Dhru Purohit Show - Use These Fasting Secrets to Reverse Aging and Increase Your Lifespan with Dr. Valter Longo

Episode Date: May 12, 2022

This episode is brought to you by ButcherBox and InsideTracker. We all know that fasting has amazing benefits: reduced inflammation, increased cognitive function, fat loss, decreased risk of metabolic dysfunction, and the list goes on and on.  But is there a correct way to fast? Is fasting for everyone? Should we exercise while we fast? How do we make the most of our fasts and how do we optimize our diets when we aren’t fasting?  Today on The Dhru Purohit Podcast, Dr. Valter Longo answers all of these questions and more. Dhru and Dr. Longo discuss the key pillars of the Fasting Mimicking Diet (FMD), created by Dr. Longo to provide the body with the benefits of fasting without completely starving it. They also dive into the foundation of a longevity diet—how can we increase our lifespan and our healthspan using targeted nutrients and dietary protocols.  Dr. Longo is internationally recognized as a leader in the field of aging studies and related diseases. Known as the “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, 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 The Longevity Diet, a culmination of his 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. In this episode, we dive into:  -Why you shouldn’t skip breakfast (2:23) -What happens if you fast incorrectly (13:59) -The key pillars of the Fasting Mimicking Diet (21:43) -Exercise and fasting (24:10) -The impact of the Fasting Mimicking Diet on chronic disease (31:05) -How the Fasting Mimicking Diet impacts the brain (35:18) -The foundation of the longevity diet (38:52) -Optimal protein consumption and longevity (51:02) -Why walking one hour a day is so central to longevity (1:04:14)  -Stem-cell therapy and longevity (1:09:03) -Longevity supplement recommendations (1:15:57)  For more on Dr. Valter Longo, follow him on Instagram @prof_valterlongo, Facebook @provalterlongo, and through his website, valterlongo.com. Get his book, The Longevity Diet, here. This episode is brought to you by ButcherBox and InsideTracker. Right now, ButcherBox is offering new members a great deal. You’ll receive two pounds of FREE salmon in your first box. Sign up at ButcherBox.com/dhru. InsideTracker provides detailed nutrition and lifestyle guidance based on your individual needs. Right now, they’re offering my podcast community 20% off. Just go to insidetracker.com/DHRU to get your discount and try it out for yourself. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

Fasting means absolutely nothing. Eating could be very good for you or very bad for you and fasting in the same way. If your fasting involves keeping breakfast, you're putting your life at risk. There's no doubt about it. Welcome to the Drew Proet podcast. Each week we explore the inner workings of the brain and the body with one of the brightest minds in wellness, medicine, and mindset. This week's guest is Dr. Walter Longo.

Dr. Longo is an internationally recognized leader in the field of aging studies and related diseases. His discoveries include some of the major genetic pathways that regulate aging and life-threatening diseases and the identification of a genetic mutation that protects individuals from several common diseases. In 2015, after a number of his papers were among the most widely cited in biomedical field, Time magazine called him a guru of longevity. Currently, Dr. Longo is a professor. of bio-gerentology and biological sciences and a director of the Institute of Longevity of the School of Gerontology at the University of Southern California in Los Angeles. He's also the director of oncology and longevity program at I-F-O-M in Milan.

He is additionally the scientific director of the Creates Cures Foundation and the Volter Longo Foundation. Dr. Longo is also the author of the longevity diet, which is his take on 25 years of research on aging, nutrition, and diseases across the globe. On today's podcast with Dr. Longo, we dive into a bunch of different topics, including why some of the longest living societies in the world eat breakfast in the morning. Not our American-style breakfast, but some breakfast. What does that breakfast look like?

Well, stay tuned. You're going to learn more about that. Dr. Longo also talks. talks about the importance of pulsing fasting into our lifestyle rather than having more extreme approaches to fasting, which in his opinion have some damaging effects on the body. So it's going to be really interesting to hear about how he thinks some of the longest living societies in the world fast. This is a fascinating interview.

We cover a lot of different topics in addition to those two that I just mentioned. Stay tuned. I think you're going to love it. Dr. Longo, welcome to the podcast studio. Welcome to the podcast. It's a pleasure and an honor to have you here. I selfishly want to dive into, before we go into the fasting, mimicking diet,

the longevity diet, all your work and research that's there, and we explain how it works. I selfishly want to jump into the topic of breakfast because you were one of the first people that I had heard that there is a power from all these epidemiological studies that we've seen out there of including. including some amount of food in the morning. Can you talk about that?

And what do you mean by that exactly? Yes, I mean that if you look at now metanalysis, so studies containing lots of studies, right? They indicate very clearly, and not just for overall mortality, but also diabetes, cardiovascular disease, people that skip breakfast have problems. And now you can say, well, they have problems

because they have other bad behaviors, right? But then you still have to be surprised. Why doesn't, if you fast, let's say, for 16 hours or 18 hours and you skip breakfast, why doesn't that counterbalance, whatever bad habit you might have? You should at least get a neutral effect. But no, we see shortening of lifespan, and we see more cardiovascular disease, and we see association with more diabetes, et cetera. So that's when you have to say, probably not such a sugar idea.

and if we're going to skip something, it should not be breakfast. And so, you know, dinner, it's a possibility. I'm a fan of lunch. So I skip lunch. And I've been doing it for 20 years. And I think this seems to be the safest way to go, you know, if you consider all the studies out there. For the longest living groups that are out there that you study and that you look at, in addition to your own trials that you're doing,

in animals and then observing what happens in human beings as well too in the trials with them. What do you think is happening when people have breakfast in the morning? Why does it seem to be beneficial? And let's define what breakfast is because we live in America and as soon as you say breakfast, people have an idea of pancakes, cereals, sugary stuff. So what do you think is happening on a mechanistic level? And what does these longest living groups? What does their breakfast look like?

Yes, mechanistically, it could be that the fasting, nobody knows, first of all, right? But it's just very consistent. It could be the fasting when it gets to too long periods. So, for example, we know in people that are at risk for gallstone formation and gallbladder operation, those that fast for 16 hours have twice as much a risk as does the fast for less than 10 hours. So it could be something in that domain. For example, what if this continuous generation of lots of fatty acids and lots of ketone bodies is actually a problem? So it could be, right?

It's now pushing the cells all over the body or maybe some cells to do something that they shouldn't do. For example, what about fat accumulation in the heart or in some tissues? could that be happening and could that be causing these problems? We don't know. It could also be in the long run could be reprogramming metabolism to make people insulin resistant. So in the short term, you become sensitive. And then in the long run, you become resistant.

And so there is lots of these things that are known for all the type of dietary interventions. So it is possible that this long fasting period is. causing changes that are then detrimental. And then, you know, what is breakfast? Well, again, in these questionnaires, in all these surveys, they just call you up and say, do you have breakfast, yes or no, right? And that's all they ask. And some studies that I remember were looking at how many calories

should be in that breakfast. And that I remember 400 calories as being the cutoff point, right? you have at least 400 kilo calories or not. Yeah, so that's something that it could be a good range for people to think about, say, 3 to 400 calories minimum should be breakfast. So recently I came across this review paper about centenarians and people in their 90s and centenarians, people in their 100. And it was a small paper. It was about like 60 or so people, but it was talking about their sort of classic sort of salty breakfast they would have in the morning in Italy.

And I'm curious, what did you see people eating in Italy when they would break their fast first thing in the morning? Most people were just having breakfast, a pretty good size breakfast. Nothing like the American breakfast. And breakfast could be yogurt or milk or, you know, bread. But I would say almost everybody I know and everybody there I observed that then became a centenary, like Salvatore Caruso, who got to 110. and the oldest man in Europe, you will have breakfast every morning.

And every centenarian that I've ever met will have some form of breakfast every morning. Now, centenarians are also very probably from everything we see. They're probably a very special group, meaning they're like Emma Morano. I followed her until she got 217. And when you look at Emma, I remember this article in The New York Times talking about eating three eggs a day and 150 grams of meat every day. And no husband. That was also in the title.

Eat raw eggs and have no husband was her success for longevity. So people, journalists love the stories. But then they don't talk about the real story, which is six brothers and sisters over the age of 88. One sister made it to 102. So when you see that, everything is possible, but extremely unlikely that there is not a very strong genetic component. So now we know that in mice and our work that we do in Ecuador with growth hormone receptor deficiency, we know that just one single mutation in the genome in your genes

can make an incredible difference in whether you get diseases or whether you live long or short. So yeah, so if you're born with the right genetic makeup, then you could have no breakfast and probably still be okay. But that's an extremely rare population. So I wouldn't ever use this one in a million cases to tell people what to do. And again, most of them did have breakfast. But let's say the song didn't.

It's really relevant. Like Emma Morano, three eggs a day, 150 grams of raw meat. By the way, Carlo Bava, her physician gave her the raw meat after she made, I think, to 100, because she was starting to be anemic. And so that's when he intervened, right? But you see how the story is very different from the way it was told by the New York Times. Yeah, even in New York Times, you were quoted, just paraphrasing, you were saying, for every one of these centenarians, we'll see a different story.

So we don't want to put too much emphasis in one thing or another that's there. The reason that I wanted to bring up breakfast as a topic is that with this explosion, largely due to your research that's there and other colleagues of yours, you have so many more people paying attention to fasting ever than before. I can remember when I first got introduced to the world of functional medicine, was working with a cardiologist in New York at the time and helping him build his brand and write his books and everything. When we would talk about fasting, this is in the year 2008, still it was not widely known and you

would often have publications that would call an expert or a nutritionist at NYU or somewhere else or Cornell or this place or that. It said fasting is dangerous. We have no studies on it. And it was just lack of awareness. And there wasn't as much research that's out there. Now, there's way more research that's out there. And generally, in America, when most people talk about fasting and them incorporating it

into their routine in some sort of way and time restricted eating, they generally are talking about skipping breakfast. So how do you feel about, in one hand, there's this explosion of people talking about fasting, doing fasting, but in another, at least here in America, a lot of people are maybe missing a key component, which is that they're skipping the breakfast piece. Yes, so this brings me to what I always say in almost every interview, fasting means absolutely nothing, right? Like eating means absolutely nothing. So what do you eat, how much of it you eat, so eating could be very good for you or very bad for you.

And fasting is the same way. So I would say skipping breakfast, if your fasting involves skipping breakfast, you're putting your life at risk. There's no doubt about it. Now you could say, well, what if all these epidemiological, you know, studies are really catching something else. Yeah, it's as possible, but this is why you're putting your life a risk. You're not necessarily killing yourself, but the numbers are against you. Let's put it this way. Then you could have a genetic, you know, you could be genetically predisposed to be fine with skipping breakfast, or you could be doing lots of things that make you live very

long skipping breakfast, but you're certainly taking a chance. So, yeah, so I think that it's very important. We got to get away from, I always hear, oh, but all religions have fasting, and so it must be good for you. No, right? There's a lot of things that are out there that are. So, for example, most people don't understand that if you fast for very short, you don't even enter a ketogenic state. Let's say. How short?

What's the definition short? Let's say if you fast less in a day, right? you're not even entering a ketogenic state. But people don't know that if you fast for too long, you're now entering a low metabolic state. So eventually your body, so you have to fast for just the right amount, right? And otherwise you slow down and the body basically detox is very harsh environment. I'm not eating for a long time. So I better save everything I can.

And this, we don't know for sure, but probably involves some epigenetic changes. So the body now detecting this harsh environment changes the DNA modifications. And this DNA modification now are telling slow down, let's try to save as much energy as possible and put it away. And that's exactly what you don't want. So now imagine, and we see this in the mouse studies, right? So we feed them a high fat, high calorie diet. And then we do the fasting eating diet once a month. And after they get off the fasting, we can die, they're still burning fat, right?

But at some point, if we keep it long enough, they might start doing exactly the opposite. They still accumulating fat when they shouldn't be accumulating fat. So just the same way they may be epigenetically, we suspect they keep burning fat, epigenetically you can keep accumulating fat. And yeah, so then you have to treat this as a food-based medicine. and you have to know exactly what it does and when, and then eventually you're going to have to personalize it, right? And not just a fasting making diet,

but everything you do with nutrition. So people, for example, think I have a high protein diet that helps me losing weight because maybe I eat less fat, I eat less carbohydrate. But the high protein diet, because the amino acids are controlling the hypothalamus, the IGF1, Laptin, et cetera, et cetera. that certain amino acids within the protein diet, high protein, if you pick a certain type of diet, those can make it very hard for you to lose weight because they're now telling the hypothalamus

and the system, again, you should gain weight and you should accumulate fat, right? So we're just beginning to enter this nutrient technology world where we go from just food to food controls everything for good reasons, right? So food is at the center of reproduction. Is it the center of evolution, right? So it makes sense that it will, as we've shown, control also stem cell, embryonic stem cell like activation and regeneration. So let's give a little bit of background context.

You know, when in your work did you first come across caloric restriction? And if you could just share a little bit about what we know about caloric restriction and it's tie into longevity. And then through that process, how did the interest come? come in to say, how can we mimic some of these aspects, but not maybe some of the downsides that are typically associated with. In your case, in your story, you were looking at, I believe, water-only fasting for cancer patients. Is that correct?

Yeah. So I started with fasting, actually, in day one of my graduate work here at UCLA, we're less than a mile away, and with Steve Clark, actually, with starving bacteria. So I went from starving bacteria with Steve Clark to starving people with Roy Walford. And Roy Walfour was a superstar of nutrition and aging here at UCLA. He was a medical doctor. And so, yeah, from day one of my graduate work. And then I went, so starving bacteria to starving people and mice and back to starving yeast, right?

So I always say it's funny because at that time, everybody just thought it was the worst thing you could possibly do, right? So even my colleagues working in yeast were making fun of us for working on starving yeast. And bacteria, that was seen as also a boring topic, right, starving bacteria. So, yeah, so I worked on this from day one, and at some point they just exploded. I think it was around, I don't know, 10 years ago. But before that, it was just not viewed as a very interesting topic. People were trying to tell you, don't waste your time. It was just everybody in those days, in the day,

the 90s was focusing on growth and cancer and these oncogenes. And so no matter what system you worked down, people were excited about things that were very active. And starvation was seen as something like, why would you possibly study things that are starving? It makes no sense. And also the other thing that everybody felt it was boring was aging, right? And now it's a very different world, right? But back then people thought, why would you possibly study aging? Who cares? So, yeah, so lots have changed. But then jumping ahead, say, two years later, then we, in 2008 or so, we were doing a trial.

We had results with mice showing that if we starve mice with water-only fasting, the mice will become very protected against chemotherapy. And we will see all alive if they starve and all dead in some cases if they ate normally. And so we started a clinical trial in Norris Cancer Center in USC. And we thought, of course, everybody's going to do it. People have cancer. If I had cancer, I would have said, give me anything. Tell me what to do and I'll do it.

But there was not the case. And lots of patients struggled, refused to get in the trial. The oncologists were worried. And so we went to the National Cancer Institute and the National Institute on aging. and they fund the research on the fasting mimicking diet. So that's how we come up with it with lots of government funding. And so let's just build up the key pillars of the fasting mimicking diet. So if you're explaining to somebody, you have a center out here in Santa Monica,

I believe that's still there. Yes. So a patient comes in, they're understanding the basics of the fasting mimic diet. How do you set up the pillars of what it is and also what it isn't? Yes, if bipolar, you mean how do we get to whether it's everyday diet or the fasting-emicking diet, we get there by looking at epidemiological studies, clinical research, studies of centenarians, and then basic research focus on longevity, healthy longevity. That's how we decide what to do, right?

And so then if you think about more practically what is a fasting mimicking diet and how you come up with it, then we come up with it by making it feasible for people. So they have to be able to actually do it. And then making it effective. So we look at every ingredient, we understand every ingredient. And now every ingredient is going to affect the starvation response. So it's designed to make the system believe it's not fasting. It is not eating at all.

And so this is why it's a high fat, low sugar, and low protein diet. So that's enough. We keep just enough complex carbohydrate in there to allow people to eat it without interfering with the starvation response, you know, the fasting response. And then, of course, you have to lower. the calories, but you don't want to lower it to the point where you, in the salts, for example. So we're going to keep a certain level of salts and calories so that the blood pressure doesn't drop to too low levels. The glucose, the fasting glucose, doesn't drop to levels that are too low.

Yeah, so safety is also very important because people do this. At the beginning, people, so we have lots of clinical trials running. But even the clinical trials, they're not doing it in a hospital, right? They're taking it at home, right? This is one exception. In Italy, we're running a clinical trial for children with type 1 diabetes. That's the only trial we've ever done with it's impatient. People have to check into the hospital, the child, and the fasting-imicking diet is given to them in the hospital.

And so, like, if our listeners were watching somebody go through the process and they could hit fast-forward over the, you know, a few-day period while they're going through this fasting-making diet, what would they imagine that somebody's day looks like? And do you tell them to, like, reduce activity level or anything else like that, that, typically would correspond with, you know, like a longer fast that people would be on. We don't, I think it's good to be physically active, but it's not good to exercise, right? So it's okay to be walking and you can walk a lot. You just have to pay attention, make sure that you feel fine, but don't exercise. Lots of the exercises require quick, high levels of glucose or sufficient levels of glucose.

and if that is not available, then you know, you can have somebody pass out. This is not that common, but so lots of people could do this and exercise. So in fact, we finished a trial where we looked at young athletes that were working out, and we thought that by the end of the fasting and making died, their performance would be reduced acutely, and then we were hoping that acutely would be reduced and then eventually maybe even be better. But we were surprised to see it was not reduced, right?

So they could still lift weights at the same level. But maybe because the weight lifting may not require as much influx or levels of glucose as some other... sport activity. So we don't know. So we recommend that people don't do strenuous exercise, at least. You know, I've heard you in a past interview say that if you look at through, you know, the fasting, mimicking diet and what you're trying to achieve by putting people on it,

you're trying to recreate a little bit of like an evolutionary biological history. If we look through that lens, we're trying to create a circumstance that used to exist but no longer exists because of our modern lifestyle. What is that circumstance and situation that you're trying to put the bodies in? And how could you compare that to thousands of years ago when we would naturally be in that process? Yeah, the circumstance that we didn't understand, actually,

molecularly, and now we are understanding more and more. We now have lots of evidence, both from clinical trials and mouse studies, that there is a switch. And so in, let's say 10,000 years, ago, if it was summer, and there was a lot of fruits available, you want to eat it all, essentially, right? And then you want to become insulin resistant, right? So we think of diabetes and insulin resistance and obesity as a bad disease, but they

might not be a disease at all, right? So it may be part of our necessity to become, like, the emperor penguins of the South Pole, very big. So then when the winter comes or when they're in their case, they go several months with no food, then you can survive. And so of course then we unavoidably will have met that period of no food. But since, I don't know, 60 or 70 years ago, that never comes. So it's just the summer and the eating period.

And so this is why people are stuck in this insulin-resistant fat accumulating mode all the Where previously we should only had it for a little bit of time, and would you say that it was part of our survival as a species? It had to be. I mean, it's hard to go back 10,000 years and be sure, but it had to be because we see it in the penguin and lots of animals, right? So, yeah, it had to be that when it was, it's not necessarily the summer, but when the food, the moment of the year where you could get lots of food, you had to eat as much as possible because it was almost guaranteed that, there'd be maybe several months where there was nothing available. And yeah, so that then was required for the survival of the species. And so today, contrasting with our modern life, just for folks that are more new to your work

and your research that's out there, we, through our modern life, processed food through refined carbohydrates, a plentiful amount, through too much protein, which also we'll talk about in a second, too much of the wrong type of fats that are out there. we are in this permanent environment where it's difficult for people to set that same circumstance up because there's too much abundance that's around us. So in a way now, you're trying to help us step back because if we don't, the world is heading in the wrong direction. Is that a fair assessment of? Yeah, it's not difficult as impossible, right?

Because are you going to, let's say that it takes three or four days minimum of no food. to switch. Are you going to get that? So with people now being told for the past 20 or 30 years, you should eat six times a day. So that's what we heard and this panic about eat, eat, eat, because otherwise you're going to have problems. So most people are just scared to go even one day with no food.

And I always found entertaining this idea of five or six meals a day because I always thought, imagine the millions of people that might get to 8 p.m. one day and say, I only ate twice today. So I have another three or four meals to go, you know? And not surprisingly, when Sachin Panda looked at the feeding pattern, people ate for 15 hours a day, right? So, yeah, so there's lots of opportunities to eat and lots of opportunities to overeat. and zero opportunities, of course, considering also the medical community and like you were saying earlier, oh, no, no, don't fast because no forms of fasting because that's dangerous.

So then, yeah, you'll never meet that, those five days that are required to get you in the winter mode and start instead of accumulating fat, burning fats. You know, we talked a little about cancer patients. You talked about doing this with like kids who are type 1 diabetic. what are some of the things that you see when you put people on this that are in some sort of disease state? And then also, because you've had this explosion through the larger company, El Nutra, and like the system of people going on pro lawn and being able to buy the box and do it at home, you have a huge amount of people in the wellness community that also realize, like,

look, even if I eat really healthy and I eat better quality food, I actually am not really fasting for that long of time. So let me go on the program and do it. So first, with people in disease states like how profound are the results like what have you seen and then let's talk about people probably a lot of people who listen to this podcast too who think of themselves as pretty healthy but then go on it and what do they see yes so um we had in our clinic for example we followed a doctor right and in this physician uh was on lots of medication for hypertension and diabetes right so diabetes and hypertension And so our team started working at him. But after nine months of the everyday longevity diet, things started to change for his weight

and things started to change a little bit for his blood pressure, but nothing was changing for his fasting glucose. It was still 130. And I'm telling you the story, but I also have the clinical trials. And then it does three cycles of the fasting. I think making that. And you see the chart going like stable, stable for nine months to as soon as he starts with the FMD, then the switch, right? So just to make it clear, he did three cycles and how much time in between those cycles each roughly?

It was maybe a couple of months, two or three months between each cycle, let's say. In the clinical trials, we did that once a month for either three cycles or four cycles. But in his case, he did that every two or two or three months or so. And yeah, so now the combination of this two worked extremely well, whereas you can imagine if after nine months you have this diabetes and you're starting to get discouraged because you're saying it's not working. And I don't know, I've changed my diet. It was not a huge change in his diet, but it's a significant change. And so, yeah, so two years later now is now the weight is there. the blood pressure is back to normal, the fasting glucose is back to normal, it doesn't have diabetes,

it doesn't have hypertension, and he's off drugs, all of the drugs, right? So he went from three or four drugs to zero. So that's what you want, right? So you want two years, you don't want two months, oh, look how great it is and your cure from diabetes. No, you want to take a slow, you want to make sure that it's reasonable and feasible for that person, for the rest of their lives, and it's not that invasive and so they're going to maintain it because sometimes and we'll get back to this but i just want to make this point you've shared that sometimes when people go on a very invasive program even if they get short-term results if they yo-yo that's very dangerous and we'll we can talk about that a little bit later but i just want to make that note yeah yeah sure yeah so it was worse than not having done

anything at all right so if you start cycling more than 10% of weight loss and 10% of weight regain it would have been better to do nothing at all. Stay at your original weight and do nothing. Mind-blowing. That's really mind-blowing for a lot of people. So this doctor that you had going through the program, he's a perfect example of somebody who is able to get off of, you know, medications and make these dramatic changes in their life.

What do you find for people are some of the anecdotal things that you hear from people who consider themselves as maybe eating a more whole foods diet? They're not eating ultra-processed foods, right? It doesn't mean that their diet is perfect or this or that, but there could be a wide variety. What do you see with those individuals? I would probably put myself in that category. When they go and they do fasting-mimicking diet, what kind of things do they notice? Anecdotally, well, first of all, what I talked about with the doctor was then confirmed by clinical trials.

So we're about to publish intervention on diabetes patient and hypertension patients, etc., etc. So it seems to be very much consistent and supportive. But, I mean, of course, people talk about memory improvement, you know, and being able to do things and remember things much better. There are reports of the skin. Lots of people say the skin, my skin looks better. I look younger. And for example, memory, what would be going on that your memory,

that you'd have better memory or better focus? because I've had some friends that have gone through the program, and they have shared things like that. What's going on inside the body that would lead to those sensations? Yeah, so if you look at Alzheimer's research, it's focused on lots of drugs, targeting, beta-meloid accumulation, and lots of specific targets. If you look at what happens with a fasting-making diet in your brain, I challenge anybody to come up with something. they will alter brain metabolism more than fasting and a fasting mimicking diet. So your brain now, after five days, on a fasting mimicking diet, is probably getting about 50% of its energy from ketone bodies.

And those ketone bodies, we're starting to suspect may not come from the liver. They may be coming from the brain itself. So now the brain may be making ketone bodies. So, yeah, you're changing brain. metabolism and you're modifying the type of cells that are in the brain. We're about to publish a paper in mice modifying the inflammatory state of the brain, but also probably modifying the systemic, the system, like Laptin, grayling, all these hunger hormones, IGF1, growth factor, insulin level.

So all of these are systemic, all over your system. but they also make it to the brain and they're regulating brain function. So you're changing so many things that it would, we don't know what the effects are going to be. We're also doing a trial in Alzheimer. We already recruited the first 30 patients. So our hope is that this rewiring of brain metabolism, and but particularly the movement from fasting mimicking conditions to regular diet, This, it could be the answer.

Now, it's not only about fasting, but it's about going from fasting to refeating. And this we see very clearly, for example, when we take mice, we damage the pancreas. They stop making insulin. Then we do cycles of fasting, making diet, and refeeding, and we see the cells of the pancreas regenerating and start, and we see a pattern, an embryonic developmental pattern. What does it mean? the pancreas is starting to look a lot like it looked when the mouse was first born. So is that happening in the brain?

Well, it's a little harder because, of course, lots of the cells of the brain, the neurons don't divide, or most of the neurons don't divide. But what if there was so much change in the brain cells that now you have a rejuvenated brain, or less certainly less inflamed and rejuvenate. We don't know in humans. We know in mice because we looked at brain, neural stem cells, and they are increased. And, you know, the mice are doing better cognitively. So we see them having better memory longer during aging. We don't know in people, but that's certainly what we're hoping for.

So those are some of the things that people notice, you know, memory, better skin, more energy is a lot, is one that I hear a lot, you know, like a better resetting. in terms of like their blood sugar sort of balancing throughout the day. So jumping forward to this topic of refeeding, you know, in America, we tend to take things to extreme. So if somebody says that fasting, mimicking is good, immediately somebody thinks, well, I'm just going to eat this way forever, right? Help us understand why that's really maybe not the right approach. And what then does the foundation, which is really the longevity diet that you wrote about

inside of your book, what are the foundations of that to maintain some of the beneficial things that we want to do in between these fasting periods. Yes. So people especially those they may have disorders, like eating disorders, I tend to say, okay, well, now I'll do this all the time. I'll do it once every two weeks. And no, you don't want to do that. And in fact, I say you want to do it when you need to do it.

Now, in a country where over 70% of people are overweight or obese, and now Europe is about 50%, so Europe is not that far behind. Lots of people need to do it quite often, right? So it could be, let's say, three to five times a year. And, but that's it. So if you do it three times, that's 15 days a year. If you do it five times is, you know, 25 days a year. So, yeah, so that's, of course, in the diabetes trial, for example, we asked

the patient would do it every month for 12 months. But they had diabetes, and most of them were obese with diabetes, right? And the idea there is get where you need to get, and I cannot talk about the results very much, but it worked very well, right? So get where you need to get in 12 months, and then maybe you go to six times a year, and then you go to four times a year, and eventually you might be okay with, say, three to four times a year. And yeah, but then the refeeing is as important, and the nourishment is as important as the restriction, right? So you have to have enough proteins.

So, for example, one thing I teach my students, a lot of people that are vegan, you know, view this almost as a religion. And there's nothing wrong with be vegan. You could be vegan and very healthy, but lots of vegans have problems. Why? Well, for example, fractures, right? fractures, different types of fractures can be as high as three-fold higher in the vegans compared to the carnivores. Wow, and there's actual like studies for that to support that up? Of course, yeah.

And there's also studies looking at the percentage of vegans that are deficient in amino acids, right? So, yeah. So, and of course you can block that problem by eating, let's say you eat too much, Legumes, you're going to be deficient. If you eat only legumes, if you eat seeds, legumes, and nuts, now you can balance the lack of certain amino acids in the legumes with the presence of these amino acids in the other foods. But you have to be very consistent and maybe have a dietitian following you

that knows what they're doing, right? So, yeah, so then in the in-between diet seems to be age-specific, first of all. So up to age 65, lots of legumes. lots of whole grains, some nuts every day, watching the weight, refined carbohydrates are okay, but it should be limited. The sugars a little bit, I always say, you want to put sugar in your coffee? Put sugar in your coffee. Don't be thinking that you can never have anything with sugar in it.

These are obsessions that make no sense. Our body is fueled by sugar. And so, you know, four grams in a little bag of sugar to put in your coffee, make no difference whatsoever. Can I ask you one question about that? Yes. Often the advice around not doing it is that maybe from a habitual standpoint or if people are wearing like continuous glucose monitors and they see,

if your day starts off with sort of this bigger glucose spike that happens and people tend to put a lot of sugar inside of their coffee and whatever it might be, that you tend to maybe anecdotally a lot of people see that there's more cravings for sugar throughout the day. Do you think there's any truth to that? I would say that if you are not happy, you're never going to make it, right? If you're not happy with what you eat. With what you eat. If you start gaining extreme, an extreme doesn't have to be, you know, 10% carbohydrate.

It could be 50% carbohydrate when you're really happy with 70. So if you're not happy, you're not going to make it. If it's not enjoyable, if you don't enjoy your life, if you don't enjoy your diet, you're not going to be able to keep up the regular basic things that we know that end up working. It's just a matter of time and you're going to stop it. And you're going to regain weight and you're going to start eating. And you're going to rebel against all these restrictions. And this we know from hundreds of studies, right?

Yeah. So if the sugar makes no difference to you, that's okay. Don't have it. Absolutely. But if you're thinking, oh, I wish I could have a little bit of sugar in that coffee. And a little bit of sugar means four grams, not 40 grams, right? And then it means that the rest of the day you probably don't have any sugar. So that's perfectly fine.

But it's not sugar that's getting, it's not sugar from coffee that's getting people in trouble. It's the Coca-Cola's and the other liquid calories and other things that are drinking, drink in high volumes. That's really like, if we tried to add the same amount of sugar in our coffee that you get from soda, it would be actually very difficult. You'd probably throw your coffee out because it doesn't taste me. Yeah, yeah. But most people, I mean, I wrote a book a few years ago for children nutrition, right?

Then everybody said, oh, the Coca-Cola and the trash food is what's a problem. And we realized there was not a problem at all, at least in the Southern European children. The problem was pasta, pizza, potatoes, rice. fruit juices, they were having a pound a day of this, right? Wow. And the sugary drink, they had once a week. So there was like, there was no comparison between rice and bread will get into circulation about at the same speed as table sugar.

Totally. So it's very location specific, for instance, in like Mexico. I think Mexico has the highest consumption of soda per capita. In the United States, but you have both, right? In Mexico, you're going to have lots of rice. and lots of potatoes. Sure. Yeah.

Exactly. Right. So if you have bought, then you're going to be in trouble. But so our recommendation was watch out. You have a, you have to put it all together. All these things that become sugar very rapidly. Whether it's rice or bread or potatoes or pasta, pasta is a little bit slower, but you have to say, how much of this do I have every day?

There's this refined carbohydrates or those that can become. I'm sugar very quickly. And that's what you need to intervene. Not so much the four grams, but the 40 grams you might get from a small dish of potatoes, right? Sure. So why are you worrying so much about the four grams in the coffee in the morning? And then you're going to have a small portion of potatoes and think it's great. Or rice, right?

Rice. How many people think, oh, I just had white rice? Great. I mean, it's healthy for me. Well, that's sugar. That's like basically pure sugar. So for these things, and we've done a lot of episodes on this topic, we talk a lot about metabolic health. I'm a big proponent of, you know, people, at least for a period of time,

wearing a glucose monitor, just seeing, you don't have to wear it forever, but, you know, just going through that experience, because we totally underestimate how much sugar is in our lifestyle, even if you think that you eat very healthy, if you shop at Whole Foods, you shop at Trader Joe's, these other places, packaged foods just ubiquitously, just has a lot of sugar and things. So you were explaining the principles of the longevity diet, so you're saying that carbs is okay. You know, again, you're talking about primarily carbs, getting a lot of from vegetables. So how much do you want to be limiting these refined carbohydrates too in terms of amounts when you're laying out the principles of the longevity diet for people?

Yeah, again, you want to enjoy what should what you eat. So like I have pasta almost every day, right? Usually for dinner. For dinner. Dinner. But I, when I have pasta almost every day, I need to have just a coffee with one bag of sugar, four grams, for lunch. That's my lunch, right? That's it. So if I have normal lunch of any kind, and then I have that dinner, and my dinner is huge, right? I don't have a huge dish of pasta, but, you know, 70 grams of pasta, and then lots of, you know, legumes, a lot of chickpeas, black beans, et cetera, et cetera, and then lots of vegetables. And sometimes a little piece of fish? Well, then I fish maybe two to three times a week.

Okay. Two or three times a week, yeah. So to me is something that I know. I've seen it with my grandparents. I've seen it with the Okinawans. I've seen it with the Lomalinda people. I know. Nobody can argue with me that, oh, no, people can't do that.

You mean you're talking about like the pasta at night and the carbohydrates at dinner? I've seen it all over the world. The Okinawans was sweet potatoes and rice, right? And they had record longevity. And the Sardinians is Minestrone's and the Calabrians in Minestrone. and Loma Linda is, you know, similar Mediterranean-like lifestyle here in California. So, yeah, so you can be very long-lived and very healthy with a high-carbohydrate diet. And there's a meta-analysis in Lancet that came out a few years ago showing it's better to have an 80% carbohydrate diet than have a low carbohydrate diet.

And the 20% carbohydrate diet had the highest overall, I did the 60% of a 60% of a diet, risk of mortality, increased risk of mortality compared to the 50 to 60% carbohydrate diet, right? And this was just looking mortality, lifelong mortality or mortality risk. So yeah, so you have to enjoy it. You have to have enough so you can maintain it for the rest of your life. But then you cannot have so much that you're going to start increasing your body mass index, your waist circumference, and your fat percentage, right? So probably a good idea from time to time to go to the nutritionist, the dietitian, and measure my either do a dexia scan or do an impedimentary and ask your doctor or dietitian how much fat.

Because you could be thin and have 37% fat. And that makes you obese, basically. So, yeah. So then people shouldn't worry anymore about counting calories or anything like that. It should be more like, what is the consequence of what I'm doing on my fat percentage, on my muscle mass, on my waist circumference, et cetera, et cetera. So those are very easy. You can do it literally, you know, the fat percentage you can buy something at home

and then maybe have a feature check every year or so. And so this is very easy to do. And it allows you to say my fat percentage is now 25, too much. So maybe I'm having too much rice and too much fruit. juices and too much sugar, et cetera, et cetera, I need to cut down. And if your muscle mass is decreasing, proteins, certain amino acid, lucene, et cetera, in the diet might be deficient. You might have to go higher and not just in that protein level, in the variety of type

of protein. So you might have to have more fish or more, you know, nuts, for example. and if you're vegan to compensate for the lack, as I was saying earlier in the legumes. Since you're mentioning about protein, we'd love to just touch on this a little bit. Help us understand what you've seen in the literature of how much is too much. You've talked a little about too little. You know, you talked about some of your vegan students. You talked about that.

You talked about fractures. And again, if your muscle mass, is that probably the best indicator? Is that if your muscle mass is going down, regardless of what your dietary sort of approach is, you need to be thinking about a more sophisticated approach with protein in your diet. And is that the best indicator is muscle mass? Muscle mass is the quickest indicator, right? So you can get a... Do you really a dexa, right?

Not just you're just looking at yourself. You should know a little bit about... Yeah, but you can also have something at home that gives you an approximation, right? They cost $100. Smart scales. Yeah, some scales measure your fat percentage, right? So it gives the approximation. Then you can see if it matches once you go to the...

doctor and get the Dexa, you're pretty close, then good, right? So you can do that. So, yeah, the muscle mass and the fat percentage give you a good idea of, are you really getting in the wrong track? But then eventually, I think we'll love to do frailty measurements, right? So it's about if you go up the stairs, how quickly can you go up the stairs, right? Can you still run? Can you, you know, if you go and walk for two hours, are you okay with it, right? So all these things are measures, simple measures of frailty. If you start struggling, going up two flights of stairs at the airport, you're frail, right? You're becoming, you're having problems, right?

So you need to make sure that it's not just about the muscle mass, it's about the functionality. And, yeah, going up to stairs is a good way to assess whether you have big problems. But eventually, we even do it for mice now, there are a battery of frailty tests. They look at everything, including walk speed and the ability to blow into how much strength your lungs have, etc., etc. So those, I hope soon enough, we're starting to do that in the clinics, in the foundation clinics. And I think within a few years, everybody should be doing these things, right? So assessing, based on your age, your frailty and functionality should be this. And you could also do it with the Horvarton or the Levine biological clock measurements.

So now you have ways to do it at the level of DNA or the level of blood, but those are more molecular. But you want to make sure that those molecular tests match the actual functional tests. Can you still run? Can you still go up the stairs quickly? you. We've had a lot of physicians on this podcast that have come on and when I talked to them about if there was one test that people got that would kind of give you a good idea about just their health and their metabolic health, often the one that keeps on coming up is like fasting insulin, right? How much do you give weight to that in your clinics and would you toss out a different

marker of something that people could look at to see are they headed in the right direction or not headed in the right direction? Well, of course. First, I would start with the stand-up doctor blood test, right? Look at every single one of the markers, right? And if cholesterol is too high, you're not in the right direction. If your blood pressure is 137, you're not in the right direction. And if you're fasting, glucose, and insulin are too high, you're not in the right direction. So each one of these, of course, tells you part of the story.

And in any of them that are in the wrong range are telling you that you're going to have a problem. It's just a matter of time. And you're going to be on drugs. We know that after age 45, you know, the average American is two or more chronic conditions. And that's the reality of most people. And then by the age of 65, you're up to three or so. Going back to the fasting, mimicking diet, one of the things you had mentioned is that the percentage of calories that come from fat is higher than a lot of people would assume, you know, in a program for longevity. You said, I think it's like 40 something percent.

45, yeah. 45 percent. When somebody's continuing and they're in the reffeeding process and they're doing the longevity diet, again, you don't measure calories and we don't talk about measuring calories on this podcast either. But if you would generally look at some of the longest living societies and communities that are out there, what do they think of when it comes to fat as a makeup of their diet? And what are the best quality, what are the best types of fats that they're including? And what are some of the most worst types of fats that they're including in their diet? Yes. So if you look, it goes from zero to 30.

So Okinawa, very low fat, very low fat diet. and they still get to record longevity. And the Greeks, the Italians, the Lomalinda people, pretty good levels of fat, maybe 30% or so of the calories are coming from fats. And what you see over and over represented all the pillars, not just the centenarians' observation, are the olive oil, the almonds, the hazelnuts, the walnuts, the salmon, dark chocolate, say 85%. So those are pretty consistently appearing over and over and over, like in the as a positive association. So I would say to those that argue much lower fat diet,

I would say that the evidence from almost all the pillars is against it. as long as they come from these sources. Now, when you look at animal-based fats, animal-based proteins, everything turns around. Now you've got a problem. And so all the Harvard epidemiological studies over and over and over are showing high animal fat, high animal proteins, shortened or greatly shortened lifespan or increased mortality from overall mortality as well as cancer mortality, cardiovascular mortality, et cetera, et cetera. Yeah, so then pretty clearly, if you think put it all together, you get 30% calories from fat, lots of olive oil, lots of nuts, and maybe a variety of nuts.

Don't exaggerate because nuts are also an allergen. And so some people, they hear like, oh, this is good for me, quinoa, right? It's just another. So they hear about, you know, walnuts are good for you, and they start eating, you know, 50 grams of walnuts every day. Well, you do that, and it wouldn't be surprising if six months later, if your family especially doesn't come from a high nut consumption history, you may develop an allergy to that.

And then you stop eating walnuts completely. So, yeah, I think it's good. And, of course, we've seen this with gluten. And the celiac, not just the celiac disease, but also the gluten-sensitive. So a small percentage of population has an autoimmunity against gluten, but a larger percentage of the population probably has developed sensitivity to gluten, right? So it's the same thing with these healthy foods. Olive oil I haven't seen very much, right?

So it may be that olive oil is, you can be fairly high in the famous Astrook study. There's a New England Journal of Medicine paper on thousands of people. They were giving them a ton of olive oil per day and observed them for five years. And then they had to stop the trial because the olive oil oil people were doing so well compared to the low fat group. Right. I saw that. Yeah. So yeah.

So olive oil doesn't really seem to be associated with much allergies, intolerance, et cetera. But, yeah, so the nuts, you got to pay attention. And also the salmon, you got to pay attention. There are some toxins. that accumulate in the fats of the salmon. So you can't just say, oh, this is good for me. So I'm going to just have 10 a day or 10 a week. So it's good to say, okay, maybe I have salmon once or twice a week.

And maybe olive oil I can have every day, limited amounts. Maybe I can rotate between 20 or 30 grams of different walnuts, hazelnut and almonds. So that's probably a good way to do it. And where does dairy fit into this? You know, one of the things that people anecdotally sometimes talk about, you know, my business partner very well, Dr. Mark Hyman, he was spending time in the Blue Zone region in Italy and with the families. And he was mentioning how a lot of them are, you know, have goats and sheep and they eat

cheese throughout the day. And one of the things he was saying is that they'll preseason the cheese by getting their goats and sheep to eat from the shrubs. of certain types of food so that by the time they make the milk, it has the flavor of rosemary or has the flavor of this, that. Where does that come in? Because I guess the question is that even in Loma Linda, and I understand that one of the challenges now is that a lot of people are not really eating and living the way that traditionally

those regions did. So it's becoming harder and harder to do those studies that maybe originally inspired like the work behind the blue zones. But yeah, where does dairy fit into this, if at all? Yeah, so the Okinawans, of course, had zero dairy. Sure. And I would say when I visit the Centennanaries in Sardinia every year, and I would say when I really spend a lot of time with them,

they would say that dairies were there, but they were expensive, and sometimes it was much more about vegetables, and there is where they used to sell it. So they can get more vegetables or bread or anything, all the things that they would sell it so that they could have more money for other stuff. Yeah, exactly. But that doesn't mean they didn't have dairy, but not very much, right? Not as much as now. The shepherds, they would go and for months be away, they may bring for three months a year or whatever.

They may bring dairy with them, cheeses with them. And so there was probably a lot more common, but it was. seasonal and probably never made it to more than three or four months a year. And of course, these chaperers are also walking maybe 10, 15 miles a day up the hills in Sardinia. So, yeah, like you said, it was a very different world. And also, the genetics are certainly, I bet that the genetics are way underestimated. the studies right now on the Sardinians and to try to figure out genetics versus lifestyle.

And I think they're both important. But of course, if you start already like Emma Morano with a very strong genetic advantage, then the red meat or the eggs are not that big of a problem. And we know this also from studies of cholesterol, right? So some people and have three eggs a day, zero changing or very little change in cholesterol. And some people have three eggs a day and this cholesterol goes sky high. So, yeah, so we know that genetics can affect does that cheese give you a heart attack or not? So, yeah, so I would say that for most people, cheese does not come up in this new meta-analysis,

a huge study that came out in plus medicine just a few months ago, confirmed that the cheese and even the white meats, it was in the neutral range. Neither bad for you nor good for you. So if you have low amounts of it, it's probably okay. But the legumes came out on top, whole grains were under it. The nuts were way hard up there. And no red meat, no processed meat was very important for the life expectancy increase. But the white meat and the eggs and the cheeses,

came, or eggs actually were in the negatively associated with longevity but the cheese I think was neutral. So do you avoid eggs in your own life? Maybe two a week. Two a week.

Got it. You know, you're mentioning about the sheep herders and one of the things that you said is that they were walking a lot and one of the things, you know, part of the longevity diet is not just a diet that you eat, it's a lifestyle that you live and tell us how you came to the conclusion that walking an hour a day is so central to the aspect of longevity. First and foremost, food interventions, nutrition interventions, fasting in the fasting

mimicking, those seem to be at least the way you've shared it before, a higher weight. But in addition to that, the movement piece of which walking a day is one part of it, we'll get to exercise, rigorous exercise in a second. But how did you find out that walking one hour a day was a crucial piece? piece of the puzzle. Well, there's a lot of, I mean, first of all, I rarely meet centenarians that don't have that story of working in the field or being shepherds or doing some manual labor, right? So that's already a good indication.

And we're talking, but not an hour a day. We're talking seven or eight hours a day. So I thought that an hour a day is a good compromise for people. and you got to find the time, right? So you should not have the excuse, I don't have time to walk one hour per day. And then there's a lot of studies now that are proposing or indicating that people

that regularly walk, they do better than everybody else. And from a habit standpoint, is there a way that you, you know, you're busy, you have all your work, your research, your for-profit companies, which have a major non-profit element, you know, all your shares being donated to the greater good of public and addressing chronic disease

and helping to cure chronic disease for people, but it's a busy life. So on a practical level, what are some of the things that you've figured out for your own life to get in and squeeze in those hours or as close to it as possible? Yeah, so the way I did it, well, first of all, and I guess we're going to talk about it,

I recommend 150 minutes of exercise a week. and I do about an hour every other day. But the walking, to me, it was just picking two places per day that are 15 minutes away. And then getting in the habit of going twice a day, 15 minutes. I say, get coffee, come back, get whatever, and come back, and that's an hour. So once you get used to it, then you're sort of looking forward to it. it just gets you away from whatever it is that you're doing on your computer or anything else. So like your lunch, for example, you said you sometimes skip lunch and have coffee.

Well, most days it sounds like. So you would incorporate that there, for example, have a coffee shop that you could walk to? So while I'm in the United States, while I'm in Italy, six months a year, I have lunch every day and I gain some weight. Well, I'm in the United States, Monday to Friday, I don't have lunch, right? So I'll go and get coffee 15, 20 minutes away. So that's already 40, 45 minutes, just that one single walk. And then, you know, I definitely get over one hour a day of walking. So, yeah, so I think that's very important.

And also, I never touch elevators. I do anything as physically as possible, right? The groceries, just any opportunity I have, I try to do it. all away and without hurting myself but you know so for example you know pushups um almost every day and and it's things that they maintain you physically working and using most of the muscle that you can use in your body um yeah so but but for sure stairs and and and walking is a lot out of my day. So as an Italian, I got to get your recommendation for like the coffee shop that's worthwhile for that 15 minute walk both ways. So since I live not too far away from here,

I'll have to get your favorite coffee recommendation so I can start going there too. Yeah, yeah. I want to talk about a little bit, you know, in addition to we've talked about the food piece, which, you know, we've addressed the fat, the protein, the importance of a lot of a lot of plant-rich foods inside of the diet. We talked about the fasting piece. We talked about now the movement piece that's there. Are there other elements that make this a complete picture from your eyes of getting all these benefits so that we could potentially live longer or at least to the highest of our genetic potential in our lives?

Is there anything else that you want people to be thinking about in this context of even if it's not your exact research, it's kind of periphery around your research? Yeah. So I'm very interested now, Peter Diamand. this and others are talking about a stem cell therapy, right? So I think it's really interesting, and I think it's, we need a lot more research, more clinical research in, you know, what can stem cells and which type of stem cells can be injected in somebody in a mouse and then in a person.

And what is the best way to get into, I mean, of course, an embryonic stem cell. say a totipot and embryonic stem cells can rebuild a human being, right? And so is there a way to, and we're starting to work, well, we've been working on this for a while, but now we're starting to focus more and more on it. Is there a way to partially rebuild organs and systems by looking at certain type of stem cells? But then the biggest trick is how do you get him to do that, right? So let's say the brain is going to be the ultimate challenge.

So, yeah, this brain, the great majority of neurons are not dividing. So how do you replace neurons, this incredible network of neurons, with new ones, right? So, I mean, these are, of course, a science-borderline science fiction questions, but we're very interested in that, in, you know, so much. the realistic things now you're starting to hear about oh you know had knee pain and injected the stem cells and magic and I don't have any pain anymore what is it true when is it true and why is it true and how do we make it better and can we actually you know completely replace somebody's blood and immune cells and non-invasively and so now you have a you know a younger immune

system. Yeah, so I think we're getting close to this kind of interventions and it's still very scary. I always tell people I was in the lab back in the 90s, early 90s where my, not me, but somebody in my lab, together with a group in the East Coast, they discovered the gene for Lugaric disease, amyotrophic lateral sclerosis. And it was a mutation in the SOD1 gene, suproxidase. And so when that happened, we thought, great, you know, in a few years we're going to have a cure for Lugaric disease. And now 30 years have gone by, and we still not even close to a cure for Lugaris disease. And we knew, we know, like one of the mutations that caused the disease. And you think, how long could it possibly take now that we have that?

That's what everybody thought, right? So my point is it takes a lot longer to go from, it's possible or I know what causes the disease to safely implemented on people without risking their lives. And without risking it, they get a cancer, they get some big problem. You know, look at the vaccine, right? There's a big movement around the world. I don't want to get vaccine. And I had top world top scientists, my friend saying, I'm.

I'm not going to get the vaccine, a vaccine, right? Because they're worried about the long-term consequences, right? And do you feel they're just in that feeling? They certainly made some good arguments. So I think we all felt we don't have the time to take weeks to go through all the literature and figure out, I mean, I'm not a virologist, so I didn't do that, right? So nobody I know did that. So I stop everything to take two or three weeks.

and figure out, could they be right? I didn't do it. So I don't know. I mean, to tell you, I mean, probably not. Probably the virus is more scary than the vaccine by far. That's what it looks like. But did I review the literature carefully? No, I didn't.

And so until that, and maybe together with a team of specialists, I don't know. Yeah, so just to put it next to, let's say, stem cell therapies or any other therapies like that, especially all these drugs we hear about, you know, take this and take that. What do you know? How do you know what's going to happen to you after 20 years of that? Could I have you, could I have presented to you cocaine, you know, 50 years ago and told you, this is magic. You should take a lot of it. It's going to make you feel great.

So, yeah, so I think there's irrational exuberance, which might hide actually some success stories. And I don't mean to go slow because we love to go fast on this, but we love to go fast and careful because we don't want to take anybody's ability to get to 110 healthy, which is a clear, it's a real thing, right? It's a reality. We don't take that reality away from anybody. I'd be like I would feel very bad for the rest of my life if I knew that even one person, I shouldn't have done that, right? I told them something and this shortened their life. So for these other things, and you mentioned Peter Diamantas, there's a hopeful optimism, but there's still a lot of work to do is what I'm hearing from you, right? There's a hopeful optimism, but we got a lot to prove and show to see if these things.

Yeah. Well, and there is a reality there, too, right? So for certain things, we might be getting very close, right? Let's say the knee injury, I don't know. Again, I'm not an expert on all the literature on that. But it sounds like we're starting to have some success story, finally, right? After 40 years of this, I remember I think it was the UK Minister of Health 30 years ago saying, this is going to be the miracle.

Stem cell, stem cell, stem cell, 30 years ago, right? Finally, 30 years later, we're starting to see some success stories. So great, you know, are there some things that have been given to lots of people, lots of clinical trials? They're safe and effective. And let's start with those as soon as we can. But then the rest of it, yes, we need a lot more funds, a lot more tests, a lot more science and a lot more careful thinking of yes it could do a lot of good for me could also do a lot of bad for me we started the interview with you saying everybody skip breakfast so we're so

excited about the the efficacy of the 16 hours that we forget that most studies show that breakfast skipping kills you early on that note right now because longevity is even more popular than ever before and everybody's writing a book on it and everybody's talking about it now and a lot of them of course referencing your work and your literature and then putting their own spin on different aspects of it some that's backed up some that's not backed up probably a lot that's not backed up there's a lot of conversation these days around you know the use similarly to what you were sharing the the use of things like resferatrol and other supplements that people might be thinking about exploring if somebody foundationally was doing a lot of the things you recommend because again it's always

that foundation first inside of the longevity diet and then depending on your disease state or your risk for you know certain disease incorporating in the fasting mimicking diet into your routine at a frequency that makes sense for you if somebody had those how do you feel about them dipping their toe in the water with some of the quote unquote longevity supplements worth it not worth it, or let's wait and see? I will say, for the great majority of people, let's wait and see. And I will want the pillars, right? I will want the epidemiology, human epidemiology, to be there.

I will want the centenarian data or certainly like metformin. Methorming is starting to get in a good range. You don't have the centenary, but you have 50 years of people taking it, right? Okay, so it's starting to be good data, epidemiological, clinical from it, mouse research. And by the way, metformin doesn't do a lot for a mouse. So that already should maybe make you wonder. But it's got potential. So, yeah, so I think there are a few things out there that may start having data from multiple pillars, indicating safety.

and so especially for a category of people, they could be very useful, right? So if you're obese and insulin resistant, metformin might be a very good idea for you if you're not willing to do anything else. Now, will metformin block you from doing something that clearly is going to work? And so if that's a case, then I think that it's a problem, right?

So if you could do something that reverses, as we've seen with lots and lots of people in the trials, but you don't do that because you have this magic drug, then I would say not a good idea, right? For those they can do it and they can really fix the problem from its source, right? So fix the insulin resistance from its source. Deplete, go down to the right level of fat accumulation, you know, go down up to the right level of exercise. of weight training, et cetera, et cetera. That is by far the right way of doing it because it's going to also make you feel better. But I think that lots of these drugs have potential,

and so we just have to wait and see, you know, what are the risk and what are the potentials. I'm a little concerned about as I was even, you know, so my laboratory first discovered the TOR, Ciscanase Pathways role, in aging over 20 years ago. And I was always worried about rapamycin. So we were receiving rapamycin from Mike Hall back in the mid-90s.

I remember we were testing this in yeast. And we saw a little bit of lifespan extension, but not very much. But I was always worried because it was intervening at the center of life, right? So we intervening at the center of a cellular function. And I thought, it's a little scary, right, to be blocking. it's a blocker, right? So it's blocking this pathway that is at the center of growth, it is at the center of protein, synthesis, et cetera, et cetera.

And yeah, so I am also concerned from a fundamental, from a theoretical point of view and an evolutionary point of view, I'm concerned about blocking interfering with the heart of a cell and the heart of a human being. I'm less worried about when you interfere, for example, and that's one drug we're working on, growth hormone receptor, because now you're looking at the master regulator.

So the growth hormones that are regulating almost everything. So I think I'm less concerned about that than that I am when you're going right into the middle of a cell because then you have to say, if you keep doing that for decades, what's going to happen? Now, if you keep doing that with growth hormone, we know it's going to happen because we have people they have growth hormone receptor deficiency,

and if anything, they live longer, they don't get diabetes, they rarely get cancer, they're cognitively doing better. These are humans, not mice. But the mice have the same phenotype. They live 40% longer, by the way. So when you see that, you know, worms and flies and mice and humans, then it's good news.

We don't really have that yet from most of the supplements out there. So, yeah, so I think that's also at the theoretical level, something that should be kept in mind. What is it going after? Methormin is something else is going to the middle of the cell and interfering with mitochondria respiration, interfering with gluconeogenesis, the generation of new glucose. So interfering with some of the growth pathways. And also probably the question is, compared to what? You know, pharmaceutical companies don't often have to talk about.

about their drug that's being developed in comparison to, let's say, dietary interventions. It's sort of like, here's what this drug does on its own. Well, could you get that same benefit through some sort of lifestyle modification in the case where people might be taking metformin as primarily an optimization tool, not because they're diabetic? You know, that's also a question that's there compared to what that's also available to us. Exactly, right? So you don't want to get in this mentality of, oh, yeah, this lifestyle change, but that's just so that one day I can have a drug that does the same. And there's also another reason for that, the psychological advantage. We're underestimating the importance of a reasonable challenge, right?

So what's a reasonable challenge? So if I told you you got to run 100 miles a week, that's not a reasonable challenge. It's a tough, tough one. You're never going to be able to do it all the time. But if you say, you know, walk an hour a day and do, I don't know, 10 miles a week, that's reasonable, right? So then would you recommend that people stop running because we have a pill for it? I don't think it's a good idea. Even if we had the pill and it was safe and I knew that, oh, I have the running pill. We're going to tell children, don't worry about it.

Don't run anymore because we got a pill for you. So I would say that's a bad idea no matter what. So all this biohacking and all this technology should not take away from this very important aspect of once in a while it may not be a bad idea too fast for five days, right? These have this challenge. Forget the benefits that you get, but also the challenge of or just stop eating. That's okay. What happens when you stop eating? Or the challenge of, hey, I have to go and run up up the hill or, you know, a lot of.

of staircases. Yeah, can I get a pill so I avoid staircases? And so the world is moving more and more in this direction of avoiding any effort than anything. And not surprisingly, a lot of psychological disorders are going up with it. So, yeah, I'm almost shocked in the United States how little we talk about this, right? The importance of difficulty and doing challenging things to build your character to build who knows your spirit, all the aspects that come along with it. Yeah. Yeah, I did a presentation with some people from Connie, this sport, national sport association in Italy. And the director was saying, now we have a lot of children that don't even know how to do basic physical games, right? Because they never done it, right? They're now

some of the things that for my generation were normal because we had fun. doing it and now there's so much protection and so much trying to avoid anything they could hurt you or they could be difficult for the child that they forgot how to do it. They don't even know how to do it anymore. So yeah, I think it's let's not underestimate the power of the challenge and just say, I did it. And this is why sometimes we do these fasting challenges and people are so happy the end of it. And the beautiful thing about that is, and I've had friends do it together, it's in community. There's something beautiful about doing something with other people. By the way, if people who are listening to this podcast, you know, as we start to wind down

and I'm honoring of your time that's here, if they wanted to do this fasting challenge that you guys host, can we put the link in the show notes? Do you know when the next ones, you know, they happen regularly throughout the year? Is that you guys because I'm Professor Longo of University of Southern California. I speak as Professor Longo, and I am the founder of a company, but I'm not. So we'll ask your team. I try to stay away from anything that is commercial.

And as you pointed out, I donate 100% of, I will donate 100% of the shares. And I've already started doing that of the company to charity. So, but yeah, the company has programs. And that's up to you to, if you want to talk about it. You can certainly talk about it, but I can't. Sure, sure. Well, we'll have the links.

I know the CEO of the company, pretty well. We've spent some time together. He's a very fantastic individual. He's a good guy. He's a good guy. I can say that. Yes, yes. That's allowed. We can say that. He's a medical doctor. He's a medical doctor as well. Fascinating. Beautiful story. He told me all about his life and everything over dinner one day. Really beautiful. A couple quick questions before we wrap up and then you can send our audience, all the places that we want to send them to. Wine. You know, just give us a little bit on that, right? Is it in the right doses a good stressor that's there? Or is it one of those things that if you're not drinking right now, it's not necessarily

something that you have to be thinking about or do you fall somewhere in that spectrum? Yeah. So I just got in a little bit of a friendly fight with two of the world top epidemiologist of aging, right? And the argument was over this. Alcohol and diseases, right? Okay, yeah. Yeah.

So their opinion was you should not drink at all. And I said, you know, I'm surprised. And I think if you're drinking law to moderate, you should continue to do that. And that's a recommendation in my book. And then I went back and looked at it because I wrote a new book. It's going to be out of offering about a year on cancer. And they confirmed. So the meta-analysis confirmed that law to-model.

moderate drinking, let's say, up to five drinks a week. Overall, if anything, is associated with a little bit improvement in lifespan. But there are some cancers for which alcohol is a risk factor. And so if you have, it's listed in my original book and it's going to be listed again in my new book. So if you're a risk for some of these cancers, then you probably shouldn't drink. should you start drinking, I don't think there's so many advantages that you should start drinking, but if you're already drinking, I think it's perfectly fine to continue in the law

to motor range and but check on these five or six cancers for which alcohol is a risk factor. Beautiful. Dr. Longo, this has been a fantastic conversation. I really appreciate you squeezing me into your schedule and us being able to get to do this in person. I mean, I don't know about you, but in-person conversation is just so much better than having to deal with Zoom and then deciding, do I interrupt you, do I not? If I have an interesting point to chime in and just your dedication, your energy in this space, and your commitment to really helping the lives of a billion people or more through your work, it's just truly inspirational. You know, it really is inspirational. So I thank you for coming on the podcast. And we'll have the link to

your longevity diet book. When your new book is out on cancer, we'd love to have you back on the podcast to get a chance to chat about that. And also we have a foundation, non-profit clinic here in Santa Monica. It's createcures.org and people that are interested in be helped with lots of these things. We have a team of dietitians there. And soon enough, we shall have physicians. But right now, we don't yet have them. We used to have them. And then now going through some of the paperwork that is needed to get them back there. And you guys also at one point in time, I think you were talking about a fundraiser. A lot of our audiences here in Los Angeles.

Maybe we'll let them know if you guys do something. Yeah, absolutely. I mean, if you go on the website and you're interested in donating, you'll help us. You know, yesterday, for example, we had a Griffith Park. We had a race together with Finish the Rite, this organization in Los Angeles. And, you know, our part, of course, was create cures. and I mean, the real focus of the foundation is how people that are in trouble, like, advanced stage cancer, you know, people with major diseases and beginning to have this multidisciplinary team that I was talking about earlier, you know, the dietitian, the molecular biologists, the physician, the psychologist, we don't have psychologists yet, yet, but we will soon hopefully. So, yeah, the need for them to work together in people that cannot wait seven or eight years.

for a FDA trial to be finished, you know, treating something that is untreatable right now. Yeah. And a couple of things I'll mention, again, you don't have to mention it, but I can get a chance to mention it. I love the fasting mimicking bar, right? When people ask me, like, what is a good bar to have around and that actually works and, you know, has some good evidence behind it? Fasting mimicking bar, I'll put that link in the show notes.

And obviously, if you want to do the pro-lon method with the fasting mimicking diet, with the box and everything, we have the link to that inside of the show notes as well. And as a small token of appreciation, because I know you're a huge dark chocolate fan, I brought one of my favorite dark chocolates, no affiliation with the company, but I'll give it to you afterwards. Dr. Longo, thank you for joining the podcast. It's an honor to have it.