The Secret Power of Fasting for Longevity and Healing | Dr. Valter Longo

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 and 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 at the director 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 you're 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'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 a University of North Texas, and I was studying music. It was one of the best programs in jazz performance. That's. 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. A rock musician. And I said, there's no way I'm doing.

They're gonna dress up in those funny costumes and. No, no, no.

Yeah.

Or look at them for that matter. But yeah, so I said, I'm not gonna do that. But of course, there was an excuse. I think I really was, my instinct told me that I was interested in aging. I was interested in medicine. And I always thought, what an incredible combination of something that scientifically is a super challenge. about as high as it gets. And then medically, I already at that time I thought this could have effects on many different diseases, not just one. So yeah, that was the switch to biochemistry and then the rest of it. I mean, from the very beginning, all I wanted to do was study aging. 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 achieves 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. 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 Walter was, and I started studying starvation in bacteria and yeast, and I saw that you can 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 magical 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 in 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 historically scarcity. You can't go to the grocery store, you gotta 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 would 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 studied 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 that's we started with water only fasting, particularly for cancer, and then.

We moved to- For animals, water only fasting.

The beginning was just 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're, you know, 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 an oncologist, you- eat nothing. Yeah, the oncologists were very much resistant to that and patients surprisingly were more resistant to it than the oncologist, 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 was 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, and we learned that most people are like that. And this is where the fasting-mimicking diet idea comes from, you know, to worry about also the safety of the fasting and the compliance and, you know.

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 were 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 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 some of the people that I've been talking to, they were saying 10, 15 years ago, they were attacking these immunotherapy scientists and saying, come on, this is an old idea. It's never gonna work. You know, 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. What we 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. is the moment where you rest, right? But not just rest at the general level, but probably having all kinds of systems like DNA repair, etc, etc, do their job. And so it is a moment of rejuvenation, if you will, right? 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 just did the opposite, two opposite things. And then, you know, kill the cancer cell and then regenerate the pancreas when it's damaged and promote the regeneration of the liver, et cetera, et cetera, et cetera. So yeah, so I think that maybe that's what was always there for, identify things that are dysfunctional, old and replace them.

It's a way of cleaning up house.

Cleaning up 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 check 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, we have not been, we cured lots of mice with combination of chemotherapy and fasting-mimicking diet. we've never been able to do it with just, for sure, with the chemo alone, but also with the fasting making that alone. So the chemo and the fasting making that work about as well, but you combine them and they're very powerful.

So, 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, multiples.

Synergistic for sure. And so the point is that we're not about For drugs against drugs, we're about patience. How do you get somebody to get 110 to 110 healthy?

And if you have cancer, 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 gonna be very, very important together, together with the fasting mimicking diet. And we'll see, you know, the ketogenic diet is also emerging as a potential co-treatment. You know, Lucantih has done really great work combining ketogenic diet with PI3K 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.

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, and this is a fact.

These drugs don't even do the same effect.

And this is a fact. If you just look at cancer, and in fact, I had somebody that came to me recently and said, you know, when we use these cancer drugs, we got a problem because we can lower insulin and we can lower glucose. 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, inflammatory, etc. Environment. Yeah, so it would take many, many drugs to get the effects of fasting and nobody argues with this. It is not an opinion anymore. Now, you could argue that all those changes may or may not affect cancer, you know, we have to still see, but we have lots of clinical trials now and certainly mouse data indicating that it does and that's 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 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, let's- 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 bit of a distinction, why? Because we can see that if you add back proteins to the fasting-mimicking diet, you cut out half of the effect, right? And if you had sugar, you cut out the other half. So if you had sugar and proteins, you now eliminated the effect pretty much of the fasting-mimicking diet. So, so, you know, the ketogenic diet, if it was a high fat and, and that's what the fasting making 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 magic, because we want to keep the proteins low, right? So as 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-carb, very high-carb, very low-carb, 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 do this back and forth. And so I don't want to introduce it. 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 vegetables.

It's not starch. It's all vegetables and nuts which have carbohydrates. But it turns out to be 45% carbohydrate of that kind, right?

So in the vegetable group, 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, some. So you have tomatoes, you have broccoli, you have all kinds of vegetables, and, but they do contain lots of carbohydrates. And, and 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 70 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, etc., etc. And now you have this big increase in these protective anti-inflammatory bacteria, which you don't get with the water-only fasting. 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. So, you know.

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 beefed bacteria, etc. Growth, right? 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? So it's a really complex 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 the bacteria from the fasting mice, fasting mice, exposed mice, and we transfer into recipient mice, they have some of the effects, they show some of the effects, but not all of the effects, right? So it means that that micro, 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, right? 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.

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 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 it's very recapitulating of how we may get Crohn's disease and colitis, you know, a lot of toxins from the outside, right? And so you give it this toxin and you're doing water only fasting, guess what happens? they have more leakage, they have more blood in the stools, right? 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. So 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 would 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 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 intestinal stem cells are getting activated, very potently. And then during the refeeding, they give rise to rebuilding, the inflammation is moved out, and you actually shorten the colon, and then you start the FMD cycles, and it goes back to its regular size. It's really remarkable, the fact that it's amazing.

So we know a lot about aging in terms of what are the mechanisms that are driving it. It's inflammations, and they 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? Inflammation, in fact, one of the criticism in the paper was- 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, you know, damaged mitochondria, you have just general damage. As you move forward, any system is going to accumulate protein aggregation, right, in the brain, phosphorylated tau, beta amyloid, oligomeric amyloid, right? So every system is got, it's junk that it 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.

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, it's the inability to get.

Rid of junk and waste. And in fact, one of the things that happened in this paper that we just published, interleukin, I think it was TNF-alpha and several other pro-inflammatory marker were way high in the fasting-mimicking diet.

Really?

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. 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-mimicking 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 gonna come back down. So once you repair it, once the autoimmune problem has gone away, Now they're gonna come back down. In fact, we looked this also in the paper, we have human inflammation, body inflammation. So what you see is that in people that have high C-reactive protein. It's a marker of 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 calorie 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 it, the reservoir. That's a food reservoir.

So you don't need the ab roller, you just need the Proline diet.

You don't, interestingly, it didn't take it from subcutaneous fat. It only took it from visceral. And we showed this in mice with the scans and in people with the DEXA. So that's for sure one way, one of the major ways.

I gotta pause here 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 temporarily you see the lean body mass as measured by DEXA 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 Pretty much 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 intervention. So that's one way. The other way we think that makes a big difference is almost everybody will say the following. When after I got through one, two, three cycles of the FMD, I started looking at food differently.

So.

Yeah, you want some water?

So after I went through one, two, three cycles of the FND, I started looking for food differently. And so, for example, if somebody had lots of sweets and lots of candy, lots of starches, etc. Etc. They 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 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 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, on, on, rational or thinking about it.

So, we were talking a little bit before about the ketogenic diet combined with fasting 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 when you should do what or if you should do any. What is the expert's opinion here? Because you're probably one of the ones 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. 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- People are referring.

To like time-restricted eating where you eat.

Within an eight-hour period.

Curious.

Yeah.

So if you, if you look at time restricted eating and the work by Sachin Panda, but if you look at all the data, you would say that, 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 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, you 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 already 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 slightly increasing gold stone formation, but it's very slight. When you get to 16-18 hours, then you start seeing twice as much risk of, you know, go blood removal, not the nicest thing that could happen to you. So that's the thing. So yeah, so there is all kinds of fasting.

And what about ketogenic?

So yeah, so ketogenic diet, again, what does it mean? You know, does it mean that you're gonna do it for a month? Does it mean that it's gonna be low protein, high protein, animal based? So again, we are ketogenic, we gotta 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. No, it doesn't work like that. It's like, well, exactly what does it do? And show me the data on thousands of patient, etc. Etc. So here I think we need to say, in my opinion, a, a little bit higher fat, you know, ketogenic, not ketogenic, but certainly I think the 60-30-10 is an ideal diet if you for all time. So 60% carbs, mostly from vegetables and legumes, 30% fats, mostly from olive oil, nuts and fatty fish.

Yeah.

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, etc. Etc. Now, for you specific uses, I think that the ketogenic diet can be modified, be more extreme.

Right.

So if you, you have somebody that has, you know, overweight, obese, all kinds of other problems. Yeah, that's where I see that. you know, 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.

-There'S over 2 billion people on the planet.

-Exactly, exactly.

So, 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% protein, 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, you know, I'm just thinking, I think it'd be good to come up with things that we know, and that's what I try to do with the book. Come up with things that we know there is no way it is bad for you. I came up with this denominator where there is no way, I don't care what they need to, 200 years of publications, to say that this is why? Because the centenarian is one of the pillars. These guys have been doing this for over 100 years and in different parts of the world.

They eat real food, they don't eat.

A lot of sugar. They eat real food, yeah. 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 gonna 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 a 60% vegetable and fish and legume diet. I think it's reasonable to have 30% fats. And if somebody cannot do it only from vegetable sources, whatever you can add some animal sources, that's okay. And 10% protein, 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 sort of 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 the two cups of yogurt or five ounces of nuts or, you know.

Yeah.

So more, more protein. and more variety. I think we were talking earlier about Emma Morano and the fact that the Dr. Carlo Bava, 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 forgot 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? And it's a funny story, actually. She went to him one day, and.

You knew her, and you hung out with her.

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, a journalist came to me and he said, oh, you eat meat every day. This is gonna give you cancer. She was, I think, 107. And so, but I thought it was very entertaining, right? And also very telling of the very naive approach in nutrition, right? This guy is telling 107 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.

Or maybe the flu. She might die of the flu.

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 you're gonna have all kinds of problems. So this is why I think, you know, you and I are now, and a few others are now moving into, you know, sort of, generate in this field of complexity. 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 powerful drug, 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 thousands and thousands of components and the body's got thousands and thousands of genes and now all these join, you know, get together. This is where nutri-technology word 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 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's 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 your models, there's a gene that gets activated or 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. like Emma Morano, 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 an 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's 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 gonna be associated with the level of proteins, okay? 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 high or 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.

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 exactly what journalists say, at least some of them. No. 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, in a sense. 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 pulsatile and it's very hard to follow. But IGF-1 now, most clinics can cheaply measure it. And so if somebody's 72 and it's 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. 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, in the, in the research, you, 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 how just the essential amino acids. So if we took mice, they had, they were, 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 alternate 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 are building blocks.

Of protein, amino acids.

Yeah, let's say we'll just simplify by saying, let's say we have the high protein, no protein diet, alternating. 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 older. 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, has three different mutations that promote Alzheimer early Alzheimer in humans. And then we're doing another mouse model, so EPOE mouse model for Alzheimer. And yeah, so we'll see, but our hope is that because the fasting mimicking diet, the revolution, and by the way, the Alzheimer 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 that 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, 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?

So, 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 on things that are more extreme. And I'm not saying, 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 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, increase body fat, all right? They activate a lot of pathways.

Yeah, the question is, if you took, say, 200, 85 year olds, and this is gonna 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 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, I mean, those are the things that need to be determined. I was always very afraid, and I know the neurologists in Europe and in the USC were very afraid to take people with close monitoring and putting on putting them on, say, 90% fat diet, revolutionize their diet. Because they're always saying, not with my patients. So, you know, there's the same war that we had with the cancer patients.

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 can have amazing results.

Yeah, we were in the same choir, right? We were in the same choir. But I mean, when we first did this with cancer patients, It was a war. 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. We just published in Nature Reviews Cancer. And immediately after the publication, the complaint from the nutritionists in cancer centers.

Oh, yeah.

And the complaint was official and said, well, but in the standards in the European Association of Nutritionists and Dieticians says this, at least 1.2 grams of protein per day should be between 1.2 and 2 and on and on and on. 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, Dr. Rubinstein, for example, 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 everybody agreed. And nobody, you don't hear any oncologist complaining about chemotherapy. I 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, 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 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, said we don't want to get in worse. 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, and see what happens. If they're fine, then we maybe we push it to 800 calories a day and combine it with the FMD. So, but, and then we'll see the results of other trials that are being done on Alzheimer's and lots of groups are doing that. And then we decide.

I think it's a good way to do it. 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. 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 it, 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, it was 60% fat. 6-0. 6-0 or 60% carbs. and then the protein was like 20% and the rest was, you know, 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 it just the data 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.

You look good. You look good. And then you die earlier.

I have, like, six 10% body fat. Now what am I gonna do?

Yeah, no, no, not to do with body fat.

We're gonna have some pasta tonight.

The body fat you're gonna have lower with high fat diet. Yeah, well I guess that's your point.

Yeah, my muscle mass is 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? 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 stress and from movement. And so there is all kinds of things that could happen not in somebody your age, but let's say, you know, 70, 75, 80, Right? So what about that fat? Is it hurting them or is it helping them? Even in the mice, you know, the mice that respond the worse to calorie restriction. Earlier you mentioned calorie restriction and the extension of lifespan. Actually it turns out that a third of the mice live longer than calorie restriction, a third of the mice have neutral effects, and a third of the mice live shorter.

Really?

And guess which one live the shortest? The one that have the lowest fat storage capability. so, so it's, it's tricky, right? On one side you can have central adiposity, the fat, the visceral fat driving and the liver fat driving lots of diseases. And in fact. 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, 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, right, let's say, or the carbohydrate in general, but you know, because also the fruits, right, fruits people talk about fruits, 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. Exactly. Get up when you're 80. and the Italians, you know, lots of these little villages that have super longevity, including Molochio, you in the old days, lots of these 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, etc. Etc. 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 it? Keep that? And maybe that you keep it until you, 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 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 longevity diet, which is fairly high carb of the good kind, only of the, as much as possible the good kind. So I saw, you know, tons of vegetable 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, right? So I'm just saying if everybody could do it, we can go back to it. And they did not have insulin resistance.

No.

They did not have, they had these people in Okinawa and Italian towns, Zero.

Cardiovascular disease food and they weren't exposed to toxins. They were not exposed to. They weren't had the chronic stress we have.

Yeah, exactly. But I don't think that I think going back to their diet is not gonna. So I don't think that by being low carb you're gonna counterbalance more the other problems that we have now.

Right.

So I think that, you know, whether it's low carb or high carb, you know, we have to see, but certainly if it's a vegan pescatarian 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 pescatarian? Some data suggests could even be better, right? But some data suggests could be worse. So it's really tricky still.

Yeah.

So 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 MICE 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 inside of the cell and at the organ levels. The point is- Okay, 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 program. I mean, yeah, this is what we discovered scientifically, but I don't want to make it my program. But yes, so 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 mice, they stop making insulin and then you start, only then you start the fasting-miking diet and you see that the pancreas is now turning this embryonic developmental program and and all these genes that are only turned down when the pancreas is first generated, when the mouse is born, start getting turned on. Many genes, right? So it's very clear it's a program. It's not just simply few genes around. All of them are around. And of course you want to do that. When you repair your skin after you cut yourself, that's a program, right? You don't, things are not just getting repaired by chance. Everything, every cytokine, every stem cell, it knows exactly where to go, it gets recruited, it binds to something else and slowly it just rebuilds everything, remarkable. And I always say, 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.

Now, 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 or misses idea.

You don't?

No, I don't. I think it's much more in a very strongly evolved program. if you don't have any food, you gotta break down components because you're not gonna make it. 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. 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.

-But no food?

-No food, yeah. Nothing. You know, beasts of course. But so the program-- you- had 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 as possible.

So that's what the Bears do. They gave 500 pounds in the summer and then they hibernate all winter, lose it all.

Right.

And that's what we used to do. And not everybody used to that, but certainly in, in very long periods of our history, that's what we used to do. So, yeah. So I think that in the 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. Very low. Yes. It's very low. This is harsh. The, the prisoners, when they came out, I think they had about BMIs. So at BMI, you are at the limit between life and death.

That's body mass index.

So imagine now this person that is emaciated, re-expanding as it happened after Auschwitz to some people died because they started eating too quickly. But other than that, 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. Right, so imagine the program that is responsible for that rebuilding, right, 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, 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 is coming in, and so you slowly start expanding, expanding, expanding. And, and same thing for the muscle. I mean, the 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 wildly here, but it may be tenfold, right? And maybe that, that, that you now 90 of your muscle within six months post this anorexic state is now new muscle. So how you go from there, from. point A to point B. And the only way is to have satellite cells coordinated in a coordinated way beginning to rebuild.

And this is the stem cells that are part of this process, right?

Yeah, stem cells are central in this process. Some of it is going to be cellular. So the cell gets smaller and smaller and smaller. So it could be the very small muscle cells and then they reexpand, right? Or very small liver cells and they reexpand. Discussion we had recently at a conference that I organized is how much of the sell that 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, a lot of it's laboratory research, some of it's clinical research. What biomarkers are available to us today What tests can we do the average person and say, 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 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, we're about to do an app and I think the company El Nitra that I found that is gonna 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 maybe even more than the sort of epigenetic clocks, the stuff that over at UCLA and others came up with. I like that because it's also, it's 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 that are, that are included. There's, I think, nine or ten markers. And, and now they're going to generate an app that way you could just go to the app and put in the markers that you can get done in any clinic, and, and they 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 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, you know, whether it's telomere length or is senescence cells or, I mean, it, 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 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 senescence 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 gonna have the telomeres getting longer.

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 telomeres? For example, I would rather see my white blood cell count and my lymphoid myeloid ratio.

Right.

I think that will be more telling. 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, so the cognitive performance, Right? FMRI, get an FMRI. I mean, if you can perform well in an FMRI younger, that's a functional assessment. It means that your brain is working better. And, you know, so now you covered your muscle cells, your adipocytes, your brain cells, you know, maybe your liver, how quickly can your liver get rid of certain molecules that are not toxic. So yeah, functional performance to me, like, like response to an antigen. And you can look at the titer of the antibody.

Right.

So some of these things, I think soon enough are going to be much more useful than how long is the telomere.

Because, yeah, the dynamic 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 an exciting time to be alive because you're seeing all these advances happening in an accelerated way and your work has been really such a breakthrough in terms of our thinking about aging. 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 diet kit that you can basically go online and get and do this intermittently and see how you feel and what happens to you. It's accessible now and what's amazing is you've taken all the profits from this and from your book, the Longevity Diet.

Big mistake.

Hopefully, you'll pay for your travel. But you're doing something good for the world and then you're taking the money from that plowing that back into further research.

What we're doing is I started this foundation called Create Cures and we're hoping, as I told 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's, look at the Parkinson's, look at all these different things. And really, in a foundation 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 it's about, you know, getting people to 110 healthy is 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 gonna be owned by the foundation now. I will donate 100% of my shares to it. So that means that the foundation is gonna get lots of funds. The more this company grow, the more the foundation grows, and the more we're gonna do all these things. You know, everywhere in the world, people are saying, you know, the pharmaceutical companies, they have lots of money, everybody's working on drugs, and there is no money for food research. Well, you know, now there is.

Right.

And, and, and it's 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. I borrow some from research. Yeah, of course. I'm gonna apply for a grant because.

We'Re trying to do food as medicine research. Of course. So the people, we already have a grant program, and, and you, you're welcome to apply already now. And so, but I think, you know, in a couple of years, we're going to have another level of great programs for scholarships, fellowships, trainings.

Because of the growth of Prolong.

Because of the growth of Prolong and the growth of the company. Yes, 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? Can you imagine decreasing wiping out diabetes? Because it's probably number one- It's not patentable, right?

It's not patentable.

I don't know what it is, but it's crazy that the NIH invests such a minuscule amount of money compared to the money that goes into everything else to say, find me a way that you can achieve what's already achieved by color restriction without the side effects of color restriction, right? You figure there 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%, that's deserving of health of our funds. And it didn't happen. It's not going to happen. And the only way to do it, I think, is 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. The next generation of things, whether it's you, Mark, do it, or somebody else in the university.

I mean, you know, we spend 60 billion funds from the government on pharma research. We spend a billion on nutrition research. And that has to change. That has to change.

So, we are that billion, we're lucky if 50 million go into healthy longevity, nutrition and healthy longevity. So, lots of the nutrition research is going to acute specific effects. But it should really be, how do we get to 110 healthy? Everything else comes with it, right?

So in a sense, you're not studying disease, you're studying the science of health.

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, you do anthropology and you 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 gonna keep you healthy until 110. I mean, you know, we do what we can. It's not gonna be any miracle there, but I think we can really at least achieve what it was already achieved in monkeys. No way that we're not gonna 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, you know. 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, you know, ProLon 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 next 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 they're 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 you were going to to blow up or sort of demystify one thing that people commonly think about nutrition. What would it be?

-A one element culprit. -High this, low that. -Right. -Much more complicated than that. And I think that it is time.

Now to.

Find the trusted sources. and just say, yeah, I, this guy or this woman, I trust them. 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 agree. I agree.

I mean, that's all meaningless. It's got to be age specific, person specific, but also personalized, but unpersonalized at the same time.

Yeah.

And already people are saying common principles. We scare people, say, because every time I they start laughing, it's like oh, well, it's 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 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 does it take? 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, you know, then we don't have a solution for you. You know, 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 cost. 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 of seeds, eat good fats, have lots of vegetables.

It's basic principles. But the devil is in the 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 arguing with that. But it's extremely difficult. And then when you get old, you got a double problem now.

Yeah.

You know, so now you're vegan, you're gonna. Yeah, of course. You're gonna lose muscle. You're gonna. You're gonna need more nourishment from simple sources like the cheeses, the. The milk, Etc. Can help you when you're 93 years old.

Right.

So that.

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, 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, so. 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 health.

Oh, you'd be surprised.

I actually 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. Eat a lot of plants, don't eat a ton of meat, eat good food.

For example, I give you another simple example. Yokina, I think. You mentioned it earlier. Get up when you're 80% full. It's a big mistake. I say eat more, not eat less. Every time I present. Every time I present. So the devil is in the details.

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 European-.

We're getting 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 micro molecules 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.

Overeating isn't good.

No, no, I don't mean overeating. I mean eat until eat the right.

Things until you're satisfied. 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, if it's fiber, if it's what I describe, you know, 300 grams of chickpeas and 200 grams of vegetables and 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 messages the brain, stop eating, right? So it's the same thing. So I think you see that the devil is in the detail, little things. And every time I present, everybody says, oh, you're gonna tell us to eat less. It's like, I never say to eat less.

I never worked on calorie restriction.

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 gonna 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 vaulterlongo.com that's vaulter 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 fmd.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 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 and 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 Doctors Pharmacy.

Thanks, Mark.