Episode 549: Dr. Valter Longo: What 30 Years of Longevity & Fasting Study Reveals About The GLP-1 Trend

Hi guys, it's Tony Robbins. You're listening to Habits and Hustle. Crush it. Welcome to Habits and Hustle with me, Jen Cohen, where we break down the mindsets and strategies behind extraordinary lives. Today, I'm joined by Walter Longo, one of the world's leading voices in longevity science. He's a biochemist, director of the USC Longevity Institute, and the creator of the Fasting Mimicking Diet, backed by over 40 clinical trials. For more than 30 years, he's studied what actually helps people live longer and healthier. Not trends, not hype, but what the science consistently proves. And what he's found challenges a lot of what you're hearing right now, from intermittent fasting to high-protein diets to GLP-1 drugs. In this episode, we break down what really works, what doesn't, and the simple science-backed approach your body is designed to respond to. He also shares how he lives himself. No shortcuts and no extremes. This one will change how you think about aging and your body's ability to heal. So let's get into it. we today have a very special guest on habits and hustle we have someone that i've been wanting to have on the podcast for probably like three or so years i've heard exceptional things about him and i'm sure you guys have already heard of him his name is dr walter longo he is a doctor and he's gonna actually you know before i'm not even going to tell you he's going to tell you himself. Dr. Longo, what kind of doctor would you say you are? You obviously do a lot of longevity, cancer research. Right. Yeah. So I have a PhD in biochemistry from UCLA next door here and an undergraduate degree in biochemistry and what's called post-doc in neurobiology. So it's a training that you do after the PhD in neurobiology. But I've actually been trained in a lot of different disciplines, you know, from endocrinology to oncology to, you know, gastroenterology or at least, you know, the clinical research part of that, right? I'm not a medical doctor. I don't practice medicine. But I certainly do a lot of clinical trials, human clinical trials on all these topics. Well, I got familiar with you a little bit before, but you wrote the book Fasting Cancer. This is my latest book. That's your latest book? My first book was Longevity Diet, which was 2018. Yeah, like seven or eight years ago. Right, right, right. But when did you write Fasting Cancer? When did it come out? No, Fasting Cancer came out very recently, like six months ago, yeah. So I was familiar with you, of course, before that, but that was the book that really kind of struck my, like the whole idea of cancer to me is the scariest thing in the world, right? To most people. To most people. It's like the biggest fear of everybody. And so that when I saw the title, I was like, oh, my God, like I need to like delve into all of the stuff and all the research because you've been doing so much research on longevity and obviously aging and fasting. I mean, can you tell people just let's start with the thing that you're most known for, right, which is the fast mimicking diet, longevity diet. What is kind of your whole hypothesis that we should be fasting? it's what should we be doing in terms of like how do we live the longest and healthiest right so that's really my focus and the focus of the institute that i started at usc is how do we make people live as long as possible as healthy as possible right that's what we've been working on for 30 years and even before then when i was at ucla i was a student roy walford and roy at the time was the most famous person in the world he was a medical doctor at ucla and he was focused on how do you make people live longer healthier and um yeah so i think that um after all these years when we come up with i came up with something called the longevity diet and then i came up with something called the fast mimicking diet so these were also we were also thinking about things that are feasible right that people can actually do and not just something that's very beneficial. For example, we can go into it if you want, GLP-1, right? Most people abandon them, you know, within a couple of years. And you, for those to be effective, you need to do it permanently, right? Or certainly very, very long term. So to us, that's not feasible, right? That's not a good idea. It may work. You may get very good effects short term, but then what did they achieve? Maybe I achieved that I gave you side effects and then now you regained all the weight and you're even unhealthier than when you started yeah but so the longevity diet is the what do you do every day right and and the and the fasting making diet instead is what do you what can you do once in a while right is it possible that you can just do in this case five days of a vegan diet that mimics fasting right so then the idea was first developed in in simple organism then in mice and then in people can you eat but get the same responses molecularly as if you were water-only fasting. And that's what a fasting-making diet is. So it's a low-calorie, low-protein, low-sugar, high-fat, plant-based diet that does all these things that water-only fasting does. But it has advantages because, of course, it has salts, it has carbon sources, meaning it has energy backups, right? Glycerin, I saw it. Does it have glycerin? is glycerol and yeah and the glycerol the job of glycerol is for example people um going back to glp1 right so glp1 uh receptor agonist most of these drugs you lose two to two to one or three to one parts of fat for limb mass right yeah so you're losing a lot of muscle essentially while you're doing this and uh and so in the with the fasting mimicking that we don't see that right and one of the reasons is because it's an evolved process that has the job of just making you lose the fat you know you don't want to lose all right if you think about history and you're fasting you do not want that organism to be losing muscle right right you want to have it so that the muscle is protected and one of the ways the muscle is protected is glycerol right so the fat is broken down and glycerol now can be used to make sugar for the brain and instead of taking muscle to make sugar through what's called gluconeogenesis. So now the glycerol is used to feed the brain instead of the muscle being used to feed the brain, or certainly amino acids released from the muscle used to feed the brain. So this is just one of the many tricks that we have in the fasting-making diet to make sure that we get lots of benefits and no side effects or very little side effects. So let me start from the beginning. Okay, so you first write this book in 2017-18, The Longevity Diet. Now, is the longevity diet, is the diet the fast-mimicking diet? Are they one and the same? No. The longevity diet is everything, including the fasting-making diet. So the longevity diet is, for example, a pescatarian diet, fish plus vegan or fish plus vegetarian, actually, probably. And those seem to optimize longevity but also minimize frailty, right? So people can live long but can live long frail. For example, the southern Italians are famous for many having a lot of centenarians, but the southern italians are also some of the most frail people in europe right so you don't want to have you want to live a hundred to a until 100 and be sick for 30 40 years or even be frail i mean you know you cannot go up the stairs or you cannot go for a walk or you cannot do lots of things that you want to do yeah so that's um that that's what the this longevity everyday diet is And then it has other components, for example, 12 hours of eating and 12 hours of fasting per day, right? So we're staying away from the 16-hour, 18-hour fasting for lots of reasons, which we can discuss. But we picked the 12 hours because of safety, feasibility. People can do it. But also because it just takes longer for it to be effective. but in the end, it can be very effective without the problems that the 16 hours causes it. What's funny because, actually not funny, I mean, fasting for a long time was very trendy, very trendy, like the intermittent fasting, the water fasting. And I feel lately it hasn't been as popular, right? Because people are coming back and saying it's not something that people like to do whatever and i was noticing that the people that were like super into fasting they were like shortening their windows from like a four-hour window like it went from like the 16-hour window to the eight like to the there's other people they're only eating within a four-hour window you're within a two hour i was gonna say some are even in a two-hour window yeah or not eating at all for five days with the water fast why did when did you realize and what are the what are the benefits of or what why now have you noticed that doing 12 hours is just even better than doing a 16 or these long stretches of diet i mean the longevity diet is is uh based on five pillars right but but meaning that it's not just a lot of diets are based on epidemiological data right you look at these studies of which this which that and how do they compare the longevity diet is based also on centenarians. What did the centenarians all over the world, Okinawa, Loma Linda, California, and Sardinia, et cetera, et cetera, what did they eat? And then how do you make a mouse live longer? How do you make a rat live longer? How do you make a monkey live longer? And so those are all important in addition to the epidemiological data to come up with something that it's less likely to be affected by the new study, right? Somebody's, every day something new comes up. And if you do that, you're going to go crazy. Because then each, if you look at any study, they're always going to prove everything and everything against it, right? Yeah. And the opposite. So from the very beginning, we say 12 hours. I say 12 hours. Because, for example, I was noticing there was old data, but very good data. They were saying if you skip breakfast, you live shorter with twice or much higher levels of cardiovascular disease, right? And so then I started thinking, this is really strange. Is it just about the breakfast or is it about the 16, 18 hours of fasting, right? Right. And then, you know, there were also data showing that after 12 hours, your cholesterol, your circulating cholesterol level go up. The LDL levels go up and they keep going up the longer you fast. And then I was looking at data, and this is like 10 years ago, or gallstone and gallbladder operations. Women that were fasting for 14, 16 hours, they were twice as likely to need people with gallbladder disease, twice as likely to need an operation. So, yeah, so all of that from the very beginning. And then the feasibility. I was a student of Roy Walford back in the 90s, and he was talking about something called calorie restriction, which is what if you severely restrict your calorie every day of the year? and then I was noticing that nobody was doing that, right? And so I always thought, you know, it may be good for the lab, but it's not good for people, right? Because, you know, to do calorie restriction, you have to be losing a lot of weight. I'm already pretty thin. Imagine me minus 30 pounds, right? That's what calorie restriction looks like. Yeah, so I thought it cannot be something that pushes people all the time to the edge. And, you know, so the 12 hours made sense scientifically, clinically, and also made sense feasibility-wise. It's just easier, and most people can do it. And I think I got it right, you know. And now we're starting to see the data indicating it may not just be skipping breakfast. It may be any 16 hours. And there's a study published last year indicating that any time you do 16 hours, you are putting yourself at twice as much, twice as higher, twice higher risk for cardiovascular disease and also overall mortality, increase overall mortality. Really? What about, how about the fact that you just end up eating more? because when I, for me, when I skip, let's say breakfast, let's just go with the breakfast thing. When I don't eat breakfast, I'll just end up eating those calories anyway later on during the day because I'm just like, I'm making up for it. Like my body also has a, I don't, what do you believe in like baseline? Like, do you feel like everyone has a baseline weight that you can only modify so much where it gets to be uncomfortable? Or do you think that we can all, or is it not about that at all? I mean, I know you take it from a health perspective, but for the weight piece of it because a lot of people are doing the fast for weight as well right right yeah so first of all the the breakfast keepers uh there was no other information it was just people just keep breakfast yeah they do worse right yeah and for a long time the idea was all they do worse because they have bad behavior there yeah but it doesn't look like that right it doesn't look like that's what it is yeah so i think that it probably is about fasting right for so long right it's just too long and and somehow the body is particularly if it involves if it's 16 hours and involves skipping breakfast the body you know has negative responses right it does it turns into a modality maybe it's the cholesterol maybe something else but something is negative about it right and then you know the this your second question about the the weight it's yeah the body likes to go back to a weight that at which you were stable right so if somebody's overweight 30 pounds and you stay in this 30 pounds overweight long enough the body likes that because it understands that that's a good situation right it might not be modern in modern time a good situation but it was for the history for a hundred thousand years right you know homo sapiens have been around so so it tries it tries to keep you there it tries to keep you there but that's where the fasting mimicking diet kicks in, right? So, for example, in the documentary, you know, it's going to be shown very soon, and the premiere is going to be shown. In the documentary, we're showing that the body likes to go back to a certain weight where it's stable. And so if you try to move it, and so in the documentary, we're showing a doctor, right? In this doctor, we had, was overweight, obese, hypertension for a long time. And so we put him on the longevity diet, on the everyday longevity diet. And the doctor after nine months doesn't change at all. He loses a couple of maybe three or four pounds, but doesn't change at all. Then we start the fasting-making diet. So again, he had been about maybe 90 kilograms in a very steady way. And so the longevity diet, this like maybe Mediterranean diet, but taken to even more extreme, doesn't do anything, right? So now we put him on the fasting-making diet. So in about six months, the following six months, eight months, he does three cycles of the fasting migi diet. Then you see his weight comes down, his glycemia comes down, his blood pressure comes down. Now he gets rid of, he was on Zampik and other drugs. He gets rid of drugs and he gets rid of not just the glycemia drug, the diabetes drug. He gets rid of the hypertension drugs and his weight goes back to normal, right? So probably what happens is that we are locked, people are locked in the weight modality until there is a very strong message switch, right? Get out of it, right? Get out of it because now you kept the fat and now the three cycles of the fasting making that come around and it just pushes you to start burning fat versus accumulating fat, right? So, yeah, so people are stuck, but they can get out of it. The fast-fimicking diet is certainly a good way to do it. So the fast-fimicking diet can actually trigger you to get out of that baseline diet that you're been stuck with. Yeah, the fast-fimicking diet can do that. But now I think it's important for people to understand that if you go too long, right, if the restriction is too long, and these are studies that have been done for a long, long time, now you can get into something called the thrifty mode, right? And the thrifty mode now is tries to save energy as much as possible, right? So if you fast for too long, that doesn't happen. The body doesn't switch into a catabolic, into burning fat. If you fast for too short, if you fast for too long, now the body starts being worried about, I may have to save energy because I might die like this, right? So if I don't start putting away, keeping the fat, then I'm going to be in trouble. And so now you enter this thrifty mode. In this thrifty mode, we're worried that it may be epigenetic, and that may be why it's so hard for people. Once they get into this fat-saving mode, it may be so hard for people to get out of it because basically everything tells you eat and go maybe in a lower energy expenditure mode, and that's what was shown, meaning you are burning less calories. Right, right. If you enter that, then you get a problem. You get the opposite problem. So if you do too short, you don't enter the catabolic mode. If you do too long, you enter the energy saving mode. And this is why people underestimate the power of understanding the science and understanding that you have to do it just right. So then you unlock it and you can keep going. And now you can go to a different weight, right, which could be 30 pounds lower than you. Right. It's a very delicate balance, it sounds like. Well, it's a delicate balance because it's a program that is there to protect you from starving to death. Right. And it's also, you know, there to protect you from, hey, maybe it's good to keep saving fat, right? Right. And in the majority of the history of human beings, and not just human beings, any organism, you know, starving, it was a real possibility, right? Right. And so, you know, and there is no more pressure, natural selection pressure than starving to death, meaning that evolution is very much aware of the danger that could kill you. And then it wants to eliminate those as much as possible. And certainly starving to death is probably one of the most common ways that people have died in the last, you know, 100,000 years. Wow. So can you just give us a very brief description of people who don't know and they're not familiar with what the fast mimicking diet is? What does it contain? If someone says, hey, Dr. Longo, what is this fast mimicking? What do you mean by this? Yeah. So the fast mimicking diet, when I first developed it 20 years ago, I started developing it. The idea was to first make it fasting mimicking. And then you use a lot of, again, low protein, low sugar, relatively low carb, but not too low. So your body, just to interrupt you so people understand. So when you say fast mimicking, it's basically your body thinks it's in fast mode. But you're basically giving people little things to eat and drink to supplement so they don't feel that ravenous feeling and deprivation of a normal fast. Would that be? can yeah the deprivation uh but also um i think that it's very important to the deprivation also includes the just the opportunity to stop and have a meal right so yes people i think there is a problem with you know you need to have a certain amount of foods and calories but also the routine of having breakfast of having lunch right psychologically yes psychologically that's very important and then of course lots of other things that that need to be in there uh like i mentioned you know the the salts and all of that yeah so then the fasting making diet as the i mean the molecularly and without going to the details there is four markers you know igf1 insulin like growth factor one has to go down glucose has to go down and then something called igfbp1 which is an inhibitor of the growth factor has to go up and then ketone bodies they have to go up right so Ketone bodies are these byproducts of fat breakdown. And so this is where ketogenesis, the word ketogenesis, comes from. So now this diet that I just described, lots of vegetables, lots of nuts, lots of oils, olive oil, they have the job of changing those markers. And, of course, the fasting-making diet theoretically could be made with lard, for example. Theoretically, even lard will make it a fasting-making diet, but it wouldn't make it necessarily a healthy fasting-making diet. Right, right, right. Okay, yes. Then the idea was let's match the fasting mimicking properties with the very healthy ingredients of the longevity diet, let's say, right? So can we take ingredients from Okinawa, from Loma Linda, from Italy, and then use those to make the fasting mimicking FMD? Yeah. So is there like a so when you do a fat like you basically was it a lot of trial and error to figure out the exact like you had like to kind of figure out what to do, like the balance like 20 years ago. How were you kind of figuring this out? Like what was your team doing? Were they trying different foods? Were they incorporating? Were you trying it in rats? Like, how did you kind of figure out this ratio of salt or glycerol or whatever you put in that thing, like, to figure out that perfect balance of how your body doesn't feel deprived or it's not burning lean muscle? Because that was the other concern, right? Like, people don't want to burn lean muscle. So that's another thing. How did you kind of figure out the measurements? Like, how did you get the recipe, so to speak? Yeah, I mean, we've always focused on the genetics of longevity and the genetics also of weight loss and weight gain. So we already started from understanding the connection between ingredients and the consequence of having that ingredient, right? So then it was just a matter of testing it out. So, for example, you know, we knew that we had to have low protein in the diet. And now people shouldn't mix the longevity diet with the fasting-making diet. You know, the longevity diet is normal protein. The fasting making diet is very low protein, right? But it's not just the protein, but the amino acid content. So meaning that you could have a relatively low protein content, but if it comes from one source, especially animal source, the amino acid that we want to have very low, and usually what's called essential amino acids, the amino acids are high, are too high, right? So it's not just protein level, but then protein type. And even between two vegetable sources, you can have a two, three-fold difference in the content of certain amino acids, right? So then that's why, you know, you want to have – so we were more thinking about amino acid level, right? Really? Yeah. And then we're picking protein sources, just to give you an example with the amino acids, protein sources that will contain low levels or higher levels of those amino acids. Yeah. So then everything in the FMD goes through that reasoning, you know, whether it's – you know, fat. And so you could have any fat, but then you have olive oil and it's got monounsaturated fats. And so each ingredient was tested in mice. And then we're looking for the effects in mice. Then first, you look at the short-term effects, right? What happens in a couple of weeks. But then eventually we started doing the lifelong studies, right? And that's really, those are the very expensive ones and they're the ones that you need to then have a chance to make somebody live longer healthier right so for example a few years ago first we did it in normal mice and then we did it in mice that were fed a very bad diet right so we wanted to test both right and um and you know for example the mice that had a very bad diet uh this was published a few years ago we showed that you know they get very big right and they get very unhealthy and and uh um And it's really remarkable how unhealthy they become. Because I thought, what's a Western diet going to do to a mouse, right? I thought maybe I'd make it a little bit shorter. It almost cuts their lifespan in half, right? And it just completely messes up cholesterol level, heart function, inflammation, insulin resistance. So, okay, so this is a bad diet, right? Fine. And the mice become very big. Then we start with the fasting-making diet once a month for five days. And we thought it's probably going to make them a little bit better, right? We thought just mice on the normal diet and mice on this really bad diet. And the mice on the bad diet for 25 days a month and a good diet for five days a month, they're going to be in between. They were not. They were like identical to the mice on the good diet. And so that was very surprising to us. Wow. So just five days a month of this FMD, how can it be? 25 days it five times as much bad diet than good diet And yet the five days were enough to bring everything back Cholesterol heart function glycemia insulin resistance name it So now we just finished a 500 trial in southern Italy with overweight and obese people I cannot talk about the results. Why? Because it's not published yet. Are they good? Well, we'll see. But the idea is, is it possible that, you know, it's not really about good food and bad food. It's about the role of the bad food. So we think of bad food as something that every day does a little bit of damage to you. But that study showed that it's not true, right? Because otherwise, you know, you got 25 days of damage every month. Right. So then you don't come back from that with five days. And so, you know, either there is a regenerative process that brings you back or maybe the food is just pushing you into a modality which then accelerates the aging process. So it's not doing damage, but it's just pushing you, let's say, in an insulin resistant modality, in an inflammatory modality, et cetera, et cetera. And that eventually, if you don't unlock it every month, then that makes you age faster. So, okay, so you said a few things. So one question I have is how have you revamped the diet from 20 years ago to now? Like what are some of the findings that you have kind of revised that you know now that you didn't know back then? Well, I mean, 20 years ago, it was the mouse version, right? Right. And we use it for cancer. You know, now there's a lot of fast-mimicking. There's one for Alzheimer's that is very different from the one for everyday people. It's very different from the one in cancer. Cancer is much lower calories. So let's talk about that. So you basically took the diet and kind of tailored it to disease-specific. So there's a specific fast-mimicking diet for an Alzheimer's patient versus a cancer patient versus… Versus autoimmunities, yeah, versus diabetes, versus pre-diabetes. Wow, talk about that. I'd like to know the difference. How much different can they all be? Well, I mean, for example, the cancer one is much lower, 600 kilocalories, because with the cancer, we need to get quickly in and out, meaning that the cancer patient gets chemo and the chemo is gone within a few days. Let's say it gets chemo. It could be getting chemo, it could be getting immunotherapy, kinase inhibitor and lots of different therapies. So we need to try to achieve these changes in IGF-1, et cetera, that I talked about before quickly, right? And so because, you know, we don't have the time to get there more slowly. But for Alzheimer's, for example, it's the opposite. We have high calorie. We add an extra 300 or 400 kilocalories per day because now we're dealing – we just finished a trial in Italy. we're dealing with people that might be as old as 85 90 and we cannot give them a 600 kilocalorie which is what we so for normal people is 800 to 1100 kilocalories per day for cancer is 600 and for alzheimer is 1400 right so yeah because we don't want to push somebody's 85 right to a very restricted diet and and you know that was probably a good idea because so far we've had very little, you know, high grade toxicity, meaning like the type of toxicity that makes the doctor worry, right? So it's minor things like a little bit of a headache and things like that. But you really don't see that we haven't seen very much of the grade three, grade four toxicity, which makes worry, makes clinicians worry. So what do you do in the Alzheimer's fast mimicking diet? like besides adding more calories are you just adding bigger portions what are you adding any specific ingredients and we're adding lots of i mean in the alzheimer is not just uh calories it's also other things so we add caffeine and it's a ketogenic supplement that we actually give give patients between the cycles right so so they did a cycle and then all day 25 days in between cycles that got these 300, 400-kilocalorie ketogenic supplements. So high fat, very healthy, most of it from nuts and olive oil. But there was also caffeine and some other things in there that have been associated with protection from cognitive decline. So, you know, Alzheimer's is a little bit special because there's really nothing out there that works, right? And so we felt, let's just go all the way, which we usually don't do because then if you put all these things in there, you don't know what worked. But we thought, especially because we were talking to neurologists, I remember, six or seven years ago, and they were telling us, you know, good luck, right? Because by the time somebody's got early Alzheimer's, I mean, their brain is so damaged that it's going to take a miracle for anything to bring them back, right? That's when we started thinking, okay, let's just go with everything we can. And, yeah, we'll see. But in mice, it works very well. But, you know, I think it's a lot rougher. because in mice we start early right right yeah if you start in an 82 year old patient that has already been diagnosed with alzheimer it's not helping yeah we don't have high hopes yeah it's you're right past the point i'm also asking because my mother was diagnosed with alzheimer's recently a year ago i'm looking thank you and i'm looking for anything and the truth of the matter is like once you've kind of hit some a place there's nothing that you can really reverse yeah i mean Everything is possible, but it's extremely complicated compared to other diseases, right? Once the nervous system is badly damaged and, you know, your brain undergoes atrophy and a lot of the brain cells are lost. So, yeah, it would take like some remarkable regenerative process. To do it. Yeah, to bring it back and bring it back without doing damage to the very delicate nervous system, right? So it's not just you got to bring it back, but, you know, you also have to save what's left that is still working. Exactly. Because Alzheimer's patient can still function relatively normal physically, right? Not all of them, but many of them can. And so you have to preserve all of that. You cannot add to it. And then, you know, you have to restore learning and memory. But it's just, it's a rough, you know, enterprise. It is. What's interesting, though, people who have been diagnosed with cancer have been prescribed fast mimicking diets. It's been kind of known and researched to have had pretty remarkable results on cancer patients. Yes, so there are many trials now on fasting-migging diets and cancer. And the one that is most studied is triple negative breast cancer for good reason, right? The triple negative is much more aggressive. Mortality is very high at five years, right? And that's one of the most common cancers in the planet. So the multiple trials now are showing patients that did chemotherapy alone versus, So, I mean, patients with fasting-mimicking diet plus chemotherapy versus chemotherapy alone, they do much better, right, survival-wise. How much? What's the percentage? Four years, about three and a half, four years, it was about nearly twice as high, the survival, in the FMD plus chemo versus chemo alone. Oh, wow. Yeah. And then the new study, which is published by the Vernieri Group, is showing progression-free survival, which is not overall survival, but it's like how long you live without the cancer progressing, right? So they're showing improvement in that and also improvement in what's called complete pathological response, which basically is what they call a surrogate for overall survival, right? And so this is much higher in the patients that do a fasting-migging diet compared to what they normally expect from the database, right? So, yeah, so then multiple trials are now showing with some of the most metastatic, in the metastatic cancer, the most aggressive. The initial trials are very promising. Now, for the earlier type of cancer, somebody is going to receive, let's say, surgery. That's a different story, right? So we're trying to be maybe more careful, and we're saying, you know, if you have a 98% chance of being cured, maybe leave it alone, right? You know, just take your 98% and don't. So the foundation that I started, they follow lots of cancer patients every year, and usually they put them on a longevity diet, the 12-hour time of sitting eating and lots of other things, you know, muscle training and aerobic exercise, but they don't. We usually, in the early stage cancer patients, we don't. Not that we have any evidence that it's not good for you, but, you know, certainly it makes a big difference for mice and cancer. But we're just saying until there's a trial that is showing superiority versus the therapy alone, we just don't feel like we should recommend it. What about protein? Because you said like the longevity diet, you said it has five pillars. We talked about the centurion pillar. We didn't talk about the other four. But that has fish in that. You said it has fish in that diet. Fast mimicking is vegan, like you said. What is your take on protein? Because do you believe that too much protein can actually age you quicker? Yeah, I'm writing a review now on proteins. And it's interesting, right? Because if you look at overall all the science that has ever been done, if you, you know, proteins, what's called calories, is what I was talking about earlier, which is normal calories, you reduce it by, let's say, 20%, 25%, right? That's the most successful anti-aging method ever done, right? If you look at, you know, thousands of studies, right? By reducing your calories by 20%. Yeah, reducing and not below excess. I mean, reducing it is normal calorie intake, let's say, whatever, 3,000 kilocalories, and you reduce it by 25%, right? And that's the best aging, that's the best way to slow down aging. Yeah, if you look at the literature, that would beat any other intervention because there are literally thousands of studies, including human studies, showing remarkable effects, right? And so if you think about the second one, it's probably protein restriction. Or if you think about it, the only one that doesn't require you to eat less is protein restriction. Mice, rats, you know, and the monkeys, they live longer. They were caloristic, but also protein restricted. Yeah, so I think if you look at all the studies, the indication would be that a sufficient but low-protein diet that is mostly plant-based is going to make you live longer or a lot longer. Now, if you look at the epidemiological data only, which is what most of the podcasters, let's say, talk about, then you could get lots of different answers. You can get high protein is good for you, mid protein is good for you. That's why I'm asking, yeah. Especially in the fitness and wellness world, right? We're all told that we need to be eating a lot of protein, especially in midlife, right? Like to keep lean muscle on. All you hear now is protein, protein, protein, creatine, creatine, creatine, like anything to kind of increase your protein. So you're saying the opposite. You're saying if you want to live longer and age better, stop eating so much protein. Yes, for sure stop eating so much protein, but have enough protein and have proteins that include proteins, let's say two-thirds of very good quality amino acid profile, right? So, for example, if all your protein is coming from legumes in your law, you're going to have a problem, right? Right. Yeah, so I think the vegans, you can be vegan and very healthy, but you need to pay attention to what you're eating because otherwise you're going to end up being malnourished, right? So it's a lot easier. And this is probably why the doctor has always recommended, yeah, eat a little bit of everything. Yeah. Because it's much less likely that somebody eats meat once a week and fish two or three times a week and chicken. Those are going to do pretty well. Now, they're not going to do as well maybe as those that are vegetarian and they have a more restricted diet. But they're generally going to do pretty well. So then you have to look at what you're trying to achieve. So if you're trying to achieve a long lifespan, but you also want the strength, I think it's probably good to – I go back to the pescetarian diet, pesco-vegetarian. Right, like fish. Fish, but also some eggs, maybe up to three eggs a week. Only three eggs a week? What if you eat three eggs a day? Well, I mean, the data indicates that, you know, after three eggs a week, you know, in general, I mean, let's put it this way. They're not lots of we're going back to epidemiological studies. Lots of studies say it's fine. Right. If you have if you don't have too many eggs. But some of the biggest ones are showing that past three eggs a week, you're starting to see a mortality increase. Right now, you know, it's it's an association. It doesn't mean the eggs were causing it. But that's not a good start. If you start seeing this particular food, the eggs are normally not associated with living long, meaning it's like legumes are, and whole grain wheat is, and nuts are, and olive oil is. But the eggs, you don't see it. So it's either neutral or negative. That's usually where you see it. Now, red meat is always very negative. And then white meat, it's negative to neutral. and eggs and and there is usually you know neutral to bad yeah so i think that probably okay for most people like if somebody has to have lots of eggs it's probably okay but you know maybe not maybe not if you're saying like maybe it's neutral at best is neutral at best at best yeah so but okay So dairy, like Greek yogurt, would that be neutral? Generally, lots of the dairy would put them in the center, right? Neither good for you. So, for example, this is very nice work done at Harvard, looking at what are the ingredients that are going to get you to 70 or 75 healthy. And, you know, and you have the, in this case, fruits. I'm not you know I think it should be more limited because if people hear you know fruit is at the top then they can you know eat too much fruit yes but but I say you know vegetable and fruit and nuts and legumes and a whole grain were at the top and then you know the bread meat and the processed meat was at the bottom right and then you know and the lots of the the eggs and the dairies and the yogurt and in the center right so probably you know if you're not looking for a record, you know, if you, most people are not looking to get the record longevity and they're basically, it's not a bad compromise to eat, you know, yogurt or any, and of course it's very high nourishment, right? So then certainly in the, as you get to 65 or older or 60 or older, those are probably the type of ingredients that might help you not become frail. So, So then there's also the idea of different stages of life. For different foods. For different food and food quantities. Right. So once you get to a certain age, then most people start losing weight. And that weight loss is usually associated with living shorter. Right. Right. So that's why when you get to 65, and for somebody it could be 60, for somebody else it could be 70, right? Right. Chronologically, chronological age. So when you get to that point, you want to stay there and stay strong, right? Right. And so, yeah, so to stay there, stay strong, some people might have to have, you know, yogurt and eggs or more eggs and more yogurt. Some people may not, yeah. I guess you're right. You've got to think about all the different, like, there's so many different benchmarks that you're like, or like different variables that you're looking at, right? To like what will make someone healthy. But you're saying that, what's fish, do you think fish is neutral? No, no. Fish is positive. Fish are neutral to positive. Neutral to positive. Yeah. Okay. The pescatarian, the pesco-vegetarian, they tend to do better than everybody else. What about salmon that's farm-raised, though? Like fish that's farm-raised, is that still neutral to positive? We don't know that, right? So we know there are toxins associated with it. And so usually the recommendation is maybe eat it once a week, right? So if you have a farm-raised salmon, yeah, once a week. So you limit whatever toxins that are associated with the fats in the salmon. And because if you think about so many food, so much food, it's got toxins in it, right? So much. Yeah. And so if you went around and analyzed, so for example, I tell people, most people don't know that brown rice has got arsenic. Yeah, arsenic for sure. Yeah. So, I mean, and the mercury and the acrylamide. And a lot of it is in vegetables, right? And so, yeah, so I think that you also have to say, I got to eat something. So maybe rotate a lot, right? And don't eat the same foods all the time. And don't eat the same farm-raised salmon three times a week or the same tuna twice a week because, you know, the mercury poisoning is a reality. And so, yeah, so then instead of scaring people with, you know, don't eat anything, because then people go into the modality and say, well, I can't eat, you know, I cannot have anything. But, yeah, you can. But try to, you know, if it's salmon, if I'm raised, make it once a week. So what about you? Because you said that brown rice does have arsenic, which some of us know. Do you recommend to people to have white rice then and stay away from brown rice because of that poison? I mean, it's a poison, right? But, you know, if you had, let's say, once a month, it's got maybe twice as high as some of the white rice, right, or two or three times. it's not like 20 times higher right yeah so so i think that the bigger problem comes in when somebody and you i i meet these people all the time they say i eat it three times a week right that's when you're going to get in trouble right and that's when you may get end up with arsenic poisoning like mercury right so if you start having swordfish and tuna three or four times a week that's going to be a problem if you have tuna once a month you're probably going to be okay You'll be okay. What do you eat? What does your diet look like? Yeah, my diet is really everything that I preach, right? So I have a lot of whole grains in the morning, for example. Then I have like an almond spread, both of those I get from southern Italy, and I store them. And then, you know, I have some fruit, and then I skip lunch. And, you know, it's not necessarily a good thing, right? But that's an example of a compromise, right? So for me, whenever I don't skip, I've been doing it for 20 years, and that's the only way, together with the fasting-micking diet, that I can keep the weight that I want. That you want. Yeah. Going back to your question earlier, you know, my weight is probably set like 20, 25 pounds higher than I am. But you've changed it. To keep it there, I have to do lunch, and I have to do the FMD, and I have to do the longevity diet, right? So then at night I have these big, you know, minestrones with the legumes and lots of vegetables and olive oil and pasta. But, you know, I have maybe 75 grams, 80 grams of pasta and, you know. So the mistake people make is to have a lot of these starches and little nourishment, right? And you got to turn around. You have to have a lot of vegetables and legumes and little pasta or rice, right? white rice or brown rice. And, yeah, those are the ideal combination, right? And that's how people used to do it because they were poor, and that's all they had. You know, the minestrone is all over Italy, right? Because in Liguria you have the Genovese minestrone. And in the south, what it was is people were poor, and at a certain point they were running out of food, and they were just grabbing anything they had. and put it in, right, so that you get an extra meal. So that's gone now, right? Even in Italy, nobody does that anymore. And now you have these big, you know, rice dishes and pasta dishes and whatever else, right? The starches that, you know, of course, are going to make you gain weight and they're going to make you insulin resistant and they're going to make you die earlier. So how often would you suggest people even doing fast-mimicking diets? Like what would be the, what's the most optimal to get optimal results, to live the longest and healthiest? How often? Yeah, I think that it depends, right? So, for example, in the diabetes trials, it's every month for either six cycles or 12 cycles, right? These are patients that have diabetes. But the case that I told you earlier, this doctor only did three times, right? Right. In six months. And it still worked, right? so so i think that yeah you can start with the doctor in this case of in the case of a diabetes patient could start with every month and then move to once every two months and then every three months and and take it from there you know for everybody else i think maybe like three times a year three times yeah maybe even two i maybe i do once or twice right but i skip lunch you know and i do the longevity diet and i do everything else so so yeah to me it's not as uh i i don't need as many but you know most people are overweight and obese and and they have lots of other issues and so as those issues come around so for example stanford is published on on crohn's disease the university of miami published on the fmd and ulcerative colitis and university of rome published on fmd and iposmia the loss of olfactory function smell and taste right and the ability of the FMD to restore taste, smell, loss. So, yeah, meaning different people have or don't have different problems, and then they have to decide how to use the FMD based on where they start, based on baseline, right, where their starting point. What about fasting in women? Because there's a lot of chatter about fasting not being great for women, hormones, especially as women are in middle age? Yeah. I mean, fasting, again, is good, bad, and neutral. It doesn't mean anything. We just mentioned, right, 16 hours, 18 hours, probably not good, 12 hours, probably very good. And yeah, so I think that probably is very good for women and, you know, at least 50% of the patients in the many 40 clinical trials that are being completed now with the fasting-making diet, I would say the majority are women and And they did very well in the great majority of the trials. So, yes, working very well for women. I think what we still need to define, so, for example, we just finished a trial on polycystic ovarian syndrome and one on endometriosis. And we're going to be publishing those soon. And, yeah, I think the timing is still, you know, somebody's period, for example, when is the best time to do it? Right. So we were talking to endocrinologists and some of the female specialized endocrinologists saying, you know, maybe there is a period where it's not going to work very well. So I think soon enough we're going to start publishing, you know, don't do it in this moment. But, yeah, besides maybe that one week a month where it might not be ideal to do it, I would say that the effects have been remarkably positive. Can fasting help prevent cancer or can it help only when you've already been diagnosed and help potentially with the diagnosis? Yes. So there is no doubt that diet prevents cancer, meaning like if you have the perfect diet versus the bad diet. And now in mice, we were able to show about a 45% in female mice, 45% reduction in tumors lifelong. So big, big effect. But also, it looked like not only it was a 45% reduction, but many of the tumors were benign versus malignant. Oh. Yeah, so it's a dual effect. And they happened later. They were benign and they were much lower overall But yeah then you know whereas with some of the diets like midterranean diet you know there about like a seven percent lower cancer risk right more cancer mortality risk lifelong which is not a lot but you know uh better than nothing it's better than nothing and um yeah so for for these newer diets and more you know at least scientifically diets that have expectation to be much stronger like fasting-micking diet, longevity diet, we need to do a lot more work, right? So now we're starting to do the first trials with, you know, for example, the Calabria trial that we just finished. I also had an arm that was doing both the longevity diet and the fasting-micking diet, right? Yeah. So now, you know, we're about to publish several studies in mice that we do the longevity diet, you know, for the entire life. So we'll see now what they show on cancer prevention. But, yeah, the expectation is cancer will be lower or much lower. Or certainly it will happen later and it will be, you know, some of the malignant cancers will show up as benign tumors. So let's talk about the GLP-1s. We touched upon it at the beginning of the conversation. Do you think there's any potential side effects to GLP-1s? Like, do you think a GLP-1 could possibly show it's a cancer-causing medication, medication, peptide later down the road? Because people don't know, right? They've been using it for diabetes for so long or for many years. Yeah, yeah. And now everyone and their dog is using it for weight loss. Right. People don't know. And everything is possible. It's also possible that it's going to reduce cancer, right? So that will be the expectation based on... Because it does help with inflammation. it may help a little bit with inflammation but it just lowers your your your risk factor for cancer which is obesity and diabetes right right so those are risk factors for cancer and so if you reduce that uh you know then for example cardiovascular disease now we know that glp1 at least initial data, it reduces about 10%, right? So people on GLP-1 have about 10% cardiovascular disease, reduce risk. Now, you know, in my new book, which is not in English yet, it's called The Weight of Longevity, you know, I'm comparing it to just a Mediterranean diet. And I'm saying the Mediterranean diet seems to have a 30% decrease in cardiovascular disease, right? So now don't show off. Please don't show off the GLP-1 10% effect when the Mediterranean diet is showing 30%, right? And it doesn't have any side effects. And now we're saying that we could probably do much better than the Mediterranean diet. But even if you just use the Mediterranean diet, it's so much better, right? You get the weight loss and you get lots of benefits. So I think that there is a long list of side effects of GLP-1. And now the new studies are showing something very scary, which is you do it, you're going to need to continue doing it. If you stop, you're going to regain the weight. And when you regain the weight after you stop, you regain the weight much quicker or quicker than people that have lost the weight with diet. Right. So and at least the potential mechanism that I saw was that you're not making your own GLP-1 because, you know. you're getting the drug it's like when you take testosterone your body stops taking testosterone so it could be the same thing it could be the same thing right so this is what the scientists that published the paper i think speculated or they have some evidence for it but either way it was clear that wow they regain weight more quickly and so and probably because they were no longer functional right so so it's really condemning you to be stuck it's a little a bit like addiction, addictive drugs or, you know, addictive foods, right? So all of a sudden now I give you something that you can never get away from. A hundred percent. Also though, it's, if you're burning a third muscle, right? So you're burning some muscle off your body, your metabolism will obviously slow down. So when you get off of them, your body doesn't have the same accelerated metabolism or whatever metabolism you have because you don't have as much muscle to burn. Not only that, but now what you regain is fat, right? Right. So we're not even counting that you regain the fat more quickly, but you're not regaining the muscle or you gain a lot less muscle, right? Yeah. So that really may condemn you to be stuck on this drug that has got so many side effects for the rest of your life. I know. Certainly for decades. It's scary. Yeah, scary. And, you know, I think what's problematic, very problematic, is that the physicians are not saying this, right? The physicians are now saying, well, you know, and I can see that when somebody has tried. I mean, so if you look at our foundation, you know, sometimes we have doctors, we have PhDs, we have nutritionists, sometimes they cannot do it, right? So they can take somebody, and for most people, great, they do very well and they become better and they become healthy, but some people cannot. So I think it's fair to say, hey, I tried everything, we've been trying for three or four years, and it takes two to three years, as happened for the doctor that I was talking about earlier, it took them two years to get back to normal, right? From diabetes, hypertension, obesity, to a normal person, right? Right. And so if the team, let's say in his case, worked on him for three years, and after three years he's just still stuck on all these problems, then I think it's okay to be on JLP1, right? Right. And I think it's okay to say... If he tried everything. I tried everything, but not the way it is now. You go to the doctor and the doctor, you know, says, you know, I don't know if you want, spend the money and go to a dietician. Right. But the system is not really there to provide what we provide as a foundation, or the clinicians provide the foundation, which is, I'm going to follow you. I'm going to be your friend for the next two or three years so that we find a way to get you back to full health. That's not reimbursed. That doesn't exist. And so either you have the money to pay for it or you don't get it. And what you get reimbursed is the drug. Right. So the doctor says, come on, you know, I don't know anything about nutrition and I cannot follow you every couple of weeks and to see how you're doing. I cannot be your friend. Right. You know, so I'm just going to give you a drug to begin with. That's what the that's a big problem. Right. Then I'm just really surprised that the media are not talking about more and the doctors are not talking about it more. Say, hey, you know, please reimburse the rest. Right. because once the rest is reimbursed, then it's a fair game to say, hey, you need GLP-1, right? Because at least get that 10% lower cardiovascular risk because you're not going to be able to do the Mediterranean diet. You're not going to be able to do the longevity diet. You're not going to be able to do the FMD or whatever. And yeah, so then we do the second best and the drug is certainly valuable in that sense. Well, no, I've seen myself with friends of mine who are on it and they lost a lot of weight and they looked great. And then when they got off, they thought, oh, great, now I'm at lower than my goal weight. And they gained the weight plus more within a month. Within a month. People were gaining like 40 or 50 pounds in a month. That's scary. But even more scary is what is the chance that somebody can stay on it for five or 10 years? I know, exactly. Is that because I think it's over 70% abandoned within two years, right? But what about five years or 10 years? Because if the answer is 95% are going to abandon, then you're making a big mistake, right? Right. Everyone's going to be overweight again. Everybody's going to be overweight, but with all the side effects, they come with those five years of the drugs, right? What are the side effects that you've seen? Well, for example, neon. So this is ischemia, optic nerve ischemia. And then there is, you know, certainly studies showing both things, but certainly multiple studies showing depression, anxiety. Some studies are showing positive effects, but some studies are showing very bad negative, like doubling of suicide rate. So now who's right? I don't know. But certainly it's not good when you see all those studies in major journals indicating twice as high anxiety and depression and suicide rates. so yeah so then i'm not saying it they're they're you know conclusive meaning right or we know that but that's not uh you know a good association to to see those type of studies and so yeah then we just say the muscle loss potentially bone density although that that doesn't you know again the muscle is very clear the bone density is not very clear some studies are showing no no loss of bone density but then again it's pretty short term right so what if you did for 10 years you know then are we going to see then the bone density loss exactly we're going to see osteoporosis increase for sure somebody that has been on it for 20 30 years yeah so it's just a minefield and um and i think uh you know people are just walking through it right then what about the fact that like you said people get off of it or abandon it as you put it within two years why is two years the point where their people are just getting off of it yeah this is the papers that i saw multiple papers uh they don't show why so it could be that you're satisfied with what right you think you got it you think you got under control or it could be that you're depressed or it could be that that you have big side effects right so you know the doctor for example that we followed had major side effects right so yeah so there is a lot of gastrointestinal side effects and and lots of issues so yeah but for All the reasons combined that over 70% were no longer doing it. What about the fat? What did you think or have you heard that after a time period, people's bodies tend to acclimate on the drug? Because people can eat through their appetite. I have a lot of people I know who have worked great for a year, year and a half, even two years. and now they're just eating back to where they were because they've, like, their body became so acclimated to the drug. So unless you keep on increasing it and increasing the dose, you're kind of screwed. Yeah. I mean, that's certainly, you know, in need of more studies. But also, if you think about drugs, GLP-1 is one case, but also statins, right? They're really, we think of drugs as very sophisticated, right? So there's a lot of studies behind it. And, you know, now you have a molecular target and this is going after this receptor of GLP-1. But the drugs are really dumb, right? Because now you have the human body and this is like this perfect orchestra with every moving part. You know, there is three and a half billion years in the making, right? Three and a half billion years of evolution. And so now you have that. And what we were saying earlier, right? The fasting response and the fat is broken down and it's preserving, it's making glycerol. so the glycerol now is preserving the muscle. So this is very sophisticated. And now you're replacing it with, keep pushing the same button, right? Okay, so somebody's sitting there and pushing GLP one button all the time, right? If you think about it, it just doesn't look good, right, compared to this sophistication of the human body that now you have somebody pushing the button. So in the majority of the cases, it's just a matter of time before you're going to get bad results from somebody pushing the same button 10 times a day for the rest of your life, right? right? So, yeah. Well, they keep on coming up with a new, like it was first the GLP-1, now there's like, it works on two receptors with trizapatite, now it works on three receptors. Yeah, but the more you do that, the more you do that, probably you have now a potentially synergistic trouble zone, right? Because if one drug can cause problems, now two drugs may cause five times more problems, right? Or at least the potential, we don't know. Because now you're interfering with two pathways, right? And then if you have three, now you probably, you know, there's probably, I don't know, I'm speculating, you know, but, you know, now as you imagine, let's take a car, right? And let's take, I mean, a good example is that, you know, you take a laser that is very powerful, right? And you start using the laser running through your engine and every part of your car until the car goes a little bit faster, right? Okay. And then you say, okay, wow, you know, now I found a point where the laser, you know, it makes the car go faster. So let me keep doing that, right? And now you're going to do another laser, another hole through your car. So that goes a little bit faster, right? Well, I guess what's probably going to happen if you ask any mechanic? Well, by the time you have poked three or four holes in my car, it might go faster, but it's going to break down, right? Yeah, yeah, yeah. So you can think of this as the same way, right? It's really putting a hole. I mean, yeah, it can achieve an effect like weight loss, but it's really not coordinated with the rest of the trillion cells in the human body. Totally, yeah. It's just on its own, and it's just, you know, I put a hole in there, and that's not the way you want to make a car go longer. Yeah, so you're setting your car up for breaking down, right? Right. And so, yeah, so I think at the theoretical level now, and A, I'm saying at the theoretical level, but yet we know that every drug out there eventually, so the new data, for example, and statins shows that people that have less than 170 or so in LDL don't live longer, you know, don't have a decrease in mortality if they take statins, right? So I think that, and these are like JAMA, New England Journal of Medicine, you know, meta-analysis, right? This is not like one study. These are studies that are looking at all the studies. Right. And they put it together and say, hmm, that's really interesting. People that have, you know, LDL 160, LDL, not total cholesterol, they seem to do better than people that have very low cholesterol. So how do you explain that, right? And so, yeah, so I think at the beginning you get the story, oh, you know, this should be in the water, like statins should be in the water. They're so good for you. And then 20, 30 years later, you get the story. It's like, no, the meta-analysis, so maybe you shouldn't have taken it. So, yeah, so I think that, again, I'll go to the GLP-1 thing. If you need it, you need it, right? So some people, for example, the studies, I think it was New England, it was showing that for people that already had cardiovascular event, there is no doubt that statins were good. Right. It reduced your mortality by 10%, no doubt. So that was very clear even after 20 years. But that was the only group that seemed to be benefiting from the statins. and um yeah so i i think that we need to uh have a system that is uh they can help you do it the right way and then with all the tools like including the fmd the 12 hours and lots of other things you know that can help you because you know if it's not feasible if you're asking people to do something like italians in the mediterranean diet you know probably less than 10% of Italians are doing the Mediterranean diet. Why? It's just, people don't like to be told what to eat, right? And, and that includes me telling them what to eat. But this is why we're saying, okay, yeah, you can have the longevity diet and this is what we do in the clinic. Or you can have the FMD, right? And look at the mouse and look at the people, right? You know, they, they have a crazy diet and, and at least they do the FMD, right? So. Let's talk about a mouse for a second, right? Like, has there been any like data, about anything talking about how a mouse correlate to a human? Because I've seen studies that say that doing tests on mice doesn't necessarily correlate to how a human will behave or perform. It correlates. It doesn't necessarily mean that humans are going to behave the same way and respond the same way. So, yeah, most of the drugs that you see out there have been tested in mice first. So immunotherapy, chemotherapy, just name it. Cancer drug, diabetes drug, GLP-1, you know, everything goes to the mouse. And usually that's how it starts, right? It starts with, oh, it works for the mouse. And then let's come up with a drug that will do the same in people. Yeah, so the mouse is a very good model. What else can you test on? Well, you can test that in rabbits. You can test it in rats. You can test that in some cases they require monkey studies, you know, because it is so dangerous for a person. and so they may require a primate model. Yeah. But those are expensive and ethically, the medical field is trying to move away from using monkeys. But is a mouse and a rat the same thing, I would imagine? No, no. The rat, for certain things, is a better model, right? And the mouse is a better model for other things. It's easier to work with mice. But I think that, for example, we have shown the FMD cycles being able to cause reprogramming and stem cell-dependent regeneration in mice, right, in multiple. So the pancreas, the gut, and different systems. And so a year ago, we published, for kidney, we published it in the rat. And so we now show that we can damage the rat kidney and then start the fasting-making diacycles, and the rat kidney goes back to being functional after six FMD cycles. So that was particularly important for us because it's just unlikely that you're now testing in two different rodent models and you're getting very similar effects. So that makes your case much stronger moving to people. Of course, we've already done 40 human clinical trials. And in fact, in that trial, we had a small human trial for chronic kidney disease patients. And it worked, right? It worked very well for them, too, right? So it's preliminary, but it worked. So, yeah, I think that having studies in mice and rats and then in humans is the best way to go. Wow, okay. You have these labs both in USC and in Italy right now? Yeah, the lab in it is still open, probably close by the end of this year, but it's too much. But yeah, the Italian lab was focused on oncology, molecular oncology, so cancer. And in the U.S. lab here, USC is instead focused on aging and regeneration and, you know, fasting and longevity diet, etc. What other findings have you found in all of your work beyond fasting that help with aging backwards or slowing down the aging process? Yeah, so, yeah, the longevity diet. So now we're going to publish several papers on that. And then, you know, protein restriction has always been one of the things that we worked on. For example, some years ago, we used mice that have this genetic mutation that give people Alzheimer early. And so it's called triple transgenic mouse. It's got three bad mutations that make this mouse develop this bad learning and memory. And then in the first paper, we alternated one week of very severe protein restriction and one week of normal proteins, right? We just kept going back and forth, and it made a lot of – it wasn't as good as the fasting mimicking diet, but it was very good, you know, very good effects, right? So just alternating very low-protein diet with normal protein diet, week, one week on, one week off, that made a big difference. Yeah, so – How much of a difference? Like 20%? Oh, you know, we looked at lots of different things, but, you know, in some of the cognitive testing, it made a big difference. Really? Yeah. But how much? Can you give me an example? Like, give me a data point. Oh, well, you know, usually we look at restoration of normal function, right? So in some cases, it was bringing it back to normal, right? Oh. Yeah. So now you see a big effect of the genetic mutations. And then what you want to see, you have a controlled mouse and you have a genetically modified mouse that's got this cognitive impairment. And then you do the alternate protein restriction. And then many of the, really several of these changes went back to normal or close to normal or, you know, no longer is bad. Right. So a range of effects. What's your take on all these supplements or peptides even? You know, everyone's taking all these peptides for longevity, right? You have so many. Do you have any, like, do you have an opinion on all these things? Yeah, I think it goes back to what I said earlier, which is the sophistication of the system versus something comes in. So it's like a GLP-1. Yeah, so it's the same argument, right? The exception would be like in the case of rapamycin, right? So rapamycin is a drug that blocks a particular pathway, which we and others have described as being pro-aging or aging accelerating. So if the peptide or whatever or the drug goes after a master regulator, then I think it could be triggering this sophistication, right? But those are very rare. So most things you do are going to, you know, act downstream somewhere, meaning like they're blocking something that is down there, right? It's not the master regular up here. Right, right. So if a peptide change, for example, growth hormone or IGF-1, these very high-level master regulators, then it's got a chance, right? Because, you know, it could be telling the body, don't go in mode A, which would be, for example, high reproductive mode, high growth, right? So at a certain age, we're not reproducing and we're not growing, right? Right. So why is it that we're putting all this energy into reproduction and growth pathways, right? It makes no sense, right? Right. So then a lot of organisms we know, for example, 30 years ago, we made unicellular eukaryotes, unicellular organisms live 10 times longer, right? 10 times. Yeah. And so you do that by, we did it by fasting them and by imposing two genetic mutations, which push them to be in this what we call maintenance mode. So don't worry about growth. Stop growing and, you know, and stop reproducing. Right. Right. Just focus on yourself. Right. So interesting. Right. Yeah. So if there are master regular and there seems like in all organisms that have been tested, there are. If you turn on the switch to stop focusing on the next generation and then focus on yourself, that can make a big difference. So, yes, there could be peptides that eventually hit that switch. If they hit that switch, I mean, the science fiction switch will be one that doesn't affect metabolism. It doesn't affect performance. It just affects your not growing and you don't need to grow and you're not reproducing. And you can stop it when you want to reproduce. So you could say, okay, whatever, I use it until I'm 34, and then at 34 I stop for a year, I reproduce, and then go back on the peptide, or it could be a dietary intervention, or both. Or about just even the fact that a lot of people are taking, NAD is really popular. NAD, metformin is very popular. You're saying the only one that can maybe move the needle is repromycin. Well, metformin is also a little bit of a master regulator, right? Yeah, okay. Yeah, yeah. But the data, if you look at metformin effects in mice, it doesn't make even a mouse live longer as far as I remember. Rampamycin does and does in a very consistent way, right? Yeah, so I would say if you made a mouse live longer by whatever peptide, you made a rat live longer, let's say 20% longer or something like that, at least, right? If you made the mouse live 20% longer, you made the rat live 20% longer, okay, then it starts, and then it's very safe. Like, let's say metformin. Then I think you'll be a good candidate, right? But, you know, we don't have anything like that right now. And rapamycin is probably the only one. Should we take that? Should everybody be taking it? No, no, no. Because rapamycin also causes hyperglycemia. And yeah it not good And that where maybe it might be good for a mouse and not necessarily for a person right so so uh yeah but that tells you that the potential is there for some drugs to to go after master switches and then eventually you know we're gonna say hey this is really safe but of course you know the fmd is already there right there the fmd may be done three times a year, it's already doing all of this with no safety issues. Well, FND also takes out all the senescent cells, right? Isn't that like a benefit that people get? Yeah. Well, four things, right? One, autophagy, right? So you need three, four, five days, probably the whole five days for autophagy. So the cells start eating themselves, right? And that's one. Then clearly is doing stem cell activation. And now we're seeing it in multiple human clinical trials. We've seen major increase in either stem or progenitor cells. And then reprogramming of cellular level, right? So, you know, now the hardest thing in aging research is how can you take an old cell and make it young again, right? And it's called, you know, cellular reprogramming, epigenetic cellular reprogramming. And but now we're shown over and over and over the FMD refeeding cycles do that in a very amazing and coordinated way. And then metabolic reprogramming. Right. What I said earlier, the fasting, mimicking diet, refeeding are now metabolically rewiring your system. I mean, it's not a cellular province necessarily, but it's more, it could be cellular somewhere, maybe in adipocytes, but it's basically telling your body, stop accumulating fat, start using fat. And the beauty, if you look at our work in mice, rats, and humans, is that it keeps on going, right? So it's not that you do the fasting-mimicking diet, and then a week later, it's all gone. You do the fasting-mimicking diet, and then for months, actually in the first trial, we did the USC, three months later, 60% of the effects were still there, right? So after three FMD cycles once a month, we stopped, and then we look at three months later, and then you see about 60% of the changes that are still there, right? So, yeah, so I think drugs are okay, but I would say that we probably haven't been as loud as others, you know, in advertising, you know, I think the people that do some of these peptides and pills have been louder than us in claiming and over claiming. We've been, and also the companies involved, I think there have been more, stick to the data, stick to what you know, don't over claim. And maybe that's why some of these other things are more popular than the FMD. I think they're both. I mean, I think that people who know, know. I know, like, the community of doctors I know who prescribe the fast-mimicking diet to patients just for their overall health, never mind for, like, you know, longevity or for cancer, it's pretty extraordinary. Like, I think people who know the research, I mean, I think it kind of speaks for itself. It's just more about people who know, know, and if you don't know, you don't know, right? Right, right. Yeah, but I think now there is soon enough an opportunity to make it mainstream, right? Yeah. And it should be mainstream, right? Because of all the things we say, it's going after Crohn's and colitis and cognition and inflammation, and it's going after cancer cells. And it's doing it in a safe way. I don't think too many people are arguing if you do this three times a year, if you do this vegan diet three times a year, that you're not going to find too many doctors say, oh, no, this is going to cause problems in the long run. You're not eating every day. You're not restricting. So you're not into calorie restricting every day. You're not into yo-yo dieting. You're actually not even necessarily into vegan every day. No, I'm not. You're not. So you're saying the longevity diet is eating fish, more like a Mediterranean diet. I say Mediterranean is from Mediterranean people, right? So if your genes are from Norway or from Sweden or from Japan, you shouldn't have a Mediterranean diet. You should have a longevity diet that is personalized for you, right? Which is about fish, typically. Which is still going to be about low-mercury fish and low-toxin fish. And it's going to be about legumes of different kinds, right? It's going to be about whole grains. It's going to be about oils And maybe there's a few different ones The olive oil is definitely good But it doesn't mean it's the only one So if you come from There are other vegetable oils that are good Like what? Well there's some You know I haven't investigated as much as I've done For olive oil But you know there's some Like maybe sunflower Or some of these vegetable oils That have good data behind it But, you know, I don't want to – I've never spent the time because I'm so happy with the results of the olive oil. And it just covers so much of the world population that, you know, can deal with that. And then I think the nuts and the dark chocolate. So there's a lot of sources of healthy fats that are fairly confirmed to be healthy or very healthy for you that, you know, we never investigated. But it doesn't mean there are not other oils, for example, or fats, sources that, you know, eventually could be as good as olive oil. Okay. But you're basically just saying, though, that for 15 days of the year, five days, you know, maybe even every quarter, is a good chance. It can give you a fighting chance, so to speak, to really live longer and healthier. Yeah, I wouldn't call it a fighting chance. I mean, the data is just spectacular. already. I know. No, no. I mean, you know, it's like, oh, you're saying it's a good, oh, yeah, I'm saying it, yeah. So basically, let me, let me, let me re-say that then. Basically, you're saying that if someone does fast mimicking at least every quarter, let's say for five days, the chances of them living longer and healthier are spectacular based on your research. No, no, no, no, no. That's going too far on the other side. I mean, I think the results have been spectacular, especially in mice and especially in rats. I mean, really unbelievable, right? You They're taking a kidney or pancreas that is completely damaged irreversibly and then restoring its normal function, right? I mean, it's hard to believe. That's pretty amazing. Yeah, right. That is spectacular, though, doctor. Yeah, that's what I was saying. That part is spectacular, but it's in mice and rats. Now, the 40 clinical trials are showing really remarkable results with insulin resistance, glycemia, and inflammatory markers, and cholesterol, and blood pressure, and over and over and over, in a very consistent way, clinically, right? Yeah. So those are very good. Yeah, so I think that it's not a fighting chance because, A, if it's making your cholesterol lower, if it's making your blood pressure lower, if it's making your glycemia lower, if it's making your biological age younger by two and a half years, at least based on a number of factors, and the measurement of the number of factors, I mean, it's hard to imagine how you would die in the same time. Everything is much, much better, but you're still going to die on the same day. Yeah, so much, much less likely. There's no guarantee, but... You're stacking the deck. Yeah, so... You're stacking the deck for you. You're doing all the right things. You know, if you combine the longevity diet and you combine the sleep and the 12-hour time received eating and you combine it and put the two, three cycles a year of fasting-mimicking diet, I think, you know, you're getting into this 15, 20 years of life expectancy increase range, right? based on lots of data. And also, if you look at the Harvard studies, the chance of getting to 75 without needing drugs, with cognitive, being cognitively functional and healthy, only less than 10% of the U.S. population is in that group, right? Yeah, that's amazing. One chance in 10 right now with the way, if you look at the general behavior of the population. Now, if you do all the right things, that study showed that you're doubling your chance of making it to 70. So now all of a sudden, it could be 20, 30 million people. That's amazing. That all of a sudden are getting to 70 or 75 healthy just by making those changes. Yeah, and this is not even counting the fasting-making diet. This is just changing your everyday diet and following a few things that everybody can follow. So, yeah, so I think that, you know, that that's the way to go. There's four or five things you can do. And, hey, you know, if you can do them all, do them all. Right. It's amazing. What is the documentary really going to be focusing on? This? All of this. All of it? All of this, yeah. That's amazing. Cancer, diabetes. The doctor that I talked about is in there. He talks. Oh, yeah? He'll tell the story. There's cancer patients that basically say, you know, I was in trouble and then I came out of it. But I think that what we also done, which was very important compared to lots of our documentaries, I pushed the director and the producer to put in the clinical trials, right? I said, you know, don't make it about a case. Case is irrelevant, right? But make it a – tell the story with the case, but then let's show the three or four clinical trials that have been completed and that, right? Yeah, so I think that that's what's special about this documentary is that, you know, do it right, you know, science-wise, but also have the emotional part, but don't be too focused. And maybe it doesn't make it as entertaining, but it certainly makes it, you know, very convincing, I think, that you have, you know, multiple clinical trials backing up the story. And when you talk about your lab in Italy that's focusing on cancer, what are a couple of findings that maybe we haven't heard of that you've kind of brought to the surface? Yeah, the exciting new findings are what we call starvation escape path with targeting. So meaning that we take the fasting-mimicking diet. And now we're starting to do this in patients, right? In the old days, it was like, okay, let's combine chemotherapy plus FMD, immunotherapy plus fmd fine and it works so much better together than as i would say there now we're saying okay what if we instead look at how the cancer changes after we give them the fasting making diet right and you see rewiring meaning the the metabolic pathways and not just metabolic the the cell changes completely its modality to adjust to the fasting making diet then we can learn is we do something called RNA-seq. We can learn how they change and why they change. And then we can use drugs that are already available to target those. And this works extremely well. And it can go pretty fast. So we're very excited about this can be used for any cancer because, you know, it doesn't matter. You expose them to the fasting-making diet. You look at how it changes and you do this computational analysis. And eventually we're going to do it with artificial intelligence. And then it tells you, okay, these are the drugs you need to kill them all, right? And, yeah, so I think that we're very excited about this and hoping to get a lot more funds to keep it going. 100%. Because it's got a lot of potential. Do you take any other supplements just for your health? I take multivitamin and then I alternate between like vitamin D and vitamin B12. You alternate? And omega-3. Yeah, I alternate because, you know, I probably don't need each all the time. I don't think it's good to get overloaded with supplements. But I alternate. Yeah, so every four days or so, I'll get... To take a break? One or the other, yeah. Oh, wait. So you take vitamin D once every four days or four days on one day off? No, no. I will take it every four days. I'll just say three days. Three days and then I'll switch to B12 because a lot of my diet is vegan, vegetarian. And then I'll have, let's say, omega-3. Usually I mix algal oil and fish oil. What about exercise? Have you done any type of research on the effects of exercise for longevity, aging well, health span? In addition to the fasting? Yeah, I'll say something that is not going to give me a lot of friends first, and then I'll rewrite. Exercise, whether it's in animal studies or in human studies, does not compete with nutrition and fasting, right? It's very far. And so I was just in Italy and this Rosetti group was showing the data in, you know, sick days or, you know, the number of sick days in your life. And it was a sevenfold between the effects of lack of exercise versus a bad diet, right? Sevenfold difference in how impactful is a bad diet and, you know, how sick you're going to be in your life versus how is no exercise you're going to be. now that said i think exercise is very important right you know so it's that extra thing that that um right because nutrition is oh it's 80 of it at least i you're saying it's 100 no no i'm saying it may you know this data suggests there may be 85 right yeah 85 of the lifespan extension and the health span extension that you get is going to come from nutrition and fasting or nutritional intervention, and then the extra 15%. But I think that exercise is very important mentally. And so, I mean, I'm all 100% behind exercise, say 150 to 300 minutes a week, muscle training and all of that. I think it's very important. But why is it important if you've seen the data that says it's not important for health? that's not important for uh how sick you are right but for your mental health yeah it doesn't mean that you're not going to be happier mood yeah serotonin and lots of other things that happen when you when you exercise and so yeah so i think that and that 15 is not it's not you know it's not insignificant right so having a 15 extra yeah benefit it's very important right so and you never know, right? So, you know, as part of my classes, I also show the effects of exercise. And some of the really remarkable effects are on cancer patients. And you'll see these results where they're showing people that are exercising regularly, and they have cancer, and they do so much better if they're exercising versus not exercising, right? And you're thinking, is it possible that... So I don't know if it's a motivation thing or if it's an actual you know physiological effect but the ones that exercise they tend to do so much better uh you know in progression and and survival and lots of other things yeah so it's the mood and the mental elements of it right it could be mental it could be that helps them fight you know they're fighters and they're going to do it in with all different things but some of these these uh this some of these trials are randomized right so it's not like you pick the ones that are more motivated you take 100 people and you divide them by two and you say you exercise and you don't and then maybe you cross it over right so some of this data is real it's not about selection of motivated patients but some of it might be affected by bias yeah wow gosh you're right you you didn't make a lot of friends with that one i'm kidding no but i i think i i mean people know more or less that it's also with like weight loss right like you can exercise until the cows come home but if you're not eating properly or eating the right foods you're going to gain weight it's just it is what it is you know and there's a bigger problem that you know exercise and there was a paper actually they came out you know this is a big loose biggest loser right there but then end up in being a real paper right yeah and the real paper went and followed and i'm forgetting what journal it was and it went and followed and most of them i think they were doing like hours a day of exercise right yeah yeah yeah so so i think when the the camera is on and the show is on right whatever your show may be you could do that eventually you're gonna be upset you know and you got problems and you don't have time what are you gonna do then right right and that's it you're still gonna eat and you can still eat the right food but are you gonna take the forget the six hours but you're gonna take the one hour a day and go exercise every day most people don't right you know in the long run if you get older and as you get get more things to worry about you may say you know what i don't feel like oh it's raining outside or it's too hot or it's too cold you know yeah so there's a lot of so so so the compliance and the feasibility that i was talking about before with the mid-geranian diet eventually you're gonna have it also for the for the heavy exercises right and then you're gonna have like my brother and my sister for for example, right? My brother was a soccer player. And I told, and I was a soccer player. And I told my brother, you got to stop, right? Yeah, no, no, no, no, no. And now he's limping, right? Because it's hip, right? Yeah. And my sister was a teleathron runner and now she has a hip replacement, right? Right. So, you know. Too much, if anything, is not good. Well, it wasn't even too much. They weren't professional. They were not professional. Right. But it was like they enjoyed it and they did it all the time. Right. until they had to get surgery, right? Oh, I see your point. So now they have to stop exercising, but they have to be eating right to keep, they have to learn the discipline of eating properly. Yeah, they're both eating the longevity diet, right? Yeah, of course they are. But they're not doing soccer anymore. They can't. And they're not doing triathlons anymore. And, I mean, it's just we're three, and I'm the only one that, you know, I played until I was 45, right? Yeah. How old are you now? 58 yeah yeah so so i played whoa whoa you're 58 yeah yeah and this is okay and like this and this is you haven't done anything to you could you look really young no no i haven't done anything god forbid yeah yeah and so this is all just doing a fast mimicking diet living a certain longevity diet fast mimicking diet and uh yeah and i was gonna say longevity diet too just your your diet i should say yeah yeah and and habits daily habits but you're saying because You didn't really, you exercise, you played soccer, sorry, you played soccer, but then you didn't play after a while, like after 45. Yeah. After 45, I stopped, right? And I started doing biking and things that, and my hip is still my hip and I still don't have any problems, right? So yeah, to me, it was very important. I mean, somebody else could say, and there was a case with my brother and my sister, I don't care. I'm just going to keep doing it. Okay, fine. But keep in mind, I mean, it's okay, but then keep in mind what the consequences could be. So in my case, I said, you know, I don't want to be 60 and needing a hip replacement. And so far, I'm good. So I can still do my bike every other day and lots of other things. And, you know, they don't put me at risk for inflammatory conditions. Yeah, absolutely. Is there anything we haven't covered, Dr. Longo, that's important for people to know about? No, I think we've pretty much covered it, yeah. Are you sure? Because you're here right now. I want to make sure that I got everything done with you. Yeah, I think with the diseases, we talk about cancer, Alzheimer's. Yeah, I think we covered a lot of ground. I like factoids. Is there any facts that you can share that maybe we haven't? Any kind of data points that we haven't covered, no? I think, you know, one thing that I was going to say that I didn't say was we're now going through, you know, I mean, I'm doing this review on proteins, but it's more like longevity diseases, right? And so, you know, that's consistent with what we've been saying. The other thing I'm having my team at the foundation do is the muscle part, right? So then we're looking at hundreds of papers on plant supplements, plant protein supplements and animal products. And so I think that what we're going to conclude is that probably what we already concluded before, 0.8 grams plus training, plus muscle training, 0.8 grams per kilogram or 0.37 grams per pound of body weight is enough for the majority of people, even if you want to build muscle, right? but in fact if you look at all these hundreds of papers you know those that are in the one to 1.2 they tend to have an easier time building muscle right so so i would say don't do it but if you care so much about muscle uh oh okay then then i think the 1.1 to 1.2 of good quality amino acids like some animal proteins and some oh i know i was gonna ask you okay so wait so you're just saying that like you're if you can have 0.8 uh grams of protein it's it's you don't need to have one one so the whole thing is one gram one yeah well now people are advertising two grams for muscle yeah for muscle and so now for sure what we're concluding is two grams 1.6 gram is not needed you know it's very little difference right you know very few papers are showing If you have 1.6 versus 1.2, you do better with 1.6. Very few. Most of them show no effects at all. And also, most of the papers show if it's animal-based, it's not superior to plant-based. As long as it's a good mix of plant-based supplements, right? A lot of them are actually showing total protein intake that can also come from supplements. Okay, you said that a few times about amino acids. What if you just take nine essential aminos? like a yeah you could do that but the data you know we don't know what the consequences are I think you know but that way you're not eating as much protein but you're having the building blocks to protein yeah no no I mean theoretically I think it can work but it wouldn't be you know those essential amino acids are going to be the one driving the aging process right so if you look at the studies in mice and rats is always essential amino acids, right? The one that accelerates the agent, essential, right? So brain chain amino acids, methaenine, so almost exclusively. In fact, if you look at the non-essential, they're the only one, like glycine, that seem to be doing good if supplemented, right? Really? So restriction, if you look at the restrictions, they're all on essential amino acids. they work, making rodents longer lived and healthier, much healthier, right? If you look at the few cases of supplementation with amino acids and living longer is glycine, which is a non-essential amino acid. Non-essential. Non-essential, right. So, yeah, so then if you do what you said, yeah, it's just like then you might as well eat proteins, right? And that's okay, right? In fact, it may be better to eat proteins because now you have the non-essential, including glycine, that may be beneficial. Because it turns out that glycine is an inhibitor of methionine. It facilitates methionine decomposition, right? Yeah. So the higher the glycine, the less methionine you're going to have in the system. So it's going back to, probably it's going back to the essential amino acids, lowering essential amino acids. lowering essential amino acids. Okay. Wow. Dr. Longo, thank you so much for being on my podcast. Oh, you're very welcome. Thank you. It's been a long time awaiting for me, so I appreciate this. And where do people find, I mean, they can buy your book, Fasting Cancer or the Longevity Diet book from 2018, but they want to know more about you or where can they find you? Yeah. So Facebook, Professor Walter Longo. Facebook? And Instagram. Okay. Yeah, most USC faculty now have Facebook and Instagram. So most professors anywhere. Yeah, so Instagram is the same professor, Walter Longo. And then the foundation, Create Cures Foundation, is here in Los Angeles. And we help lots of people and, you know, including those that cannot afford it. That's great. Well, thank you again for being on the show. Thanks a lot. Transcription by ESO. Translation by —