 even five days a month are sufficient. And this included insulin resistance, included longevity, included cardiac function in the mice. Dr. Longo, Walter, good to see you again. Welcome to the podcast. Thanks. Thanks. Good to see you. So tell us a little bit about your background for those people who don't know, and I don't know who that would be, but and what led you to, you know, studying longevity and how fasting correlates with with it. Yes. So I started actually working an agent in college in my second year in college. I always, that's all I've ever done. And, and then I was lucky enough to work with Roy Walford, the UCLA and Roy was one of the gurus of nutrition and longevity back in the early 90s. So it was 30 years ago. I started working in Roy's lab. And, you know, after that, I moved to biochemistry from the pathology department, but I started studying starvation. So Roy was famous for calorie restriction, what happens to humans and mice when they're eating less. And but I ended up switching to starvation in bacteria, then in simple organism, and then noticing that no matter what we start, they will live longer, they become stronger. And so from this observation in bacteria and yeast, baker yeast, then I became a big fan of fasting at a time when everybody was not very impressed by aging research and even less impressed by starvation research. Both of them were considered to be just silly topics, you know, at least back then. So tell me, I know you and I have talked before. I've had the pleasure of having you on the podcast before. I know actually it's been about a year now that the study came out in nature aging, which I think really catapulted the whole idea of fasting or time-restricted feeding. Can you tell me about this study and what was the most exciting discovery that came out of your work with Dr. Masson? I think that with Mark, it's been mainly about collaborating in trying to find out, you know, what kind of fasting fast, I always say fasting is a word, doesn't really mean anything. It's like eating. So should you eat? Well, of course, what you eat, how much you eat, and when you eat matters, right? So same for fasting. And so with Mark, I think it was very important that the sort of collaboration for many years to starting to define what are the things that seem to really work? What are the things that are safe that have been demonstrated to be safe for a long time? And so how can we extract from all these ideas something that is likely to make you live longer and healthier or much healthier? And so I think that from that discussion, a few things emerge. And one of them is certainly the 12 hours of fasting and 12 hours of feeding. And the other one, I think at least in my case, is the fasting-mimicking diet done maybe three times a year. Yeah. So for those folks who don't know about the fasting-mimicking diet, and I've actually given you tribute in all my books about the fasting-mimicking diet, can you tell us what that means? What it entails? I think for about 100 years that the aging field has known that some type of color restriction can be very good for you. But it was very clear from the work of Walford and also the working monkeys that it's also very bad for you. And so from back in those days, 30 years ago, I started thinking it's got to be a way to get all the good and none or very little of the bad. And so, and thanks to the work that we were doing in Simple Organism, I thought, is it possible that maybe we starve a system temporarily for three, four, five days, and then we go back to a normal diet for months? And could it be that that effect last month? And so initially it was done with water-only fasting. And then as we started doing, now it's almost 15 years ago, clinical trials and cancer patients at USC, we realized that this was not going to go anywhere. Water-only fasting was not going to go anywhere. I think it took us 10 years to finish a small study on water-only fasting and chemotherapy treatment. And so from there, the National Cancer Institute and the National Institute on Aging Sponsored Research on Fasting Mimicking Diets. So we approached them and said, we think we can develop FMDs that are as good as water-only fasting in causing these fasting responses. And so, yeah, we were funded by the government and eventually we came up with the first demonstration in mice and then now demonstrated with many clinical trials beginning with normal people, but then cancer patients out to immunities, Alzheimer, diabetes, and hypertension, etc., etc. Now I think there's about 30 clinical studies that are either being finished or currently running on the FMDs. So let's back up for a second. You mentioned, of course, that fasting has some good things about it. And what are the good things that you're trying to achieve with fasting, number one? And number two, how do you eat and not be fasting? I guess is the second question that everybody says, well, wait a minute. If you're eating, that can't be fasting, but you're saying it's a fasting mimicking diet. So what are the good things about fasting? Yeah. So the clinical trials are now consistently suggesting, number one, probably this reset, and the reset seems to be affecting almost everything. So when you look at the mice, we actually show, we demonstrate regeneration. So the organs shrink during the fasting mimicking diet, and then the stem cells are turned on. And then when the mouse refeeds, we see many different organs beginning to have the stem cells generate new stem cells and generate new cells. And so basically regenerating the organ, or at least part of the system or organ. And so that's probably at the center of a lot of these resets. And one of them seems to be insulin resistance, right? So probably now we come from a history of eating lots of the times and fasting lots of the times. And now we eat all the time. And so the system probably goes into insulin resistance for a good reason to store fat. But at some point, you want to use the fat. So it looks like the fasting and the fasting mimicking diet switch the system back into fat utilization mode. Now, if you go too far, this can change, right? Then you might enter a thrifty mode, where now the metabolism slows down. So our job was to get it right, just to the point where the ketogenesis begins, the breakdown begins. It is feasible for the patient, but the thrifty mode is metabolic slowdown does not begin, right? Yeah, so that's the idea. And of course, there could be lots of other things that are involved in addition to the stem cells, autophagy is certainly a name thrown out there a lot. But it's not clear how much of it happens, when it happens, you know, how long you need in the various cells to actually get a lot of autophagy done. It doesn't seem to happen a lot in the first two or three days. It probably is happening starting day four or five of the fasting mimicking diet. And then, you know, what is the fasting mimicking diet? It's a low calorie, low protein, low sugar, high fat vegan diet, right? So my idea was to, well, we knew what each ingredient was doing to each factor. For example, IGF-1, IGF-PP-1, ketone bodies and glucose. So a lot of people did just names, but let's say that these are markers that we know to be very important for the starvation response. So first, we wanted to get the levels of the macronutrients or the proteins, et cetera, to make sure that all those move in the right direction. And then we wanted to do it in a way consistent with the longevity zones of the world, right? So I figured you were a Loma Linda, so you were aware of the type of diet that these zones consume. And so I thought it was a good idea to not just pick ingredients that could get these changes, but pick ingredients that were also very healthy. So should somebody do this a lot of times, it would help in other ways. And I think it was a good idea. And we have some evidence, for example, from microbiota changes that seem to be caused by the content of the diet and not just the fasting component. Yeah. Now, you and I have come under, maybe I'll use the word attack that protein restriction is part of a fasting mimicking diet. But animal protein seems to be much more mischievous than plant-based protein in terms of its amino acid content and activating mTOR signaling. Can you take us through your reasoning, why a vegan diet, why not just have animal protein and cut the calories? Yeah. So I'm not a fan of the vegan diet, first of all. So I'm a fan of what I call the longevity diet on which my book is based. And it's a pescetarian, essentially a pescetarian diet. But I think we need to move away from names and get into, and I think you agree with that, into age-specific, sex-specific, person-specific, et cetera, et cetera. But I say in general, fish plus vegan seems to be very good. And then up to 65. And then after 65, it seems that more of a variety of foods helps the elderly keep up. So it seems that the 80-year-old doesn't do very well with a vegan or even a pescetarian diet unless there is a lot of animal proteins or enough animal protein. So we published on this in 2014. And what we published based on the United States population studied by in the enhanced database, it was very clear that if you restrict the population, the US population, that protein restriction, fairly severe protein restriction, they were doing very well. But that was only true up to 65 years of age. When we look at the 70, 80, 90-year-olds that reported having a very low protein diet, they did very poorly. So this is why we can start coming up with this idea of age-specific, age-range specific nutrition. And so why is that? Well, there's amino acids that are very low in the legumes, particularly the legumes. And lots of people that have vegan diets may get a lot of their proteins from the legumes. And also, I think even if you get it from the legumes, which are very low in certain essential amino acids, it's very difficult to get, let's say you're somebody weighing 70 kilograms, or let's say somebody weighing 120 pounds, is very difficult to get the 50 grams of proteins that you would need from just eating the legumes. And even if you do get it, they're going to be very low in certain amino acids. So that seems to be actually very beneficial up to age 65 or 70. And then it appears to become very detrimental. So I agree with you. I call my diet a veg-aquarian diet, which I guess is a pescetarian diet. I concentrate on eating greens. And then we tend to supplement with wild shellfish, mollusks, clams, and oysters, and mussels. But that's another subject. So, but you specifically, and we'll get into this, you have a diet package that's called pro-long, love the name, that is a five-day vegan fast. And so during that time, you definitely see, at least for a limited time, a benefit of just strictly avoiding animal protein. Yeah. So when you're talking about the periodic fasting-mimicking diet, yeah, then we go 100% vegan. And I think it's very, very important to get the, so because we already have very low protein, but I think by being vegan, we get certain amino acids to be even lower, which is exactly what we want. So we want to have a fasting response when you're not fasting. So we have to use lots of tricks. That's one of them. But in the FMD that we test clinically, we have lots of tricks, each trying to achieve something, something different. And including making you less hungry, including having reserves for people who's gluconeogenic reserves so that the liver can make new glucose. And we have tricks in there also to make sure that there are reserves in case you need more glucose so that you don't pass out. So yeah, so there's a lot of technology actually in those five days, but we try to make it so that for people it's just five days of vegan food. So in your book, you talk about the five pillars of longevity. How did you come to narrow those pillars down to five concepts? So I had spent 30 years doing this with lots of the world experts on nutrition and longevity. And I just thought about what would be important for me when I'm designing a clinical trial when I'm designing an epidemiological trial. So and when I'm trying to come up with with something that I feel is not going to be disputed or found to be wrong in five years. So how do I come up with that? And I just thought I was very surprised that most of the data out there comes from epidemiological studies, and as I was doing my own epidemiological studies, I think I learned that wait a minute, depending on what group you select, you can get the opposite results. So I thought epidemiology is an incredible pillar, but you cannot be alone. It has to match, so how do you make a mouse or a rat or a monkey live longer? It has to match that and it has to match what about the clinical trials? What if I randomize two groups, 100, 100, and I give them low protein, high protein, what happens to them? How long does it last? And then I also thought one of the most important pillars was the centenarians. If I go around the world and I do this all the time and I speak to the centenarians, do they do what I, what these are three pillars allow me to come up with? Or do they do something completely different, right? And then finally, I just thought from physics and reductionism, what about a car or a plane? How do they age? What are the problems that accumulate? So if you take a car, for example, one of these big dilemmas is should you run a lot or not? And the data is not that easy to understand. It's good to run 100 miles a week. And some people say yes, but then I go to pillar number five and say, well, is it good to drive a car for 300 miles a day? Most people say probably not. So in the long run, I don't think it's going to be such a good idea. So yes, I think that pillar number five, complicated systems allows to look at a plane. So for a plane, it's good to fly a plane around 10 times a day for 50 years and never change its parts. So probably not. So yeah, together we look for the common denominator. And I feel and I think I got I got absolutely right, you know, yesterday, plus medicine published a study from an Norwegian group showing meta analysis or meta analysis on food. And sure enough, you know, what came out of it was a pretty much the longevity diet. So fish, and then lots of vegetables in the talk about low protein, but certainly it would be hard to have high protein diet eating like that. And the fruit was there, but it was not it was neutral. It looked like about like a neutral effect. So probably good and bad, right? As you also pointed out in your book. Yeah. So which of the if you're going to choose one of those five pillars, what do you think has the most impact? Or are they really all equal? I think that I mean, maybe the complicated system would be not necessary per se. I mean, I it's not easy to make the scientific case that that's gonna gonna be essential. But yeah, I would say the other and the centenarians you could argue it's it's just observation. But I think they're all equal. Yeah, because in the end, if you don't actually see something being practiced by a lot of people for 100 years, you do you are introducing no matter what the numbers say, you are introducing a certain level of risk. Right. So for example, as we're starting to think about rapamycin and drugs that treat aging. So a lot of people are getting excited about potential drugs that you treat aging. But but then you have to say, well, will it be okay? Eventually, if I make everybody lives 8% longer, and I make 10% of the people live 20% shorter, right? I don't think it's okay, right? And I would rather say, you know, everybody should live normal. And I'm not I'm not advertising this type of diet, right? So yeah, so I think that, you know, let's say rapamycin, if we had, you know, thousands of people that made it 100, and almost nobody that that we heard from saying, I think I died a lot earlier because it's rapamycin. So that would be good to have before making the recommendation to healthy people right now, not necessarily to somebody who's got a disease, but to healthy people. Well, let's go out on a limb. Do you think we should have a low dose rapamycin trial or an intermittent rap, rapamycin trial? Yeah, I think that they're going to do it, right? Metformin is going to be tested, then rapamycin is some form of taurine inhibitor is going to be tested, and that's good, you know, I mean, we're the one that discovered that that role of that pathway in aging back in 2001, in yeast. So I'll be very happy if somebody and metformin is interfering with the same pathways. But metformin seems to be affecting both of the what we described as the sugar pathway, and the protein pathway, aging pathway. So yeah, I would love to see it, but I think it's a, it's a long to come up with a conclusion that I give this to somebody and they're, everybody's going to benefit and almost nobody is going to be negatively affected, it's going to be very hard. So this is why I really like the nutrition. For the next 20 years, I see the nutrition dominating. And then eventually, yes, we may have enough data 20, 30 years from now to say, okay, we get this pill, look, you know, people, we've been studying this for 30 years, nobody got hurt by this, we have epidemiology on it. And, and everybody's living 12% longer. Yeah, so I think at that, at that point, it might be much more convincing to go with the drugs. I want to, that brings up a really good point that I talk a lot about, including in my new book, Unlocking the Keto Code, metabolic health or what I call metabolic flexibility. And I think you and I both agree that one of the things that's killing all of us, particularly in America, is that, that most people actually have no metabolic flexibility, they're not able to shift in their mitochondria from burning glucose as a fuel to burning free fatty acids or ketones. Tell me about the effect of fasting and the fasting mimicking diet on metabolic health or maybe give me your thoughts on our poor metabolic health in the United States. Yeah, so I think it connects to what we were discussing earlier, right? So that eventually organs, particularly, I think there is a dual process, regulated by the same foods, probably mostly by proteins and sugars, right? And, and one of them is fat accumulation. And which goes along with insulin resistance. And the other one is actually aging, right? So I think you have a parallel effect on obesity, overweight, accumulation of fat, establishment of insulin resistance. And on the other side, you're pushing the growth factor, growth hormone, IGF one, and also insulin, you're pushing those to, to be accelerating something that cannot should not be accelerated. Nothing's growing. Nothing is reproducing. So essentially, we are in a reproduction mode all the time, but nobody's reproducing. Yeah, so, so I think that that, first of all, the fasting mimicking diet is going after what's going after all of it, right? Because I think it was there for that purpose, not the fasting, my fasting was there for that purpose. I think fasting was there for the purpose of resetting the system periodically, right? And so since everybody starved once in a while, there was no need to, to impose it. It was, it was like normal. Yeah, normal and unavoidable. So, so, you know, I don't, I don't need you to, to make you tired biologically, because you're gonna sleep anyway. So in this case, I don't need you impose biologically fasting, because you're gonna fast. But, but, but then it was probably a, as I mentioned earlier, resetting this catabolic mode, fat burning mode, and then telling the cells of the, of the fat and muscle, etc. Okay, now it's not time to be resistant anymore. Now let's embrace insulin and let's bring in the, bringing the sugar. We don't need to have in lots of insulin, you know, accumulating fat anymore, because we're using it. So yeah, so on one side, that's a process. And then on the other side, I think that as we see now with many clinical trials, you have long term effects on leptin, long term effect on IGF one. So you do the fasting making diet, but the effect on IGF one goes on for months. So we looked at three months after the end of the diet, and it was still there. So, so yeah, so long lasting effects that are, I think representing a anti inflammatory, anti ageing modality, it doesn't last forever after, you know, after a while, I think it's starting. So even already at three months post, we see about 40% of the effects disappearing, right? So suggesting that by six months, you're getting back to where you started, right? I mean, provided that you go back to a terrible diet. So in fact, a couple months ago, we publish, you know, what happens to mice, if we give them a terrible high sugar, you know, bad, lots of fat, lots of sugar, lots of calorie diet, and the mice become huge. And then, but we do it together with five days amount of the FMD, and we pretty much reverse all the, all the bad effects of this, you know, high, high calorie diet, sort of Western high calorie diet. And yeah, so then suggesting that even five days a month are sufficient. And this included insulin resistance, included longevity, include the cardiac function in the mice. So cholesterol levels, cholesterol level should up to very, very high by 30 months in the mice. And in this five days amount of the FMD brought it back to normal. So yeah, so I think that that's really an overall very broad effect, underlining the probably evolved nature of it, right? So it'll be strange that it affects inflammation and affects IGF1 and affects cholesterol, blood pressure, I mean, name it, right? So I can be if it wasn't there for the purpose of fixing things and also differential effects as somebody that starts with a blood pressure 110, we don't lower it. If somebody starts with blood pressure 110, 100, we might even see an increase in blood pressure, right? And same thing for glycemia. We see lots of people in the 70s going up in fasting glucose, right? And that's, I think, exactly what we want, you know, we don't want to, in coloristic instead, does the opposite push everything down and down and down, possibly, you know, reaching a threshold, a minimum threshold, which should not be surpassed. Yeah, I know your mentor was Ray Wulford, and I've certainly studied him extensively when I started down this path. And, you know, he was the father of calorie restriction. What mistakes were made in calorie restriction? Why isn't that, at least for humans, a great viable long term solution? Yeah, I don't think Roy made mistakes. I think Roy was just too early, right? It was a period where molecular biology didn't exist. The whole genetics of aging field was started by a group of us actually back then. And so they did not have those available. He didn't have those available. But I think, you know, in the end, the mistakes of the problems with calorie restriction are, first of all, is the chronic nature of it, and the fact that, you know, it pushes your weight and muscle and bone, etc., to a very low level, which most people, whether it's healthy for you or not, will not want to do. So already 99% of people are out because if you look at Wulford during biosphere two years when he was under calorie restriction, he did not look good and he knew that, right? So he knew that. And then I think it's also the trade-offs, right? It's probably, we see that the refeeding part of the FMD is as important or maybe more important than the fasting. And so because the refeeding is the building moment. So calorie restriction, calorie restriction refeeding never comes. And so, and also calorie restriction, now we know there is the thrifty mode is entered. So now, let's say you lose 20% of your weight and you go to a very low BMI body mass index, but now your metabolism might slow down 30%. And so now you have to eat almost nothing to not gain weight. So, yeah. So then if you look at the monkey study, you'll see a button which can, I mean, at the end, at National Institute of Aging, you see no effect or little effect, soma diseases. But in Wisconsin, you see a big effect on diseases, diabetes, incredible effect, cardiovascular disease, about a 50% decrease and cancer, about a 20, 30% decrease. Sorry, 50% in cancer and 20, 30% cardiovascular. But then if you look at overall mortality, the monkeys are living a little bit longer if their calories take that. But not that much longer. So then, yeah. So this is suggesting the trade-offs are pretty high. And so we learn a lot from it, but I think we need to move to more feasible and more effective intervention. Let me ask you your opinion. What do you think Dr. Raphael DeCabo from the NIH has certainly proposed that maybe a part of calorie restriction, certainly in an animal model, is that we're controlling the time of eating of these animals and that the calorie-restricted animals are going to eat all their food very quickly because they're hungry. And it's the period of time of fasting every 24 hours that may be having a huge effect from the calorie restriction. Do you have any thoughts on that? Yes. So this work both by Rapha and by Sachin Panda. And yeah, I think that I recommend 12 hours of fasting and 12 hours of feeding. I think as you go to the breakfast keepers, you start to see negative effects. And it doesn't mean that the fasting is causing the negative effects, but I always was worried about why is it that the people that skip breakfast are consistently living shorter. And so one concern would be with the 16-8 or so, not with the 12. I always say, I've never seen any negative studies on 12 hours, 12, 13 hours of fasting every day. But as you get to the 16, particularly if breakfast keeping is involved, now you start seeing the negatives. And you have to think about, is it possible that the ketone bodies are now potentially putting these very high levels all the time on ketone bodies are potentially putting a strain on the cardiovascular system. So we don't know, it may have nothing to do with that. But I think that with these 16 hours all the time, and maybe the cycles, could it be that it's just very high levels and very low levels, and it's just going back and forth is causing some problems, or is there something having nothing to do with fasting. So yeah, it could be, and it could be, if you did that with skipping dinner, now you don't have the problem at all, and you'll have a much longer lifespan. So it'd be nice to know to have the dinner skipping studies, which may be difficult to do because maybe not too many people skip dinner. Yeah, when I wrote my last book, The Energy Paradox, I really wanted to have people skip dinner and just eat breakfast and lunch. And I couldn't get my patients to do it. And it's hard for me because my wife and I really only see each other at dinner. And it's like what I'm going to watch her eat. Well, you know, I'm not, and it's very hard to implement. But you, correct me if I'm wrong, this past year, during COVID, you published a study looking at giving people a fast bar, your basically nut bar, for breakfast as their only food. And you showed that they stayed in ketosis for four hours, even after eating that bar. And you want to elaborate on that? And I agree with that, by the way. And I mentioned it in the new book. Yeah. Yeah. So I think that that study had to do with having breakfast, not interfering with the fasting. Right. So the idea was if there's something about breakfast that is not having breakfast, that is detrimental, let's let's give the patient back breakfast. But let's allow at least a, you know, a moderate level of ketogenesis to continue. Yeah. So I think that that's definitely a step up from skipping breakfast. You know, that was my thought, right? So, you know, could it be the best step up or maybe health way, but even if it was health way, it was really designed for people that were going to skip breakfast anyway. And so maybe now they can have breakfast, you know, and continue to get some of the benefits of the fasting. Did you find any benefits to doing that rather than just skipping breakfast? I mean, was there a positive outcome of having, you know, a fast bar or, you know, a handful of nuts? The trial was designed to just look at, you know, can you have breakfast and have the fasting effects at the same time, right? Yes, that was the design. It wasn't designed to see whether the ketogenesis or the high level of ketone bodies would have additional benefits. You know, of course, there's a lot of studies suggesting that lots of benefits of the ketone bodies. But that there was not the design of the study to look at what the ketone bodies can do. I'm sure everybody wants to know because they always want to know about me. So what do you do? I mean, are you having a fasting mimicking diet one week a month or just describe your day? Well, I mean, I have I have a very fairly strict longevity diet, where fish maybe three times a week with some variety and then, you know, lots of legumes. I mean, tons of legumes every night and tons of vegetables, you know, I probably have seven or eight servings of vegetables per day of legumes and vegetables per day. Then I have, you know, pasta almost every day, but I have limited amounts. I saw I keep it about 70 grams. That's my that's my dose at night. I don't eat lunch unless I am back to my ideal weight. So now, for example, for a pass, when I'm in Italy, it's very hard to not have lunch. So I have to say I failed to have the lunch skipping mode in Italy. But then I come back to California, and then I'm able to do that and just have coffee for lunch. It works better for me. And so, yes, Monday through Friday, I just have coffee for a tall American coffee for lunch. And that works very well. I mean, that allows me to control my weight very easily. And the beauty of that, and this is why I talk about it in my book, I don't know if you mentioned that in your book, but the beauty of that is that you suffer for about a month, a month, month and a half. And at the beginning, when you do that, it's terrible because you're looking for lunch. And then basically, I've been doing it for 20 years. For the rest of your life, it's just complete lunch becomes completely optional. So your brain rewires probably to understand that I already know it's optional. Sometimes we have it sometimes we don't have it. And now by having the weekend lunch, I always have lunch for the weekend, even if you're in California. But having these two things, and I think my system is very well adapted to going back and forth. And I understand that that's just completely optional. Yeah, so I think now we're starting a study, a clinical study in Southern Italy, where we're going to do this and try to make it, you know, tested and see what happens. And, and, you know, what the compliance is. So we're taking a population of 500 people, and we're splitting into two. And then we're going to do a randomized crossover trial, where we basically put everybody in the ideal, you know, longevity diet, both fasting making diet and longevity diet. And then the fasting making diet, I do it, I do it maybe a couple times a year, just because I have such a strict already longevity diet plus every day, skipping lunch. I don't want to overdo it yet. Great. Now, you, I know you've been doing this for, you know, 30 years and working and studying longevity. What are the, can you share some of the results that you've witnessed from your work and specific people overcoming, you know, major illnesses or other stories you can share? Yeah, so I was very proud of the clinical trial randomized 125 patients in and done by 12 Dutch hospitals, looking at breast cancer patient receiving chemotherapy with or without the FMD, the fasting making diet. And, and we actually saw those response, right, the more cycles of the fasting making diet, the better the either the clinical or the pathological response was of the chemo against the tumor. And so I think there was a difference between those that never did the FMD and those that they did almost every cycle. The FMD is a five fold difference in the portion of non responders, right? So, you know, remarkable. And I understanding that is one of the sort of larger level studies. And now we've done maybe about 10 studies on this topic and cancer and FMD. So the cancer looks very, very promising. And we just finished a study on hypertension. We just finished a study on diabetes. I cannot talk about the results, but let me talk about the ones that we already published, which is the 2017 study where we saw pre that lots of pre diabetics coming back to a non completely non pre diabetics state. And, and we also saw, you know, the people that have mild hypertension return into to normal if they were not taking drugs. And yeah, so let's say that everything is consistent with that. And also, HP1C, HP1C is seems to be there seems to be a good effect on lowering that. So the hope is that the hope is that we provide sort of like a food medicine type of intervention for metabolic syndrome, pre diabetes, diabetes, and probably also a portion of cardiovascular patients. Is there a difference in gender? Do men and women respond differently? Are there tricks for men or women? We have done now, people don't realize how expensive and and painful mice, mouse studies are. But that we finish finally male and female with the FMD lifelong, right? They have to say that we see very similar effects in both sexes. And in the clinical trials, thus far, when we analyze the males and female people, we don't we see very similar effects. So yeah, so it's good news. And obviously, when you try to move it from mice to people, then I guess it'll be very surprising if it works, you know, they say mice rats and and people but in people just happen to work only in one sex, you know, but it's possible. But yeah, that's not what we're seeing. We're seeing pretty pretty similar results thus far. No, that's good news because, you know, a lot of times we we hear on the internet that women should be careful. This is not what a woman wants to do. It works great on men, but be careful women. And I get that question all the time. But you're not seeing that. I think everybody should be careful, you know, and I, you know, I, I see some irrational exuberance as a green span, you say, yeah, so, so I will avoid this idea of, oh, I'm fasting and I cook it up at home and I, yeah, this is just going to do eventually more damage than good, you know, what I see right now is probably going to do more damage than good. And particularly, seeing the latest, you know, the latest thing, the flavor of the month, and I'm going to go home and try it, right? Yeah, so I think I really encourage people to, to think about the five pillars and think about 30, 40 years of accumulated research versus thinking about, oh, I heard this on the news, I'm going to go home and do it. Yeah, so let's, let's try to see what a few things that can be done, how they should be done, what they should be done with, right? So somebody that has got BMI of 18 is very different. Somebody's got BMI of 28. And, and so, and somebody, as you pointed out in your, your first book, you know, there are ingredients that seem to be very good for you. And maybe they're very bad for you, you know, and like tomatoes, for example, right? So, so, so yeah, I think things that are, everybody wants a simple, simple solution. And, and the solution is way more complicated than people realize. It's not that hard to do, right? The good news is, once you got the experts telling you, okay, you don't eat tomatoes, right? Then it's that hard, or maybe only eat the tomato paste, right? Yeah, exactly. So then it's not hard. But if you don't know, it's devastating to you. And so, and so, yeah, so I think it's the same for fasting, you know, you got to work with products and people and doctors that know what they're doing. And then it's easy. Don't worry about it. It's not about revolutionize your life. I have two clinics for the foundation, my nonprofit foundation. And, you know, we tailor everything to what the needs of people are. Yeah, you know, okay, I can't let you go eating a lot of legumes. I eat a lot of legumes. I eat a lot of beans. I eat a lot of lentils, but I soak and pressure cook them. And I had Joel Furman eat to live on my podcast recently and got him to admit that he pressure cooks his beans. What say you, Walter? I don't know. But I am my, I mean, clearly, I think you're absolutely right. Once there is a moment of microbiota disruption, right? Yes, which is probably in a pretty good percentage of the population, right? Yeah. So once the disruption, which you talk about also happens, then I think the legumes may start becoming a problem to lots of people. I mean, not cool. I never tried the pressure cooking. But, you know, I've been thinking about it for a long time. I want to try it out, right? So, so, but, but I would say, you know, I think in the past, it was not an issue because people were not exposed to all these antibiotics and all these drugs and, you know, and crazy interventions. But now that almost everybody is, you know, so how many people are out there that have enough of a disruption where that, you know, those prebiotic ingredients are now causing a problem? Yeah. So I think absolutely very interesting. Now we I have several people in the lab working on that. So working awesome with your ideas. And so, you know, we're trying to get the science out of it, the exact, you know, what's about all these different ingredients. And some of this is remarkable. I mean, we see dead mice, you know, on some of these these ingredients that everybody eats. And that that somebody is shocking, right? So, so absolutely. I think that's it needs a lot of a lot of research. And and the pressure cooking, I mean, is there a scientific explanation? So is a breakdown of a particular ingredient? Is that is that what the pressure cooking? Yeah. Yeah, pressure cooking actually can break, you know, these lectin proteins, it won't break gluten interest interestingly enough. But, you know, there's actually an Italian company, and I have no relation, Jovial, that actually soaks and pressure cooks their beans. And I actually use their brand and and they're fantastic and they're from Italy. So, you know, come on. There you go. Try them. Yeah. Yeah. What is it called? Jovial, like a happy person. Yeah. Jovial. And they they have it in glass jars. So it's in lots of stores nowadays. So look for it. And we'll talk. Well, listen, it's been great, you know, having you on the on the program again. What's on the horizon for you? What's what's next? You're always so busy. I think we are doing lots of clinical trials. And now we just approached the FDA for the first, you know, FDA track on cancer drugs, you know, food based, you know, fast immune diet for hormone therapy treatment. And so we put together 11 of the some of the best hospitals in the world, MD Anderson, Mayo Clinic, etc. And we're hoping to start very soon, a large trial and on that, which is FDA track. Yeah. So I think I hope that, you know, we'll we'll start lots of uses of these FMDs and diseases with the doctors with what I call the team, right? So we need, you know, nutritionist, dietitian, doctor, psychologist, and, and yeah, so I think that's a future is to have these teams having the tools, but also the teams that can apply it. And that's what we're working on now. Great. And where can people find you? Where can they find your company for fasting, mimicking diets, etc. Yeah, okay, the company, I cannot mention it, but it's easy to find, right? So I want you mentioned it before, I did. Yeah, I happened to still the beans. But I also we have a foundation clinic in Santa Monica here is called create cures foundation clinic. And, and so everybody should should consider it with especially cancer patients and people with big problems. But but everybody is is welcome. We have a group of dietitians that are very well qualified. Great. Well, again, thanks. Thanks for having coming on the show again. And we'll look forward to reading more about you almost every month. You publish a great new study and keep up the good work. Okay, thanks a lot. Thanks a lot. Bye, Walter. I hope you enjoyed this episode of the Dr. Gundry podcast. Make sure to check out the next one here.