44. Dr. Valter Longo: Fasting Myths Busted: What Science REALLY Says About It!

Fasting has been praised as a powerful tool for weight loss, metabolic health, and longevity, but is it always beneficial? The truth is, fasting can either optimize your biology or work against you, depending on how, when, and for how long you do it. Research now suggests that skipping breakfast, a common intermittent fasting practice, is linked to higher cardiovascular risk and increased mortality. At the same time, strategic fasting has been shown to trigger cellular regeneration, reduce inflammation, and even reverse certain disease markers. So, how do you get it right? In this episode, we break down the biggest mistakes people make with fasting, the science of fasting-induced repair mechanisms, and the critical role of refeeding in longevity. We also dive into the controversy around high-protein diets, how different macronutrients impact aging, and why a personalized approach to nutrition is essential for long-term health. To guide us through the latest research, I'm joined by Dr. Valter Longo, a globally recognized expert on longevity and nutrition. As a professor at USC and director of the Longevity Institute, his groundbreaking work on fasting and aging has reshaped how we understand diet and disease prevention. His research led to the development of the Fasting-Mimicking Diet, a clinically tested approach designed to harness the benefits of fasting while maintaining proper nourishment. Let's get into it. We Also Discuss: 01:41 - 03:33 – The Biggest Mistakes People Make with Fasting 07:32 - 08:44 – Personalizing Your Diet for Longevity 18:26 - 20:30 – How Processed Foods & Starches Impact Your Metabolism 25:51 - 26:36 – The Hidden Dangers of Excess Protein 31:54 - 33:47 – The Right Way to Think About Fats 40:22 - 41:49 – How Fasting Triggers Self-Repair Mechanisms 46:39 - 48:32 – Fasting vs. GLP-1 Drugs—What's Better for Metabolic Health? 47:33 - 01:38 – Can Fasting Reverse Biological Age? Thank You to Our Sponsors: TruNiagen: Whether you are looking to stay sharp, feel more energized or simple age better, go to https://www.truniagen.com/ IFit: If you are looking to elevate your home gym fitness experience with the best in fitness tech, choose IFIT. Go to https://www.ifit.com/ Nexthealth: NextHealth: Your destination for cutting-edge health optimization—from IV therapy to hormone balancing. Explore at https://www.next-health.com/ Vitaboom: Vitaboom: For supplements you can trust and wellness solutions tailored to your health, visit https://vitaboom.com/https://vitaboom.com/ Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram: https://www.instagram.com/darshanshahmd/ Learn more about Dr. Valter Longo Website: https://valterlongo.com/welcome/ Instagram: https://www.instagram.com/prof_valterlongo/ Facebook: https://www.facebook.com/@profvalterlongo/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:51Dr. Darshan Shah?

  Hello, everyone, and welcome back to Extend. Today, I'm going to be tackling one of the most powerful and misunderstood tools that we have in health and longevity: fasting. So if you're one of those people that have skipped breakfast and have wondered afterwards, is this bad for me? Or is this helping me? And why? This episode is definitely going to be for you. In this episode, I'm going to answer many of the questions that you might have, such as, does fasting really reprogram your cells for better aging? And does it help clear senescent cells? How do we balance fasting with nutrition for our health? What about our protein intake and our intake of nutrients? And how does it affect our hormone levels? To break it all down for you, I'm going to be joined with one of the premier researchers in fasting, Dr. Walter Longo.

• 1:36Dr. Darshan Shah?

  He is a leading expert on longevity and fasting science. He's written many books on this topic and done incredibly deep research. In this episode, we're going to dive deep into some of the biggest mistakes people make with fasting, why skipping breakfast might actually not be the best idea, and how fast it can activate your body's natural self-prepared mechanisms. We're also going to explore the truth about high-protein diets and their risks, as well as what the longevity diet really looks like, by Dr. Walter Longo, and how it can help you optimize your health for the long run. Dr. Longo is a professor of gerontology and biological sciences at the University of Southern California and a director of the Longevity Institute. I met Dr. Longo when

• 2:19Dr. Darshan Shah?

  I invited him to speak at a conference that I was hosting, and ever since then, he has been a fan favorite. With decades of research, he has pioneered some of the most influential dietary interventions in modern science. He's the author of the book, The Longevity Diet, which is a bestselling book that outlines how nutrition can be used as a tool for longer and healthier life. Whether you're a seasoned biohacker, or you're just curious about fasting, and the current state of the research, this conversation is going to be packed with game-changing insights for you. So let's dive into this episode with Dr. Vulture Longo.

• 2:56Dr. Darshan Shah?

  Dr. Longo, thank you so much for joining me on the podcast today. I really appreciate you being here, and I've been a huge fan of your work for many years. I was sharing my story with you where I had my own health struggles, and fasting was an integral part of my health journey, and helping me just kind of reset my biology. So thank you for joining today.

• 3:17Speaker 01

  Well, great, and thank you for having me. Very happy to be here.

• 3:20Dr. Darshan Shah?

  Yes, and what I love about you, Dr. Longo, is that you are not just a scientist, I mean, you're an incredible scientist, and you know so much about this world of aging, and healthy aging, and longevity, but you actually can take the science, and you've turned it into a practical tool for us to use. And I can't wait to dive into that with you. But you've had so many conversations around fasting, and I know that's one of many topics that you can speak intelligently about, very intelligently, but I would love to hear, out of all the conversations you've had, what is one of the things that many people get wrong when they think about fasting?

• 3:56Speaker 01

  Probably this idea that fasting is this great intervention, no matter how you do it, and when you do it, and who does it. So, yeah, it's not, right? So it's very powerful. Probably, I always challenge people and say, well, come up with something that's going to cause more gene expression changes in the human body than fasting. And so far, nobody's even come up with an Idea of what that could be, which is remarkable, right? So extremely powerful, but it could be powerful in your favor or against you or neutral, right? So, so I think that this idea has been around for, you know, thousands of years and people have been doing it.

• 4:37Speaker 01

  It does not mean it's good for you as a word, right? You know, so, so I think, you know, clearly you see, for example, now skipping breakfast. You know, a lot of people that skip breakfast, you could argue, but people that skip breakfast have more cardiovascular disease, have more overall mortality. I mean, it's an association, we don't know about causation, but that's not a good association to start with, right? So it's all the kinds of fasting were so good for you. Why is there a clear in meta-analysis association between skipping breakfast and so doing sixteen or more hours of fasting? And, you know, mortal overall mortality, cardiovascular mortality. So, yeah, that's just an example of

• 5:20Dr. Darshan Shah?

  Right.

• 5:20Speaker 01

  of how it can probably work against you. So now we know, then eventually people did clinical trials where they hospitalized patients and gave them the same exact food and they started at eight AM or they started at twelve. And the people that started at twelve had lower energy expenditure and more hunger, right? So just by, they fed them the same food, right? So these are some of the now epidemiological, but now we're starting to see also the clinical trials supporting not such a good idea to skip breakfast, right? And so, yeah, those are just examples, but I, I, I think we could go on for, for hours about the good, bad and neutral.

• 6:01Dr. Darshan Shah?

  Right, it's, I make that point over and over in this podcast. With every intervention, it's so nuanced, right? There's a dosage issue, how with fasting would be, how often? What type of fasting with medications, you know, even with nutrition, right? There's certain things that amount you eat makes a big difference, whether it's small amounts, medium amounts or too much. And there's also an N of one issue where it's your particular biology is different than your friends. Or your spouse and everyone has a different reaction to different interventions. So I'd love to dive deeper into that with you. But before we go into fasting in particular, I consider your particular area of expertise.

• 6:42Dr. Darshan Shah?

  And you teach on this in Italy and here at USC is nutrition. And I'd like to start just with a big picture overview of nutrition. And some of your thoughts around what have we got right in nutrition? What have we got wrong over the last 50 years in nutrition science?

• 7:01Speaker 01

  If you look at nutritional science, you have very different opinion, at least from a minority. I think if you look at the, you know, majority, certainly people are gravitating towards, I said, the Mediterranean diet and some of these safer versions of what I call the longevity diet. But yeah, so I think that, you know, we're certainly moving in the right direction. But also I think we're not doing a very good job of what you just said, the personalization. You know, so I always say, you know, a lot of people can have the Mediterranean diet and do very, very well.

• 7:39Speaker 01

  And, and then you have a lot of people that can be eat tomatoes and, and they have major inflammatory responses to it and gut issues. Yeah. Yeah. So I think we really need to move away from words like Mediterranean diet or whatever. And move into like a personalized longevity diet. What is a, I mean, there are some common things, like, yes, a lot of the things about the Mediterranean diet are good. But we cannot possibly think that something that has been around for 60 years. And it was just an observation by Enzo Keys in Southern Italy in the, in the area that you were telling me you visit very often. You know, so this place called Acciaroli in a few little towns near Naples.

• 8:21Speaker 01

  Yeah. So we cannot say, well, we're going to make the whole world eat whatever Enzo Keys observed and, and observe. Uh, then being associated with, you know, general good health. Yeah. That's not the way you do science, you know? So, so, yeah, then I've been talking about five pillar science. So what about the epidemiological? What about, how do you make a mouse and a rat live longer? You know, what about clinical trials? And, and you know, centenarians? If you visit centenarians in Okinawa and Lomelinda and, you know, in Calabria and Sardinia. What do they eat? How do they eat? You know, is there something that you see very commonly? Yeah, so you put it together and, and, and, and I think that's not done, right? Almost at all, right?

• 9:03Speaker 01

  So it's, it's, everybody's a, you know, a, a champion of all the dash or, or this or that. And, and there's little science, I think, being done. It's more like, you know, thirty or forty years of observation of this ingredient, that ingredient. And, uh, or that diet, people that adhere to the Mediterranean diet do ten percent better than people that don't. I mean, that's, I think, what we are, are, are becoming addicted to and, and we need to move away from it then.

• 9:33Dr. Darshan Shah?

  You know, you mentioned personalization. And so I think that's a topic that many people are accidentally figuring out what is the best for their particular biology. Are there any markers or any tools that you use to help people think about? How do they personalize a diet or personalize dietary recommendations to their, to their own biology?

• 9:54Speaker 01

  Yes, so, so we have a foundation both in the U S and clinics and in Italy. And so we, it, it's a long process for us, you know? So usually the typical person goes through like a journey of a couple of years, right? So we're, the, the nutritionist learns and we have PhD nutritionists as well as non PhD nutritionists. It takes the time to understand, you know, everything about you and what you eat and what you cannot avoid eating and what may be bothering you. Out of a list of hundreds and hundreds of ingredients, right? So, yeah, so we take the time and, and sometimes, in, in most cases, it, it takes over a year to learn, oh, we didn't know this.

• 10:38Speaker 01

  It was this problem, right? And, uh, and, and sometimes it takes understanding whether you had mold in your house, right? Uh, and it may take, you know, understanding whether you might have mercury poisoning or, or, yeah, yeah. So we see it as a, you know, when you go to graduate school. You get a project, right?

• 10:59Dr. Darshan Shah?

  Right.

• 11:00Speaker 01

  Yeah, so the nutritionist in our clinics, they sort of get a project. The project is the patient. It's your, you know, let's make him healthy, right? Or her healthy. Yeah, so it's a long process. And then eventually, in most cases, whether it's weight loss or, you know, we have lots of cancer patients, for example. At some point, you've, you know, and not for everybody, but the great majority of people, you find something, okay, this works, right? This works for this person. We're successful. We're doing good. Let's keep going.

• 11:30Dr. Darshan Shah?

  Yeah, I completely agree with that. I think it is a process. It's always good to have a professional that understands the ins and outs, that can help you personalize. You know, in our business, we like to tie all of our patients who are nutritionists, if they can do it, or dietitian, if they can do it, because it takes trial and error. It takes someone to be your coach through it. It takes behavior change. There are a lot of different aspects to this. And hopefully, we have a day in the future of this country and the world where everyone has access to this, either through artificial intelligence or through a live human, but I think it's necessary, right?

• 12:04Speaker 01

  Yeah, yeah. You know, I've been talking to, especially the Italian government, but also here. So we're trying, but I think the mentality, it may be the business, right? The business is about, you know, you train the major clinic. Yeah, the business is about procedures, right? Procedures bring in a lot of funds to a lot of these clinics and centers. And so I think there is not a lot of motivation. And maybe there's lobbying against it. I don't know. I mean, I don't want to get into politics, but certainly there is not a lot of motivation in changing the system. The system brings in an incredible amount of money. And so, yeah, why can't you get the nutritional consultation reimbursed, right?

• 12:48Speaker 01

  We have a nonprofit clinic and we cannot get reimbursed for a nutritional consultation. That's crazy, right? That's a foundation clinic that will not be able to get reimbursed for nutritional to a cancer patient.

• 13:01Dr. Darshan Shah?

  That's crazy.

• 13:02Speaker 01

  How crazy is that, right? So, yeah, so then you have to say, well, you know, that's the way it is. We try to change it, but it's not going to be easy.

• 13:11Dr. Darshan Shah?

  Yeah, I mean, the incentives are so misaligned for health. They're all aligned towards disease management. And so if there's no disease, there's no incentive to provide any reimbursement, unfortunately, in our current system.

• 13:24Speaker 01

  Yeah.

• 13:24Dr. Darshan Shah?

  And hopefully, we can, you know, I know you and your company, what we're doing, we're trying to be part of that change. But it's going to take some time, but hopefully, the listeners of this podcast take matters into their own hand and make the change for themselves. And it's going to take some time, some of your own personal funds to make this happen. But I think with the advent of artificial intelligence and also kind of a mindset shift that people are having is going to become more and more the norm, I think, to focus on nutrition as a science.

• 13:54Speaker 01

  Yes, although I worried that we're moving more and more into a, let's say, you know, a robot or whatever, the computer telling you. And psychologically, I already see that people need the opposite, you know? They need somebody that says, okay, come in, let's talk, right? Let me help you, right? So I'm very worried that we're going to replace these physical problems with still a physical problem plus psychological problems, right? So, so I mean, AI is great, I think, to just help you implement things. And but I think eventually having people that you can even go once a week, right?

• 14:38Speaker 01

  I mean, I love to see that, the idea that, you know, once a week you go see somebody and it's reimbursed by the government or by the insurances. And you sit there and you can talk and you can, you know, talk about your problems. And it's kind of like, you know, a personal assistant that helps you, you know, be happier and healthier, right? So, so yeah, rather than I'm talking to a robot. Yeah, which is great. I mean, I'm not against that, but, but yeah, I think people are getting, you know, I remember a few years ago, I was at a GSA meeting, Gentrological Society of America, the biggest conference in the US for aging. And you know, and somebody from the N I A, National Science and Aging, say, you know,

• 15:21Speaker 01

  the biggest problems for older people in the United States is, is loneliness, right? Absolutely. So, you know, there you go, right? It wasn't, you know, all the pills that they take. I mean, that's a huge problem, but the loneliness was a bigger problem, right? Absolutely. So, so I think we, young people now, loneliness is becoming a big problem, not just with the old, right? So, yeah, so is that what you wanna do? You wanna push more A I? Yeah, I think we gotta go exactly. And another thing, you know, that I wanna mention, I just wrote an article for the Corriere della Sera, the Italian newspaper, about this, you know, the struggle, you know? So, we're, we're, we're coming up with pills, right, to replace everything?

• 16:03Speaker 01

  And, and so I made the point, say, well, can you imagine if you had a pill to replace jogging, right? Or a pill to replace going up the stairs, you know, I mean, just the exercise part, or swimming, right? And I say, you know, I think that struggle, you know, having to go through it, you know, just, I mean, I, I, in my example that I give, like, it would be one thing if I say you gotta, you gotta run ten kilometers a day, right? Most people are not gonna be able to run ten kilometers a day. But, you know, a hundred and fifty to three hundred minutes a week of exercise, plus an hour a day of walking, you gotta do it. I don't, there's no pill, even if there was a pill that could do that, don't take the pill, just, you know, do that, right? And so that alone, I, I, you know, that, that struggle, I think, is also very important.

• 16:47Speaker 01

  The opposite of where we're going, GLP one, you know, everything is becoming, you know, and, and we can talk about it, but with a lot of side effects, but even if there were no side effect, even if GLP one gave you like no muscle loss, no bone density loss, no ischemia, and it just made you thin, I would say, forget it. Let's have a person that helps you, you know, get there. That's so much better. And psychologically, I think it's gonna be so much more positive and rewarding for you to, you know, to, to make that. But, but it's hard, right? It's hard.

• 17:20Dr. Darshan Shah?

  There's something very important about being able to do hard things, you know, and the less, part of I think the biggest problems we have right now in our modern civilization is we've eliminated a lot of the hard things that we do. We're, we're living in a time of comfort crisis, over, over comfort, right?

• 17:36Speaker 01

  Yeah, and if you look at centenarians, you know, everything was done by hand, let's say, right? You know, they walked, they went up the stairs and, you know, and there was no machines to do anything, right? So, so now there's a machine for everything. And now we're, we're coming up with machines to even do, you know, very basic things, right? And, um, yeah, don't go walking, cause we have a, we have a drug for you and a machine for you that, you know, it's gonna allow you to sit and be obese and, and, you know, and live to a hundred.

• 18:14Speaker 01

  So that's crazy, right? So we're allowing it, we're allowing it. So I'm not sure who's, who's benefiting from this, you know?

• 18:20Dr. Darshan Shah?

  Yeah.

• 18:20Speaker 01

  Being other than, other than corporations that are making money, yeah.

• 18:24Dr. Darshan Shah?

  It seems like, you know, such a great thing, this invention of technology, where we can pull out our phone and order groceries and it comes to our front door. We don't even have to go to the grocery store anymore. But in reality, it's taking away key aspects of life that we've evolved to live in for centuries, right? And it's just too much.

• 18:44Speaker 01

  Exactly, and I mean, it's perfectly fine to have it if then you have a mentality of, okay, fine, you know, I have my groceries delivered, right? But I make it a point of walking an hour a day and never take an elevator, you know? And so, so I think if you have, you know, if you focus on the things that are so important to you and you still do them, then I think it's fine to have the delivery and the technology. But I think that's not what's happening. I think we're eliminating almost everything. Now I go to the little towns in Southern Italy and, you know, and if I walk from the central square, I mean, it's like, you know, half a mile, right? Everybody stops and they're worried that I'm walking.

• 19:29Speaker 01

  We give you a right.

• 19:30Dr. Darshan Shah?

  Really?

• 19:31Speaker 01

  So this is like little towns have record longevity in the middle of the southern Italian mountains. And and it's almost like to them, walking is almost like an embarrassing thing.

• 19:42Dr. Darshan Shah?

  Oh, my gosh.

• 19:42Speaker 01

  And I think this is crazy. What happened, right? I mean, this is the, yeah, so it's almost like there's something wrong with walking. Um, so, yeah, so I think that, um, yeah, those are, and that's surprising, right? You don't hear the governments talk about this, right? And you hear them about, yeah, you hear about GLP ones all day long. Uh, but none of this, right? So.

• 20:05Dr. Darshan Shah?

  Yeah, it's it's pretty incredible. Going back to kind of our our new overall nutrition, how much of an impact do you think? This processed food industrial machine of making processed food since World War Two? How much of an impact has that had on our overall health?

• 20:20Speaker 01

  I think a bad impact, obviously, but I think that it's also allowed to hide maybe the bigger problem, right? Uh, so the ultra-processed food, I think, is alarming. You know, I've been interviewed, a lot of television interviews about this ultra-processed food. And and it seems like the the documentaries was focusing on ultra-processed food. But then it was not focusing, I'll say, a big bowl of rice, right? Of white rice and a big plate of potatoes with the skin on it, right? So so I think that, you know, when we, I published a book called Longevity Starts in Children. And when we investigated and we talked to pediatricians in Italy,

• 21:05Speaker 01

  we realized that everybody was blaming ultra-processed food. And nobody realized what was going on in in Italian children, which is probably not as as as much a case here in the US, but probably also here, which was they ate one pound a day of high starch food, right? And it was perfectly healthy food, you know, rice, potatoes, pizza, pasta, you know, and fruit juices, right? And then when we looked at the ultra-processed food was less than thirty grams a day. And when we look at sugary drinks, it was one can a week. So clearly, the problem was not coming from the ultra-processed food.

• 21:49Speaker 01

  The problem comes from what I call the five Ps in Italian, which is pasta, pane, pizza, potato. So bread, pasta, pizza, potatoes and proteins, right? Uh, that's where the problem was coming from. They were eating two to three times in several age ranges, just like the United States. And the United States is worse. Two to three times more proteins are recommended by all pediatric associations in the world.

• 22:12Dr. Darshan Shah?

  Oh.

• 22:13Speaker 01

  And you know what was worse? No pediatrician knew this. Every pediatrician told us the story of ultra-processed food. And this is ISTAT, the official government data, right? So, so none of the pediatrician told us, hey, I think these kids in Naples and Calabria and all over Italy are eating too much potatoes and rice, you know, and pasta. Uh, yeah, so, so, yeah, so absolutely, I mean, ultra-processed food is really bad, you know, it's even worse than the than the, uh, than the simple food, but we need to worry about the rest. Now, I eat the five Ps every day, right? Almost every day. So, so I want to make sure, because sometimes people say, oh, what is he saying?

• 22:56Speaker 01

  Now, uh, people, uh, I think a lot of people see it that way. No, absolutely not. That's great, you know, I eat pasta every day and rice is fine. All of this is fine. You just cannot have excess of it, right? That two, three hundred calorie excess of it. And then if that allows you to become insulin resistant, that's when you're gonna have a problem, right? And, uh, yeah, so they, and that, that's why it takes a nutritionist that, uh, that knows what they're doing to guide you through it. They say, okay, there's nothing wrong with pasta. You're fine. Okay, but we're gonna decrease, you know, like you say, your pasta and bread. You know, you go to a restaurant, you know, on most places in the world, right? And you get this, this big basket of bread, right?

• 23:37Speaker 01

  And you're, you're about to order pasta and so, okay, just get rid of the basket of bread. That's okay, right? And you can have the bread, maybe as a sandwich, uh, for lunch. And so all of it is okay, but the, the lack of understanding of the danger of this, you know, the simple starches is, is definitely a big, big portion of the problem, bigger than the ultra-processed food.

• 24:01Dr. Darshan Shah?

  Yeah, so it's mainly the effect on the metabolism, metabolic health is where the starches are really causing the biggest issue.

• 24:09Speaker 01

  Well, if you eat a bowl of rice,

• 24:10Dr. Darshan Shah?

  Uh huh.

• 24:11Speaker 01

  It gets into your bloodstream as sugar as quick as uh table sugar, right? So to the body, doesn't matter whether it's a bowl of rice or you just eat sugar, right?

• 24:22Dr. Darshan Shah?

  Yeah.

• 24:23Speaker 01

  So and most people don't don't understand it. So so that everybody understands that now in Italy, they're passing a sugar tax and New York did it, you know? But nobody's passing a white rice tax or a potato tax, right? So i- i- it's just, you know, it's just entertaining because from a scientific point of view, you you you just have to laugh at the at the lack of, you know, basic understanding. You know, how can you fix a problem if you if you don't talk about the problem? You know, in a scientific way, and then you have the professionals that can say, hey, you know, it's not easy, right? So eh to to have minor changes, not big changes, and nobody is gonna do ma- major changes today, right? Most people are not gonna do major changes. You gotta do minor changes and you gotta take years to do it.

• 25:08Speaker 01

  And you have to do the right ones so that people can eventually get into uh a mu- a much better, you know, a healthy status.

• 25:16Dr. Darshan Shah?

  Right, but but and you're absolutely right. It takes a little bit of a course correction, a minor correction, but over the course of weeks and months and years, it adds to better health in the long term. And I think developing good routines and habits around these small changes makes a bigger difference than making a major intervention all at one time.

• 25:34Speaker 01

  Yeah, and I think if you look at the data, I think between the sixties or seventies and now, there is a difference of three hundred kilocalories per day, mostly carbohydrates, right? So that's it, right?

• 25:45Dr. Darshan Shah?

  That's so interesting.

• 25:46Speaker 01

  The solution potentially, I mean, with some tools, right? Like the fasting making diet and, you know, now there's technology that can help you maybe eat a lot and and get benefits, you know, is so but but yeah, the difference that got us there uh seems to be mostly that two, three hundred kilo calories per day coming from carbohydrates and probably from from this uh four Ps. And so, you know, so that that's not very much, right? Two hundred calories less, it's a piece of bread, right?

• 26:17Dr. Darshan Shah?

  Yeah.

• 26:17Speaker 01

  Eh eh one piece of bread. The last per day in ten years, it's a tremendous, you know, kilo, pounds and pounds of fat.

• 26:25Dr. Darshan Shah?

  Yeah.

• 26:26Speaker 01

  And and that's in that sense, then there is a whole other scientific food composition. And there's lots of other things that you could do, which are unrelated to obesity and overweight. But but certainly in a country in Europe now is is very close to the United States levels. Europe, I think sixty percent overweight and obese. Italy is fifty and US is seventy five, right? So so I think that certainly that's one of the problems that we need to address. But I think, you know, the longevity science goes way past that.

• 26:57Dr. Darshan Shah?

  Right. Um, we talked about starchy vegetables and carbohydrates. What about proteins? You mentioned proteins were one of the five Ps that children were over consuming. What is the biological mechanism of protein causing being a part of the obesity problem?

• 27:13Speaker 01

  Yeah, so we don't know yet, we're able to publish that. But but so I cannot talk about the details. But but certainly, you know, if you look at, you know, Harvard, Frank Hu and colleagues publish, you know, papers on protein intake and and diabetes, right? And it was about a forty percent increased risk of diabetes in people with with high protein, but only if it was animal proteins, right? So so now we're we're soon enough, we're going to publish on the on the why. Yeah, so I think that the proteins are clearly associated with lots of problems. If it's too high and if it's animal. Now, the story evolves, I don't want to talk about the plant so much.

• 27:56Speaker 01

  But I think, and we published ten years ago, you know, the risk for overall mortality was way up in people that had a high protein, but only up to age sixty five and also cancer mortality. Now, if it was a high mostly plant based proteins, the overall mortality effect disappeared, but the cancer mortality effect did not disappear, right? So it still meant that if you have a high protein, it's plant based. It was not as bad as animal based. But it was still there. So I mean, we don't know all the details, but overall mortality, cancer mortality, and now Harvard, a few years ago, Frank, who published on the diabetes.

• 28:40Speaker 01

  And it was great because there was three different cohorts, like forty thousand people, big cohort, the physician and nurse studies, three different ones, identical results. High animal protein intake, forty percent. This is not a small number, right? Forty percent, over and over and over, right? So epidemiology is very clear, and I think, you know, we have a pretty good idea what it is. And so hopefully soon, we publish and we can, maybe.

• 29:08Dr. Darshan Shah?

  Cliffhanger, yeah. We'll talk about it some more for sure. That's a cliffhanger for sure. I'd love to hear the mechanism of that. Is part of the, so the recommendation for protein is one point six approximately grams per kilogram. Is that what you're considering? A high protein diet? And where would you aim for, for protein intake? For people to kind of avoid some of the risks associated with, with the cancer and more?

• 29:32Speaker 01

  Yeah. So again, I think it's personalization. So we actually about half of that, so zero point eight grams per kilogram. But I think that we, in some ways, may need to move away from the idea of proteins completely and move into the idea of amino acid profile, right? And yeah, so I think that it may be, you know, so if you eat a lot, if your diet is all legumes, one point six, it's perfectly fine, right? But if your diet is all, you know, red meat, one point six is not perfectly fine. So yeah, so I think that that's another complexity, you know, and eventually that's

• 30:15Speaker 01

  the kind of thing the AI and, you know, applications can handle, right? So that's the good news with, with AI and application, that, that kind of, because maybe you'll say, you know, I had this, this much of a steak and, and then, you know, they'll tell you, it'll tell you, okay, stop, right? Did you add enough for the day? So right now, I think it's a little hard to do, but, but, you know, there are apps that you can really use to. To maybe guide you, you know, so we're working on our own. So once that is out, I think I'll make it free, right? So everybody can use it. And so, yeah, so that would be a tremendous help. So that people don't worry so much about protein level.

• 30:58Speaker 01

  But they worry about what they like to eat and say, okay, I'm already up there because of the amino acid profile.

• 31:04Dr. Darshan Shah?

  I see. So really, you're Apple focusing on the individual food's amino acid profile. And depending on the amino acids intake, it will give recommendations based on what direction to head and what, how much protein you should eat for the day.

• 31:18Speaker 01

  Yeah.

• 31:19Dr. Darshan Shah?

  Yeah, I think that's so much more helpful than these general recommendations of grams per kilogram per day, because like you said, that's not personalized at all. It's not personalized to individuals, not personalized to the food choices, any of it.

• 31:31Speaker 01

  Yeah, well, some foods have five to 10 times difference.

• 31:35Dr. Darshan Shah?

  Yeah.

• 31:35Speaker 01

  Of amino acid content, right? And, you know, five to 10 times, right? So imagine that, like you go from one gram per kilogram to 10 grams per kilogram to get the same level of one or several amino acids. So this is why if the difference was 30%, you know, and sometimes it's between plant-based sources, right? You could have a five-fold difference in amino acid content between two different plant-based sources. That's why, you know, yeah, if it was 30%, you could say, just talk about protein. But when you're looking at five to 10-fold, you can see why you can no longer use protein as, you know.

• 32:11Dr. Darshan Shah?

  As a macro. Yeah, exactly. You need to, and I talk about this a lot. Every food is so different and reducing it down to three macros as a big concept does a disservice, I think, to most people because it's much more complicated than that.

• 32:25Speaker 01

  Yeah.

• 32:26Dr. Darshan Shah?

  Yeah.

• 32:32Dr. Darshan Shah?

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• 33:51Dr. Darshan Shah?

  Just so we touch on the third mackerel, let's talk about fats. Fats have been demonized for many decades now due to studies like KEES study and more. And I think that there's a resurgence on the talk about fat, because fat can help with satiety, fat can help with inflammation reduction. What are your thoughts around fats and how people should think about fats?

• 34:14Speaker 01

  Yeah, the thoughts are that probably plant-based fats are generally okay, but some plant-based fats seem to be very good. Yeah, so then, and we have a standard where we look at longevity. We look at, let's say, New England Journal of Medicine meta-analysis, and lots of centenarians use the same thing as I was saying earlier about the five pillars. So if you do that, you get the almonds, you get the walnuts, you get the olive oil, you get the salmon if it's coming from the right sources. Of course, now it's hard to get salmon that is not contaminated,

• 34:55Speaker 01

  but I think you can, or you can have the right amount so that you don't get into a toxin or toxic level range. Yeah, so I think those are, I like to see it like that. You don't need to have, I don't think you can think about fat is good for me. What's not, right? This is how we make mice. You know, very big and living shorter. We give them lots of sugar and lots of fat.

• 35:23Dr. Darshan Shah?

  Right, right.

• 35:24Speaker 01

  And they become huge and they die. I mean, it's unbelievable. We published it a few years ago. I couldn't believe how much shorter and sick these mice were if we give them lots of fat and lots of sugar. Yeah, they they like thirty, forty percent shorter, heart problems, cholesterol problem, everything is like. It's like little humans, right? And yeah, so so you cannot think the fat is good for you. But you can think that maybe, let's say, thirty percent of your calorie comes from the right fats. Seems to be a very good thing, you know, and yeah. So the Okinawa ones didn't do it, but the Southern Italians did it, the La Malinda people do it. And so also the Centenarian pillars, you know, you could probably go either way because Japan.

• 36:05Speaker 01

  If you look at Japan, now it's a lot higher because they eat a lot of fatty fish.

• 36:11Dr. Darshan Shah?

  Right.

• 36:11Speaker 01

  But historically, like the Okinawa ones did not eat a lot of fatty fish.

• 36:16Dr. Darshan Shah?

  Really?

• 36:16Speaker 01

  Yeah, very little fish. And and they did very well, right, with that, right? So it it it seems like that that's but but the Japanese now do. And they still have, they're on top of the world for for longevity and life expectancy. So, yeah, so I think that's, you know, thirty percent of those fats and and a few more, right?

• 36:39Dr. Darshan Shah?

  Right.

• 36:40Speaker 01

  They they seem so, yeah, those are the ones, the only ones that are in my diet.

• 36:43Dr. Darshan Shah?

  Got it, got it. Okay, makes sense. And then how do you, moving on from macronutrients, how do you think about calories? And so there's a lot of people doing calorie restriction, just as a general rule. There's an entire society of people just doing caloric restriction. And how do you think of calories and how that leads to longevity?

• 37:05Speaker 01

  Yeah, so I started right in in in the laboratory Roy Wolf for here at UCLA. And Roy, back then, you know, in the early nineties, was the world, you know, top expert in in calorie restriction and nutrition and longevity. And I always thought it was a bad idea, right, you know, from the very beginning. In fact, the whole lab, we all went to Arizona when they were in lockdown. Up in this biosphere two environment, you know, so we saw him come out.

• 37:31Dr. Darshan Shah?

  Yeah.

• 37:32Speaker 01

  And they look terrible, right? So they spent, I mean, most people don't know this story, but they spent two years sealed in this like base, a future, future moon base that was built in the middle of the desert of Arizona. And they, you know, they were growing, growing their own crops and, and they were, you know, calorie restricted for about a year and a half to two years. Yeah, so they look terrible and um I always thought this is not the way to go. And now, uh, you know, but I, I thought, I, and I still think it's an incredible lesson, right? Because whether it's mice or people or monkeys that are calorie restricted, the, the, at least short term benefits are incredible.

• 38:10Speaker 01

  It's a really, if you look at it, you say such a simple intervention, it revolutionizes the health of, of an organism, right? But then long term, you start seeing the problems, right? And, and this is why in, in one of the monkey studies done by Rafa de Cabo and, and uh, and others at the N I A, there is not even lifespan extension, right? There's a lot of hunger, right? So the poor monkeys that were hu- hungry the whole time and, and they're not getting a benefit. They got a be- benefits on cancer and other problems. Now, the Wisconsin study showed lifespan extension and showed, you know, benefits on, on diabetes, cancer, cardiovascular disease.

• 38:50Speaker 01

  But if you look at the overall mortality curve, it's the, the calorie restricted monkeys and the non restricted monkeys much closer than when you look at age related disease mortality. So it's a big effect on age related diseases. But then probably trade offs, right? So what happened? Probably, yes, you don't get cancer, but you may end up dying of an infection.

• 39:15Dr. Darshan Shah?

  Right.

• 39:15Speaker 01

  Or some other event that the body now is less resilient against, right? So, so maybe more resilient against cer- certain things and less resilient. So you, you have to, of course, use that energy, give up something, right? And what you may give up is a subset of macrophages or, or T cells that may be very good at fighting a particular virus, right? So I'm speculating here. But but I'm not speaking about the mortality curve.

• 39:41Dr. Darshan Shah?

  Right.

• 39:41Speaker 01

  Uh, becoming much closer together and and so indicating that, yes, there are, there are probably trade offs, yeah.

• 39:48Dr. Darshan Shah?

  Got it, got it. So, you know, a lot of people, when they look at the latest, a lot of people are talking, scientists, doctors are talking about the latest research with fasting and they're saying a lot of the benefits from fasting are probably coming from caloric restriction. And I think.

• 40:02Speaker 01

  Well, they're not, yeah.

• 40:03Dr. Darshan Shah?

  And, yeah, exactly. And so I think that, um, I think that the there's distinction that needs to be made in the different types of fasts. And you alluded to this earlier where you were talking about skipping breakfast, for example, or the traditional intermittent fasting or time restricted diets. Can we talk a little bit about that before we talk about some of these diets that you speak about?

• 40:25Speaker 01

  Yeah, yeah. So we actually did that, right, in mice and and now we're, we're looking at the, we did many human trials. But but in the mouse trial, we look at per month, uh, there was no calorie restriction. So we did the fasting mimicking diet, four days, uh, twice a month. And yeah, the mice overate everything they underate during those eight days, right? So, yeah, and we suspect the same is true for people. Uh, so there is no calorie restriction or or very little, let's say very little. So, yeah, so I think that it's much more of a regulatory, so we just published a paper in fasting mimicking diet and kidney disease and damage in collaboration with Laura Perrin here at Children's Hospital.

• 41:04Speaker 01

  And then a pilot clinical trial in collaboration with Alessandro Laviano and Silvia Lai in University of Rome. And but basically, what you see is that it's something remarkable, right? You, you damage the kidney and we already published this for the pancreas, but we've seen it again in another organ. It was really spectacular. So you damage the, the, uh, the, the kidney. And and all the cell types, we do something called special transcriptomics, right? So we get to sort of at the molecular level, look at every cell and lots of genes in different cells. So this pattern, this beautiful pattern that in the, in the rat kidney gets completely destroyed.

• 41:43Speaker 01

  And then you start the cycles of the fasting making diet and you slowly see it going back to its original state, right? And you see this Yamanaka factor, this reprogramming factor being turned down and you see all these developmental genes. The same genes that are turned down when the mouse, when the rat is first born, right? So what does it tell us? It tells us that the human body, and I always use the example of the skin, right? You cut your skin, couple of weeks later, prepare, right, for what happened, right? So now, is it possible that all the organs have the same capability, but they just need the fasting or fasting making diet to give that order? And it's gotta be done, you know, in a certain specific ways, in certain cycles.

• 42:27Speaker 01

  So we ran a clinical trial, and the clinical trial was three cycles of the fasting making diet in kidney disease patients, right? And we thought, it's a, it's a long shot, because it's a small trial. And sure enough, in both arms, small arms, seven patient in one, six patient in one, but in both arms, identical incredibly beneficial results, so decreasing proteinuria, decreasing and, and, you know, reversal of, of the glomerular filtration rate defects. So, and then in circulation, we saw the progenitor, the kidney progenitor cells tripled. That's so interesting. Yeah, so, so, so it's, it's, it's suggesting that what's happening in the rat is also happening in people.

• 43:12Speaker 01

  We'll see, I mean, we don't get to go and look at what happens in the kidney of a patient, but certainly now we're seeing in mouse, we're seeing in the rat, and now we're seeing evidence of all of this happening in many clinical trials, human clinical trials. So, so, yeah, so I think that's a lot more this reprogramming than, you know, the calorie restriction. And, and, and by the way, is, a lot of it is the refeeding, right? Yeah. So the calorie restriction, I think, is an opportunity to shrink, you know, autophagy and lots of other things. So the system shrinks, a lot of cells are actually killed or removed. And then in the re-expansion is when the regenerative processes are, are turned on. And that's when then you see these.

• 43:57Speaker 01

  Uh, you know, this like incredible repair and and rejuvenation effects, right? So we don't only see repair, we also see, you know, people now.

• 44:08Dr. Darshan Shah?

  Yeah.

• 44:09Speaker 01

  At least based on biological markers, becoming younger.

• 44:13Dr. Darshan Shah?

  So fasting can activate this regenerative mechanism. So from there, and I know the research is still coming out, is it your idea that maybe when we do have organ damage or injury, maybe after a heart attack, that maybe fasting is part of the solution for the repair process?

• 44:29Speaker 01

  Yeah, I mean, we're talking about heart attack, we did that experiment. We took mice and we gave them dobutamine. So we do, you know, cardiac damage and then we do echocardiogram and we look at recovery. And if you do fasting, they're so much faster at recovering, right? So, so, yeah, so absolutely, we've done this with so many systems. Yeah, so the the body knows how to repair itself. It's called what I call rejuvenation from within, right? So you just have to learn how to trigger it in a way that doesn't, you know, more damaged than good, you know?

• 45:03Dr. Darshan Shah?

  Right.

• 45:03Speaker 01

  So, for example, I always give, and I wrote a review with with oncologist M D Anderson. And I said, you know, and I wanted to point that out in the review that if you do in mice, and now we're doing this also in clinical trials, if you give them fasting mimicking diet or fasting, and then you give them chemotherapy, let's say on day four of the fasting, the mouse is protected and the cancer cells are sensitized, right? But if you do intermittent, every day fasting, every other, I think, every other day or every day fasting, let's say sixteen hours, you get the opposite. Now, doxorubicin, and and so, and if you look at the heart.

• 45:43Dr. Darshan Shah?

  Right.

• 45:44Speaker 01

  Doxorubicin toxicity is greatly reduced, right?

• 45:48Speaker 01

  So you so three or four days, then you get the he he hit the mice with the chemo. And then you wait and then you refeed, you know, after the chemo is mostly gone from the blood. But if you do alternate, and this is the second study is not ours, you know, so a group in England. It was like, what if you fast every other day and you do the same exact experiment? You know what happens? The opposite. Now they're refeeding together and we always warn people about that and nobody listen. And and so you do every other day fasting, so you give him doxorubicin. And now the doxorubicin high dose is combined with the refeeding. And now it's exactly what we predicted that you will get increased cardio toxicity, right?

• 46:27Speaker 01

  Because now you have growth factors going up and the heart is being told to reexpand somewhat in the same time when the cardio toxin is present, right? And and and that's a recipe for disaster and that's exactly what happened. Now imagine how many people now are doing exactly that. They're doing alternate day fasting or sixteen hours with, you know, chemotherapy. And and and their problems, I don't know, but it could be that a lot of people died because of of this really bad idea. And and and this is how important is to, I think, in the clinic in the future, have the M Ds together with the scientists, right? Yeah.

• 47:10Speaker 01

  Just to make sure, because, you know, patients may ask the oncologist, well, shall I do it? And the oncologist may say no, or may say, ah, sure, not a problem. And fasting is just a word, right? It's like, OK, you know, we go home and if you want to do intermittent fasting sixteen hours or whatever. Well, guess what? It it could make a big difference, right? And now you that doxorubicin, it could be lethal. And now, as you know, you're a physician, there is a lifetime dose of doxorubicin, right? And so if you make it three times more toxic, now, yeah, the the lifetime dose should have been reduced three threefold, right? Wow. So, yeah, so the this is just examples of of our, you know, you need to know the science and you need to have the oncologist and and the collaboration, you know.

• 47:54Speaker 01

  I think it's really remarkable when we collaborate, you know, when the PhDs and the. And the MD is a collaborate, truly collaborate, then it's really, you take it to another level.

• 48:03Dr. Darshan Shah?

  You take it to another level, for sure. So, so the programming of the fast is incredibly important, exactly when you're doing it, for how long, and that's where a lot of your research has been. I know you started some of the research around cancer, diabetes as well, right? Is it also just as important with treating diabetes?

• 48:20Speaker 01

  Yeah, no, diabetes actually is by far the most advanced fasting mimicking diet intervention, right? So, so now we did a trial, including prediabetes patient in 2017. Then we did another one last year when we compared fasting mimicking diet cycles with Mediterranean diet, and that included a lot of prediabetes patients. And then University of Heidelberg and University of Laiden did two separate trials on diabetes treatment. And, and the data, and now there's another trial that is coming out in a couple of months. They will also include diabetes patients. All of them showed the same, right? Major reduction of A1C. And in the prediabetes, if the fasting mimicking diet is, is used in the absence of drugs,

• 49:05Speaker 01

  no limb body mass loss and no bone density loss, right?

• 49:08Dr. Darshan Shah?

  Wow.

• 49:08Speaker 01

  Something that you don't see with the GLP-1. So you see both muscle loss and, and, and major muscle loss. And limb and, and potentially, and loss of bone density. Yeah, so I think that the diabetes, you know, I'm pushing to do a large trial and we're trying to get three or four universities, you know, to the 500 patient trial, which I think will be the conclusive one. But, you know, these five trials are pretty consistent. And the beauty of it is that in the latest trial, in, in the Heidelberg trial, 70% of patients, and, and the Heidelberg trial was with all kinds of diabetes drugs. And 70% of patients reduced drug use, right?

• 49:54Speaker 01

  Which is remarkable. So you get A1C reduction and plus seven out of 10 within six months. This was six monthly cycles. Seven out of 10 patients were able to reduce the dose or the number of drugs that they were taking.

• 50:08Dr. Darshan Shah?

  Wow, incredible. After how long of a trial?

• 50:11Speaker 01

  Six cycles. It was Heidelberg and the University of Laiden was twelve cycles. Twelve monthly cycles. But I think the idea is that that's what you do on year one or six months. And then you could reduce it, let's say, maybe half, right? So we've seen a lot of patients in the clinic and, you know, they don't, they don't do twelve cycles. You know, they might have done in a year and a half, let's say, seven, eight cycles. And, and that together with longevity diet seems to bring, you know, most, most people back, you know. So, so, uh, yeah, so I, I, I think that, yeah, of course, if you add a terrible diet and that's all you're willing, you're not willing to make any changes, you know, you might need six to twelve cycles on year one.

• 50:51Speaker 01

  But, um, but even for them, I think, um, uh, probably, um, you know, year two is, is much more, much easier, right? And, and that's also very good for the patient to feel like, okay, I'm doing this. But, you know, five days from now, I'm going back to my normal diet. Nobody's gonna tell me what to do. And then I'm doing this once a month, but a year from now, maybe I'll do it once every four months. And so we now have a large trial, which is almost finished in southern Italy. So we went to the, the worst place in Europe and my, my parents' home, home land. And, and we basically say, well, what if we do the fasting making diet only every three months, right?

• 51:31Speaker 01

  So I cannot talk about the results, but we were almost done. We are a patient for hundred and ten or five hundred. And, uh, yeah, so soon enough, we'll, we'll, we'll publish on that. But, yeah, only every three months alone or with the longevity diet. So with this everyday, uh, pescatarian diet. And so, you know, and, and the point was, you know, hey, some people are not gonna change anything, but some people wanna change. And so let's see what happens in, in, in the ideal everyday diet plus or. Just the FMD for five days every three months and no other lifestyle changes required. And in fact, we told them, don't change anything, right? So just for the sake of the trial.

• 52:11Dr. Darshan Shah?

  And their normal diet is one that's not a healthy diet for the most part?

• 52:16Speaker 01

  Yeah, most part very unhealthy and all of them were overweight. Plus one risk, disease respect. So high cholesterol, high blood pressure, high A1C. So that was the inclusion criteria.

• 52:29Dr. Darshan Shah?

  So I think the take on point there is that fasting mimicking diet works. Whether or not you're doing lifestyle intervention is what you're seeing, right? So if you're a diabetic, type two diabetic, and you want to use this as an intervention, like you said, either a monthly cycle or even every three months, it can still work as an intervention for your diabetes to reduce your hemoglobin A1C.

• 52:53Speaker 01

  Yes, yes. So I think that the biggest effects we see is people that have, they start the worst, right?

• 53:00Dr. Darshan Shah?

  Right.

• 53:00Speaker 01

  Yeah, so that's where we see it. And if somebody is a vegan and athlete and, you know, running 50 miles a week, you see some effects, but not as much, right? Yeah, so there are, yeah, I think that then, of course, we're preaching the longevity diet and 12 hours of time restricted eating and lots of other things, but in being mostly vegan. But yeah, the reality is a different one. And I think after, you know, since the 60s, we've been preaching healthy diets. And we went from 10% obesity to 42% obesity or 40, maybe more than that now. So it doesn't work, right?

• 53:41Speaker 01

  This idea of preaching to people, oh, be healthy and change your diet, it doesn't work. And so, and I think the drugs are okay. I mean, you know, and GLP-1 included, it can be, you know, very important for some people. But it should be for the people. For whom everything else failed, right? You know, we we we should have had the nutritionist and the physician and they are reimbursed to get you be healthy and then a couple of years later, we couldn't do it. Okay, now now you get to have the drug, right? And it doesn't work like that. And and so this is a good time to change it, you know, we'll see what the new administration is gonna do, but certainly it'd be nice to see this type of things reimbursed, right?

• 54:26Dr. Darshan Shah?

  Absolutely.

• 54:28Speaker 01

  You know, and I don't think it's a matter of left or right. I think everybody agrees, right? I I I think everybody always agreed, but nobody did anything about it, right? And so now it'd be really nice that somebody, you know, makes it a reality to be able to be reimbursed, to to help slowly somebody becoming healthier.

• 54:48Dr. Darshan Shah?

  Yeah, absolutely. I mean, I think, you know, there's so much talk around the GLP ones and I mean Medicare might even reverse reimburse GLPs now, it's coming in the news and we're reimbursing thousands and thousands of dollars for these GLP one medications, but we're not reimbursing interventions like this that can have just as profound as an effect potentially.

• 55:10Speaker 01

  You know, I'm speechless, right? So that's all we can say, but because, you know, hey, people should be out on the street and and say, come on, you know, this is my health, this is my diabetes and cancer and cardiovascular disease. You know that Alzheimer almost doubles in people that had previously had diabetes.

• 55:28Dr. Darshan Shah?

  Sure, right.

• 55:29Speaker 01

  So, you know, so they're all connected, number one, to aging, right?

• 55:33Dr. Darshan Shah?

  Absolutely.

• 55:34Speaker 01

  And number two, to obesity. And then smoking, of course, and all that, but but those, everybody knows, right? But I think being overweight, being obese, and having a bad diet, you know, that can change in in in smart ways, right? So so, you know, I I always say with the longevity diet, you eat more and maybe even more calories. And people are like, no, come on, this is not possible. I'm telling you, it is possible. You can eat a lot more food for sure, and maybe even more calories and lose weight. And but yeah, somebody's gotta be there to to guide you through it and.

• 56:09Dr. Darshan Shah?

  Absolutely.

• 56:10Speaker 01

  And make sure it's it is. It is consistent with your lifestyle and your happiness because you know you take everything away, then they'll do it for three months and then they'll go back to whatever.

• 56:19Dr. Darshan Shah?

  Yes, it's making it sustainable for sure, which I've I do the longevity diet myself, specifically when I'm fasting and I have I actually enjoy food more, you know, it's it's actually becomes more tasty, you can eat more, like you said, and I want to talk more about the longevity diet, which was one of my first books I read from you, actually. But before we do that, I want to talk about GLP-1s a little bit more since we touched on it. We have hundreds of patients on GLP-1s and we do exactly what you say. We make sure that they've tried many other things and failed and had a really good try before we start them on a GLP-1. And one of the things that we're considering is pairing the GLP-1 with a fasting mimicking diet as kind of the primary first intervention, once we get

• 57:04Dr. Darshan Shah?

  their GLP-1 dose stabilized. How do you think that type of a protocol would work?

• 57:10Speaker 01

  I think it can work if somebody, if a physician is very careful because it causes insulin, you know, increases insulin. And so the danger is now the fasting mimicking diet is going to be an insulin sensitizer, right? So the danger is get somebody into hypoglycemia. So but if you have a continuous glucose monitor and you have people like in your clinic, they know what they're doing, then I think, you know, so we did a trial in Geneva with children, right? And and I and I said, be careful because, you know, the combination of the sensitization with insulin injection in the type 1 diabetes.

• 57:51Dr. Darshan Shah?

  Right.

• 57:51Speaker 01

  You know, could surprise the nurses, could surprise the physicians. Exactly what happened then later. Luckily, they were hospitalized, meaning that this was not a do it at home trial. You had to go into hospital and the child had to stay there for five days. But but I think that that is a real possibility. And so very careful and then try to remove the drug as soon as possible, right? Yeah. So that if it's not like that, I think that then then it's a good way to go, you know? And sometimes it may be like just to get the patient. So for example, there's a physician in Brazil that was doing it with cancer patients. And she was doing liraglutide with FMD, just because some patients struggled at the beginning.

• 58:34Speaker 01

  So so liraglutide lasts a lot less, right, than than than some of the other GLP one agonists. So she was doing that just to get the hunger, remove the hunger, but not get the patient in this longer term, you know, hypoglycemic danger zone, right?

• 58:51Dr. Darshan Shah?

  Right.

• 58:51Speaker 01

  Yeah. So and and and she's she's she says she's done it with a lot of patients. And to her, it worked very well, you know.

• 58:58Dr. Darshan Shah?

  Very interesting. Yeah. And we do tie it with a continuous glucose monitor with every patient as well. When we're doing it. So very, very interesting. I'm glad I asked you that question.

• 59:10Dr. Darshan Shah?

  This episode was brought to you by Next Health, a health optimization and longevity clinic located in Los Angeles, Manhattan, and soon to be opening in Montecito, Nashville, Miami, and many other cities, United States and Canada. Next Health is the Apple Store of wellness, where you can optimize your health span and lifespan using cutting edge technology. I actually founded Next Health eight years ago to give my patients a place to go get extensive biomarker testing done and provide them with all the tools that I use to get my health in order. The longevity circuit in Next Health using hyperbaric oxygen, sauna, cryotherapy and LED light is a game changer. In addition, the doctors at Next Health measure thousands of biomarkers

• 59:54Dr. Darshan Shah?

  and put into place a longevity optimization plan using advanced tools like ozone, plasma exchange and peptides. Go to www.nex.health to check it out.

• 1:00:10Dr. Darshan Shah?

  This episode was also brought to you by Vitaboom. Vitaboom is a revolutionary company that sends you a custom supplement protocol based on your needs using blood-based biomarkers. You could either send them your latest blood test, or they will send you a finger stick test for blood analysis. Vitaboom then curates and ships. An extremely convenient monthly box of daily supplement packs that have your custom protocol in them. What's great is that they also provide all the best brands like Timeline, Tru Niagen, and many others for your custom daily packs. I love mine especially for travel, since I don't have to bring 10 bottles of supplements with me and just open up a daily

• 1:00:52Dr. Darshan Shah?

  pack for every day that I'm taking my vitamins and supplements. Go to Vitaboom.com and check it out.

• 1:01:02Dr. Darshan Shah?

  Let's talk about the longevity diet. Can you give us kind of the high points of what the longevity diet is?

• 1:01:08Speaker 01

  Yeah, so the longevity diet diet tries to, I try to go around the world and think about Kinawa and Lomelinda and Calabria and Sicily and Sardinia and basically say, well, you know, if you look at all the epidemiology and you look at all the clinical trials and you look at all the centenarians and basic research, what seems to be very clearly and very consistently associated with mice living longer and people living longer. Yeah, so that's what the longevity diet. And so what it is, is a mostly plant-based plus fish, low mercury fish, right? And maybe three, four times a week. And this is true for 20 to 65, because then we think that, you know,

• 1:01:52Speaker 01

  the over 65 in most cases is going to need a little bit more proteins. And so realistically, if you think about people hearing this, if they just did fish three or four times a week and they're 72 or 82, they may get in trouble, right? They may get in trouble in malnutrition. So yeah, then we're saying after that, you might want to make it every day, probably have a some type of either high amino acid source, plant-based, or animal protein source. So yeah, so then generally it's a 0.8 grams, 0.37 grams per pound of body weight per day. So it's very low until age 65. And then, but it's got to be good quality protein. So it should be a mix.

• 1:02:35Speaker 01

  So seeds and nuts and tree nuts and they have a lot higher level. Of some essential amino acids. So then if two thirds are coming from seeds and nuts, then you're okay. If legumes are making up most of it, then you get a problem. Or you will have a problem long term, right? So then you gotta have zero point, zero point thirty seven per pound, not per kilogram, per pound, per day. And um, and then, you know, it's a olive oil or the whatever oil happens to be healthy and and from your ancestors area of the world, right? So some, some different people have different oils.

• 1:03:17Speaker 01

  But certainly the olive oil is being tested, you know, with so many trials, you know, some big trials and and it looks pretty good, right? It looks pretty good. The data looks pretty good and not just for cardiovascular, but also the data on cognitive looks good, yeah. So the almonds, the, the walnuts, the asal nuts, very consistently you see them in La Malinda trial, you know, seven day Adventist population living longer, an average in the Californians, and you see this high consumption, you know, mostly vegan, high consumption of these nuts. And yeah, so those are some of the rules. And then, of course, the whole grain cereals, yeah, or all grain,

• 1:04:03Speaker 01

  whole grain based food, that seems to be important. Yeah, and then, you know, try to stay away as much as possible from, from all animal products. You know, with the exception slowly with, say, some eggs and some, some, a little bit of dairy, it's okay. Like yogurt particularly, you see lots of centenarians that consume yogurt. But then, you know, it's gotta be personalized. So different people are gonna have different requirements. But eggs, it looks like up to, say, three eggs a week. It is a New England meta-analysis, I think it was. And in the show, no negative effects, you know, then as you go higher, then you start seeing,

• 1:04:46Speaker 01

  at least epidemiologically, you start seeing problems. And yeah, so, so.

• 1:04:52Speaker 01

  Yeah, essentially, that's that's a longevity diet. So lots of legumes, lots of greens, walnuts, almond, hazelnuts, and then, you know, olive oil, fish, and small fish preferably because of the mercury. And just watch out, you know, I mean, I always tell people rotate, you know, so a lot of these foods are going to have toxins associated with, you know, lots of fish, doesn't matter what it is. So, I mean, it's probably good to say, if you're gonna have, you know, branzino or sea bass, you know, have it only once a week. And then, so don't have the same fish three or four times a week because if it happens to contain, you know, one of many toxins,

• 1:05:35Speaker 01

  then at some point it could get you in trouble.

• 1:05:38Dr. Darshan Shah?

  Yeah, absolutely. The longer the fish lives and the larger the fish, the higher the chance of toxins, right? And so specifically mercury and heavy metals and others. And so sticking to the SMASH fish is the acronym I give to my patients, salmon, mackerel, anchovies, sardines and herring, I think is a good, good idea for fish, right?

• 1:05:59Speaker 01

  It's a good group, yeah.

• 1:06:00Dr. Darshan Shah?

  Yeah, exactly. Okay, so let's now dive into some of the mechanics of the fasting mimicking diet. So you've licensed some of your science to Al Nutra is the company and you have what's called the ProLon diet, which is awesome because it's a kit that you get at home. It's a five day kit that you can use and you can experience the fasting mimicking diet yourself. And so can you talk a little bit about the thought process about that kit that you get and what's included in there and why?

• 1:06:29Speaker 01

  Yes, so, well, first of all, I give almost everything to charity with the exception, I think 5% I'm allowed to invest in other longevity companies, but I cannot take the equity from it. So it's basically 100% donated to charity.

• 1:06:44Dr. Darshan Shah?

  That's incredible.

• 1:06:45Speaker 01

  So Al Nutra, I don't, I don't take a penny. I never took a penny and I will never take a penny. But I think, you know, the, I always thought it was very important to, you know, standardize it, right? And my first thought was, if we standardize it, I hope That we get universities to basically say, hey, can you send me three hundred kits so that I can test it? And that's exactly what happened. So we get requests all the time. Maybe once every couple of weeks, some hospital, some university around the world says, I'm thinking about this trial, you know, what do you think? And so we help them. So the company definitely was good for that. But then, of course, we realized this is,

• 1:07:25Speaker 01

  you know, I founded it fifteen years ago and realized that, you know, there was a lot more used for the, for everyday, not just, you know, so for people to use it frequently, let's say, not every day, because you can do that. But yeah, frequently. So, yeah, so then the kit is basically designed to be okay for most people, to make it as easier as possible. And in fact, you know, recently we sat with the FDA in the regional meetings and for cancer, using it for cancer, and we, and what we were afraid of that will happen, happen, which is

• 1:08:07Speaker 01

  the FDA struggles, and you know, we're gonna keep working with the FDA to try to get to the next level, but struggles with sixty components in a diet, right? So, so we were talking like, what if you got a seven component, right? But then we thought, is it reasonable and fair to give cancer patients, or any patient for the matter, the same seven ingredients for five days? So probably not, right? We'll probably make it harder on them. And, yeah, so then, yeah, we have to figure out how to standardize it even more. But that was the idea. Standardize it in a way, there'll be like FDA, so food is medicine, right? Food in a box is medicine. And it's real food and it's, you know, plant-based, right?

• 1:08:49Speaker 01

  And a lot of it is organic. So that was the idea, that maybe eventually people do it every four months. And that's it, you know, and two to three times a year. And just to get lots of these benefits to help prevent problems or bring back some of the problems that are in the early stages and before, you know, medicines are needed. So yeah, so there there was the idea, I think it's it's worked remarkably well. I think we finished thirty five trials. And by we, I mean lots of universities, right? You know, and and going from, you know, there's been work at Mayo Clinic and and the University of Miami, Stanford, USC, Leyden, Heidelberg.

• 1:09:32Speaker 01

  Uh, yeah, so a lot and lots more, University of Indiana. Yeah, so then this is uh still going and and and hopefully, you know, in the next three or four years, we expect another thirty or forty trials. And of course, what we're doing is a little dangerous because why? Because you you's handing over, you you're giving a kit. And you don't know, they could come back and say it made a lot worse for my patient, right? So so so yeah, so I think unlike a lot of pharmaceutical companies, we've been very, uh, you know, open and and say, okay, test it out. If it's negative, it's negative, you know, we'll uh, we'll have to publish that and maybe it's worse than nothing, right? Never happened so far, so we've been the, you know, it's everything is going remarkably well.

• 1:10:15Speaker 01

  But, you know, I think it's important to um, you know, to do it like that and and uh and to let independent people uh, say, okay, this is great or or not, right?

• 1:10:27Dr. Darshan Shah?

  And you you said thirty five studies, but you have many more still coming, right? There's still.

• 1:10:33Speaker 01

  Yeah, no, yeah, now there's maybe another twenty or thirty that are are ongoing or about to start, right? So so I, yeah, I think it's it's only this year, I think we're looking at six or seven new one being published. So from all over the places, right? So, yeah, so I think it's um, it's good and and it's working out at least.

• 1:10:53Dr. Darshan Shah?

  Right.

• 1:10:54Speaker 01

  Better than we had had hoped, yeah.

• 1:10:57Dr. Darshan Shah?

  So when I look at the fast, the prolonged kit specifically, or just fasting mimicking diets in general, what I say to my patients is that there are. It's a spectrum of benefits, right? So first, number one, if you have chronic disease, diabetes, you know, even if you're trying to avoid dementia, if you've had any aspect of cardiovascular disease, this could be a good intervention to reverse that chronic disease process. Secondly, it can help you avoid chronic disease, so adding to your health span. But thirdly, also, even if you're a healthy individual, it helps you feel great as well. I mean, I could just anecdotally for myself, for my patients, you have more energy, you have less, you have more mental clarity, you are able to sleep better,

• 1:11:42Dr. Darshan Shah?

  all these benefits to your day-to-day life as well. So it seems like it's a good intervention for almost everybody, whether you have chronic disease, you're trying to avoid chronic disease, you're just trying to feel great, or like, you know, you talked about a lot, add to your longevity, right?

• 1:11:58Speaker 01

  Yeah, I think so. I mean, we did a trial, in fact, two trials, and we looked at biological age using these Morgan Levine markers and this blood circulating blood levels of cholesterol and lots of other markers. Then I use, and they're plugged into the ENHANCE database to predict mortality, right? So, yeah, based on that, then after three cycles of FMD, people became two and a half years younger, right? Two and a half years younger. So, yeah, so it seems to be working. Now, I always say, this is not something, so far, we've never seen anything negative, right? But that's impossible, right? It doesn't matter what you do.

• 1:12:43Speaker 01

  It could be like, I drink a lot of water from, you know, Arrowhead Mountain, and eventually, you know, somebody's gonna publish, well, guess what? If you drink too much water from Arrowhead, this happens to you, you know? Yeah, so I think that with that in mind, you know, because it is a medicine, right? Or something very close to a medicine. I would say You know, if you're in perfect health and and you can maintain it, you know, maybe a couple of times a year. Yeah, that's reasonable to to do it and and that's it, right? If you're thirty two year old, you run a lot and you know, you you have a longevity diet. Yeah, maybe a couple of times a year. And then do it as you need to do it, right?

• 1:13:29Speaker 01

  Do it as you need to do it. Yeah, I'm a little bit overweight. Okay, well, that's starting to be a little bit of a problem, right? I have an inflammation, a small inflammatory, and now this is gonna be the next, the year of the inflammatory papers, right? So they're coming out, right? So so from independent universities with independent funding, you know, my company had nothing to do with it. And so, yeah, so I think that, you know, inflammation, insulin resistance, you know, cognitive, we finished the trial in Genova, we'll see the results. Clearly works very well in mice, you know, in making them learn and remember better. But, yeah, we we need a bigger trial, I think, to to have conclusive evidence or to hope

• 1:14:14Speaker 01

  to have conclusive evidence for for cognition. But certainly, I mean, with diabetes doubling the risk for Alzheimer, almost doubling, seventy five percent increase, clearly, you know, if you start in an Alzheimer patient, you you may fail or may succeed. But clearly, if you start twenty years before you're gonna get Alzheimer. I mean, it's it's hard to imagine how this FMD is so powerful against diabetes, how diabetes is so linked to Alzheimer.

• 1:14:39Dr. Darshan Shah?

  Yeah.

• 1:14:39Speaker 01

  And how this will have no effect on, I mean, it's possible, right? I mean, I'm not saying that we know for sure, but it's unlikely that will not at least help you, you know, postpone or certainly potentially prevent cognitive decline.

• 1:14:54Dr. Darshan Shah?

  Absolutely. I mean, Alzheimer's is basically diabetes type three is referred to as a.

• 1:14:58Speaker 01

  Exactly.

• 1:14:59Dr. Darshan Shah?

  And so if it's helping with diabetes, it goes to reason that it would definitely help prevent Alzheimer's disease. And so a lot of my patients with APOE positive genetics, we we talk about the Prolon diet as well. As far as frequency of this intervention, we touched on this a little bit, how would you advise people think about how often to do this type of diet? And I would say for the healthy individual versus someone with chronic disease?

• 1:15:27Speaker 01

  Yeah, so I think that, first of all, having somebody there, not just a physician, but a physician that spends enough time with this type of interventions and a dietitian, that those two, I think, at least once or twice a year, you know, go there because I think otherwise you're gonna have a problem. But yeah, then, as I was saying, I see, say, if you're perfect, healthy, young, maybe a couple of times a year. Majority of people, maybe three to four times a year, you know, say seventy-five percent of Americans are overweight or obese, right? So that three to four times a year for that group.

• 1:16:09Speaker 01

  And then as you get into disease states, then you gotta come to the foundation clinic, I think, you know, and, and we work, you know, so we have programs for cancer patients. We say, we follow thousands of cancer patients every year. We follow lots of diabetes patients and, yeah, so I think then it's just a different job, right? It's a lot of work and it's hundreds of hours. I mean, in some of our programs, you know, we have maybe over a hundred hours a year of time with the team. It's a team of molecular biologists, physician, nutrition experts, yeah, so, and, and there's a lot of strategizing.

• 1:16:48Speaker 01

  I do a pro bono again, but I think, you know, I, I can see that, you know, when I'm in that team with the physicians and we look at each case, so you love the oncologist and the oncologist comes up with the, with the therapy, but then we're like, no, okay, what if we do this and this and this? And then let's, let's see the results and, and then talk again in a couple of months, right? Yeah, so that's what I, you know, everybody should have access to this, but, but, but I mean, people, this is, you know, available to everyone and so please, you know, the, the foundation's called Create Cures and.

• 1:17:26Speaker 01

  Yeah, and so there are programs for everyone, even those that cannot afford it. We're small, so you know, we do what we can. But certainly that that that's part of a lot of patients that come have the discount or free, right? So so based on their income.

• 1:17:42Dr. Darshan Shah?

  Got it. And we'll put a link to the show notes for your foundation so people can find you.

• 1:17:45Speaker 01

  Oh, thank you.

• 1:17:46Dr. Darshan Shah?

  As well, for sure. So the ultimate kind of fasting diet is the water fast. And so a lot of it's a lot of talk right now on social media about water fasting. How does that compare to the fasting mimicking diet?

• 1:17:59Speaker 01

  I mean, we have a country that is seventy five percent overweight and obese. But then we're talking about water fasting and nobody's gonna do it, right? I mean, I've done it once and I, you know, and I've actually visited the Buckingham Clinic. We specialize in water only fasting in Germany.

• 1:18:15Dr. Darshan Shah?

  Germany, right?

• 1:18:15Speaker 01

  And, you know, it was excruciatingly difficult for me. And I'm not saying because I came up with the fasting mimicking diet. Most people don't know, if you look at our papers originally, I mean, my I started working on fasting as a graduate student, starving bacteria with water and or buffer and starving yeast, right? That was my first project, you know, after I left Wolf's Lab in nineteen ninety four. So and then we did all the papers were on water only fasting, right? Until fifteen years ago, all a hundred percent of our papers were just water only fasting. And then our first clinical trial was on water only fasting at USC Norris Cancer Center.

• 1:18:55Speaker 01

  And you know, and we just, we went to the fasting mimicking diet because it was so hard for people to do and the NIH, specifically the NCI, and then the National Institute on Aging, sponsor the development of the Fasting Mimicking Act, right? This comes from the US government and like lots of things, right? In in technology. And so this technology comes from the surprising failure at Norris Cancer Center. Well, we we me and the oncologists were like, nobody wants to do this thing, right? As it possible, you know, they're cancer patient, they're highly motivated. We had all the, in our, in our mind, we had all the reasons why they would all do it and they will do it all the way, but they didn't do it, you know.

• 1:19:37Speaker 01

  So, so it took us forever to finish this small pilot trial. And, uh, yeah, so I think, you know, people are used to eat. And then you have the safety, the salts, right? The hypertension, the hypoglycemia, you know, the ability to control it, the ability to standardize, you know, is a lot of things that, that are in place. The, and one of the many, uh, the, the need to go through a physician. If you're gonna do it, because, you know, the water only, it could make a big difference or it could make a big problem for you, right? But at least with the F M D, you love to go to a physician and the physician may say, please do not do this, right?

• 1:20:20Speaker 01

  And there's a lot of cases where we say anorexic, uh, certain cancers, people with kidney disease, people with liver disease. I mean, we're treating liver disease and kidney, but that doesn't mean that if you have liver or kidney disease, you could just, oh, I'm just gonna do 10 days of water only fasting. It could kill you, right?

• 1:20:36Dr. Darshan Shah?

  Right, absolutely.

• 1:20:37Speaker 01

  So, so it's putting so much strain on, on the liver or the kidney that you could end up dying from, you know, improvising at home. Uh, and, and, and all it sounds scary, but it's exactly what I'm trying to do, right? I'm trying to make it, make sure that people say, don't do this, right? Don't, don't think that you can just improvise this at home. We've seen it with cancer, with lots of people, and it was a disaster, right? And, and I got attacked by a lot of physicians because they were like, what are you doing? You know, you, you, people are cooking it up at home, right? The, the cancer treatment and, uh, uh, so there's no control by physicians, there is no control by the oncologists, there is control by, by any healthcare professional. Yeah, of course, some of them may have benefited, but, but a lot of people probably got hurt by it.

• 1:21:19Dr. Darshan Shah?

  Yeah, no, that's, that's a really good point to make is that this is an intervention, right?

• 1:21:24Speaker 01

  Very powerful intervention.

• 1:21:26Dr. Darshan Shah?

  It's a very powerful intervention. And so it's, it's using food, but it's a powerful combination of food combined with the amount of time you're doing it that can cause some major changes and you have to be very careful with who, who uses it.

• 1:21:38Speaker 01

  Yeah, I mean, if you, again, and we've done this for mice, but if you look at the human body and day five, their fasting mimicking diet, it completely revolutionized.

• 1:21:49Dr. Darshan Shah?

  Right.

• 1:21:50Speaker 01

  The liver, the brain, you know, the brain now you'll have about half of the energy coming from ketone bodies, right? And in the liver, the gene expression will be completely different than for the, that it was in every day during the rest of your life. And your kidney and your lungs and, you know, and your blood and your bone marrow. And so it's just changing everything, right? And, you know, there were three papers in, in Cell a few years ago, they looked at, all of them look at fasting and different immune cell population in different places. And it's really remarkable. And in the same issue of Cell, three papers looking at fasting and the fact that immune system, it's really remarkable, all the changes that, that they were showing.

• 1:22:33Speaker 01

  And I think they were shocked when they, when they look into it to, to find out how much it happens in just a few days of a mouse fasting, you know, so, yeah.

• 1:22:43Dr. Darshan Shah?

  Yeah, that's fantastic. What is, speaking of the topic of longevity, you know, I think we've established the fasting mimicking diet has multiple effects with longevity from glucose regulation down to even at a cellular level, autophagy, et cetera. What about at a mitochondrial level? Do you see effects on fasting at the mitochondrial level?

• 1:23:03Speaker 01

  Yeah, so we, we published that in, in, in mice and of course, you know, you can't, it's hard to look at mitochondria, although, you know, we could, we could do it, we're thinking about some blood cell tests, right? So, so that's a possibility. But, but in mice, clearly, if you look at the fat cells and you look at the mitochondria or the fat cells or the gene expression of fat cells, the mitochondrial genes were much higher and many, so it seemed like the fat cells were, were getting to after the fasting mimicking diet in a high metabolic, high mitochondrial, energy dependent mode and stay there for a long time, right? Even after we.

• 1:23:43Dr. Darshan Shah?

  Even after the fast, huh?

• 1:23:45Speaker 01

  Because you see that, you know, if you look at, we, we use. A high fat diet, a high fat, high calorie diet as a control. And in four days after the fasting making diet, you know, so that the mice that are on the high fat diet, they don't have higher ketone bodies. But the mice that are on the high fat diet and they've just done four days of the fasting making diet. Then we look at four days after returning to the high fat diet and the ketone bodies are still high, right? So it's it's probably keep burning fat even after returning to the to the bad diet, right? So so that that's probably why, and I mean, in this paper, the picture is really worth a dozen words

• 1:24:29Speaker 01

  because you see the control mouse, then you see the high fat, high calorie, high sugar diet mouse is huge. And then you see the same diet for twenty six days a month, plus five days for twenty five, twenty six days a month, plus five days of the fasting making diet. And their mouse is identical to the control mouse.

• 1:24:51Dr. Darshan Shah?

  Incredible.

• 1:24:51Speaker 01

  And the lifespan is statistically not different from the control mouse. Even though for the entire life, we kept these mice on this worst diet that you can imagine. Yeah, so so, yeah, so this tells you that it's a continuous fat burning process. Yeah, and this is why I'm surprised that that everybody is so much focusing on on drugs.

• 1:25:15Dr. Darshan Shah?

  Yeah.

• 1:25:15Speaker 01

  Because drugs, including GLP one agonist, they're really interfering with this beautiful, you know, program that that the body, the human body, or programs that the human body has. And so, and of course, as you interfere, you know, for a couple of days is one thing. When you interfere for years and years and years, I mean, it's hard to imagine how that's not going to lead to problems, right? So then, with the only exception, if you, I think, were working on the master regulator, right? Which are very few, right? So you have to, if you get to the very top and you can say, let's say there was a switch somewhere.

• 1:25:53Dr. Darshan Shah?

  Sure.

• 1:25:54Speaker 01

  And you can switch it on and off and and that's, yeah, so that, let's say that you have,

• 1:25:58Dr. Darshan Shah?

  Interesting, yeah.

• 1:25:59Speaker 01

  Like yeast, for example, I always talk about that. Yeast have three modality lifespan. One, it's, you know, they live about three days. Then you starve them and they live about sixteen, seventeen days. Then you you sporulate him, you know, you make him into a a um an organism, a version of the organism that can live a hundred times longer, right?

• 1:26:20Dr. Darshan Shah?

  Really?

• 1:26:21Speaker 01

  Yeah, so now, based on the these switches and you do it with acidic acid, starvation plus acidic acid. So all of a sudden, the yeast goes into a modality where it goes from three days to three hundred days.

• 1:26:32Dr. Darshan Shah?

  Oh, I see, right.

• 1:26:33Speaker 01

  And so, yeah, so I think that those are the only uh exceptions, but other than that, I think the drugs, within most of the times, are interfering, you know, interfering with cholesterol synthesis and and lots of other things. Yeah, so you you're trying to make a lot of cholesterol and you block it. Well, you know, cholesterol is involved in hormone synthesis, is involved in in lots of cellular functions. And so what's the consequence of that after thirty years, right? So uh yeah, so uh there there are consequences to to drugs and and um and uh yeah, I think, you know, so let's say for immunotherapy, you could say, well, there are consequences to immunotherapy. Okay, but you have advanced stage cancer.

• 1:27:15Dr. Darshan Shah?

  Sure.

• 1:27:15Speaker 01

  Okay, so that that that's a reasonable moment where you wanna say, I have to take, I have to use something that normally I would never imagine. But if you have overweight, obesity, diabetes, prediabetes, metabolic syndrome, I mean, this is just not the way to do it, yeah.

• 1:27:32Dr. Darshan Shah?

  Right, right. Yeah, I see what you're saying. I mean, look, humans have evolved for millennia, uh having times of starvation where they had to fast. It was just you in the environment, right, or no food available. And so our biology is uniquely suited to create adaptations to this type of activity, right?

• 1:27:50Speaker 01

  Yeah, yeah, but people shouldn't confuse it with, because a lot, that's a great statement, but a lot of people take that statement to say, well, see, this is something what we've always done. And people maybe were starving for three weeks, someone's just gonna start for three weeks.

• 1:28:04Dr. Darshan Shah?

  Different, right.

• 1:28:05Speaker 01

  You know, people ten thousand years ago were living, if they were lucky, to, you know, forty five years of age, right? And average less, but I say, you know, once you make it past ten, you probably make it to forty five on average. So they were not trying to make it to. Hundred and ten.

• 1:28:21Dr. Darshan Shah?

  No.

• 1:28:21Speaker 01

  They're making it forty. So, so the, the, the, be careful, I mean, not you, but, but the, the people listening, thinking because it was like that, whether it's a paleo diet or it's fasting for three weeks, that all of a sudden it's good for us. No, I mean, we have a different mission is, which is maybe going against evolutionary pressure, meaning we wanna live too long. Right. Yeah. So if you wanna live too long and not get out of the way and make sure that everybody else is an opportunity. Yeah, you, you have to do more than just learn from the past. You have to, you know, learn from lots of science and be careful because, for example, three weeks of fasting might get you into a thrifty, hypometabolic mode.

• 1:29:02Speaker 01

  And now you switch to a, a energy expenditure, eh, saving mode, right? So you wanna save energy because the system is, is detecting an environment, there is no food for three weeks. We're gonna die, right? We're gonna die very soon. So then it switches you, but now the switch may very well be epigenetic in nature. So now you're gonna be stuck there for one, two, three years, right? So the big why, because the, the system is saying, okay, we got close to death. So let's make sure that we don't get back there. So from now on, everything that comes in, I'm trying to try to store it, right?

• 1:29:38Dr. Darshan Shah?

  Right, right.

• 1:29:39Speaker 01

  Yeah, so.

• 1:29:40Dr. Darshan Shah?

  That's such a good point.

• 1:29:41Speaker 01

  And you think about the, eh, evolutionary pressure.

• 1:29:43Dr. Darshan Shah?

  Right.

• 1:29:44Speaker 01

  To do that, to execute that, whether you like it or not, think, okay, I'm gonna protect you. I'm gonna put the food away, make you a little bit slower, you know, a little bit less active or whatever, but I'm gonna put the food away because I've already seen a big problem, you know, a year ago. And I don't want you to get back there.

• 1:30:04Dr. Darshan Shah?

  Right.

• 1:30:04Speaker 01

  Because, you know, in the old days, three weeks without food probably meant that you are close to.

• 1:30:11Dr. Darshan Shah?

  Long-term problem, yeah.

• 1:30:11Speaker 01

  You're close to a, a, a, you know, a final problem.

• 1:30:14Dr. Darshan Shah?

  Right, right. That's such a good point. So, speaking on longevity, um, we've talked about fasting, we've talked about the longevity diet. I know your goal is a hundred and ten healthy years, right, for you personally?

• 1:30:26Speaker 01

  Well, no, I mean, for me, like, one twenty, right?

• 1:30:28Dr. Darshan Shah?

  Oh, okay.

• 1:30:29Speaker 01

  Yeah, yeah, yeah. I probably. Dead tomorrow. But, uh, but, you know, so I, I'm always very scared, you know, of everything because now I said a hundred and twenty, I gotta make it there. But, uh, yeah, so, I mean, it doesn't mean that, that I'm gonna make it there, but, but certainly, you know, I like that goal, right? I like that goal and, um, and I like that goal because it's so unlikely that I get there. And only one person has ever made it in the history of human being, you know? And I followed the number three person for many years, Emma Morano, she got to a hundred and seventeen. She was the oldest person in the world and, and so, um, you know, I've seen a hundred and twenty, I've seen a hundred and ten in men and, and, and close to a hundred and twenty in women. And so I think, you know, hey, it's, let's give it a shot, right?

• 1:31:15Speaker 01

  Let's give it a shot.

• 1:31:15Dr. Darshan Shah?

  Right.

• 1:31:16Speaker 01

  You know, and if I die tomorrow, that's okay.

• 1:31:20Dr. Darshan Shah?

  Well, you're definitely helping all of us potentially live a longer, healthier life. I'm wondering, what other interventions are you doing besides the fasting mimicking diet? Besides the just overall dietary pattern that you recommend? Are there any other interventions that you're looking at?

• 1:31:34Speaker 01

  Yeah, so we, we do, uh, twelve, we have a sort of a moderate version of the time we sit eating, right? So twelve hours, uh, so twelve hours of fasting, twelve hours of, of eating. For cancer patient, even when they go into remission, we, we make it, you know, um, fourteen hours. Uh, because, you know, they just, they have or they've had a big problem, right? And recently, yeah, so that and then I personally, uh, and I recommend, although we have very little data, I skip lunch Monday to Friday. And that's the only way that I've been able to keep exactly the weight that I want for many, many years. And, and, and so, you know, uh, that's my technique.

• 1:32:15Speaker 01

  And, and I don't wanna, I have a, I have regular meals on the weekend because I wanna make sure I don't become malnourished. And, and, and, and so I think I, I found that balance in, and, and I think, you know, I've seen so many people struggle with the weight, uh, because they don't use techniques like the fasting mimicking diet or the time we sit eating or the lunch skipping. And, uh, but I also see people going to the extreme and then they get to the opposite trouble, right? Uh, which is what we discussed earlier. Now, maybe your energy expenditure slows, your hunger increases and, and lots of other problems. But yes, so, so you have to. There is probably a reason why we eat three times a day, right?

• 1:33:00Speaker 01

  Plus a snack, because it makes us happy. But also, you know, there may have been an historical reason that people that did that tend to do better than everybody else. But then with modern conditions, that three plus one becomes almost like in the United States, a guarantee for being overweight. And so that's where you have to go and say, what was the minimum intervention that I could do, say 12 hours? Come on, we cannot do 12 hours, right? And people are like, is this even fasting? They call it whatever you want, you know, 8 a.m., 8 p.m., 9 a.m., 9 p.m., right? So stick to it. I do it and, you know, very rigorously. I mean, sometimes I violate, it's okay. And then, you know, Monday through Friday, the lunch, you know, somebody invites me to lunch, it's okay, I have lunch, no problem.

• 1:33:43Speaker 01

  But, but I think that, and the importance of that, and if I don't, we don't do it, hopefully somebody does it, but is that after, it took me two months, I forget when I started, maybe 20 years ago, it took me two months of hell, right? To get to the point where I was not hungry anymore and lunch, right? So right now, you know, it's lunchtime, I don't care, you know? It's like makes zero difference to me whether I have lunch or not. Now, if you take breakfast from me, or you take dinners from me, or even the snack that I have at 5 p.m., I go crazy, right? But lunch is completely neutral to it. So, very important, right? Because, you know, and this is again, the clinics and the, and guiding people, because

• 1:34:26Speaker 01

  if you ask somebody to do that, and you don't tell them, look, it's gonna go away in a couple of months, right? You gotta stick with it, and then they're gonna fail, right? But if they have the nutritionist and they have the physician and say, don't worry about it, you know, and, and this is why so many people skip breakfast, by the way, right? Because at some point, become effortless. They don't care, you know, there's like, I never had breakfast, you know, it sound like if you give me breakfast, maybe you make me, make it worse for me, right? And that's, but the breakfast seems to be the wrong meal to skip, right? And the dinner is probably the best meal to skip. But, you know, most people are socially, are not gonna skip meal, they are also

• 1:35:07Speaker 01

  You know, for lunch, you're at work. It's a lot easier for a lot of people to say, okay, I don't have to eat lunch. It is like me, right? I'm at USC most of the days I'm at work, so I just have coffee for lunch.

• 1:35:20Dr. Darshan Shah?

  Yeah.

• 1:35:20Speaker 01

  With no, with with little sugar and that's it. Yeah. So so those are the things and the main things and. And then, of course, hundred and fifty to three hundred minutes of exercise per week. And one thing I tell people, I think it's important, like it was for me and a lot of people that we advise, have the, you know, the bicycle at home.

• 1:35:43Dr. Darshan Shah?

  Right, right.

• 1:35:43Speaker 01

  Yeah, have one of those home bicycles that have a high resistance so that you're like paddling up uphill. And why is that? Well, because I think that people, as it was for me, you'll always say, oh, you know, I, yeah, I was supposed to go running this morning, but I got a meeting, you know, and there's always an excuse, right? And so now I I notice when I clone this, this, the bikes that I keep at home in in Genova, Milan and Los Angeles, the three places where I live.

• 1:36:13Dr. Darshan Shah?

  Yeah.

• 1:36:13Speaker 01

  And I have no excuse, right? So every other day, it's one hour of this. And I don't, it doesn't matter what happens, right? I have to do it. If I have a meeting at eight A M., I start at seven, right? Or I do the meeting while I'm cycling. And yeah, so I I think that's very important to have, you know, ways, it's inexpensive with a hundred dollars, you can get a used.

• 1:36:35Dr. Darshan Shah?

  Right.

• 1:36:36Speaker 01

  You can get used one of these bicycles, just to make sure that it's a little hard to paddle. Because otherwise, if if it's just a, then it it's pointless. And then one hour a day of of walking, right? So I I really make it a point every day. Like I go across USC campus and then in my area I walk. And nobody walks, of course, right? In Los Angeles, there was a song about that. But but yeah, the simple things, but you gotta do them, you know?

• 1:37:03Dr. Darshan Shah?

  Yeah. Are there any supplementations that you take or?

• 1:37:06Speaker 01

  Yeah, I think multivitamin and omega threes. I take every other day. I alternate between those. Yes, so those are the only ones I take. You know, and I think the. A lot of people that are deficient for a lot of things, you know, like vitamin D and B. Yeah, so I think there is a lot of opportunities out there for supplementation, but it's got to be done in a careful way. And in a, in a, in a way that it makes sense to, uh, to prevent that. If you take one pillar, like the mouse studies, right? It's really hard to make a mouse live longer with any supplement, right? But I think there is a lot of deficiency, they could make the mouse live shorter.

• 1:37:46Dr. Darshan Shah?

  Sure.

• 1:37:46Speaker 01

  So if you have one of those and you supplement, uh, yeah, now you, you save yourself from maybe a disease, maybe, uh,

• 1:37:53Dr. Darshan Shah?

  Makes sense.

• 1:37:54Speaker 01

  Worse, right? So, so in this sense, I think it's very clear that you need some, some supplementation of things that you're missing for whatever reason.

• 1:38:02Dr. Darshan Shah?

  Yeah, no, that's a good way to put it. The supplements probably on the longevity front, there's less effect than actually treating a deficiency, like a vitamin D deficiency.

• 1:38:12Speaker 01

  Which most people have, right? I think Bruce Haines had published on that and the great majority of people had one or more deficiencies.

• 1:38:18Dr. Darshan Shah?

  Right, absolutely, absolutely. And then, you know, you're at the pinnacle of longevity science, Dr. Longo. What are you the most excited about coming up? Either personally in your lab or you've seen doing, uh, research going on elsewhere?

• 1:38:32Speaker 01

  Yeah, obviously, number one is the fasting making diet, making it to all these disease treatment. We're gonna see big disease coming out of big universities and very successful trials in the next 12 months. So this is great.

• 1:38:47Dr. Darshan Shah?

  So exciting.

• 1:38:47Speaker 01

  It's been like fantastic. And then, you know, that I think is gonna motivate, I hope hundreds of hospitals saying, hey, we wanna do whatever it is that they wanna do, so come to us, we'll help you. The, the diet is usually given free of cost to the hospitals and the universities, unless they have a grant and then they just pay for the, the cost of making the diet. But that's it, right? So, so it's very straightforward, it comes like with lots of help and, and so, yeah, so we're really excited about that. And then, of course, I'm very excited about Belmont's, um, reprogramming work in, you know, Alto's lab and, and, uh, you know, and I recently presented with, with him at, at a meeting in San Diego.

• 1:39:31Speaker 01

  And I think, you know, he, he's doing the right job of saying, this is not easy, right? To, to, to, to do multi-systemic reprogramming with Yamanaka factors. And I mean, this is basically turning on this. Genes that the FMD turns on, by the way, but turning on all four in a forceful way or three out of four in a forceful way and just pushing the organs to reset and become embryonic like, right? So, you know, I think Belmonte, I mean, David Sinclair has been a lot bolder and, and you know, the potential in Belmonte has been more, what I suspect, which is like, it's

• 1:40:12Speaker 01

  very difficult, you know, I always, and I think I did it in a meeting where, where you were also present recently. And I said, you know, in my lab at UCLA, I remember, you know, in the nineties, somebody, not me, but somebody came up with a, the gene that causes Lou Gehrig's disease. KLS, right? And, and so it was nineteen ninety-five or something like that. And we thought, this is incredible. In a couple of years, we're gonna cure Lou Gehrig's disease. That was nineteen ninety-five. This is two thousand twenty-five, and we're still not even close to helping people with Lou Gehrig's disease, right? So I think that if you look at that compared to embryonic reprogramming in multiple systems

• 1:40:54Speaker 01

  and making a, a, a mouse truly younger, I mean, yeah, it could happen by lots of, lots of luck, right? Or, or it's gonna take a long, long time, but that's extremely exciting. And so now we're trying to say, how can we combine forces? I, I was talking to one of his former postdocs and we're, this morning, and we're like, how can we combine forces to, you know, have our knowledge of, you know, programs that are guided by evolution with the technology? Is there a way to, you know, cooperate to make this Yes. wishful thinking a lot more realistic, you know, and guiding this reprogramming of multi-systemic reprogramming? So, yeah, we were just at the beginning of that and we're, we're applying for grants in that domain. So we're very excited about.

• 1:41:40Speaker 01

  Uh, you know, making a, let's say, a, a three-year-old mouse, two years, two years old, right? And that would be already like an amazing achievement, yeah.

• 1:41:49Dr. Darshan Shah?

  Sure, sure. It's incredible. I mean, if you think about the time that we're living in, where, you know, Yamanaka factors, for listeners who don't know what those are, those are four factors that if you put them into any cell, you can actually reprogram them back to a pluripotential stem cell that can make any type of tissue. Just having that knowledge at this moment in time is just mind-blowing. So it's an exciting time to live in. But I do agree, you have to be a little bit measured with how complicated and difficult it is to control this biological activity, because humans are complex. And so I think we need to be a little bit measured about how we talk about these type of therapies coming into our current existence.

• 1:42:32Dr. Darshan Shah?

  But you never know, like, we're surprised every day with what science can deliver to us.

• 1:42:37Speaker 01

  It could be that you hit a switch and it was all like, but this is why we're going back to what we do, right? We're basically saying, you're gonna have to come our way.

• 1:42:47Dr. Darshan Shah?

  Yeah.

• 1:42:47Speaker 01

  To, you know, because that switch, if it exists, if it's an evolved switch, then yeah, it could work, because like I was saying about the kidney, right? We damage the kidney, then we do the fasting mimicking diet. And it goes from this mess to, you know, back to its

• 1:43:01Dr. Darshan Shah?

  Right.

• 1:43:02Speaker 01

  beautiful organized organization of multiple cellular types, all functional, right? So, so yeah, so that switch is gonna have to be turning on something that always existed, right? For that purpose. And it's hard to imagine how something existed to make a mouse, a three-year-old mouse, two-year-old. But, but yeah, it could be that, that we, we get surprised and, and we'll see. But we, we, we'll keep on trying. I'm sure Belmont and Sinclair and, and lots of us are, are, are gonna do more and more work in that division and we'll see what happens.

• 1:43:40Dr. Darshan Shah?

  It's incredible time to live in. Well, Dr. Longo, thank you so much for joining me today. This was a fantastic conversation. I will definitely be providing links to everyone to experience a fasting mimicking diet by getting Prolon. And then also, how can people find you and more about the work you're doing?

• 1:43:57Speaker 01

  Yep. Thank you. Thank you for having me. Great, great discussion.

• 1:44:00Dr. Darshan Shah?

  Yeah. How can people find you?

• 1:44:02Speaker 01

  People can find me, who can follow me in Creative Cures website, but also Professor Walter Longo on Instagram.

• 1:44:12Dr. Darshan Shah?

  Okay, great.

• 1:44:12Speaker 01

  And then, you know, the book, of course. Yeah, so the Creative Cures is the clinic here in Los Angeles. And Professor Walter Longo is probably, and Facebook also, I think it's also Professor Walter Longo.

• 1:44:26Dr. Darshan Shah?

  And your book is fantastic on Amazon as well.

• 1:44:28Speaker 01

  Oh, thank you.

• 1:44:29Dr. Darshan Shah?

  And I'm looking forward to having you back next year because there's a lot more research that's going to be published over the next 12 months. And I'd love to do a deeper dive into some of these disease states and how the fasting mimicking diet has affected those.

• 1:44:42Speaker 01

  Yep, sure.

• 1:44:43Dr. Darshan Shah?

  Great. Thank you very much, sir.

• 1:44:44Speaker 01

  Thank you.

• 1:44:52Dr. Darshan Shah?

  That was a fantastic episode with Dr. Longo. He is a true pioneer in this field. He's writing another book about fasting and cancer. And we'll have him back on to talk about those topics because I believe that's also really important. But here are my top 10 takeaways from this particular episode. So number one, not everyone should be skipping breakfast. Intermittent fasting advocates often talk about skipping breakfast as their main meal that they skip. However, research has shown that skipping breakfast might, for some, lead to hormone changes, increased amount of stress hormone release, cortisol, and also protein deficiencies in some. So some studies even suggest that eating earlier in the day can lead to better energy

• 1:45:35Dr. Darshan Shah?

  expenditure throughout the day and metabolic function and glucose control. So I think that skipping breakfast is very controversial and it just really needs to be individualized from person to person. The rule of thumb that I use is if you feel great when you skip breakfast, keep doing it. And you can do further testing with a continuous glucose monitor and just monitor your protein intake. Make sure you're getting enough protein the rest of the day. Number two, fasting is one of the most powerful triggers for gene expression. Dr. Longo challenges anyone to name any intervention that causes more gene expression changes than fasting. So far, no one has found an answer. Fasting fundamentally reprograms your biology at the DNA and methylation level.

• 1:46:18Dr. Darshan Shah?

  Number three, some studies suggest that high protein diets may increase your risk of diabetes. A Harvard study showed that a high protein intake, especially from animal sources, can increase the risk of diabetes. The impact is so strong that upcoming research may soon explain why. Number four, the longevity diet by Dr. Walter Longo can make you biologically younger. There's a very precise diet developed by Dr. Walter Longo called the fasting mimicking diet, or FMD. After three cycles of this diet, participants shaved 2.5 years off their biological age and their biomarkers of aging. This isn't just about the weight loss with this diet. Fasting actually does activate some real rejuvenation mechanisms at a cellular level.

• 1:47:04Dr. Darshan Shah?

  Number five, white rice can spike your blood sugar, just like table sugar can. So, a lot of people believe that rice can be a healthier carb, but metabolically speaking, as far as blood sugar spikes go, for many people, a bowl of rice, whether it be white or brown, can elevate bloodstream blood sugar. So, once again, a continuous glucose monitor can help you personalize and individualize your choices to rice and other carbohydrates that you might think are healthy. Number six, fasting can trigger organ repair and regeneration. So, there are some clinical trials that show that fasting can help regenerate kidney cells and improve biomarkers of kidney function, such as proteinuria and glomerular filtration rate.

• 1:47:46Dr. Darshan Shah?

  This is a real powerful intervention, because there aren't many drugs out there that can do the same thing. Number seven, the body can rebuild itself after fasting, but only if you're refeeding correctly. The magic of fasting isn't just in depriving your body of calories. It's actually also tied to how you re-feed, or when you start eating again. Studies show that fasting can trigger repair mechanisms, but the regrowth phase, the rebuilding phase, has much more to do with how you're refeeding. Number eight, GLP-1 weight loss drugs like Ozempic and Terzepatide can be disrupting longevity power. So Dr. Valto Longo believes that GLP-1s can cause muscle loss, bone density loss, and metabolic adaptations that might work against long-term health.

• 1:48:31Dr. Darshan Shah?

  Dr. Longo warns that even if the side effects are minimized, skipping the hard work of behavioral change could have downsides. So this is something I talk about all the time. And of course, more research needs to be done. In our practice, we are able to have people on GLP-1s and not lose muscle mass. And that's because we focus on behavior change, increasing protein intake, and strength training while people are on GLP-1s. Number nine, ultra-processed food isn't the only problem. There are healthy foods that can be overeaten as well. So the biggest issue in childhood obesity in Italy, where Dr. Longo is from, is overconsumption of pasta, bread, and potatoes. These are not processed. These are actually very healthily made. This

• 1:49:12Dr. Darshan Shah?

  shows that portion control, not just food quality, plays a major role in health. And number 10, fasting can actually speed up recovery after you have a heart attack. Animal studies show that myosite fasts recover from cardiac damage from a heart attack much faster than those who don't. This suggests that fasting has a role in post myocardial infarction rehab in humans as well.

• 1:49:37Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you like this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best, and it's always important to seek their guidance.