, right? So absolutely, I, you know, I published on that, and I got attacked for talking about low protein diet, mostly vegan, but then again, the, when you allow people to have sufficient diet to the big population, it makes it much, much less likely that they're gonna lose a lot of lean body mass, that they're gonna struggle, and also makes it less likely that they're gonna switch back, right? So if you say, I'm gonna allow you to have fish plus a vegan diet, lots of people are fine with that. If you remove everything, then it's just harder for people. Now, if somebody can be vegan for ethical reason or whatever, great.

• 45:01Valter Longo?

  I mean, I think it's absolutely doable. There are no reason not to be vegan, it's just that you have to pay attention.

• 45:10Rich Roll?

  I think that we would also agree that this protein obsession that we find ourselves in the midst of is really a red herring. I mean, most people, people are walking around worried about their protein intake, when in truth, they're probably taking in two to five times more protein than they need.

• 45:31Valter Longo?

  Well, absolutely.

• 45:31Rich Roll?

  And yet, every product at the grocery store is emblazoned with a message about how much protein it is, with the implication like, "Oh, we must be not getting enough, or we need more." And what I like about your work is you stand in a contraposition to that idea.

• 45:47Valter Longo?

  Yeah, absolutely. And I'm the first one that will say, "We're going to have an epidemic of over protein, of eating too much protein, and we're going to find out the consequences very soon." I mean, in our paper, we show three to four fold, increasing cancer incidence, right? And 75% increase in overall mortality in the following 20 years for people that were 65 and below. And even for the 65 and above, it was the moderate protein intake. It was not the high. It didn't need to have high protein intake. Moderate was sufficient. I mean, in fact, in my book, I talk about maybe increase the protein intake by 20% when you get to age 65, 70, below the minimum recommended, right?

• 46:32Valter Longo?

  So yeah, absolutely. But then again, if you look at fish, and I have to go with the science, and if you look at most studies, fish is always on the positive side, besides the mercury fish, you know, the swordfish and the tuna, etc.

• 46:46Rich Roll?

  That's a big problem.

• 46:47Valter Longo?

  But most studies are showing beneficial effects, right? That's why I have to say, even though some people could argue, "Well, ethically, it may or may not be the best idea," but if you look at the science, the fish plus vegan seems to be the way to go.

• 47:05Rich Roll?

  And what is it, I think, when you, you haven't sort of said it explicitly, but this relationship between meat intake and the incidence of cancer, like what is going on there? Because I think when you say that to somebody, like, basically saying, Meat causes cancer, is that what you're saying? And if it's not, if it is, if it isn't, like, I want to kind of clarify that.

• 47:28Valter Longo?

  Yeah, I mean, I don't say that. Now, the World Health Organization says that. So does every other major association. I think the National Cancer Institute, you know, now this is USDA. I think it's also now reduced the recommendation on protein because of that. So red meat particularly is now recognized by almost every major association specializing in cancer to be a risk factor or certainly something that you want to avoid in high quantities. In our case, you know, we had multiple papers. We and Harvard School of Public Health published a series of papers, all of them in agreement

• 48:12Valter Longo?

  with this idea, particularly for red meat, but just also for high protein. So after our paper, we published one with Ajovanucci at Harvard and also confirming that the plant-based diet was protective compared to a variety of diets that included a high protein from animal sources.

• 48:36Rich Roll?

  And what is the active component in meat or red meat that's causing these problems? Is it the high density of protein? Is it the hormonal breakdown in it? Like, what can that be drilled down to?

• 48:51Valter Longo?

  Yeah, nobody knows for sure. I mean, there's a lot of speculations, some of it having to do with the him content. And I've heard different stories and different hypotheses. It could be, are they fed steroid hormones? Are they fed antibiotics? Who knows, right? What is in that meat? And so probably the combination of high proteins, but also other molecules that make it into the meat out there are probably contributing to make it very clear that particularly the red meat seems to be detrimental. But in our paper, we showed that all the animal, high protein diet from all animal

• 49:36Valter Longo?

  sources were detrimental. And a high plant-based diet was no longer detrimental.

• 49:45Valter Longo?

  High protein from plant-based sources was no longer detrimental for overall mortality. So there's no effect, but it still was detrimental for cancer. So it still showed up. If somebody had lots of proteins from vegetable sources, that still was associated with an increased risk for cancer. But that was, in most cases, a combination of animal and plant-based.

• 50:13Rich Roll?

  Right, I got you. What about saturated fat?

• 50:18Valter Longo?

  Yeah, so I think one of the points that I make in the book is that this demonization of ingredients or macromolecules has been very, micronutrients has been very bad. So we should start making distinctions between types of micronutrients. So fats are actually very good for you. A number of studies now looking at the nuts and looking at the olive oil and looking at salmon, et cetera, they're all positive. But when you look at, you know, the high saturated fats diet, then you see problems.

• 50:59Valter Longo?

  Now, what will happen if you have a low sugar, low protein, high saturated fat diet? Nobody knows. Is it possible that that would be okay? Possible. I wouldn't go in that direction because we don't have those studies yet. And it's potentially, I mean, if you want to kill a mouse earlier, you give them a high saturated fat diet.

• 51:24Rich Roll?

  Right.

• 51:24Valter Longo?

  And so.

• 51:25Rich Roll?

  Yeah, I think there's a lot of confusion out there right now. I mean, on the one hand, you have people like Colin Campbell, even, you know, Joel Kahn and the others, who are, you know, cautioning people against their saturated fat intake and, you know, indicating that the studies seem to point to a higher incidence of cardiovascular disease with the intake of these things. And then on the other side of the fence, you have a whole group of people and some emerging excitement about this notion. That everything you ever heard about saturated fat is wrong, that you should be putting butter in your coffee, and you should be in ketosis and pricking your finger and, you know, like, taking exogenous ketones. So where do you come down on the ketogenic diet? Where do you come

• 52:10Rich Roll?

  down on this kind of dissension amongst health professionals about this subject?

• 52:17Valter Longo?

  Yeah, I call it the 0.5 pillar strategies, right? So you come up with a couple of studies showing acute effects. Let's say you eat lots of butter, and after three months, you can look at a bunch of 20 people, and they show like lower cholesterol. And this 0.5 pillars approach is very dangerous, right? Why is it very dangerous? For example, if you take mice, and you give it a low, a high protein diet, right, and relatively high fat, they actually lose weight. And, you know, if you stop the study right there, you say, oh, this is a good diet, you know? If you continue, eventually they develop metabolic diseases, and they die early,

• 53:01Valter Longo?

  right? If you give them a low protein diet, high carbohydrate diet, they actually gain a little bit of weight. If you stop there, you will say, oh, bad, bad idea. If you continue, they have less metabolic diseases, and they live a lot longer. So why is it problematic then to have 0.5 health a pillar? Well, because you're gonna get surprised. And so, if you look at many, many, many studies, many of which I list in my book, you see that the low fat, avoiding the saturated fats, over and over and over, is a good idea.

• 53:45Valter Longo?

  Avoiding the unsaturated, the olive oil, nuts, etc., it's a bad idea. So for example, the Astruc study in Spain, thousands of people, randomized trial, you put health of them on lots of olive oil, or lots of nuts every day, they had to stop the study because it was unethical for the control group. Not to have the same, right? Um, but if you look at Esselstein work and you look at the the Nornish and not just them, but lots, lots of data. You see that, um, you know, having a high saturated fat diet is associated with a lot of cardiovascular problems. Now, if you look, go around the world, you look at the um, uh, centenarian pillar, none of them have high saturated fat.

• 54:29Valter Longo?

  Not the Okinawas, not the Lomalinda, not the Sardinians, not the Calabrians, not the Costa Ricans and not the people in Greece in in Icaria. So, um, yeah, so then you have to say the animal data doesn't support it. The epidemiological data doesn't support it. The centenarian data doesn't support it. Um, you know, the basic, the basic resource doesn't support it. Um, there is really, and the, and the clinical randomized clinical study doesn't support it. So, uh, you have to say, well, in thirty years, when you have, uh, you know, a hu- two hundred more studies all supporting this, which will be almost impossible because there's already so much negative data on it. So not, not worth it, not worth to go in that direction.

• 55:12Valter Longo?

  You can do as well by being on a low sugar, low starch, high carbohydrate diet. And this is another thing, people, they like to say bad carb, good carb, right? It's not about, again, same as fat. It's about sugars and and starches, pasta, bread. It's not about carbs. Carbs contained in legumes and the carbs contained in vegetables are excellent carbs. Uh, and even the ones from starches, if you have, if you maintain it relatively low, it's fine, you know? It makes your, your diet more enjoyable. And so if you have fifty grams of pasta or rice, that's perfectly fine. If you have a hundred and twenty grams of that, uh, then you're starting to get into the problem zone, right? So, so I think that, that this, uh, uh, we really must, uh, start, uh, applying this five pillar,

• 55:57Valter Longo?

  or not five pillar, people can have seven pillars, you know, whatever they want, but certainly multidisciplinary approaches to, uh, determine whether a high butter diet is good or not versus somebody's opinion based on twenty people's study.

• 56:10Rich Roll?

  Right, I understand where you're coming from. I mean, the starch thing makes a lot of sense. I mean, that echoes the work of John McDougall. If you talk to Esselstyn, though, he's going to take a very hard line on fats and oils altogether. Like, he's advocating for an extremely low-fat diet, no oils. Granted, he's dealing with cardiovascular patients that, for the most part, are in dire need of having to reverse some pretty progressed arterial damage. So it's a little bit different, but he takes a very hard line on that. Like, what is your perspective?

• 56:44Valter Longo?

  No, no, I know. I discussed that in the book. And so I say, well, that line is one pillar line, right? So the line to go with low saturated fat is a five-pillar line. The line to go with no fats of any kind is a one-pillar line. Nobody, nothing else supports that. So if you look at the Sardinians, they always had lots of olive oil. So do the Greeks, and I think also the people in Costa Rica and the La Malinda people. So none of them. And then if you look at the clinical data, the other pillar, the ASTROC study showing that they had to stop the study against a low-fat diet. So the randomization was olive oil and nuts versus low-fat diet. So 3,000 people or so went on the low-fat diet.

• 57:29Rich Roll?

  And what was the low-fat diet?

• 57:31Valter Longo?

  It was just suggested to eat less fat, right? So now the high-fat from olive oil and nut diet was so superior to the low-fat diet that they had to stop the study. So, yeah, then that's when you have to say, and if you give a high-fat diet, and now there, I'm not sure if they also had saturated fats in there. But certainly, you know, the mouse studies are, I think, they haven't really been done. Let's say, good fats, bad fats, low carb, low protein.

• 58:11Rich Roll?

  Essentially, what you're advocating is a plant-based whole-food diet with some fish in terms of like the best protocol for long-term lifestyle management and longevity. Is that fair?

• 58:24Valter Longo?

  Yes, avoiding the paying attention to auto-immunities, intolerances.

• 58:29Rich Roll?

  Yeah, making sure you're not allergic to certain things.

• 58:33Valter Longo?

  Yeah, essentially. And then, you know, once you get to 65, then I think that things change and they'll say goat yogurt, maybe some goat cheese and some of these ingredients that may be high nourishment, eggs, for example, may be a good idea to start introducing them back just because of what we've seen, we've seen this frailty in later life that if your diet is too restrictive, you're probably going to suffer from this malnourishment.

• 59:12Rich Roll?

  So, as I mentioned, I've been, you know, plant-based for 11 years. And when I began this journey, I promised to myself that I would be objective and transparent about my experience with it, that if I started to not feel good or if my blood work was reflective of something gone awry, that I would be honest about that and make adjustments. That hasn't happened yet.

• 59:35Valter Longo?

  Yeah, but you're not 65.

• 59:36Rich Roll?

  No, I'm 51. You know, I'm not there yet, but I feel great. So perhaps because there's a lot of plant-based vegan people that listen to this who are thinking, wait, now I gotta start eating that? Like, what should I be mindful about if I want to remain on this plant-based path?

• 59:54Valter Longo?

  Yeah, well, mindful of, for example, that 30 grams of chickpeas and a salad gives you about... Three to five grams of proteins, right? And even if you take the lowest level of protein that you can consider, you know, the World Health Organization in their studies to maintain normal nitrogen balance, they talk about 0.66 per kilogram, right? So about 0.32 grams of protein per pound of body weight per day, right? This is official, based on studies, right? So if you go much lower than that, you're gonna start losing muscle mass. It's just a matter of time. And so now, of course, if you, if you say, hey, well, how much carbons a beans did I have today?

• 1:00:38Valter Longo?

  Let's say you're a 120-pound woman that is vegan. Um, you know, you're gonna need about 40 grams of protein, 35, 40 grams of protein, minimum, right? Um, now in the book I say, I talk about the fact that, you know, if you have 35, 40 grams of plant-based protein and you do some weight training, there should be plenty, right? There should be plenty to, uh, to keep a good muscle mass. But you have to do it every day, right? This is something that, that, um, something that you have to continue doing. Otherwise, you might not see it, but year after year after year, you're gonna start losing, uh, lean body mass. And then, um, you know, and, but the problem is also, are you gonna start losing, let's say, immune function? Uh, again, it's an age-dependent factor.

• 1:01:23Valter Longo?

  You might not see it until you're 62, 63, 64. You might see it in 55, you know, you may be there, uh, it may be there. You get cancer when you're 55 and that was due to the fact that your immune system is not working as well as it could have, uh, because you're protein deficient, or you're B12 deficient, or you're vitamin D deficient, or you're folic acid deficient. So it's very important to, um, to say, let me avoid the malnourishment, um, without interfering though with the, uh, with beneficial effects. So yeah, without needing to go into an area that, um, where the, the protein becomes detrimental.

• 1:01:59Rich Roll?

  Yeah, my protein needs on that equation of, you know, point three two, it comes out to about between 60 and 70 grams a day. It's just, it's not that hard. Like, I eat some almond butter, I eat, you know, rice and beans, I eat lentils and quinoa and things like that. As long as I'm just eating those foods, like, I've done the math and it seems, it almost takes care of itself. Like, if I'm just eating clean, plant-based foods close to the natural state. So it's not about going out of my way to make sure I'm eating, you know, tons of garbanzo beans or anything.

• 1:02:30Valter Longo?

  No, no, no. I mean, I do that five days, five days a week. But so my, my diet is plant-based five days a week. There's no problem. But I do pay attention. I know

• 1:02:39Rich Roll?

  Yeah.

• 1:02:39Valter Longo?

  that a certain amount of, of certain vegetable contains so much protein.

• 1:02:43Rich Roll?

  Yeah, of course.

• 1:02:43Valter Longo?

  And so, and so, once you get used to that, you don't have to check anything. So it's very straightforward. I'm just saying that I, I suspect when they compare, let's say, the vegans against the non-vegans and they show that the vegans are not doing better. In those studies, I suspect that's because so many people in the vegan group are malnourished. And that's why you see this, otherwise, I, I think the vegans should be doing much, much better than the non-vegans if it wasn't for malnourishment. So if you could turn the vegans into well-nourished vegan, then I think we'll see the superiority that we already see in the Blue Zones and in La Malinda, etc.

• 1:03:20Rich Roll?

  Yeah, I, I think that's astute. I mean, I think, my fear, and I think it's a very real fear, is that as we continue to produce all of these processed versions of meat and dairy products that are tasting better and better and better, that people that are entering into, you know, becoming vegan can easily just be eating all sorts of refined grains all the time and cookies and snacks and things like that. And they're, you know, they're like, hey, I'm vegan, it's healthy, when in fact, it perhaps might even be worse than whatever they were doing before.

• 1:03:52Valter Longo?

  Yes, absolutely. So I think that this is why I talk about, you know, once you figure out what the science and all these pillars are saying, go back to your grandparents' table and among the healthy things, pick the ones that were common at their table, you know. And so if you do that, then I think you're guaranteed, especially if you go with the grandparents or great-grandparents, that you're gonna eliminate a lot of these, these new processed foods that you're talking about. So, I mean, I don't think there are many, too, too many grandparents that ate, you know, processed foods. You know, in the past, so.

• 1:04:30Rich Roll?

  Right. There's been much, much ado lately about the relationship between chronic inflammation and the onset of so many of these lifestyle illnesses that we're seeing. I'm interested in your perspective on that and what the relationship is between inflammation and aging.

• 1:04:50Valter Longo?

  Yes, that's a little tricky. I think it's clearly there. There is no doubt that in the brain and lots of people in the Western countries have high inflammation, inflammatory markers. To me, it's more of a consequence of dysfunction than the cause of dysfunction. So I think that the body, the liver is not working well. And so you start making C-reactive protein as a, as a way to respond to a dysfunctional state. And this is why we developed the fasting mimicking diet. And the idea was to, you know, we can change everybody's habits.

• 1:05:33Valter Longo?

  But can we, for example, go after the inflammation, not just during the diet, but in the couple of months, two or three months after the diet? So is it possible to hit somebody with a five day diet? They will have long-term consequences and inflammatory state, but not just the inflammatory state. But certainly that is one way to, I think, assess functionality of the entire system.

• 1:05:59Rich Roll?

  Right. Okay. So let's, let's get into this world of fasting. I mean, when does it first become evident to you that this relationship between caloric restriction and the impact, you know, biochemically, positive impacts biochemically starts to percolate into your awareness and where do you go with that?

• 1:06:19Valter Longo?

  Yes, so first of all, a caloric restriction, which is what Wolford was doing, which refers to eating, say, 25% to 30% less all the time. It doesn't work, right? And it doesn't work for some reason we know, some reason we don't know. But even in mice, you know, the original observations were made 100 years ago. And then it turns out that about a third of the genetic backgrounds benefited from calorie restriction. A third had neutral effects and a third had negative effects, right? So I think the periodic fasting mimicking diet builds on this success and failure. Why you say success and failure? Success, because if you look at calorie restricted people or monkeys,

• 1:07:01Valter Longo?

  it's obvious that the positive effects are remarkable. For example, in the monkeys that were calorie restricted, the control monkeys, 60% of them developed diabetes. In the calorie restricted monkeys, zero. In the cardiovascular disease and cancer, reduction by 50%, 5-0, which is incredible. And what kind of caloric restriction produced that? This was 25% in monkeys, right? Now, if you look at their lifespan, not changed very much, right? So then what does it tell you? It tells you that, obviously, you could probably cure many, many diseases by doing the right intervention, but calorie restriction is not the way to do it. Because it gives you as many problems as it gives you solutions.

• 1:07:45Valter Longo?

  And this is in humans and in monkeys. Humans, we don't know for sure yet, but if you look at people that are calorie restricted, you know, men that are calorie restricted, they have BMI of 19, 18.5, 19. They look like they're really borderline anorexic. And, you know, and you have to wonder, is this sustainable to, is it compatible with a lifespan of 110? Probably not, as it wasn't for the monkeys. So that's where then, you know, back in the days, I made the observation, if I completely starve bacteria, or I completely starve yeast, they live longer and they live stronger, right? So longer, stronger, meaning that you hit them with toxins, nothing. They're very strong.

• 1:08:30Valter Longo?

  And both of them, and you know, if you look at bacteria and yeast, yeast is a eukaryote, so they've been separated by hundreds of millions of years. So I started thinking, is it possible that you could do this for every organism? And it's going to make it stronger and protective for a long period? And that's where a lot of this comes from. And so jumping ahead 20 years then is the mouse studies that we first did, which were, you know, what if you take a mouse and you give it this fasting making diet? Why is it a fasting making diet? Is, is, you know, what I was talking earlier about the nutrients determine what genes are activated or not. So if you have a certain composition, low protein, low levels of certain amino acids, and then low sugar, high carbohydrate but low sugar,

• 1:09:14Valter Longo?

  and high fat, but good fats, right? All that you put it together, then the response to the system is just like if you're giving it water only fasting. You just would give water. And you heal for four days and then you put them back on a bad diet, relatively bad diet. This is a vegan, so four vegan days for the mice. And then, you know, 10 days of an animal based diet. And then you keep doing this twice a month. Now we show that the mice live longer, about 11% longer. But the remarkable part is the cancers were reduced by almost 50%. Wow. And the inflammatory diseases were reduced by 50%. And these mice, just their cognitive abilities was much improved, right? So they just look younger, healthier.

• 1:09:59Valter Longo?

  So they live longer, younger and healthier. Then we did the human clinical trial with this prolonged fasting mimicking diet. And we did three cycles, once a month, five days, again vegan, five vegan days of this low protein, low sugar, high good fat diet. And then we give them 25 days of no recommendation. Go back and do whatever it is that you always done. No exercise recommendation, no food, no nutrition recommendation. And then we measure the effects after a week and three months after the last cycle. And, you know, I think the results were remarkable.

• 1:10:42Valter Longo?

  So lower cholesterol, blood pressure, lower triglyceride, lower fasting glucose, lower

• 1:10:47Valter Longo?

  Inflammation, systemic inflammation is measured by CRP. And lower IGF-1, which we believe is the one of the key markers, risk factors for both aging and cancer. But the interesting thing, this happened much more power, it was much more powerful in people that had the problem to begin with. So if somebody started from an ideal situation, there were a lot less changes than somebody that started with high levels of this.

• 1:11:13Rich Roll?

  Yeah, of course, of course. That's absolutely fascinating. Was there any, were you able to sort of quantify, when you said, okay, go back and eat whatever you were eating? Were you aware of, you know, the differences in how people were returning to their lifestyles? And was there any differentiation amongst that population based upon their just sort of preset lifestyle?

• 1:11:38Valter Longo?

  I mean, we knew that, again, the people that, for example, had IGF-1 levels of 300, they probably had a very high animal protein diet, right? And they responded very, very, very well. We did not follow their diet after, but what we heard from lots of people, and now, you know, the prolonged FMD has been done by over 30,000 people. So we're starting to collect a lot of data from people. And a lot of people are basically saying, it's a slow process, but every time I do a cycle, I come back and I don't feel like I have to go back to as much meat. I don't have to go back to as much sugar or as many coffees.

• 1:12:21Rich Roll?

  Well, they've done something for themselves and so then they, you know, they're more enthusiastic about taking care of themselves, I would imagine.

• 1:12:30Valter Longo?

  I think so. It may also be something about, you know, the brain realizing it that you can handle. I always think about, let's say, running a 10K run. The first time you do it, you, it's very difficult.

• 1:12:48Rich Roll?

  Yeah.

• 1:12:48Valter Longo?

  And after that, you could probably do it.

• 1:12:53Valter Longo?

  Multiple times a year and it doesn't seem that hard. I think it's, you know, realizing that it's okay, it's not that hard, you know, you don't have to have sugar all the time.

• 1:13:04Rich Roll?

  I mean, most people haven't have never gone in, you know, 24 hours in their entire life without eating solid food and just the idea of that seems so daunting. We, you know, we have this notion that we'll just perish if we do that. And to kind of undertake a protocol like that and go to the other side of it and realize like, oh, that was, I did that, that was fine, makes you rethink the human body's capabilities.

• 1:13:27Valter Longo?

  Yeah, absolutely. And if you think about, for example, the brain around day five or so of the FMD, about 50% of the fuel comes from ketone bodies, right, from fat. And in most people, that pathway in the brain has probably never been activated, right? So somebody could be 55 years of age and never once has activated this use of ketone bodies in the brain.

• 1:13:49Rich Roll?

  So then what's wrong with with exploring the ketogenic diet all the time?

• 1:13:55Valter Longo?

  The pillars. So, you know, if you look around the world, a population that are long-lived, using a ketogenic diet all the time, which in most cases to be doable, had to be a high protein diet, you know, I mean, you could come up with it, but it'd be almost impossible to do like a high-fat only, you know, low carb, it'd be almost impossible. So this will end up being a high protein, high-fat diet, and there is really no data out there. And so then you're taking a big risk, right?

• 1:14:31Rich Roll?

  Right, I got you. All right. So the genesis of this is this idea that when you fast a cell, something gets triggered in that cell to make it protective and stronger against disease and decline. Is that correct? So what is going on cellularly?

• 1:14:53Valter Longo?

  Yeah. So that's one, that was the initial observation, protection. Then we started realizing it wasn't just about protection, as I was talking about the tires earlier, it's about also repair and replacement, right? But inside of a cell, whether the cell, if the cell doesn't die, and in, inside of an organ where the cells are actually killed and replaced, right? So now the body, and I, I use the analogy with a wood burning train. And I say, imagine you have a wood burning train that's running out of fuel. It cannot make it to the next train station. So it starts burning its own components to get there, right? But of course, the, the engineer that is burning the wood will first go to the ruined chairs that are made of wood and the ruined world, you know, the damaged ones, right?

• 1:15:37Valter Longo?

  So they take the damaged components and burn those, right? They would make sense first, then you go to everything else. But the end result is you get, get to the next station and then you rebuild it, right? Now you put new chairs, new walls in. So now you have a newer train and you made it there. And that's exactly what the body does. You get rid of a lot of junk inside of the cell and also inside of an organ. And it seemed like, we, we published a paper, for example, a few years ago, a multiple sclerosis in a mouse and humans. And it seemed like the, this fasting mimicking diet was able to first get rid of autoimmune cells. And it makes sense, right? Like, like the machinist or the, or the engineer in the train, you go pick the damaged ones. I mean, it would be surprising that after billions of years of evolution,

• 1:16:22Valter Longo?

  the body was dumb enough to go pick first the, the good cells and kill them when it knows that some cells are, are, are, some cells are precancers, some cells are autoimmune, some cells are not metabolically, you know, they may be insulin resistant. And that's why we think, we see in the human trial, this rejuvenation effect. The body seems to be working like when people were much younger, right?

• 1:16:47Rich Roll?

  So, yeah, so essentially, you know, on first glimpse, it's sort of like, oh, the body is cannibalizing itself. That can't be good. But in truth, what's happening is it's purging itself of these cells that are in decline. And in so doing, stimulating, uh, stem cell regeneration for these organs and these systems to rebuild themselves with brand new healthy cells.

• 1:17:12Valter Longo?

  Yeah, not just stem cells. Now we, uh, are now, our new work is looking at inside of the cell, right? So like a neuron or a cardiomyocyte may not be, may not be killed, but it's now gonna regenerate into cellular, right? So it's gonna make, so autophagy, mitophagy.

• 1:17:28Rich Roll?

  Mitophagy, apoptosis, is that?

• 1:17:31Valter Longo?

  No, apoptosis is the killing of the cell. That we've already shown. What we're now looking at is what happens inside of the cell without killing the cell. Can you regenerate the intracellular components?

• 1:17:44Rich Roll?

  I see. I see. And so, in other words, like, take the liver, for example. I think, you know, I've read and seen where you've spoken about how you undergo this protocol, and your organs, your liver, will literally shrink, right? Because it's because it's regenerating itself and getting rid of the old and in the early processes of building the new. And then you go back to your life where you're eating and it regenerates itself. And it's actually, for all intents and purposes, it's a younger organ. Is that correct?

• 1:18:18Valter Longo?

  Yes. So, I mean, obviously, for example, we're showing that the white blood cell number declines, and then and then returns to normal, right? So it's not like declines to 20%, right? So you're not reducing something by 80%. You might be reducing it by 15%. But now 15% of the white blood cells-

• 1:18:38Rich Roll?

  That's a lot.

• 1:18:39Valter Longo?

  Exactly. But let's say even 10%. So 10%, and then you rebuild it. Now, if you do this 10 times a year, and especially speculating that what we've seen in mice is also true for humans, meaning that the body can detect this is a damaged cell, that's not. Now you get rid of 10%, which may represent 70% of the bad cells, right? I mean, I don't know. We've never demonstrated that. But certainly, we demonstrated that we could take autoimmune mice. And and within so many cycles of the fasting making diet, we can eliminate completely the autoimmunity in 20% of these mice.

• 1:19:13Rich Roll?

  Wow.

• 1:19:13Valter Longo?

  And we can reduce it dramatically in 50% of the mice, right? So, I mean, it's working in a mammal very well. And we've shown it with the pancreas. We can destroy the pancreas, make it not generating insulin anymore. And then we start with the cycle of the fasting making diet. These embryonic genes are turned on. And the only time you see this gene turn on in this manner is only when the mouse is first born.

• 1:19:37Rich Roll?

  Right.

• 1:19:37Valter Longo?

  And so they're turned on and they start rebuilding the pancreas, you know, and the insulin producing cells. It's really remarkable process. Now, you know, in humans, we're starting the trials now. We, you know, there's a lot of work to be done and people have to be careful not to think about, oh, okay. Now I'm gonna, I have diabetes type one, I'm gonna go do it. It's, you know, it's still dangerous to do it, but it looks very promising. And now we're gonna start clinical trials on Crohn's and colitis, Alzheimer, diabetes, cancer. Of course, we'll be doing trials for years now. We're done with a few of them and we're doing more, you know, multiple sclerosis, et cetera.

• 1:20:17Rich Roll?

  What do you think is the number one study? Like, what would be the first study that needs to be conducted to answer some of the lingering questions that you have? That you would like answers to?

• 1:20:28Valter Longo?

  Well, the first one we're gonna do where I think it's gonna work, as it already worked with a hundred patient clinical trial that we did, is metabolic syndrome and prediabetes and pre cardiovascular state, right? So all the people, which is half of the United States.

• 1:20:43Rich Roll?

  Most people, yeah.

• 1:20:44Valter Longo?

  Half of Americans. But a third of Americans are either prediabetic or diabetic, about a hundred million people. So, yeah, so we think, because we already done it and we saw very clear results. Now we're gonna do that, we're gonna start very soon, about four hundred patients, randomized at USC. And yeah, so that, we have high hopes that that's the way to go. You know, maybe three times a year, do this, you know, in the trial, we're gonna do three cycles monthly. But we envision, because in the past trial, we saw that three months after the last, the third cycle, we still saw about sixty percent of the changes remaining.

• 1:21:23Rich Roll?

  Wow.

• 1:21:24Valter Longo?

  So then, of course, sixty percent, and they were lower, but they're still significant. And so we suspect that, you know, it takes about three or four months to get rid of the effects of three cycles. So, you know, I think we envision that this be an option for.

• 1:21:39Valter Longo?

  You know, for doctors eventually to say, yeah, I could give you drugs. Or maybe I could let the body fix itself.

• 1:21:46Rich Roll?

  Right.

• 1:21:47Valter Longo?

  And and see how far you can go with this. And then, you know, if nothing, nothing works, then maybe we can, we can go to the drugs versus, you know, go into the drugs first and.

• 1:21:57Rich Roll?

  Yeah, get to the root cause of what's generating this in the first place as opposed to putting a Band-Aid on it.

• 1:22:02Valter Longo?

  Yeah.

• 1:22:03Rich Roll?

  So this fasting mnemonic mimicking diet protocol that you've developed, it entails, you know, a protocol in which you have, you know, these foods and you're on a very strict schedule. And the idea is that it allows you to eat rather than just doing a water only fast. But yet you still garner the same benefits that you would, that you would experience if you were just doing water. So it generated out of looking at water fast originally. Is that correct?

• 1:22:36Valter Longo?

  Uh, yes and no. And now we suspect and we have data that we are about to publish. That is not just about the lack, it's also about what we have in the fasting mimicking diet, right? So, and unfortunately I cannot talk about that. But it looks like there are multiple components that we have selected that have actually positive effects. I'll give you one, for example. We have glycerol in the, in the, in the fasting mimicking diet. And glycerol turns out to be a byproduct of fat, but also is what's used in gluconeogenesis to make sugar when the, to, to feed the brain. Now, if you don't have glycerol, the body breaks down muscle, right?

• 1:23:18Valter Longo?

  And so one of the observations in the clinical trial, there was no or minimal loss of lean body mass after three cycles of the FMD. And we suspect that, for example, glycerol is playing that part. I mean, this is just one of the 66 components that we have in there. And then, and this is just, I can talk about that because we already published that, but. But I think it's gonna be a lot more than than that. And always though, never trying to hack anything, right? Always sort of thinking, like in this case, what does the body make during fasting? Glycerol, okay, then glycerol it is, right? So we're not trying to come up with something, our version of, so we now have somebody in a fast state that has got glycerol, but people in a fast state already have glycerol, we just make that higher, right?

• 1:24:01Valter Longo?

  So that is our thinking, so it's what we call Nutri-technology, but it's a Nutri-technology in tune with evolution, a Nutri-technology that really respects where this is coming from, understands it and respects it, you know, because, for example, if you try to give, and this is Silicon Valley, if you try to give ketone bodies to somebody that has a normal diet, now you could have a problem, you know, I say this is. Who's not in, they're not attempting to get into a ketogenic state, other than taking exogenous ketones. Yeah, so now lots of people are doing that now, so now you think about like a hybrid car, that is now, you tweak it to work both on electricity and on gasoline at the same time, right? Well, it's confusing.

• 1:24:46Valter Longo?

  It's gonna break down, unless you have an engineer reprogramming, it could do that, but the body is not made to do that, it's either fasting or it's not, right? So now you have the sugar, you put the ketone bodies in there, what's gonna happen after five, six, seven years of that? I would strongly discourage people from from doing ketone bodies during a standard nutrition, I mean, nourishment state, right? And why five days? How did you come up with five days as the window? Well, you need to break down, right? You need to deplete glycogen, and then you have about three days where you benefit from now consuming only, and as we've shown in the clinical trial, visceral fat, right?

• 1:25:29Valter Longo?

  So the body now goes exclusively, it doesn't touch the subcutaneous fat, it goes after the abdominal fat, as it's only our major source of energy. So now you suffer last for the last three days, you break down, the stem cells are now starting to get activated, and you have a. Enough of a of a window that you can start rebuilding. If you go much shorter, there's never any destruction. Uh, there is never any cleaning up and therefore there's going to be minimal rebuilding. And, uh, um, so.

• 1:25:59Rich Roll?

  And if you go longer.

• 1:26:00Valter Longo?

  Well, if you go longer, you got now getting the danger zone, right? You get in the compliance, low compliance zone and danger zone, right? So now you do it, you need to go to a clinic. Um, so five days, um, after over thirty thousand people have done the prolonged diet. Uh, we see very little, uh, side effects that are, uh, that are, that should be reported. And, um, and so people can do it, uh, you know, they don't, they, I mean, some people of course struggle uh, with it, but most people don't. And, uh, yeah, so I think compliance is very important. If people hate it and if people, uh, feel it was too difficult, they're never gonna do it again. And then, you know, then it's drugs.

• 1:26:43Rich Roll?

  Right, so, yeah, and that's, that's also, in addition to the specific nutrients that you spoke to, just by actually providing people with a little bit of food uh, enhances the, the compliance dramatically, I would imagine.

• 1:26:58Valter Longo?

  Not just food, but also the selection of food. So we pick foods, for example, we have these nut bars and they were designed to really fill you up. So it's a kind of fat that, eh, after a while, you're thinking, okay, that's it, you know? I'm not hungry anymore. It's not very much, but it's made in a way that, eh, eh, it really makes, I mean, people. Again, it's not a ton of food, but, uh, um, it's, um, eh, it is doable and, and it's designed to, to, uh, try to make you as full as possible.

• 1:27:29Rich Roll?

  Mm hmm. Um, what about people that do do these extended water fasts? Like my friend Ray Cronice, who's been in here, I think he does these crazy, like, I think he's gone like forty-five days. And I think there's something powerful about that in that he can sit here and, and, and share his experience of that, that helps people, like we were speaking about earlier, um, snap out of this idea that we have to eat three meals a day because somebody decided that at some point. But, you know, I don't, I don't know how healthy or unhealthy that is. It sounds like you would be somebody who would say, well, he's well into this danger zone. Or has he acclimated to it because he's done it a number of times and built up to that? Or what's your perspective on that?

• 1:28:13Valter Longo?

  Well, my perspective is that, I mean, he's getting into the Wolford zone, right? So he's basically pushing the limits. Um, and, and there are reasons for not doing that that we know of now. For example, Friday, there was a paper published on, on fifteen percent calorie restriction long term. And what happens, um, it happens that your metabolism now in people slowed past the loss of weight. So now their metabolism even adjusted per weight, uh, per weight, uh, was lower than it was before. So now after forty five days.

• 1:28:48Rich Roll?

  And it doesn't come back up?

• 1:28:50Valter Longo?

  For, it may not come back up for years, right? So now, if he does forty five days of fasting, all right? Now, the body may have no choice but to reduce the metabolism to be as thrifty as possible. Now, you know, and this is why lots of people that go to these clinics and do very long fast, usually the year after they come back with the same weight that they had before, right? So now this, you get into this yo-yo. And the question is, and the evidence seems to suggest that when you go back now, your metabolism is slower. So now you have a problem, you're gonna have to eat less than you used to eat before you started this, right? All the time, otherwise you're gonna gain weight.

• 1:29:29Rich Roll?

  Right.

• 1:29:29Valter Longo?

  Um, so that, that's another reason, and, and of course, the uncertainty. What's gonna happen after you do this twenty times? Um, we don't know, right?

• 1:29:38Rich Roll?

  More studies.

• 1:29:39Valter Longo?

  More studies, but.

• 1:29:41Rich Roll?

  The control group.

• 1:29:41Valter Longo?

  Forty five days.

• 1:29:42Rich Roll?

  How many people are gonna do that?

• 1:29:44Valter Longo?

  Forty five days, you're not gonna, yeah. But now, I know the, the Buckingham Wilhelmi Clinic in Germany, they're starting to follow people. They, they do like three weeks, uh, you know, so they, they, they're trying to get as much information as possible. How many times have they done it? Do they have any problems? So that would be interesting. And I know that the True North Clinic up in Northern California, I, I, I remember talking to them and they were saying they were trying to collect data on, um, you know, people that have done it many times and, and.

• 1:30:12Rich Roll?

  They've had great results up there, and I know a bunch of those doctors. They, they've, they've turned people's health around in dramatic ways. I don't know exactly what their protocol is, but.

• 1:30:20Valter Longo?

  Water only.

• 1:30:20Rich Roll?

  Oh, it is water only.

• 1:30:21Valter Longo?

  Yeah, True North is water only, it's a tough one.

• 1:30:23Rich Roll?

  Yeah, yeah, yeah.

• 1:30:24Valter Longo?

  In a clinic, that's fine. In a clinic, you can do what you want.

• 1:30:28Rich Roll?

  Supervised setting.

• 1:30:28Valter Longo?

  Yeah, it's medically supervised. You have nurses. Yeah, and the same in Germany. Then it's different, especially if you're trying to address some problem that they know how to solve.

• 1:30:41Rich Roll?

  I think it's important to point out that what you're advocating and suggesting is very different from something else that's very popular right now, which is intermittent fasting. This idea of going, I don't know, 12 or 15 hours either every day or once a week, or I don't know how it breaks down for people. But I would imagine that your perspective on that would be that, yeah, it's fine. But and maybe there's some benefits to that. But you're not doing it long enough to really create this effect that you're looking to produce cellularly.

• 1:31:16Valter Longo?

  Yeah, well, first of all, I just emailed Sachin Panda the other day because he's one of the leaders.

• 1:31:21Rich Roll?

  Yeah, he's one of the guys.

• 1:31:23Valter Longo?

  And I say, Sachin, 12 hours is really intermittent eating, you know, it's not intermittent fasting. This is what we've always done, right? So why are we calling that intermittent fasting? That's crazy. So but yeah, people are doing that. And the problem with that is that we're starting to use these words like carbohydrate. You know, it's the same thing, you know, they don't mean anything. Because if you eat 12 hours, and that's what I point out in the book. If you eat for 12 hours, that's very good, you know, it's supported by the five pillars. Stick to 12 hours. Don't eat for 13, 14, 15 hours a day. And if you're overweight or obese, eat twice a day plus a snack and keep it 12 hours. That's the normal eating pattern. It's not intermittent fasting.

• 1:32:06Valter Longo?

  Now, 16 hours, well, no doubt that, as has been shown, you're going to have benefits on weight loss, et cetera, et cetera. Nobody talks about the problems, though. Problem number one, goldstone formation. Studies are showing that if you're fast every day for more than 12 hours, you now have an increased chance that you're gonna need your goldbladder removed. Not the worst thing that can happen to you, but also not a nice thing to happen to you. And it gets to about twofold increase in the risk of all goldbladder operation. Number two, several studies showing if you skip breakfast, which most people will do if you go 16 hours, because most people have dinner.

• 1:32:50Valter Longo?

  Now you have increased chance of cardiovascular disease, cancer, and overall mortality.

• 1:32:55Rich Roll?

  Is that, wow. I skip breakfast all the time.

• 1:32:58Valter Longo?

  Yeah.

• 1:32:59Rich Roll?

  I shouldn't admit that. Not all the time, but once in a while.

• 1:33:01Valter Longo?

  And the argument is, maybe is the people that skip breakfast have a terrible this and that. Yeah, we don't know. I mean, it's not necessarily bad to skip breakfast, but it's certainly associated with bad outcomes, right? People die earlier, not later, earlier. So then you have to say, yeah, do you wanna recommend something that multiple pillars are now are indicating to be problematic, right? And, and, yeah, so that's why, I mean, first, do no harm is a very good advice, right? And this is what, you know, people learn in the first year of medical school. So I think that we should always start with that. You know, first do no harm. Is this associated with any problems? And if it is, try to come up with something else, you know? So 12 hours is great.

• 1:33:45Valter Longo?

  Time restricted feeding, suchin is worked on that. It's shown to be very beneficial. So if you take people that used to eat for 14 hours a day, 15 hours, you reduce it to 12, great. Because that's what the centenarians do. That's what every piece of data is suggesting to be very good. 16 hours, not supported, potentially entering the problem zone.

• 1:34:08Rich Roll?

  Right, that's, that's, that's good to know. I think that's important information. There's a lot of people just launching into this world of intermittent fasting without really knowing what they're doing. And I've dipped my toe in it, so, you know, it's instructive to hear you say that. One of the things that I thought was fascinating. In reading your book and your work was this idea that that

• 1:34:31Rich Roll?

  the fasting mimicking diet will have a well will make healthy cells more resistant to like if you have cancer, right, it will make those cancer cells more susceptible to the cancer treatments to the chemotherapy and the healthier cells

• 1:34:50Rich Roll?

  strong so that they will be able to withstand those treatments. I didn't say that very eloquently.

• 1:34:56Valter Longo?

  No, that's exactly right. Yeah. So yeah, then the like we had observed for bacteria and yeast. You take a normal cell, at least in a mouse, and the early data from clinical studies is suggesting the same. We've shown already for white blood cells, for example, from humans. So if you give them chemo, the good cells know what to do during starvation. They become protected. They stop dividing or they reduce growth rate and they enter a protective mode. The cancer cells, by definition, by the way, rebel against this. They cannot. They otherwise they wouldn't be defined as a cancer cell. So one of the hallmarks of cancer cells is the ability to grow independently of growth factor

• 1:35:37Valter Longo?

  and to refuse anti-growth signals. So to rebel against the anti-growth signal. So fasting is an anti-growth signal and the fasting and the cancer cell rebel. Now you got a problem with that. And I use the analogy of imagining somebody running in the desert in the desert without shade, right? And without water. Now, if you were running in the desert like cancer cells do, you know, you have shade and water, you may make it. And so if you have, in the case of cancer cell, lots of growth factors, lots of proteins, amino acids and sugar, fine. That's what they've evolved in. That's what they understand. As soon as you start, you know, removing glucose and removing

• 1:36:18Valter Longo?

  growth factors and like IGF-1, etc., and adding anti-growth factors, now the cancer cells are going to have a problem. And that's what we see, that's why we see the fasting, fasting making diet being as effective as chemo, but particularly we see this working together and that's where the sun comes in, right? The sun is the chemo. And so, you know, you have no water and you have the sun hitting you, you're gonna be dead. It's just a matter of time.

• 1:36:45Rich Roll?

  Right. It's amazing how that's worked out, that it has the desired effect on the cancer cells, which is to hopefully make them go away, and at the same time strengthening the healthy cells.

• 1:36:56Valter Longo?

  It may have now worked out and may be evolved, right? So we're starting to suspect that, think about sleep, right? So you sleep and sleep is not there by mistake, right? It's forcing you to rest for however many hours. So we're starting to think, is it possible that because all these organisms mostly stayed yeast, bacteria, mostly they stay in a starvation mode, once in a while they start eating, right? Humans were not in that situation, but fasting was probably so common that you didn't have to force anybody to do it because they were forced by the conditions, right? So then, what if fasting was the moment where the

• 1:37:37Valter Longo?

  pre-cancer cells were getting killed? And now you use it to protect your cells in that moment of starvation from the sun, from whatever other, you know, problems and toxins you might be exposed to. So it may very well be an adapted process where you're starving, protect your good cells, protect your genes, and then get rid of cells that are, you know, not functional anymore. Also to eat them, yeah.

• 1:38:09Rich Roll?

  Yeah, in the same way that exercise is good for you, right? It's just something that we evolved, that we sort of experienced in our evolution that allowed us to, you know, weather hard times and get stronger. But we've moved away from these things. We're in a culture in which we're just eating all day long and we're sitting in chairs. So we've moved away from these evolutionary sort of mandates that keep us healthy.

• 1:38:35Valter Longo?

  Yeah, but yeah, exercise could be a little bit different. Exercise is not really removing anything, it's more damaging. So exercise may have similar effects for different reasons, meaning that when you, let's say, you had to run excessively.

• 1:38:52Valter Longo?

  20,000 years ago, that caused muscle damage and their response to that maybe build new muscle. Because now that tells you that you didn't have enough, right? So it's a different concept, probably also leading to.

• 1:39:07Rich Roll?

  There's sort of a sort of a catabolic anabolic analogy in that there's a breakdown and then there's a rebuilding that makes you stronger.

• 1:39:13Valter Longo?

  Yeah, yeah, so it's a similar idea, but but yeah, the mechanisms are quite different because in in exercise, you do damage and then you repair it rather than you get rid of and eat yourself essentially and then rebuild. But yeah, the exercise, I think, also uses some of the probably in some cases, the rebuilding might use, as we are seeing, similar mechanisms, right? So it might the rebuilding for exercise probably doesn't quite go as extreme as the rebuilding after prolonged fasting. But it may be using similar techniques. For example, we know stem cells are activated, satellite stem cells, muscle stem cells are activated in response to exercise.

• 1:40:00Rich Roll?

  What is the impact on cognition of FMD?

• 1:40:05Valter Longo?

  Yeah, so in the mouse, there are very clear impact, meaning that they are cognitively sharper. They remember better, they learn better, particularly when they're old and but also when they're young. But you see this particularly when they're old. Now we're doing, we've done some special FMDs with mice on and off on Alzheimer's. But now we're doing the the human FMD. We're testing it now in mice, multiple Alzheimer models. And the idea is, can we protect the can we protect the brain against Alzheimer?

• 1:40:48Valter Longo?

  Even when we impose the human mutation that cause Alzheimer's in 100% of the mice, right? So we have some a mouse is called triprotragenic and it's all this human mutations. They cause problems in. This beta amyloid accumulation and tau, phosphorylated tau. So, yeah, so then hopefully within a year we'll have the data on that. And we're starting a clinical trial, which has got funded by the Italian Ministry of Health for a randomized clinical trial on Alzheimer's patients.

• 1:41:17Rich Roll?

  Oh, wow.

• 1:41:18Valter Longo?

  And the fasting making diet, so that would be very interesting. Particularly because there is really nothing for dementia right now. And, and so this would be something that could be rapidly moved into the, into clinical use.

• 1:41:33Rich Roll?

  Are you familiar with Dean and Aisha Shirze at Loma Linda with their,

• 1:41:41Rich Roll?

  I forget, I think it's called the Brain Health Unit. They, they created a department there and they're having some pretty tremendous success working with early onset Alzheimer's patients. I had them on the podcast, they're doing really cool work.

• 1:41:53Valter Longo?

  You know, I'm collaborating with Charles Wang and a few others at Loma Linda, but not with the brain people.

• 1:42:02Rich Roll?

  You should meet these guys, I'll connect you. Is there anybody who, who, for whom the fasting mimicking diet would not be appropriate?

• 1:42:12Valter Longo?

  Yes, so, you know, pregnant woman, weight below, I think BMI 18.5 or something like that.

• 1:42:23Valter Longo?

  People with diseases, they're gonna need the doctor, or people are taking drugs, especially metabolic drugs, insulin particularly, very dangerous combination. You can actually die if you combine insulin and fasting or fasting making diets. Yeah, so I think in general, if somebody is healthy, they can talk to the nutritionist. And there is an expert in FMDs and they will take them through. But if somebody has a disease, they, they need to run them by the doctor. And then the nutritionist and the doctor can, can work with them to, to see if it's doable.

• 1:43:00Rich Roll?

  Right, and the, the preferred, the preferred protocol is to do this five day program three times a year, like once a quarter, four times a year?

• 1:43:09Valter Longo?

  Well, it depends, right? So if you're somebody who's a 32 year old athlete that is on a pescatarian or a vegan diet and it's, you know, everything is perfect.

• 1:43:19Valter Longo?

  Let's say you probably wanna do it twice a year.

• 1:43:22Rich Roll?

  Hmm.

• 1:43:22Valter Longo?

  Um, and uh, and somebody who's obese, who's got high cholesterol, high blood pressure, um, maybe once a month until they move to the lower category. And then it goes, you know, maybe once every four months and then, um, and then every, you know. Yeah, so I say, an average people should probably do it one, once every four months. And then depending on where they stand between the 32 year old athlete and the obese person.

• 1:43:51Rich Roll?

  Right, right, I got you.

• 1:43:52Valter Longo?

  Risk factor.

• 1:43:52Rich Roll?

  Yeah, I got you. Um, all right, well, we gotta, uh, we have to wind this down, but I have two questions. Um, but I can't let you go without asking. The first is, if somebody's listening to this or they're watching this, um, and they're health conscious, they're interested in taking care of themselves, but this is brand new information, they've never heard anything like this before. Uh, you know, what's the, what's the thing that you want people to bear in mind that they might, that might not be self-evident to the average consumer about how they approach their, their day, their diet, their lifestyle habits?

• 1:44:29Valter Longo?

  Well, I'm, I mean, you know, I, I, um, I have a list at the end of the, the chapter four, I think, in the book, and, and there's 10 things that I think people, uh, all should do that are not very hard. And, um, and of course, you know, different people will get to different levels of it. You know, so for example, what we talked about early, the 12 hour limit, um, you know, if you do 15 hours and I say 12 and you can get to 13, well, you know, at least you're close, you know, and, uh, and that's, uh, that's the idea, try to get as close as possible to all these recommendations because they're really based on five pillars. I mean, my opinion is in there, but not very much. I mean, it's more like a systematic way of, of looking at this, including our history,

• 1:45:13Valter Longo?

  you know, where do we come from? Not just systematic in Silicon Valley way of, of, you know, trying to hack everything, but more like, you know, let's combine that hacking with, uh, with our history and where we come from, you know, to make sure that we stay in tune with evolution, you know?

• 1:45:31Rich Roll?

  Great, that's a great answer. And if you were to wake up and find yourself to be the Surgeon General of the United States, what would be your primary first policy initiative? Like, what needs to change in our healthcare system?

• 1:45:48Valter Longo?

  Yeah, so I get fired within like a week.

• 1:45:50Rich Roll?

  Yeah, yeah.

• 1:45:51Valter Longo?

  Somebody tell me that.

• 1:45:53Rich Roll?

  Everybody, I ask every doctor that comes on the show the same question. I mean, every one of them would get fired for what they would want to make happen.

• 1:45:59Valter Longo?

  But it's funny, because I believe that the Surgeon General, when 50 years ago, said smoking is bad for you, and he was fired for saying that.

• 1:46:08Rich Roll?

  Yeah, I think that's right.

• 1:46:10Valter Longo?

  Yeah, yeah. Yeah, so I think that for sure, these five meals a day is a bad idea. It's accompanied this obesity epidemic in the United States and around the world. You know, when you have 70% of people in the US that are either obese or overweight, and you still recommend eating five times a day, it's entertaining to me that they don't understand that what could work in a clinic, you know, so if you brought somebody into a clinic, as we do, and you keep him there, then it could actually work. But if you tell somebody eat five times a day, then what happens is that they start eating more, and they eat for 15, 16 hours a day.

• 1:46:54Rich Roll?

  Yeah, they're not eating a banana and some almonds, they're going to Cheesecake Factory.

• 1:46:59Valter Longo?

  Yeah, so they're eating the bad food, and they're eating for more meals, longer time. So the combination of these two, I think, is the bad food, more meals, longer time. The three things are really detrimental. So I would say, if you can go to either a vegan or a vegan-besqueitarian diet, and keep it within 12 hours, and keep it to, if you're overweight, if you're one of the seven out of 10 Americans that are overweight, keep it at two meals a day plus a snack. So let's say you have breakfast, lunch, and a snack for dinner, or breakfast, a snack for lunch, and dinner. I mean, the snack could be 100 calorie low sugar, you know, like a salad or something like it.

• 1:47:42Rich Roll?

  It's a pleasure talking to you, Dr. Longo. Pleasure being here. I think your work is groundbreaking. The work you're doing is inspirational. I think we're going to be seeing and hearing from you quite a bit more. Your book, The Longevity Diet, is groundbreaking, and I wish you only the best as you continue to do more research. And it's an honor and a privilege to help you get your message out into the world. So, thank you for your time today. If you're interested in Walter and his work, pick up his book, The Longevity Diet. If you're interested in learning more about the fasting-mimicking diet, you can go to prolonfmd.com, and they have all the information there.

• 1:48:27Rich Roll?

  You have these kits that you can order. I think it's important to say that Walter himself does not profit individually off of this whatsoever. All of the money that he earns from this goes directly into funding research with... What's the organization called?

• 1:48:42Valter Longo?

  CreateCures.org.

• 1:48:43Rich Roll?

  CreateCures. And what is CreateCures doing?

• 1:48:45Valter Longo?

  Well, CreateCures is a foundation that I started with the idea, you know, I had, like, every day I have 10 cancer patients or people with autoimmunities and whatever are disease, and they're, like, desperate. And, you know, I realized that it doesn't matter who you are, whether you're poor or rich, there is really very little out there that helps you with a... in a, you know, in a serious way and say, "Okay, you have cancer." I mean, there's a lot of quackery out there, but it is not too many people, other than the oncology that tells you, "Here are the drugs we're going to give you," than people who are faced with internet.

• 1:49:14Rich Roll?

  Right.

• 1:49:15Valter Longo?

  Good luck to you, you know? And so, CreateCures is really about what can somebody do today, not 20 years from now, but today, that is going to make their therapy more effective, it's going to make the side effects lower, so it's going to help them. And, you know, in some cases, we left down the clinical studies, in some cases, we haven't, but the patient cannot wait, and so we sort of have to act now. And that we felt is important. We're doing it all over the world now with many, many different hospitals, and we're starting to see, you know, the doctors slowly being, you know, converted into understanding this difficult situation where you cannot wait... You cannot tell somebody with stage IV breast cancer, for whom immunotherapy is now working, "Oh, you know, these guys in 10 years are going to have something for you," you know?

• 1:49:59Rich Roll?

  Right, exactly. Fantastic. Thank you.

• 1:50:03Valter Longo?

  All right.

• 1:50:03Rich Roll?

  And you're not on Twitter, right? Well, ProLon's on Twitter, ProLon FMD.

• 1:50:08Valter Longo?

  No, I have a Facebook, Prof Walter Longo Facebook page where we put just articles about, you know, anybody that we feel, we sort of have a couple nutritionists and dieticians screening papers. And if we feel something is good, you know, then we'll put it out there and we usually associate it with like an article from a newspaper that describes what it is.

• 1:50:28Rich Roll?

  Cool. So I'll link that up in the show notes. And are you, do you ever like get up in front of public audiences to talk?

• 1:50:35Valter Longo?

  Yes, yes, I do that from time to time. And yeah, so.

• 1:50:40Rich Roll?

  Is there anywhere where there's a schedule?

• 1:50:42Valter Longo?

  We do a Facebook Live maybe once every couple of months.

• 1:50:46Rich Roll?

  Oh, cool.

• 1:50:47Valter Longo?

  Just so people can, you know, ask questions and login and ask questions.

• 1:50:52Rich Roll?

  All right. Thanks, Walter. Appreciate you.

• 1:50:55Valter Longo?

  Thank you. Thank you, Rich. Great to be here.

• 1:51:01Rich Roll?

  Yeah, man, that's some good stuff right there. I hope you guys enjoyed that. I very much enjoyed it and really appreciate Dr. Longo coming and sharing with all of us today. Do yourself a favor, pick up his new book, The Longevity Diet. It really is a game changer. And let Walter know what you thought of today's conversation. He's not on Twitter, but you can reach him on Facebook at facebook.com/profwalterlongo. And you can learn more about the fasting mimicking diet at prolonfmd.com as well as at prolonfmd on Twitter. I think I'm going to give this a try when I get back from our retreat in Italy and I'll be reporting my experience, my findings back to you guys. As always, check out the show notes for links and resources related to today's conversation

• 1:51:45Rich Roll?

  to expand your horizons of this conversation beyond the earbuds. You can find all that on the episode page at richroll.com. Quick reminder, Plant Power Way Italia, our brand new cookbook, is now out. If you haven't done so already, pick up your copy today from Amazon or your favorite independent bookseller, or Barnes & Noble, or wherever you buy books. I guarantee you, you're gonna love it. If you enjoyed the Plant Power Way, our first book, this one is next level across the board. 125 delicious, plant-based recipes inspired by the rich culinary tradition of Italy. If you want even more amazing plant-based recipes, perhaps recipes that are not Italian, check out our meal planner at meals.richroll.com.

• 1:52:26Rich Roll?

  We have thousands of plant-based recipes, literally thousands, all super customized based on a detailed rundown of your personal preferences. How many are you cooking for? How much time do you like to spend in the kitchen? What is your culinary acumen? What are you allergic to? What do you like? What do you not like? We also have unlimited grocery lists and even grocery delivery in most US cities, and we're expanding that capacity internationally as we speak. All of this comes to you for just $1.90 a week when you sign up for a year, and you can learn more at meals.richroll.com, or click on Meal Planner on the top menu on my website, richroll.com. If you would like to support my work, subscribe to the show on Apple Podcasts or whatever platform you enjoy this content, just tell a friend.

• 1:53:10Rich Roll?

  It's as simple as that. Also, you can support my work on Patreon at richroll.com/donate. I want to thank everybody who helped put on the show today. Jason Camiolo for audio engineering, production, show notes, interstitial music, a lot of behind-the-scenes stuff. Blake Curtis for video, and Margot Lubin for editing and graphics. And theme music, as always, by Analemma. Thanks for the love, you guys. Back here soon with another great episode. Until then, treat yourself right. You deserve to live well and long. Peace.