The Dr. Hyman Show - The Secret Power of Fasting for Longevity and Healing with Valter Longo

Episode Date: April 10, 2019

These days, we hear a lot about fasting. Intermittent fasting, time-restricted eating, and water fasting are just some of the many terms being thrown around in support of better health. And we can’t forget about the high-fat, ketogenic, and low-carb approaches that are gaining in popularity as well. Which one is best? What does it all mean for our longevity, brain health, and overall wellness? My guest on this week’s episode of The Doctor’s Farmacy is here to sift through the terminology and confusion around fasting. Dr. Valter Longo is internationally recognized as a leader in the field of aging studies and related diseases. Known as a “Guru of Longevity,” Dr. Longo is currently Professor of Biogerontology and Biological Sciences and Director of the Institute of Longevity of the School of Gerontology at the University of Southern California in Los Angeles, as well as Director of the Oncology and Longevity Program at IFOM in Milan. He is also the Scientific Director of the Create Cures Foundation and the Valter Longo Foundation. Valter is the author of an extraordinary new book, The Longevity Diet. The culmination of 25 years of research on aging, nutrition, and disease across the globe, it provides an easy-to-understand, accessible and implementable road map to living well longer through improved nutrition.

Welcome to the doctor's pharmacy. I'm Dr. Mark Hyman and that's pharmacy with an F, F-A-R-M-A-C-Y, a place for conversations that matter. And this conversation today with Dr. Walter Longo will matter to all of you because many of you probably are thinking, how do I live a healthy long life and not get sick? And this man has spent his life trying to answer that question. And he is an internationally recognized leader in the field of aging and related diseases. His discoveries have looked at some of the major genetic pathways that relate to aging, regulate aging, and life-threatening diseases. He's identified a genetic mutation that protects

men from many common diseases. And he's been cited by Time Magazine as the guru of longevity. He's quite a guy. He's a professor of biogerontology and biological sciences and the director of the Institute of Longevity of the School of Gerontology at the University of Southern California in LA.

And he also works as the director of oncology and longevity program at IFOM in Milan. And he's a scientific director of Create Cures Foundation and the Walter Longo Foundation, where he takes all the proceeds from his books and all the proceeds from the products that are designed to create healthy aging and puts it back into research. He's an extraordinary guy. His book, The Longevity Diet, is the culmination of 25 years of research on aging, nutrition, and disease across the globe.

It's easy to understand. It's accessible. It's easy to implement, and it's a roadmap to living well longer through improved nutrition. And I, for one, am all about it. In fact, I'm going to try the program now that I've read the book, and you're going to hear why as we listen to Dr. Longo. So welcome. Well, thanks.

Thanks. That was a long intro. I know. You've done a lot. You're the guy. And you happen to be the guy who everybody's talking about in terms of aging. And your program has been studied extensively across a wide spectrum of diseases. You've gotten funding from the NIH and everybody's talking about how we can use the innovations around aging that you've discovered to basically slow or even kind of reverse the process by using something that you've termed juventology, which is the science of healthy aging and something called the fasting mimicking diet. So you, you're Italian, you grew up in Italy,

and you grew up in a town that had a lot of old people, but then every summer you went to this town, in a little small town in Italy, where some of the longest lived people in the world are. And it just so happened that that's where you hung out, and there were people who were 110 and 117. We'll talk about them. What was it like growing up there,

and how did you then go from wanting to be a jazz and rock star to being a scientist looking at all this because it's quite a different framework yeah yeah so i actually i was at uh university of north texas and i was studying music was one of the best programs in jazz performance. That was my major, studying guitar. And then they told me that I had to direct a marching band. And I said, there's no way. I really want to be a rock musician. And I said, there's no way I'm directing a marching band.

You're not going to dress up in those funny costumes. No, no. Or look at them, for that matter. But yeah, so I said, I'm not going to do that. But of course, that was an excuse. I wanted to, I think I really, my instinct told me that I was interested in aging. I was interested in medicine.

And I just, I always thought, what an incredible combination of something that scientifically is a super challenge, but it's as high as it gets. And then medically, already at that time, I thought, this could have effects on many different diseases, not just one. So yeah, there was the switch to biochemistry and then the rest of it. And from the very beginning, all I wanted to do was study aging.

Yeah. And so I never went into it to be a biologist or anything else. I just went into it to understand how we age and how we keep people younger and healthier longer. Yeah. So you actually write about this in your book, which is that the studies that we've shown longevity in animals are calorie restriction studies, meaning you eat a third less calories, you live a third longer. And there was an example of a group that did this in the biosphere,

Roy Walford, you talked about, and they actually did reverse a lot of the biomarkers of chronic aging, but they also felt crappy and were tired and had lower immune systems and were hangry all the time. So you kind of came up with a new way of thinking about this, that it chews some of the same benefits and maybe even more without necessarily having to starve yourself all the time. And you call it the fasting mimicking diet. So take us through how you came to discover that this is something we should be thinking about, the animal models, and then the human trials that you're doing. Yeah. So when I was in Walford's lab many years ago, the idea, it was almost like nobody was thinking about the origin of things, right? So it's a 30%,

you eat 30% less and that's it. And I always thought this has got to come from something much more deep and meaningful than just eating 30% less. So I was observing, I went back to the biochemistry department from the pathology department where Wolfer was and I started studying starvation in bacteria and yeast and I saw that you could starve completely a bacteria or a yeast and they live a lot longer and this is permanent so it's not like you starve them for a little bit you starve them and you keep them under starvation and they live very long and so I started thinking it must be the other way around it must be the calorie restriction foundation is in starvation. And so it all comes from starvation. There is no magic calorie restriction effect.

But the starvation for a human being or even for a mouse must be periodic. Once in a while, you starve. And then the rest of the year, you find enough food to eat. And that's what I started thinking. That's historically what humans did, right? That's historical. You know, you can't go to the grocery store. You got to go hunt and gather and find whatever you can.

Exactly. And sometimes, of course, that period could be months long and not much longer than that because then you die. But let's say potentially it was very long. You go through periods of not eating for one or two months. So yeah, that was the idea. So what if you just take somebody, first we study fasting. What if you take water only fasting and then expose people, mice or whatever to it and then back to the normal diet. Could that reprogram the system into having

long-lasting effects? And so we started with water-only fasting, particularly for cancer, and then we moved to- For animals, water-only fasting. The beginning was just, yeah, water-only fasting. We took mice, we switched it to water, and we were very interested in chemotherapy protection, differential chemotherapy protection. So the idea was, can you protect a normal cell with starvation, with fasting, but not a cancer cell? And it turns out to be a really powerful way to kill cancer cells and protect normal cells. And now we have a number of clinical trials finished and many more ongoing, but it seems to be working very well.

So that was the original idea. And then we moved to fasting-mimicking diets, in part because nobody wanted to fast. And oncologists... You mean eat nothing. Yeah. The oncologists were very much resistant to that, and patients, surprisingly,

were more resistant to it than the oncologists, not having any food. And that was part of the psychological aspect. Lots of patients felt cheated. They felt like, how is it possible that my doctor tells me that the treatment here is to do nothing? But also, it's very tough. Psychologically, it's a moment when you're sick that it's very difficult to be without this comfort. Yeah, right. And this is not just cancer patients.

We learned that most people are like that. And this is where the fasting-mimicking diet idea comes from, to worry about also the safety of the fasting and the compliance. Of long-term fasting. Of long-term fasting, yeah. Yeah, so what this seems to do is activate the body's healing system, which is pretty interesting.

So most physicians, we're trained to treat diseases with drugs that suppress symptoms or target a specific pathway or mechanism. But your work has shown that you're really not doing that. You're focusing on the inherent repair systems, the regeneration and healing mechanisms in the body, the programs, as you call them, that can get activated by specific interventions, which then can be applied across all sorts of diseases. So it seems almost incredulous that you could say that eating this way, which is short periods of restricted calories for five days, could help treat Alzheimer's and cancer and diabetes and colitis and MS and all kinds of other stuff. How does that make sense given our current paradigm? Yeah. So think about cancer, right? So we've been fighting the war on cancer with Nixon. Nixon came

up with the war on cancer. And 50 years later, we now have the most effective and most promising intervention in cancer is immunotherapy. And what is immunotherapy? Immunotherapy now, for which the Nobel Prize was given in 2018, the Nobel Prize in medicine, is basically making the immune system attack the cells that don't belong, right? So allowing the immune system to attack the cancer cells that have now figured out by a couple of different mechanisms how to tell the immune system cells, stop, don't attack me, right?

So the immunotherapy is removing two molecules or inhibiting two molecules, PD-1, PD-L1, and CTL-4, right? And allowing the immune cell to do its job and so that's a great example of you know and and some of the people that i've been talking to they were saying 10 15 years ago they were attacking this immunotherapy scientists and saying come on this is a old idea. It's never going to work. We have all these sophisticated targeted technologies. And they kept saying, no, let the immune system find its way. Let it find the wrong cell. Because now you have a real cure. It's going to go everywhere in the body. It's going to attack. You just have to figure out how.

Well, with fasting, fasting is probably the most powerful natural intervention to, we believe, we're starting to believe, because it's working with so many different things, we're starting to believe that it was the moment, kind of like sleep. If you think of sleep, it's the moment where you rest, right? But not just rest at the general level, but probably having all kinds of systems like DNA repair, et cetera, et cetera, do their job. And so it is a moment of rejuvenation, if you will. So we believe that maybe fasting was the moment where the body went to the body shop and the mechanic and everything got fixed, right? And something was not working correctly, you remove it, replace it, right? So that's what we think it could explain all these very different effects. For example, how can it go on one side after the inflammation, reduce inflammation, but at the same time, promote the inflammation-dependent attack of cancer cells.

It's just the opposite, two opposite things. And then kill the cancer cell and then regenerate the pancreas when it's damaged and promote the regeneration of the liver, et cetera yeah so i think that maybe that's what it was always there for identify things that are dysfunctional old and replacing cleaning up house cleaning up in in a in a very sophisticated manner and we already know that the body can do that. I always say if you cut yourself after a couple of weeks, it's gone. Perfect repair. And yet the skin keeps getting old. And so how is it possible that it just can, so sophisticated, perfect repair, and it never does that. So yeah, so fasting potentially is one of the most powerful. I mean, I really see no evidence of anything beating it that i've ever

or even getting close to it which is radical what you're saying is you know we've had century of medical innovation and drug development and technology innovating care and what you're talking about is that food is more powerful than all of those things. In fact, you coined this term Nutra-technology, which is about treating the molecules in food as drugs. Yeah. But now let me go back to cancer, right? So we almost never see cancer-free survival when we only use fasting mimicking diets we always see it with the drugs right and so to me it was always like for example if you're talking about diabetes and lots of other things the drugs don't seem to be necessary but when you get to cancer uh we have not been we cured lots of mice with combination of chemotherapy and and-mimicking diet.

We've never been able to do it with just, for sure, with the chemo alone, but also with the fasting-mimicking diet alone. So the chemo and the fasting-mimicking diet work about as well. But you combine them, and they're very powerful. So we really are. Yeah, you were presenting at a conference this morning, and we had a fantastic slide up there showing that the effect of fasting, the effect of chemo, and the combined effect was multiples. Yeah. It's synergistic for sure. And so the point is that we're not about four drugs against drugs.

We're about patients. How do you get somebody to get 110 to 110 healthy? And if you have cancer- Why only 110? What about 120? Yeah, maybe 120. But if you prevent cancer, absolutely, no drugs are needed to prevent cancer and to just act on the aging program and on the longevity program. But if you have cancer, we really think that whether it's immunotherapy, kinase inhibitor, chemotherapy, radiotherapy,

surgery, they're really going to be very, very important together, together with the fasting-mimicking diet. And we'll see. The ketogenic diet is also emerging as a potential co-treatment. Lou Cantley has done really great work combining ketogenic diet with PI3 kinase inhibitors, for example, lots of potential there. And so I think that it's not just about the fasting-mimicking diet, but certainly the EFMD seem to be, because you just do it for four days, five days with the treatment, and then you let the patient return to their normal diet, we think that that's got high potential.

So let me just back up a little, help people understand what the fasting-mimicking diet is before we go into more detail about it because it's fascinating essentially it's very short periods of calorie restriction 800 to 1100 calories five days done a few times a year two or three times more if you're treating something serious like an autoimmune disease or maybe cancer but it's not that much time out of the space of a year to do this. And this product, this program has the ability to treat so many different things. And one of the things you said this morning that was really powerful was that it takes many drugs to do what a fasting mimicking diet does yeah i mean and this is like this don't even do the same

effect and this is a fact if you just look at cancer and if i had somebody who came to me recently and said you know what when we use these cancer drugs we got a problem because we can lower insulin and we can lower glucose we we have nothing yet that can lower insulin and glucose at the same time and he was saying that your diet is about it, right? So this is just two of the things it does. It also lowers IGF-1, it lowers leptin, it revolutionizes the growth factor and inflammatory, et cetera, et cetera, environment. Yeah, so it would take many, many drugs to get the effects of fasting. And nobody argues with this. This is not an opinion anymore. Now, you could argue that all those changes may or may not affect cancer. We have to still see,

but we have lots of clinical trials now and certainly mouse data indicating that it does in a very powerful way. So there's a bunch of things you threw in there like ketogenic diet and intermittent fasting. There's this whole field out there that's moving in the direction of some type of fasting mimicking approach, right? Not your fasting mimicking diet, but ketogenic diet is sort of a way mimics fasting and may activate a lot of the same mechanisms. Yes and no, right? So it's a good opportunity to talk about that. I think people are confused and ketogenic is the latest hot thing. What you're saying, is that necessarily necessary?

Yeah, the ketogenic diet, first of all, it can be high protein, it can be low protein, right? So that's already a big distinction. Why? Because we can see that if you add back proteins to the fasting-mimicking diet, you cut out about half of the effect, right? And if you add sugar, you cut out about the other half. So if you had sugar and proteins, you now eliminated the effect pretty much of the fasting-mimicking diet.

So, you know, the ketogenic diet, if it was a high fat, and that's what the fasting-mimicking diet is, right? The high fat. But we also have relatively, and this is the prolonged fasting-making diet, we also have relatively high carbohydrate, all from vegetables, right? No legumes, all from vegetables, because we want to keep the proteins low. So it's vegetables, nuts, and those are the major ingredients in there.

And the reason for that is that we're thinking not what happens after you do three cycles of this. We're thinking, what if you were to do 300 cycles of this, right? And I don't want, even though I could get more benefits from a lower, more ketogenic diet, a lower carbohydrate diet, I don't want to do that. Why I don't want to do that? Because I don't want people to go back and forth in this yo-yo manner to very low car, very high car, very low car, because I'm worried that in the long run, that's going to stimulate too many variation in the programs, and some of them are going to have detrimental effects. So we're not used to this back and forth and so I don't want to introduce I already have a very potent effect but not as potent as I could because we always get asked oh why don't you reduce the carbohydrate in the FMD

and that's on purpose we want to keep it so we don't push you to the edges but it's not starch right it's not starch it's? It's vegetables. It's not starch. It's all vegetables. And vegetables and nuts which have carbohydrates. But it turns out to be 45% carbohydrate of that kind, right? So in the low-calorie domain. That's an important distinction because when you say carbohydrates, people think of pasta and bread and bagels and sugar, but you're talking about plant-rich carbohydrates that are low in glycemic index. Oh yeah. These are low or very low. I mean, you have some, so you have tomatoes, you have broccoli, you have all kinds of vegetables, but they do contain lots of carbohydrates.

So at the end, it's about 45% carbohydrates, 45% fat, and about 10% protein. Yeah. Well, I mean, yeah, I mean, you take 21 cups of broccoli, that's the same amount of calories as one big gulp soda, right? They both have similar calories, they're both carbohydrates, they're both really different. Absolutely, yeah. So we're not trying to say that it's about having carbohydrate. We're trying to say that it's about to have very specific carbohydrate.

And in a paper that we are about to publish that looks at water-only fasting and the fasting-mimicking diet. And we're showing that the prebiotic ingredients in the fasting-mimicking diet, which are vegetable-based, all vegetable-based, are feeding the good bacteria, lactobacillus, bifidobacteria, et cetera, et cetera. And now you have this big increase in this protective anti-inflammatory bacteria, which you don't get with the water-only fasting, right? So now the content of the diet together with the fasting, so it's the combination of the fasting and the content of the diet driving the repopulation of the gut of the mouse to the point that it reverses IBD, right?

So it reverses colitis, it reverses Crohn's. It's a mouse model. What are the fibers and prebiotics that are in there? Is it just vegetables? Yeah. We don't know which ones are responsible for this growth, but there is a number of the vegetables that are known to promote lactobacillus, bifidobacteria, et cetera, growth.

So we suspect that the high content, and it's just, we actually have high content on one of the days, and then we lower it. So it seems to be about content, it seems to be about timing, and it seems to be also about refeeding, right? So you have the big switch doesn't really occur while you're in the FMD mode. It occurs after the mice return to the normal diet, right? remodulation or modulation of the bacterial or microbe population in the gut that seems to be then communicating with the immune system and communicating with multiple systems. And it's not the whole effect because we see much more than that. But certainly when we do fecal transfer, so we just take the FMD, the bacteria from the

fasted mice, fasted immune-diet exposed mice, and we transfer it into recipient mice, they have some of the effects. They show some of the effects, but not all of the effects. So it means that that microbe population is important, but it's not the whole deal, as we expect because we also see, for example, gut regeneration, and we see a general anti-inflammatory effect. So even systemically, the inflammation comes down. So it's affecting microbiota, it's affecting inflammation, it's affecting regeneration. And again, you have to think it's going back to

the body detects something wrong and it does all that is needed to fix it. So essentially you're challenging the body with a stress, which is a low calorie diet, but it's highly nutrient dense for a short period of time. And the body is like, oh, danger, danger. I got to put in and get all the repair mechanisms going so that I can fix this highly nutrient dense for a short period of time and the body is like oh danger danger i gotta put in and get all the repair mechanisms going so that i can fix this problem yeah but you know a really interesting thing that was just pointed out by my student the other day if you take water only fasting and you give it this toxin and so this is very nice because this is very uh recapitulating of the how we make get Crohn's disease and colitis,

a lot of toxins from the outside. So you give it these toxins, and you're doing water-only fasting, guess what happens? They have more leakage. They have more blood in the stools. So the water-only fasting is making the gut leaky and worse, right? If you do the FMD instead, it seems to maybe because it's telling the gut, I'm not fully fasting, there's still food coming through, don't break down.

Because one of the things that are very well established with the fasting is the breakdown of the lining of the gut, right? Because you don't need it. It's not as important in that moment because you're not feeding, right? So it is a good probably way to save energy. And so potentially, this is how tricky it gets. And I would never in a million years have expected that water-only fasting will make the gut more leaky, but only in combination with this toxin, right? So probably if the toxin is not there, you're okay. When the toxin is there,

now the blood is starting to get in the stool. So, yeah, so then I think this is the food that is giving the signal, don't break down completely yet, do it partially, and we see high levels of regeneration. The stem cells, the intestinal stem cells are getting activated very potently. And then during the refeeding, they give rise to rebuilding. The inflammation is moved out.

And the colon, you actually shorten the colon, and then you start the FMD cycles, and it goes back to its regular size, right? It's really a remarkable effect. It's pretty amazing. So we know a lot about aging in terms of what are the mechanisms that are driving it. It's inflammation, some of them call it inflammaging, oxidative stress, and activation of various pathways like mTOR, which is basically a pathway that's activated by protein and various other things that can, when it's over activated, can cause aging, mitochondrial injury. We have to activate stem cells in order to heal.

And it seems like this one approach of a nutrient dense, short term, calorie restricted diet seems to take care of all these things. Is that true? Well, I mean, I don't know about all of these things, but it seems the majority, and I think, for example, with inflammation and aging, I think people got it wrong, right? People think that inflammation causes aging, but it's the other way around. It's aging that causes inflammation. Very clear, you know? And inflammation, in fact, one of the criticism in the paper was- But then what's causing the inflammation? The dysfunction.

You're starting to have accumulated junk in the cells. You're starting to have DNA mutations. You have damaged mitochondria. You have just general damage. As you move forward, any system is going to accumulate protein aggregation in the brain, phosphorylated tau, beta amyloid, oligomeric amyloid. So every system has got its junk that gets accumulated. And of course, what happens in the brain if you start accumulating beta amyloid? The microglia start attacking. That's the immune system of the brain, right?

The microglia, the immune system of the brain, or part of the immune system of the brain, right? Yeah. The microglia, the immune system of the brain, or part of the immune system of the brain, is starting to recognize them as foreign. They start attacking. You begin the process of inflammation. So yeah, most of like- So it's an inability to get rid of junk and waste. Yeah. And in fact, one of the things that happened in this paper that we just published, Interlook,

I think it was TNF Alpha and several other in pro-inflammatory marker were way high in the fasting making diet really and we and all the reviewers were saying oh this is bad and we said no go read the papers if you look at these two markers they're central in what's called inflammatory regeneration so the inflammation may actually have always been good for you if coordinated what is the body is trying to do with the inflammation is fix the problem yeah so but it cannot do that because the system is so damaged and there is not the conditions to repair it so it keeps spinning the wheels so this tnf alpha and other inflammatory marker interleukins are trying to fix it, and this is not, I'm

not saying it, is very well established that these are central in the repair process. So then after you finish the fasting-may-be-canine diet, you'd assume that the markers would come down as the body repairs. Yeah. Is that what you see? Yeah. Well, we haven't looked long enough, but of course, they're going to come back down. So once you repair it, once the autoimmune problem has gone away, now they're going to come back down so once you repair it once the the autoimmune problem

has gone away uh now they're going to come back down in fact we look this also in the paper we have human inflammation uh body inflammation so what you see is that in people that have high c reactive protein that's a marker of inflammation system in our inflammation we looked in this new paper and we see that white blood cell count goes up, right? So then you start doing the FMD and the CRP comes down and the white blood cell count comes back to normal, right? And it does during the FMD, but more also after. When you look a week later, now the white blood cell count is restored to the normal levels. So you're sort of treating all these different conditions we talked about,

whether it's autoimmune, whether it's gut issues, whether it's the aging process itself, whether it's Alzheimer's. But also, it seems that just these short periods of fasting leads to reversal of metabolic diseases like weight and obesity and diabetes. How does that work? Because if you're only stopping the calorie influx for five days, how does that carry over to sustained change? I don't understand that. I think many people are wondering how, in fact, does just restricting your calories for five days a few times a year have all these long-term lasting benefits? It seems like too good to be true.

Well, yes and no. For sure is going after the visceral fat, right? So we know that the visceral fat- Belly fat. Yeah. We know from many other papers that this belly fat is so central in insulin resistance and all kinds of other problems. And so, of course, after two or three days of a fasting-mimicking diet, we have shown in the paper that everything turns into belly fat consumption.

So the body is going after, I mean, that's the reservoir. That's a food reservoir. So you don't need the ab roller. You just need the proline diet. You don't. Interesting, it didn't take it from subcutaneous fat. It only took it from visceral. And we show this in mice with the scans and in people with the DEXAs.

So that's for sure one way, one of the major ways that— I got to pause there because what you said was pretty profound. When you do this approach of short-term calorie restriction, you target the fat that causes all the chronic diseases, which is the belly fat or abdominal fat or visceral fat, and not the regular fat around under your skin or the subcutaneous fat. That is a profound, important discovery because that is the fat that we all need to target. Yeah. The other interesting thing is the lean body mass differential effects right so it's targeting the fat and it temporarily you see the lean body mass as measured by daxa go down and then you lose muscle you lose muscle but only temporarily right so usually in all kinds

of diets you lose the fat and the muscle here you lose the fat you lose a little bit of muscle when you refeed within a week all the muscle is back right so now you have an increased relative lean body mass so you now gain muscle mass you you go back to the absolute normal level of muscle but now compared to your body weight you've gained muscle mass so you have more without exercising without exercise no no. So that's one way. The other way we think that makes a big difference is almost everybody will say the following. After I got through one, two, three cycles of the FMD, I started looking at food differently. Hold on a second.

Yeah. You want some water? Yeah. There we go. yeah you want some water so yeah after i went through one two three cycles of the fnd i started looking for differently and so for example if somebody had lots of sweets uh and lots of candy lots of starches etc etc they um don't feel like eating like that as much so they all say their cravings go away their tastes change yeah i think maybe because the microbiota maybe because the brain now gets um sees the association lots of people may have never done five days of a vegan diet so often right completely 100% vegan

so it is possible that uh that the brain now recognizes the wellness that is associated with it. And then without anybody telling them anything, they begin to say, I felt better when I did that. I'm not sure. So, for example, I had some obese people that said, I used to eat pizza all the time, and I could finish two entire pizzas. And now they say, I may have a few slices and I just don't feel like continuing to eat. So it's really, I think, a conversion of the behavior based on instinct and not based on rationale or thinking about it.

So we were talking a little bit before about the ketogenic diet combined with fast mimicking diets for cancer and other things talk more about that because i think people are confused about the variations between fasting mimicking diets and ketogenic diets and intermittent fasting and and when you should do what or if you should do any like what what is the the expert's opinion here because you're probably one who knows most about this yeah so first of all i always say i hate the word intermittent fasting because it doesn't mean anything i mean intermittent fasting goes from i haven't eaten for two hours to i haven't eaten for two months right and it goes from i haven't eaten anything at all or i had lots of food in a fasting-mimicking meal.

So, yeah, it doesn't mean anything. So we need to move to what exactly did you do or what exactly should you do? And I think my book… People are referring to like time-restricted eating where you eat within an eight-hour period. Yeah. So if you look at time-restrict would uh say that i say 12 13 hours of fasting per day are very good and very safe yeah well it's normal but nobody does it anymore if you look at sachin's data it'll show uh the average is about 15 hours and i think this average of 15 hours

it comes with this idea that you should eat five or six times a day. So now, you know, to eat five times a day, you're stretching the amount of hours. And so when he did this study, and they just asked people, just mark down when you eat. It was 15 hours. It was not 12. So now I think if you went, in fact, when they went back to 12, people started doing a lot better. Now, the argument is, well, what if you go down to six? Could you do even better? Or eight, let's say, hours where you eat and the rest of it, you fast. Well, then you start seeing, A, not too many people in history did that. And B, you're starting seeing the problems.

And the problems include gallstone formation. And the problem include many, including our own trial, our own study, epidemiological study, people that skip breakfast, they usually do worse. And understandably, you can argue that there is other reasons for that. But that's not a good start, right? So I would say if you keep it 12, 13 hours, seems to me like it's a good way to go and it's very safe. There is really no negative association with even the 13 hours that I've seen. Maybe a little bit slight increase in gallstone formation, but it's very slight. When you get to 16, 18 hours, then you start seeing twice as much risk of gallbladder removal, not the nicest thing that could happen to

you. No. So that's the thing. So yeah, there's all kinds of fasting. And what about ketogenic? Yeah, so ketogenic diet, again, what does it mean? Does it mean that you're going to do it for a month? Does it mean that it's going to be low protein, high protein, animal based? That's what it is, right. doesn't mean that you're going to do it for a month doesn't mean that it's going to be low protein high protein animal based and so again we're ketogenic we got to go move away in my opinion to the world and move into what do you mean right just like medicine any drug that you

take you know say oh my it's a drug that generally blocks the cholesterol pathway it doesn't work like that it's like well exactly what does it do and show me the data on thousands of patients etc etc so here i think we need to say in my opinion a a little bit higher fat uh you know uh ketogenic not ketogenic but certainly uh i think the 60 3030-10 is an ideal diet for all time. So 60% carbs, mostly from vegetables and legumes. 30% fats, mostly from olive oil, nuts, and fatty fish. And 10% protein, mostly from legumes and fatty fish. That seems to be ideal, not based on my opinion,

but really going around the world, looking at the basic research, looking at the clinical trials, et cetera, et cetera. Now, for specific uses, I think that the ketogenic diet can be modified, be more extreme, right? So if you have somebody that has overweight, obese, all kinds of other problems, yeah, that's where I see that, let's say, a much higher fat level, a much lower carbohydrate level

being very useful to get the person to where they need to be. And that's over two billion people on the planet. Exactly, exactly. It's a lot of people who are in some places. In this country, it's 50 to 70%. Yeah. So the question is, is that reasonable and is it safe for, and how should you do it? Let's say an 80-10-10, right? That could be a possibility. So 80% fats, 10% proteins, 10% carbs. But how long can somebody stay on that? And how long can they stay on it? And how long do you want to keep them on that without risking them getting into the epidemiological data clearly

showing that low carb diets, if they're animal based, they could be detrimental. And I know we disagree on this, but I mean, I'm just thinking, I think it'd be good to come up with things that we know, and this is what I try to do with the book, come up with things that we know there is no way it is bad for you yeah i mean i came up with this denominator we're like there is no way i don't care what they they need to like 200 years of publications to to say that this is why because the centenarian is one of the pillars these guys have been doing this for you know over 100 100 years and in different parts of the world. They eat real food.

They don't eat a lot of sugar and starch. They eat good fats. And that's a recommendation, right? So if you do that, then you're for sure in good shape. Now, the argument could be, who's going to be able to do that? Okay, then we say, well, what's the second best that people can reasonably do? I think it's reasonable to eat 60%, you know, vegetable and fish and legume diet. I think it's reasonable to have 30% fats, you know, and if somebody cannot do it only

from vegetable sources, you know, whatever you can, add some animal sources, that's okay, and 10% protein. 10% protein is, to most people, is 50, 60, 70 grams of protein a day. So it's not that low, and I think- But even in your own work and your paper in Cell Metabolism, you talked about how there's a benefit when you're younger, but as you get older, you need more protein for building muscle. And you need, you know, significant amounts of, like, for example, you know, more protein that you talked about would be two cups of yogurt or five ounces of nuts or, you know. Yeah. So more protein and more variety. I think we were talking earlier about Emma Morano and the fact that the doctor,

Carlo Bava... It's a woman who lived to be 117 years old in Italy. 117, that's right. So she was already eating three eggs a day from earlier in her life. And then when she turned 95 to 100, Carlo put her on 100 to 150 grams of raw meat per day. But lots of times people, journalists talk about that, and they forget to mention that she started when she was around 100 doing this. So at 100, which is very bad if you were 45, it becomes, I think, not a bad idea at all.

And I never thought when Carlo told me that, her doctor told me that, I never thought, are you crazy me that the doctor her doctor told me that I never thought are you crazy and it's a funny story actually she went to him one day and you knew her you hung out with I used to I used to go two or three times a year and it's a funny story she went to Carlo one day and she said you know Carlo I think I need to stop eating meat and he's like why and she said my journalists came to me, and he said, oh, you eat meat every day?

This is going to give you cancer. She was, I think, 107. But I thought it was very entertaining, right? And also very telling of the very naive approach in nutrition, right? This guy is telling a hundred and seven year old to worry about eating less meat as a journalist because she's gonna get cancer he's not thinking no she's not gonna die of cancer she's gonna die of pneumonia she's gonna die because she breaks her hip and she falls

down the stairs yeah and or maybe the flu she might die of the Yeah, she's past the age of getting cancer and heart disease. Well, she might get cancer, but I mean, that's okay. You really need to worry about lots of things in addition to cancer. Because the frailty is an issue. The frailty is an issue, and the frailty of the immune system is an issue, right? So immunosuppression. If the immune system is weak, then then you're gonna have all kinds of problems right so this is why i think you know you and i are are now and a few others are now moving into you know sort of generating this field of complexity uh and i think historically it was ignored because people said it's food yeah right what

the hell could it possibly do right and now it's the most powerful drug on the planet it's the most Roger but it's very complicated and the response is very complicated so now it's probably the one of the most complicated fields in medicine right because the food is a thousands and thousands of components and the body's got thousands and thousands of genes, and now all these get together. This is where nutrient technology world comes from. It's like, what the hell happens when all this happens? When you think about it, you've got 20,000 genes, but about 5 million variations in those genes, all affected by food you've got you know the microbiome which is a hundred times as many uh genes as our own

genes which is another two million genes that get affected and you've got the chemical reactions in the body that happen every second and most people don't know that there's 37 billion billion that's 21 zeros chemical reactions in the body every second, all of which interact with food. So that, that just mind boggling. How do you even do the math on those numbers of what's actually happening instead of a single pathway, a single drug. And that's the beauty of food and why it's so effective. And I want to dig into this complexity a little bit with you because the protein issue and the protein story is fascinating. In, in your models, there's a gene that gets activated or a pathway that gets activated called mTOR.

And this pathway seems to be activated through protein and it seems to accelerate aging. When you're older, you need more protein. But like Emma Murano, she had 150 grams of raw meat. Why didn't that make her age faster if the protein activates mTOR? Yeah. So it's actually what we call axis. And the axis is multiple pathways joined together. So it starts with growth hormone, releasing hormone, growth hormone, IGF-1, AKT, TOR,

or possibly TOR without AKT. So there is a whole series of genes that are involved. And what happens is during aging, they go down naturally. So if you're 25 years old, IGF-1 is going to be very high. If you're 90 years old, IGF-1 is going to be naturally very low. So what we showed in the paper a few years ago is that if you put an adult younger than 50 on a high-protein, mid-protein, low-protein diet, IGF-1 and, as a consequence, TOR are going to be associated with the level of proteins. So high-protein, high-IGF-1, high-TOR.

Low-protein, low-IGF-1, low-TOR. If you look at a 65 and older person you no longer saw any significant difference really either higher low protein there was no change in the mTOR or the trend but no significant difference I mean overall you cannot say that there is a change no matter how much protein you eat right so stay away from a lot of meat when you're younger but once you hit 65 you can have the grass-fed steak. Is that it? That's what a journalist will say. And that's what journalists, exactly what journalists say, at least some of them. No, you know, so the idea would be that as you get older and older, you can measure your IGF-1.

And let's say that you're 72 and your IGF-1 is 280 you should lower your protein that's a measure of growth hormone yeah insulin like growth factor one right so the one that they're circulating is pretty stable right so it stays stable in the blood so it's better than measuring growth hormone because growth hormone is versatile and it's very hard to follow but IGF-1 now most clinics can can cheaply measure it. And so if somebody is 72 and has got 280 IGF-1, they're eating too much protein. Yeah. And so you can still knock it down. And these people are at risk for multiple cancer, prostate.

So where should you be? You should be, we see the ideal level 140. 140 seems to be ideal. Whether you're young or old, now it could be very old that you know may not be that easy to keep 140 uh but in general in the adult population 140 seems to be ideal but exercise increases that right no exercise does not have a big effect on IGF-1 either way, either up or down. Fascinating. So in the research, you're really talking about some really interesting things like Alzheimer's. So how would this approach benefit Alzheimer's? Yeah. So a few years ago, we published on the first paper on our just the essential amino acids

so if we took mice they had mutation, human mutation to develop Alzheimer's so all these mice develop Alzheimer like symptoms they become cognitively impaired they don't learn anymore and they do very poorly so they're mice that can't find the cheese

exactly and so if we alternated this, if we affected IGF-1, this growth factor, and we make it go up and down by controlling just the essential amino acids. So these are the ones that you need to have to have a normal function, right? The ones that people eat protein for.

Those are the building blocks of protein, the amino acids, right? So let that people eat protein for. Those are the building blocks of protein, the amino acids, right? Let's simplify it by saying, let's say we have the high-protein, no-protein diet, alternate it. High-protein, no-protein, high-protein. And we saw that this was sufficient to reduce their cognitive impairment and to keep them protected for longer as they were getting old. So now we're doing both multiple mouse studies and a human clinical trial in Europe.

A USC multiple mouse studies with two different Alzheimer model. One is called triple transgenic model. It has three different mutations that promote early Alzheimer's in humans. And then we're doing another mouse model, EPOE mouse model for Alzheimer's. And yeah, so we'll see. But our hope is that because the fasting-mimicking diet, the revolutionary...

And by the way, the Alzheimer's one is a very special one where we do it only once every two months because we're worried about frailty and we're worried about muscle loss. So we do it every two months and we give them for 55 days. Actually, for all the days of the month, we give them a ketogenic supplement. So we're pushing the ketogenic state and we want to ensure that they don't lose weight. But we also want to give them the benefits of the extra ketogenic chronic push. Yeah.

Which is important because, you know, when brains are damaged with Alzheimer's, basically it's like type 3 diabetes in the brain and it can't utilize glucose or sugar as well, but it can utilize fat or ketones, which is why you see patients and the studies show, and I've had my own personal patients, significantly improve when they have cognitive decline when you put them on a ketogenic diet. Yeah. Yeah. The problem that we saw in the early approaches was the frailty.

So if you take an 85 year old and you put them on a ketogenic diet, you might end up seeing them pass out the day after, right? Well, you need to get enough fluid and salt. Yeah. So it's tricky. So we're thinking about as you get it out there as a treatment for everybody. I mean, not everybody has Mark Hyman following them, right? So yeah, in that case, I think you can experiment much more and things that are more extreme and I'm not saying I mean I think eventually I mean there is already studies that have been published on ketogenic diet and Alzheimer and I think eventually there's gonna be ways that are to do it that are safe the question

is how long can you keep a patient on that diet and how frail are they gonna be after you know two or three months on that diet? So those are- I mean, those diets increase muscle mass, decrease body fat. All right? They activate a lot of the- Yeah. The question is, if you took, let's say, 285-year-olds, and this is going to be really what you're

looking at, or 80-year-olds, and then you put them on this ketogenic diet, how many problems are you gonna see and is it possible that if you just do a much lower uh ketogenic and maybe alternate it with the fmd every two months you get the same effects i don't know maybe not maybe you need to put them on a 90 fat diet and so so i mean those are the things that that uh that need to be uh determined i was always very afraid and i know the neurologists in europe and in the usc were very afraid to take people with uh close monitoring and putting on putting them on say 90 fat diet revolutionize their diet because they're all were saying not with my patients so you know there's

the same war that we had i mean listen by the time someone's got alzheimer's they're going downhill it's a desperate time and doing desperate interventions sometimes you can have amazing results yeah we're in the same choir right we're in the same choir but i mean when we first did this with a cancer patient it was a war i. I'm talking screaming wars with oncologists. Because they tell them, oh, eat pasta and eat tons of ice cream and have cake. We just published in Nature Reviews. I'm kidding me. We just published in Nature Reviews Cancer.

And immediately after the publication, the complaint from the nutritionist in cancer centers. Oh, yeah. And the complaint was official and said, well, but in the standards, in the European Association of Nutritionists and Dietitians says this at least 1.2 grams of protein per day should be between 1.2 and 2, and, and, and, and. And we responded and we said, look, if you look at the days where chemotherapy was first

approved, chemotherapy did tremendous damage. Forget the restriction of protein and restriction of fat. It did incredible damage and even killed a lot of people. You know, doxorubicin, for example, has severe cardiotoxicity. And we approved it. Why? severe cardiotoxicity and we approved it why because you know everybody agreed that it was worth to have some side effects even they could be deadly potentially deadly which is not the case for the diet and and everybody agreed and nobody you don't hear any oncologists complaining about

chemotherapy and say why are you now saying that we're not allowed to even test? And the words we had used was potentially promising. They attacked the potentially promising, officially with a letter to nature reviews. Unbelievable. Potentially promising intervention. What we were trying to do is stimulate clinical trials. And they managed to go after it. And so this is the world we live in yeah

it's called you know there's a there's a great book called the structure of scientific revolutions by thomas kuhn where he talks about the idea of normal science the normal conceptions and views and theories are very hard to overturn because people are stuck on their old way of thinking and when someone comes out with a radical idea like you are i'm sure you get a lot of attacks yeah and so i'm saying for the neurologist exactly the same right but we already knew we had learned from the oncologist so we came in very careful so we don't want to get in words let's try to get in there with real data mouse data human data let's collect preliminary and then say look they're fine so now with the ketogenic let's push this 400 calories a day i think it is yeah and see what happens if they're fine then we maybe we push

it to 800 calories a day and and combine it with the fmd so but and then we'll see the results of other trials that that are being done on alzheimer and lots of groups are doing that and then we decide i think it's it's a good way this is a radical change in our thinking about medicine which is that we can treat the underlying mechanisms of diseases that are all linked together through a simple common pathway which is food and certain types of eating that actually activate all these healing pathways the one thing i want to come back to though is the idea that carbohydrates are good or bad and I think this is a debate out there now that's really on fire whether it's ketogenic or you know the high carb vegan community

and there's just complete polar opposite views. You know I follow the work of a guy named David Ludwig who's a professor at Harvard who's done a lot of work on insulin and the carbohydrate insulin hypothesis and of course has been attacked for. But he did a fascinating study looking at, it was a $12 million study. It was a feeding study where they gave everybody the food for a period of time. And they looked at what happened to their metabolism. And they found that they gave them a 60% fat diet. It wasn't a high protein diet. It was 60% fat.

6-0. 6-0. Or 60% carbs. And then the protein was like 20% and the rest was, you know, they're switching over carbs and fat. 6-0. 6-0 or 60% carbs. And then the protein was like 20% and the rest was, you know, they're switching over carbs and fat. And they found that the ones who had the high fat diet had much faster metabolisms. In other words, they burned an extra 250 calories a day. And if they were insulin resistant, they burned an extra 400 calories or 450 calories a day. And that would lead me to believe that the carbohydrates that we're eating are stimulating insulin, which is really, I think,

one of the main drivers of aging is activating insulin and activating all the inflammatory pathways that go with it and the insulin resistance in the brain and cancer and insulin resistance and heart disease and insulin resistance. How do you kind of explain that? Because the data just seems all over the place. No, no, it's not. It's not. The data seems all over the place until you look at all the pillars, right? And the pillars again, epidemiology, clinical studies, basic research, studies of centenarians.

And so for example, if you look at the work by Simpson in Australia take mice and you give it exactly what you said a high fat or a high carb diet and if you give it a high fat diet they start losing weight they look great for a little bit and then they die earlier than the other mice right so so you look good but you die on you look good you look good and then you die young. You look good, you look good, and then you die earlier. I'm worried. I have like 6% body fat. Now what am I going to do? Yeah, yeah.

No, no, no. This has nothing to do with body fat. We'll go have some pasta tonight. Because the body fat, you're going to have lower with high-fat diet. Yeah, well, I guess that's your point. Yeah, my muscle mass has increased. My body fat's down. That seems like a good thing when it comes to aging.

Well, you know, it is and is not, right? Oh, no. So I think that there are probably, for example, fat stores a lot of the stem cells, right? And to the point that a lot of the stem cells for treatment are taken from fat. So what don't we know about these organs? Fat also protects organs from, uh, uh, stress and from movement.

And so there is all kinds of things that could happen, not in, in somebody your age, but let's say, you know, 70, 75, 80, right? So what about that fat? What is it? Is it hurting them or is it helping them? Even in the mice, know the mice that respond the worst to calorie restriction earlier you mentioned calorie restriction and the extension lifespan actually it turns out that a third of the mice live longer on calorie restriction a third

of the mice have neutral effects and a third of the mice live shorter really and guess which one the shortest the one that have the lowest fat storage capability. So it's tricky, right? On one side, you can have central adiposity, the visceral fat driving, and the liver fat driving lots of diseases. On the other side, potentially subcutaneous fat and other forms of fat. This could be helping an individual and a mouse live longer. That's true, but the carbohydrate load, particularly starch and sugar, not vegetable carbohydrates,

which I'll agree are good, those drive visceral fat or belly fat. Yeah, so there is no doubt, there is no doubt, that when the carbohydrate, the starches and the sugars, let's say, or the carbohydrate in starches and the sugars right let's say or the carbohydrate in general but you know because also the fruits right fruits people talk about fruit this is like some great food but a fruit is packed with sugar and some of them packed with fructose and so there is no doubt that that eventually are going to cause a problem, right? So there's no doubt. So the question is, when is that eventually? So for the centenarians of Okinawa, they used to eat 70% of

the calories from sweet potatoes, purple potatoes. They never reached that eventually because they were fairly active. They didn't overeat. You know, these Okinawans are pretty behaved. Yeah, exactly. Get up when you're... And the Italians, you know, lots of these little villages that have super longevity, including Molocchio,

in the old days, lots of the centenarians, they're not obese. You know, they may be a little bit overweight. Now, their sons and grandsons and granddaughters, you're starting to see much bigger obesity problem. So now they went from a great use of the carbohydrate to a poor use of the carbohydrate. And absolutely, once you make that switch and you have lots of pasta, bread, pizza, et cetera, et cetera, rice, then I think you're now generating a much bigger problem.

That's when I think the ketogenic diet, the low-carb, now becomes beneficial. The question is, how long should you keep that? And maybe you keep it until you reset, and then you learn how to behave, and you don't do yo-yo either, right? Because that seems to be bad too, back and forth. So you just maybe have one or two shots right use the ketogenic diet to go to to get to the longevity

diet right use the ketogenic diet get there because it's probably and i'm becoming convinced that for people that have real problems maybe that's the only way but then move to a more long term uh longevity diet which is fairly high carb of the good kind, only of the good, as much as possible, the good kind. So, you know, tons of vegetables and legumes and much little, say in the ideal dish is to me, 50 grams of pasta and 500 grams of legumes and vegetables. I mean, nobody eats like this anymore, but everybody used to eat like that 60, 70 years ago. So I'm just saying, if everybody could do it, we can go back to it.

And they did not have insulin resistance. They did not have, they had these people in Okinawa and Italian towns, zero cardiovascular disease. They had processed food, and they weren't exposed to the toxins they were exposed to. They weren't having the chronic stress we have. Yeah, exactly. But I don't think to the toxins they were exposed to. They weren't having the chronic stress we have. Yeah, exactly.

But I don't think that, I think going back to their diet is not going to, so I don't think that by being low carb, you're going to counterbalance more-carb, we have to see. But certainly, if it's a vegan pescetarian diet and it's high-carb of the legume and vegetable kind, seems to be very, very good. Now, the question is, what if it was low-carb vegan pescetarian? Some data suggests it could even be better, right? But some data suggests it could be worse. So it's really tricky. It's confusing tricky still yeah so uh in in your

work you also are showing that stem cells get activated through this process which is what everybody is excited about wants to go get it costs tens of thousands of dollars it's painful to suck out your bone marrow and fat and you're saying just by changing your diet you can activate your stem cells yes so in my city is very very clear to the point that not only you activate the stem cells but the more much more important part is this very coordinated regeneration rejuvenation program both when inside of the cell and at the organ level to the point stop you just said there's a rejuvenation program embedded in our biology that we can turn on and that's what your program does not my prog I mean yeah this is what we

discovered it scientifically but I don't want to make it my program yeah but but but yes so this the fasting mimicking diet is designed to push the body to start breaking components down, turn on the stem cells, and the stem cells, you see them, they're standing by. For example, when we damage the pancreas of mice, you damage the pancreas of mice, they stop making insulin, and then you start, only then, you start the fasting making diet and you see that the the pancreas is now turning this embryonic developmental uh program on and uh and all these genes that are only turned down when the pancreas is first generated when the mouse is born starting getting turned down many genes right so it's very

clear it's a program it's not just simply few genes around all of them around and of course you want to do that when you repair your skin after you cut yourself that's a program it's not just simply few genes around all of them around and of course you want to do that when you repair your skin after you cut yourself that's a problem right you don't things are not just getting repaired by chance everything every cytokine every stem cell it goes in knows exactly where to go it gets recruited it binds to something else and slowly it just rebuilds everything right right? Remarkable. And I always say, do you really think that we have a program so sophisticated for the outside of the body and we got nothing for the inside? There's no way.

So the inside understands that, and I think fasting, but more safely fasting-mimicking diets can trigger that program in the liver, in the pancreas, in the hematopoietic system, in the brain, et cetera, et cetera. So stressing the body a little bit with the fasting mimicking diet actually activates all this program that... I don't think it's stressing. I don't like this Ormisi's idea. You don't?

No, I don't like this Ormissi's idea. You don't? No, I don't. I think it's much more a very strongly evolved program. If you don't have any food, you got to break down components because you're not going to make it, right? So in the old days, whether you were a monkey or a mouse or a human, it could go, lots of people must have starved to death right so the program had to be very sophisticated to get you potentially there's some people that are faster for a year six months to a year so with no food no food yeah nothing you know bees of course but but but uh so the program you have to have a lot of storage. Yeah. And we used to do that. In the summer, we used to eat a lot of fruit and gain a lot of fat, right?

So that was our program. So gain fat, like the penguins, right? The emperor penguins in the South Pole. Gain fat and then try to make it through the winter while eating as little, while eating as little as possible. That's what the bears do. They gain 500 pounds in the summer and then they hibernate all winter, lose it all, right? And that's what we used to do. Not everybody used to do that, but certainly in very long periods of our history, that's what we used to do. So yeah, so I think that in that period, you're really breaking down almost everything to the point, let's say

that before that you might be BMI 13, 14. So BMI 13, 14, you're about to die. It's very low. Very low. Yeah, it's very low. This is a harsh fits, the prisoners when they came out, I think they had about 14 BMI. So a BMI, you are at the limit between life and death. It's body mass index. Yeah. So imagine now this person that is emaciated, re-expanding, as it happened after Auschwitz, to, you know, some people died because they started eating too quickly. But other than that, you imagine this person that is starting to re-expanding all the organs and systems back to normal.

Some of the organs may have tripled in size. So imagine the program that is responsible for that rebuilding, extremely sophisticated. And it has to be the only explanation. It has to be the same program that it was used when we were first born. Yeah. And so the stem cells get regenerated. It helps. The stem cells realize that the liver is now very small and that you have a liver size that is now compatible with all the food that's coming in. And so you slowly start expanding, expanding, expanding.

And same thing for the muscle. I mean, BMI 14, you have almost no muscle left. So now you might, I don't think it is two or three fold. I mean I'm just speculating widely here. But it might be ten fold. It may be that you now 90% of your muscle within six months post this anorexic state is now new muscle.

So how do you go from point A to point B? And the only way is to have cell-like cells coordinated in a coordinated way is to have cell-like cells coordinating in a coordinated way beginning to rebuild. This is the stem cells that are part of this process right? Yes stem cells are central in this process some of it is gonna be cellular so the cell gets smaller and smaller and smaller so it could be the very small muscle cells and then they re-expand right or very small liver cells and they re-expand, right? Or very small liver cells, and they re-expand.

This is one discussion we had recently at a conference that I organized, is how much of the cell death and how much is size? I think both are involved. Yeah. So this is just fascinating. The other thing that comes to mind is, as a scientist looking at all this change in the biology that happens when

you do fasting mimicking diet it's a lot of its laboratory research some of its clinical research what biomarkers are available to us today what tests can we do the average person say you made money wasn't an issue what could you do to find out the things that you want to track as you get older that change when you do this because you the things that you want to track as you get older that change when you do this because you must be following these things and i'm curious like i want to go get the 10 things i want to know about myself that are going to show me whether my approach is working or not because does that exist yes no no we're about to do an app and i think the company alnutra that i that i founded is going to have an app soon in

something that morgan levine at yale came up with and there's 10 different markers and there i think this is i really like that um maybe even more than the sort of epigenetic clocks the stuff that overt at ucla and others came up with i like that because um it's also a sort of mixing health and longevity, but she's shown that it's a very, very good predictor of mortality. And what are they looking at? Well, things like, I think, cholesterol, C-reactive protein. I don't know if IGF-1 is part of it, but there is many markers. There are included, this i think nine or ten markers and um and now they're gonna generate an app that way you could just uh go to the app and put in the markers that you can

get done in any clinic and and that will tell you your biological age but aren't there things that are newer that people can check like telomeres for example or can you measure mtor activity or can you measure activity of foxo or genes or sirtuin genes or whatever the things are that you're looking at that are a little more esoteric? Are those things that we're going to be clinically looking at in the future? Yes. I mean, in the future, yes. But right now, whether it's telomere length or is senescent cells or, I mean, there is not really a system yet to say, let's say that you take something that in three weeks makes you three years younger. I think the best is still the blood.

So the blood, for example, part of the inflammation, right? The consequence, we say dysfunction, inflammation. Well, it should go back to normal if if whatever intervention you use is working whether you're insulin resistant dysfunction marker or you have crp that is high or you have interleukin-6 that is high etc etc they should be moving back to normal so i think that that's a much much more powerful way right now and for the next few years. I know it doesn't sound as cool as saying I'm going to measure the telomere length, but you can talk to any telomere expert and even senescent expert. And they say, unless you use senolytics, the chance that all of a

sudden in one week or two weeks or three weeks, you're going to have the telomeres getting longer. About maybe six months. I mean, I checked my telomeres recently, and I'm 39, I'm 59 years old, but I'm biologically 39 according to that. Is that a valid metric? I think it's a good thing to show, right? Would you see telomere changes with FMD? I would rather see my white blood cell count and then my lymphoid myeloid ratio.

I think that would be more telling do you how is the ratio of myeloid cells and lymphocytes in your body and how strong is the immune system right how responsive are you to a vaccine for example so lots of these things can be measured now that to me is a very functional measure of aging and age-related dysfunction. IGF-1 levels, but insulin resistance. Yes, cognitive performance, right? fMRI. Get an fMRI.

I mean, if you can perform well in an fMRI younger, it's a functional assessment. It means that your brain is working better. And so now you covered your muscle cells, your adipocytes, your brain cells, maybe your liver. How quickly can your liver get rid of certain molecules that are not toxic? So yeah, functional performance to me, like response to an antigen, and you can look at the titer of the antibody right so so these things that I think soon enough are gonna be much more

useful than how long is the telomere because yes processes in the body and how they're working or not yeah and then look at the functioning of these systems and it'll tell you a lot about what's going on whether you're aging or whether you're actually reversing aging I can't wait i mean it's it's an exciting time to be alive because you're seeing all these advances happen in an accelerated way and your work has been really such a breakthrough in terms of our thinking about aging um and you've created not just this great body of research but you've also said look this stuff works i want people to be able to access this i don't want it just to be an academic ivory tower and you created this company called el

nutra which created this product called prolon which is a five-day fasting mimicking dying kit that you can basically go online and get uh and do this intermittently and see how you feel and what happens to you it's it's accessible now and what's amazing is you've taken all the profits from this and from your book longevity big mistake hopefully pay for your travel but it's you know you're doing something good for the world and then you're taking the money from that and plowing that back into further research what we're doing is i created started this foundation called create Cures, and we're hoping, as I talk to lots of doctors out there that are in the trenches, they say, well, it's very

difficult to get money to do research. And so I hope at some point very soon, and it's already happening, we now have enough funds that we can go back and look at the Alzheimer, look at the Parkinson, look at all these different things, and really in a a foundational way, say, you know, I always say, oh, you started the company, you must be telling people to do this all the time. I say, no, you only need to do this three times a year. And, you know, in the old days, the CEO got upset. And now I think he realizes it's about, you know, getting people to 110 healthy.

It's not about making money for the company. And I think if we do the right thing, the company is going to grow. And the company, 60% is owned now. It's going to be owned by the foundation now. I will donate 100% of my shares to it. So that means that the foundation is going to get lots of funds. The more this company grows, the more the foundation grows, and the more we're going to do all these things.

Everywhere in the world world people are saying you know the pharmaceutical companies where we they have lots of money everybody's working on drugs and there's no money for food for food research well you know now there is right and and soon enough you know i'm talking one or two years i'm not talking about 20 years. We might have billions of dollars. Really? Billions of dollars to devote to research. Can I borrow some for our research? Yeah, of course. I'm going to apply for a grant because we're trying to do food as medicine research at Cleveland Clinic.

Of course, yeah. So people, we already have a grant program and you're welcome to apply already now. But I think in a couple of years, we're going to have another level of grant programs for scholarships fellowships because of the growth of prolon because of the growth of prolon and the growth of the company absolutely that's so exciting and that is brilliant because it's one of the big challenges in this field is that no one wants to study food and health and aging even though like we

said it's the most powerful drug out there. Yes. And I mean, if you just look at what you said earlier, the effect of calorie restriction in completely eliminating diabetes in monkeys, monkeys, not mice, reducing cancer by 50% and reducing cardiovascular disease by 50%. I always say, how is it possible that we don't have incredible investment into this I can you imagine like decreasing wiping out diabetes because it's probably not wonderful I don't know what it is but but it's crazy that the NIH invests such a minuscule amount of money compared to the money that goes into everything else yeah to say find me a way that

you can achieve what's already achieved by calorie restriction without the side effects of calorie restriction, right? You figure that should be half of the budget of the NIH and all the government agencies that are looking at health and say, fine, we'll keep funding everybody else. But if we can reach this incredible goal of wiping out diabetes and reducing cancer and cardiovascular disease by 50 percent that's deserving of half of our funds and i'm gonna it didn't happen it's not gonna happen and the only way to do it i think is with the people that realize hey this is a good cause it's a good product are the people that basically can now fund what they want right the next generation of things whether it's you Mark do it or or

somebody else I mean you know we spend 60 billion funds from the government on pharma research we spend a billion on nutrition research yeah and that has to change that has to change so we are billion, we're lucky if 50 million go into healthy longevity. Right. Nutrition and healthy longevity, right? Right. So lots of the nutrition research is going to acute specific effects. Right.

But it should really be, how do we get to 110 healthy? Exactly. Everything else comes with it, right? So in a sense, you're not studying disease. You're studying the science of health. Or long-term health. How do you turn on healing mechanisms of the body

and repair mechanisms? And that is a very big difference from trying to treat diseases and symptoms. That is the future. And on top of it, the science of youth, right? So youth spend first. Juventology.

Yeah, juventology and youth spend first. Then once you, of course, you get to 70 or 75, then health spend, right? So then you do switch to, okay, now I kept you young until 70. Now I'm going to keep you healthy until 110. I mean, you know, we do what we can. It's not going to be any miracle there,

but I think we can really at least achieve what was already achieved in monkeys. No way that we're not going to get there. And that's a pretty remarkable achievement. And people are not going to be old and sick. They're going to be old and healthy and contributing to our society. Right. And they're not going to be anorexic like in the calorie restriction study and miserable. So that's what we have with the technology.

We have to say clearly, if they got it with such a simple intervention, 30% less calories, but caused a lot of problems, how long is it going to take us to... And I think pro-run FMD is one of the ways, maybe ketogenic diet, maybe some forms of ketogenic diet. Let's get there. But I think let's not get there in 30 years. Let's begin to get there in the last two or three years and get as many people as possible involved. And then I think within the next 10, 15 years, we can be there fully with anybody that wants to listen. I mean, not everybody's going to listen.

Some people are just going to keep doing whatever it is, taking five drugs. The other day, I looked up how many people 18 to 34 take drugs and I could not believe it, 53%. That's huge. I mean, I heard from one of the physicians at Cleveland Clinic and I hadn't verified this, but he said that 40% of the patients at Cleveland Clinic take 10 or more drugs. This is like completely crazy. Yeah. And you use food, it's one drug, but it's so complex that it does all these amazing things

it's so great so if last question if if you were going to to to blow up or sort of demystify one thing that people commonly think about nutrition what would it be like what one element culprit hide this load that right much more complicated than that you know and i think that it's time now uh to find the trusted sources and just say yeah i this guy or this woman i trust. They've been doing this for a long time. I make them accountable. And so you tell me what the complexity is and I follow it. Forget low protein, high protein, high carbs, low carbs, high fat, low fat.

I mean, that's all meaningless. It's got to be age-specific, person-specific, but also personalized but unpersonalized at the same time. And already people are saying, we scare people. Because every every time i talk they start laughing it's like oh what is it too complicated well exactly it is too complicated but we are making it very simple because now once you find the trusted source the companies and the and the experts then in books it's very easy to follow you know your book my book i think you know people can just say how long is it one week to figure it out.

People don't even want to put one single week in changing their health for the rest of their life, then I'm sorry, we're not for you. Then we don't have a solution for you. If you want to take 10 drugs, or if you want to be 19 years old and be on a drug, or you want to be 65 and be on 10 drugs, be our guest.

But I think, yeah. The culprit. That's the beautiful thing about the longevity diet is that, and you said this before, on a drug or you want to be 65 and be on 10 drugs be our guest but uh but i think yeah the cold that's the beautiful thing about the longevity diet is that and you said this before which i'd never heard before but it makes total sense you wrote on all the things about eating principles that are known to be great and no one can argue with and that are basically beyond question which is eat real food eat good fish eat lots eat lots of seeds, eat good fats, have lots of vegetables. It's basic principles. But the devil is in detail. For example, low protein, not 20%, 10%. What's the source? Vegan plus fish. So all of a sudden, if you look at Campbell, it says vegan. And I'm saying big mistake. Why? Because most people that are vegan,

it could be great. I mean, some people can be vegan and be great. I'm not big mistake, why? Because most people that are vegan, it could be great. I mean, some people can be vegan and be great. I'm not arguing with that. But it's extremely difficult. And then when you get old, you got a double problem now. You know, so now you're vegan, you're gonna, yeah, of course, you're gonna lose muscle. You're gonna need more nourishment from simple sources

like the cheeses, the milk, et cetera, can help you when you're 93 years old, right? So this is this is I think is what's really important to begin to look at the detail it's not just about yes the ingredients lots of us of course lots of us agree lots of us disagree now a lot of people say eat lots of meat and eat lots of animal fat and that's good for you so you know yeah know, yeah, in one sense we're moving, a lot of people agree with a lot of the things I picked, but lots of people now disagree, you know?

Well, the things that you say, I don't think anybody disagrees with because nobody says fish is bad. Nobody says olive oil is bad. Nobody says, they might say, oh, you could eat animal protein. Oh, maybe saturated fats aren't so bad, but the principles that you laid out, nobody's going to disagree with that as a healthy diet. Oh, you'd be surprised. Yeah, you'd be surprised. I actually kind of came up with a similar concept called the pegan diet, which was a joke because there were so many extremes of vegan and paleo.

And I said, it's just, if you look at the principles of common sense combined with science and look at all the data, it's not that hard, right? Eat a lot of plants, don't eat a ton of meat, eat good fish. But for example, for example, I give you another simple example. The Okinawa thing, you mentioned it earlier. Get up when you're 80% full. It's a big mistake, right? I say eat more, not eat less. Everybody, every time I present. Every time I present, you know. So the devil is in the detail, right? Wait, you say eat more? Of course eat more.

Why? Because you have to think about your clientele. Your clientele is not an Okinawan that was born with my parents, my grandparents, everybody eating, getting up when they're 80% full. Your clientele, the Americans or the Europeans. We get up when they're 120% full. Well, there is signals in your stomach, both at the nourishment level and at the mechanical level, that are telling your brain, now I'm full. If you're getting up when you're 80% full, the message to Americans, Europeans,

is going to be, I'm hungry all day. And guess what's going to happen? Within a year, you're going to start overeating again. If you get up when you're full because you're full of fibers, vegetables, nourishment, minerals are there, the micromolecules are there, the macromolecules, everything is there. The signals to your brain is like, okay, I got everything I need. The signal to your stomach is I got everything I need. The signal to your microbiota is I got everything I need. But overeating isn't good.

No, no. I don't mean overeating. I mean eat the right things until your stomach is full. And you know it takes 20 minutes. You have to eat slow because it takes 20 minutes for your stomach to tell your brain that you're full. And most of us have experienced that. Yeah, but if it's fiber, if it's what I described,

you know, 300 grams of chickpeas and 200 grams of vegetables and 50 grams of pasta and and in 50 grams of pasta in between that's gonna be there for hours and hours and hours right so the message for a long time during the day is like the bariatric cancer right small stomach message the brain stop right so it's it's the same thing and so I think you see that the devil is in the detail little things and every time I present everybody says oh you're to tell us to eat less. I say, I never say to eat less.

I never worked on calorie restriction. Just for five days. Well, yes, for five days, three or four times a year. Yeah, so that's the only, I mean, that's very little time compared to the rest of the year, right? Well, I'm definitely going to try it. And I thank you so much, Dr. Longo, for being on The Doctor's Pharmacy.

You're a brilliant man, contributing greatly to our understanding of aging and health and food. If you want to learn more about his work, go to WalterLongo.com. That's Walter with a V, V-A-L-T-E-R, Longo, L-O-N-G-O.com. If you want to learn about Prolon, the fasting mimicking diet, and try it, you can go to ProlonFMD.com. That's fasting mimicking diet, so Prolon, P-R-L-O-N, F-FMD.com. That's fasting, mimicking, diet. So Prolon, P-R-L-O-N, F-M-D.com. It's really amazing. I got a box at home. I can't wait to try it and I'm excited for it. So I'll share the results with you when I do it and we'll see what happens. I might

get to 30 from 39. So thank you, Dr. Longo, for joining us. And if you've loved this podcast, please share with your friends and family on social media. Sign up if you liked it, wherever you get your podcasts, on iTunes, Google Play, or wherever. And leave us a comment. We'd love to hear from you and know what you think. And we'll see you next time on The Doctor's Pharmacy.

Thanks, Mark.