HOWARD: Doctor Valter Longo, welcome to the Plant Yourself Podcast!
DR. LONGO: Thanks for having me.
HOWARD: So, you wrote an amazing book that I just finished and I’m reading for the second time: The Longevity Diet. I guess it came out in Italian first and now in English?
DR. LONGO: Yes. It’s been out in the US since early January now.
HOWARD: Right. So, I guess I’d love to begin with your story, which is such a beautiful and interesting story that the luck of the draw of where you grew up and what you brought to the United States and led you to longevity research.
DR. LONGO: Yes, so, obviously I had no idea at that time, but that my parents’ little town of a couple of thousand people would end up being among the ones with the highest prevalence portion of centenarians in the world, and then my region where I grew up, in Liguria in the northwest of Italy, turns out to be… Genoa, my city, actually turns out to be the city in Europe with the highest over 65 population, now at 28.2% and it also turns out to be one of the few places around the world to historically have a pescatarian diet, which eventually science would suggest being probably the healthiest one you can adopt. So, yes, interesting origin, one that’s related to longevity and nutrition.
HOWARD: And you know, there’s lots of studies with different Blue Zones, but most of that information came from post-World War II in the 1940s, and we know that the people in Okinawa eat very differently now. So, when you were growing up… I guess you are I are roughly the same age because you were born in the mid to late 60s…
DR. LONGO: Yes.
HOWARD: Right. So, when you were growing up in the early 70s, early 80s, were you still eating more or less traditional diet and living more or less a traditional lifestyle in terms of movement and community?
DR. LONGO: Yes, absolutely. So, when we went south for let’s say three months a year, we would very frequently, maybe five times a week, have this green beans and beans and vegetables plus some pasta dish, which is in the book, and it’s called Pasta e Vaianeia, and in northern Italy, where we spent near nine months of the year in Liguria, yeah, we would have fish maybe once a week and probably have meat once a week and chicken once a week. That was probably the typical week at the table. Of course, there were probably times when we would have meat or fish more days of the week, but certainly it was very different than it is now.
HOWARD: And you came to America to study guitar, right?
DR. LONGO: Yes, I came to the US to study jazz guitar, although I was really trained to be a rock musician. So, that’s what I wanted to do, but jazz at that time was the best thing you could study to train in electric guitar performance.
HOWARD: Hmm… so, I guess ultimately, you are going to have to study Keith Richards to understand longevity, right? [chuckles]
DR. LONGO: Well, yeah, I didn’t study Keith Richards that much, but certainly, I was very interested in Jimi Hendrix and Mark Knopfler of Dire Straits and you know, Pink Floyd – David Gilmour, and these were the guitar players that I was trying to imitate, and of course, the music school was interesting, but I think it played a tremendous role also in the scientific approach that I always had. So, I think I definitely recommend music school to scientists. I think it’s a great way to start the idea of “think differently, think ahead, and try to do things that you haven’t heard before,” and that’s something you get used to whether you do composition but also performance. That is the type of training you get.
HOWARD: Yeah, and you wrote very beautifully that music kind of predisposed you when you started doing science to look for evidence that was “in tune with evolution.” Can you talk a little bit about what you mean by that?
DR. LONGO: Yes. So, I mean that we are really the result of billions of years of evolution, and I think in most cases whether in medicine or in science, we forget those three billion years and we always try to come up with things that are really based on the last 100 years, and that’s a mistake. That’s a mistake because eventually you’re going to do, in most cases, more bad than good. Why? Because you’re not really understanding these three billion years. For example, if you block cholesterol synthesis, you may think that you’re doing something very good, but that’s not really in tune with evolution, right? You’re just blocking something… the body is trying to make something, and it doesn’t do it by mistake. It may be fooled by a series of conditions, but it is trying to make cholesterol, so to fix the problem, you have to figure out why it’s making so much cholesterol and what it’s trying to do with it, so eventually you can really get rid of the problem at its source, and I think the best way to do that is to do something that is in tune with evolution.
HOWARD: Right. What you’re talking about really is seeing the body as something with its own intelligence, as opposed to I think the way most medical and scientific research has looked at the body, which is just to understand what’s going on at a smaller and smaller level and which lever can be pushed to manipulate it.
DR. LONGO: Yeah. So, the view of the body that is not able to handle a lot of its own problems is really prehistoric, and it doesn’t mean that the body knows how to handle all of its problems. Of course, in some cases, you need surgery. In some cases, you need drugs, and in some cases, you need a combination of drugs and induction of self-repair, but you always want to start with, whether it’s autoimmunity or cancer, or a neurodegenerative condition, or cardiovascular, you always want to start with how the body can deal with this. I always say, if you cut yourself, anything exterior that happens to you, any wound is repaired to almost perfection in the great majority of cases, right? I think it’s naïve to think that after three billion years, we’ve evolved all the systems to fix the skin and everything on the outside but we have not evolved anything to fix problems on the inside. It is obvious that we have. I mean, we have done many papers showing that, so we need to start with that: exploit the body’s ability and push the body to fix itself. And sometimes it’s going to need a hand, for example, chemotherapy plus fasting mimicking diet in cancer treatment. Obviously, it’s working better than fasting alone. It means that once cancer is metastatic, it’s advanced. The body doesn’t seem to be able to do anything anymore. At that point, the drug becomes very useful, and the combination seems to work best.
HOWARD: So, when you talk about programmed longevity and programmed aging, can you explain what that means and what’s the meaning for your way of thinking about aging and staying young versus some older ways?
DR. LONGO: Yes, so I think the community is really focused on the process of things going progressively wrong and that’s what’s called aging or senescence. I never liked this idea, and you know, this is why in the book I talk about “juventology” versus gerontology, the study of youth. Why is that a big difference? Because if you look at a mouse, it lives for 2.5 years, and for 1.5 years, it’s very healthy, right? And in people, we live for 80 years, and we’re very healthy for 40 – 50 years. So, I’m very interested in the program that makes sure that for these 50 years in people or for 1.5 years in the mouse makes everything almost perfect and rarely develop any disease, and that’s what I call programmed longevity. What is the longevity program that keeps everything so perfect and what happens to that program after and can we keep it on for longer or much longer so that you live to, instead of 80, maybe you live to 100? But you live very healthy to 100. Of course, this used to be science fiction, and now it’s a reality. We’re about to go down to Ecuador in 10 days and in Ecuador, we’ve shown already in these subjects that have the same mutation that makes mice have longevity. We’ve shown that they are protected from cancer, from diabetes and from age-dependent cognitive decline. Now, we’re going down to look at their cardiovascular profile. So, this idea of program longevity is now clearly shown to be present in both in mice and humans, and we have to find ways, and that’s where fasting and fasting mimicking diet come in. We have to find ways to be able to do it without necessary pharmacological interventions, you know, eventually even a pharmacological intervention, I assume. But I think for now, dietary interventions are best.
Program aging is instead something much more for the specialist. It has to do with, is it possible that we are actually programmed to die, and you know, Wallas and Darwin had both speculated that this would be possible that we… the force of natural selection. There is a force to not only keep us healthy until we’re 50, but there is another force to kill us after that to get us out of the way. Now, that’s much more controversial. I presented with probably several papers 15 years ago about this, at least in microorganisms showing that some organisms can be in fact programmed to die and get out of the way to let the younger tribe… This is much, much more difficult to study in humans, but I just put it in the book because I thought it was interesting for people to think about that. That’s why I put it there, but I’m really much more focused on longevity program or youthfulness program.
HOWARD: Yeah, and reading it, it struck me as both sort of very plausible, I don’t want to say obvious but certainly plausible, that there is a longevity program, and I was struck by the fact that I had never considered it before, and I think that’s partly because the model I was using, my mental model was sort of like a car, like we don’t think if we have a new car, that it has some magical or intentional protection until it reaches 130,000 miles. But my experience with a car is that it works great until it all starts falling apart, and I kind of thought about the human body in the same way. There was nothing… there was nothing the car was doing to protect itself in those early years.
DR. LONGO: Yeah. Sure, and this is why in the book I talk about the car plus the body shop plus the mechanic, right? So, the car itself doesn’t have that, but the car experience, if you want to call it, does, right? So, you have the dealership that tells you to bring it in. You have the mechanics that can take care of the problems when they arrive. So yeah, there is a system to do the same even for the car. It’s just not intrinsic in the car itself but in what’s wrong with the car. So, it makes sense that the body would have done all of that by itself, and as the mechanic in the body shop inside saw that usually in most cases don’t need to take it anywhere. Of course, evolution has to take care of this because it cannot predict that we are going to have doctors, and for most of our evolution in homo sapiens and also before us, there were no doctors. So, the body had to take care of its own problems, and that’s why you want to have this longevity program to make sure that everything is renewed and fixed and also to make sure that some of the damaged cells are eliminated.
HOWARD: So, you have a photograph in the book of a young couple of child-bearing age with a baby, and I took that as a riddle, right? I never thought of it before that basically the baby is the set of new totally working cells from this couple that might be in their 30s or 40s. What’s the significance of seeing having a baby in that way? What are the implications?
DR. LONGO: The significance is really about showing that the body is able to distinguish young from old and select only young and select only nearly perfect so that a nearly perfect organism is generated. So, the significance is really about the body’s ability to reset everything to zero. Now, it doesn’t do it for itself, but it certainly knows how to do that in a very sophisticated way with high, high performance, meaning that most babies are nearly perfect. Yeah, that was the point. It was to show that all the systems that are able to rejuvenate are already there. They just only apply to the birth of an offspring and not to our own cells, but certainly there must be at least to a certain level there is… there must be. We’ve shown that there are systems that can get rid of damage and replace damage with new and young both inside of a cell and inside of an organ.
HOWARD: To some extent, does the longevity project sort of fool the genes into thinking that they are producing offspring when they are just rejuvenating themselves?
DR. LONGO: No, I don’t think so. I think the longevity program really is about something… so imagine that you started a car company and you make the decision, “I want to have this car on the road for 100,000 miles,” and in the beginning you could just build a nice car. But then eventually, you’ll find out very rapidly that that’s not enough, right? You got to have a body shop. You got to have a mechanic. You got to have somebody there replacing the tires, etcetera, etcetera. This is what the longevity program is. It is behaving based on the force of natural selection to, you know, each year starting with bacteria three billion years ago and moving on… you progressively develop a new… you learn and develop something, let’s say a DNA repair enzyme, protein repair, or immune system, etcetera, etcetera, so that the body stays almost perfect until say age 50, at which point at least historically you would have had grandchildren, and you know, then it’s okay if you get out of the way.
HOWARD: Gotcha. So, really, you talk about the five pillars and the fifth pillar is the study of complex systems, so we think of a car as an inanimate object, but a car within an intelligent ecosystem of maintenance is something else. The human organism or any organism is itself a complex system that is designed to accomplish particular goals.
DR. LONGO: Yes, so the human body is equipped with its own body shop, its own mechanic, its own repair and replacement system, the tire shop, right? So, all of it is there, not for everything. For example, there is some repairing and replacement in bones, but not that much, so some things are just built once, and they stay there, but so they are for the car, right? The body of the car probably never gets replaced, maybe gets fixed but not necessarily replaced. So, I think that we are similar in that sense. Some things are important to be replaced. For example, the liver keeps generating new cells, but the brain has some new generations of cells but not that much, at least neurons, I mean, they have new generational cell types, but not neurons or very little, and yes, that’s probably what occurs.
HOWARD: So, the way classical evolution is believed to work is that survival of the next generations then cements whatever mutation or changes or developments have occurred, so if we’re saying that we’re decoupling longevity from the evolutionary manifest, then we have to, not work against the body, but sort of work orthogonally to what the body is naturally trying to do within the species, right?
DR. LONGO: Well, yeah, we are not decoupling. We are, you know, the two things are very much combined and connected. At a certain point… I mean, what we’ve been trying to do is to utilize what’s always been around to change the program, to extend that program. So, for example, we’ve known that if you look at somebody who is anorexic, they are not going to be able to have children, and why is that? Well, that makes perfect sense by evolutionary terms because if you are anorexic and you have very little food… let’s say 30,000 years ago, if you had very little food, you would be in an anorexic state, and it makes no sense for the system to allow you to reproduce because you are going to die and the child is going to die.
HOWARD: Hmm.
DR. LONGO: So, it’s a futile investment. So, then what did evolution do? Well, it selected for a reduction in the aging process during the starvation period. Also, in the investment in protective systems and probably in regenerative systems, at least in standby regeneration, so the body is ready to regenerate. So, now if you exploit the programs or processes like that, you can potentially say, you know, we only reproduce a few times in our life, why do we need to be in a reproduction mode all the time? We don’t. I mean, we did. We used to because obviously, you would want to take any opportunity possible, you know 30,000 years ago, to reproduce. Now, that’s not the case, right? So then, the argument could be, let’s keep the body in the starvation response mode without necessarily starving. We can do this in different ways. We’ve now shown in many different organisms that these can now put the body in a standby mode so it can extend the longevity program, and of course if you need to reproduce, you can come out of it and go back into it, so yeah, that’s the idea. Now, it’s not as simple as I’m making it sound, but you know, we’re already doing it, and we’ve already shown the effects, and it’s just the matter of now getting better and better at it, always keeping in mind being in tune with evolution.
HOWARD: Hmm. That’s really fascinating to think about, you know, basically it sounds like evolution has prepared us to just walk around ready for sex all the time and that it implies a certain amount of energy expenditure that we no longer need to make and that we can intelligently funnel into these protective systems, elongating systems.
DR. LONGO: Yes. Now, of course [chuckles] “ready for sex” is a tricky one because obviously people wouldn’t want to stay in a non-ready-for-sex mode. More than “ready for sex,” I would say “ready for reproduction” mode, so it’s a better way to look at it because it looks like they can be uncoupled, you know, that you can be ready for sex, but not necessarily ready for reproduction.
HOWARD: Uh-huh. So, I know you studied with Roy Walford, who became famous for spending, what was it a year and a half, two years in a biosphere.
DR. LONGO: Two years.
HOWARD: Two. You wrote something in the book that has puzzled me for a while, which is that being on a caloric restricted diet is one of the only proven ways to extend life in just about any organism, and yet it may have contributed to Walford’s premature death. Can you explain the paradox that people in the biosphere doing something to extend lives but also harming their health being sort of miserable in coming out and looking not so good?
DR. LONGO: Yes, I think with any powerful intervention, you can have something very positive or something very negative coming out of it, right? Calorie restriction obviously was triggering or beginning to trigger something very powerful. So, if you look at the blood of Walford and others were in the biosphere too, I mean, there was a drastic reduction in cholesterol, triglyceride, fasting glucose, blood pressure. If a cardiologist looked at them, even an oncologist, they would say, certainly an endocrinologist, they would say, these people are never going to get diabetes. They are never going to have heart disease, at least based on accumulation of cholesterol, etcetera. They’re probably going to have a reduced incidence of cancer. These were eventually confirmed by somebody else who was in Walford’s lab before me. His name is Richard Weindruch at the University of Wisconsin. With the monkeys, right? That’s exactly what was shown. But yet, when they restricted the monkeys for 25 years, they had great reductions in cancer, cardiovascular disease, no diabetes, but they died just a little bit later than the monkeys on a regular diet, right? And the regular diet was not that good of a diet. It was close to a Western diet. So, that’s it. That tells you that being pushed to the limit is okay for a while, but if you do it for a long time, you are going to get good and bad and they cancel each other out. It’s not surprising that this idea that you could just beat the longevity, the existing longevity program, just by continuously restricting somebody in a severe way, I think, was a wishful thinking, maybe a naïve idea, right? Even mice. If you look at mice, the original data seemed to be very positive, but when people looked at all kinds of different genetic backgrounds, some genetic backgrounds did worse on calorie restriction. So, what Walford and others missed at the time were the molecular biology and genetics of aging, which we were lucky enough to, you know, be able to take advantage of. Of course, it took a lot of work because we are the ones that came up with the genes that, I mean me and a group of others around the United States, yes, we are the ones that discovered the genes like TOR, kinase, IGF-1 PKA, etcetera that are so essential to aging process. But that was really necessary to understand how to do the good of calorie restriction without the bad that may very well have contributed to Walford’s Lou Gehrig’s disease, although we don’t know. I mean, that’s speculation.
HOWARD: Right. But when you talk about being in tune with evolution, sort of in tune with how the human organism evolved, you know, I would think that it would be common to have periods of starvation or near starvation and periods of gluttony. Something about the ability to withstand lots of different caloric experiences might be something that would bolster the system provide positive stressor the same way that lifting weights breaks down and strengthens muscles. Is that partly the impetus behind the idea of intermittent fasting?
DR. LONGO: Yes. I mean there’s no doubt that people starved all the time, meaning that it was very frequent for humans and all kinds of organisms. Microorganisms spend most of their time starving, but even in humans, it’s pretty clear if you look at history that it was almost impossible to avoid relatively long periods of fasting and starvation frequently. That said, we really need to move away, I think, from using what people used to do to think that what people used to do is necessarily good, right? That’s why in the book I talk about five pillars because it has to be a match, it has to be a common denominator between what people used to do and what the science in epidemiological data and clinical work now show to be good for you, right? So, for example, you hear about the Paleo diet. The argument that just because people did it is good for you is a bad argument. Now, at the same time, it’s also a bad idea to say I have tested a drug or an intervention. Nobody has ever done that before, but I’m sure it’s going to work in the long run, right? I think what we really need is to have both.
Let’s say we’re talking about a high animal protein, high animal-fat diet, one version of a Paleo diet. You can say, okay, fine, people used to do that. There is a period where we might have done that, or we probably did that. Let’s look at the science and clinical data, epidemiological studies and centenarian studies, and none of them support it, right? None of it! If you look at epidemiological data, people who do that live shorter. If you look at animal data, animals put on the diet live shorter. If you look at centenarians, none of the longevity groups had that, right? So, it’s the same thing with fasting periods. You have to match it with the science and luckily for fasting, the science is very positive. You know, many of the old people with longevity did fasting, and the mouse data is very positive showing lifespan extension and protection, and epidemiologically, there is some negative data for a certain type of fasting. For example, there’s negative data for daily, let’s say 16-hour fasting. There is negative data both for gallstone formation and there’s negative data for people that skip breakfast over and over and over. Now the epidemiological studies are suggesting if you are fasting for 16 hours, you are probably going to skip breakfast, and now a number of studies are showing that people that do that because they don’t have breakfast live shorter and are more prone to cardiovascular disease and cancer. What is the reason for it? We don’t know. Is it about skipping breakfast or is it something else that people that skip breakfast do? We don’t know, but certainly, it’s a bad start, right? So, this is to address the fact that people want simple answers, and you just can’t do that, whether it is calorie restriction or fasting or the Paleo diet. You know, people love to say, “We used to do that; therefore, that’s what I’m going to do, and I’m going to live longer.” It doesn’t work like that, and we’ve shown a few years ago there’s also phases of life, you know. So, you’re probably going to have a certain diet up to age 20, another diet at least from 20 to 65, and probably there’s a couple of diets there, and another diet from 65 to 80 or 90, and another diet from 90 to 110 if you ever make it there. That’s more complex than people want to do or want to understand, but that’s what’s emerging from all these pillars, and that’s what I talk about in the book, and it’s not that hard to understand that. Supposedly, you can go for 40 years on a diet, and that’s okay. You’ll have to learn another diet and do it twice, you know.
HOWARD: So, I love the talk of the pillars, you know, preponderance of evidence as opposed to people who are trying to make money very often point to a single study, short term, of questionable funding, manipulates the data to get the result they want, and you’re looking at a very, very broad picture. So, can you talk about what the five pillars tell us about what’s the ideal human diet at whatever level of generality or specificity you think would be helpful?
DR. LONGO: Yes, so I always thought that it was strange, you know, in a courtroom, if somebody is accused of murder, you will have all these different pieces of evidence that go into deciding if somebody is guilty or not. They go from DNA evidence to what is the motive, were you there at the time, can we prove that you were there on and on and on, and then when we get to nutrition or many different problems in medicine, oftentimes we just go with one piece of evidence, right? In a courtroom, it will be laughable, you know. They wouldn’t even consider something like that. So, I always thought it was strange how science cannot even do what we do in a courtroom.
Yes, so the five pillars really are trying to address it from beyond the reasonable doubt, you know. Is it possible to say, well, I can never be sure, but this is about as solid as it gets, and we are going to go this way, we are going to convict this person, or convict this diet, you know. So, the pillars, the first one is epidemiological studies. In the book, I talk about a pescatarian diet, and if you look at the epidemiological studies, the studies of thousands and sometimes hundreds of thousands and sometimes millions of people, you have very little negative data for a pescatarian diet, meaning that over and over and over the studies are supporting a vegan, vegetable plus fish diet as being very, very healthy for you, particularly if you avoid high mercury fish and maybe some of the vegetables that may be associated with inflammation and certain problems. So, epidemiological studies are supporting a low, but sufficient, protein diet, so that’s also very important, right? Um, our studies show that if you are over 65, you probably have to increase the level of proteins and also increase a variety of foods that you eat because the body may not be as good as it used to be in processing food and incorporating… and generating amino acids and basic components that are then going to be part of the biosynthetic process. So, that’s Pillar One.
Pillar Two is clinical studies. What happens if you… the gold standard is you do a randomized clinical study. So, there’s not as much as data as there is with epidemiological data in randomized clinical studies. But certainly, if you look, for example, the study done in Spain… In the book I talk about 60-30-10, 60% carbohydrates mostly from legumes and vegetables, 30% fat mostly from olive oil, nuts, and fatty fish, and 10% protein. If you look at large randomized studies done in Spain on people that were at risk of cardiovascular disease, and they were randomized into a group that had high olive oil or high nut content in the diet or both compared to a low-fat group, meaning a group that was exposed to a low-fat diet, they did so much better if they were on the high olive oil/nut diet. They had to stop the study because it was unethical for the controls. Yes, so then there is also lots of support in one or another from the clinical studies for this pescatarian diet, and also for the fasting mimicking diet. I talk about periodic fasting mimicking diet. We’ve done our own clinical studies, and others are now carrying out studies in different forms of fast. But certainly, for period fasting mimicking diet, we’ve shown very clear effects of five-day fasting periods in randomized clinical studies.
Then you have basic research. That is Third Pillar. Well, what happens if you feed mice a low-protein diet, for example, they do much better. What if you feed mice a high saturated fat diet, they die early. So, lots of the things that… the pescatarian diet is very much low protein. Pescatarian diet is very much supported by the mouse studies, so the basic research is also supportive.
And then you have centenarian studies. What about people that have longevity, and whether it’s Okinawa or Sardinia, Italy or Icaria in Greece, a certain region of Costa Rica, or Loma Linda, California, all these areas pretty much vegan plus fish plus some meat diet, but not very much, you know. The meat is once a week type of event for most of these populations. So, that’s Pillar Number Four. It’s very important, right? Because you don’t want to come up with something that again scientifically looks great and then 30 years down the road starts killing people. It’s very possible, and it wouldn’t be the first time we come up with something that looks great in the beginning and then it turns out to be a nightmare.
And the Fifth Pillar is complex systems as we were discussing earlier, what about cars and planes because we build them, we understand them very well, so it’s also easy to see how they deteriorate. So, for example, I talk about, should you run 150 minutes a week, 300 minutes a week, or 500 minutes a week? Well, if you look at the data, the epidemiological data looks like 150 is about as good as 300 minutes, and then you start thinking about cars, and well, you know, if you drive a car all the time, tires and everything else is going to wear out, right? So, you know, assuming that the body is better than the car and can fix itself, but eventually, it’s going to get worse and worse at fixing itself. So, is it a good idea to run 500 minutes a week when 150 from the epidemiological data is already suggesting near maximization of the effect? Probably not. Stick to 150. If you really like it, you can go to 300 minutes. That’s good, you know. That’s a good level. That’s how…
HOWARD: So…
DR. LONGO: … the five pillars can help shape these recommendations.
HOWARD: So, I had a question about that and the data just around the complexity of it. So, like I was thinking, you know, I’m biased because I’m a runner, so I’m closer to 300, 400, 500 minutes a week than 150, and I feel like because I eat a plant-based diet that is very low inflammatory, I recover faster. I can run more. So, is the data on 150 minutes for people who are eating like me or people who are eating sort of the standard Western diet, or is it comprehensive?
DR. LONGO: It’s comprehensive. It’s for everybody, right? They went out and looked at everybody that runs and everybody that doesn’t run and just compared them, and the runners, not runners, but the people that did exercise for 150 minutes, I think there was a 37% reduction in overall mortality and also this has been done for different diseases, so that’s great. If you went to 300 minutes, I think it went from 37 to 43%. I have the numbers in the book, so it wasn’t a big difference, and then of course, if you go more than 300 minutes, which means an hour a day for five days a week, you’re getting into a poorly understood territory. There’s less people that do that, and it doesn’t mean that somebody couldn’t do it very well with it. It just means that it’s not a good recommendation for everybody. Then, people may be able to do it extremely well doing that, you know. Also, because some people understand for example, if you hurt yourself, you got to stop. You have to be back in an optimal or ready-to-run-again condition, right? Some people may do that, and some people may not. I think the recommendation for the masses should be, stick with 150 to 300 minutes. If somebody is an athlete and really wants to do more than that, there is some risk involved, but that’s something they’d have to consider, like in your case.
HOWARD: And to be clear, you’re also recommending people walk an hour a day and it doesn’t count toward that 150 – 300 minutes, right?
DR. LONGO: Yeah, I recommend people walk for at least an hour a day, at least a couple hours on the weekend, and then people do everything, you know, in the traditional way, so go up the stairs, try to do everything yourself, you know. So, yes, I think that it certainly makes maybe a couple of hours a day ideally to the exercise in moving, walking, and going up the stairs, etcetera.
HOWARD: Gotcha. So, I want to cover your innovation of the FMD, fasting mimicking diet. I was struggling a little bit to understand this. You have four elements that define a fasting state for the body, and so your goal was to achieve all those four elements while still giving people calories? Was that the quest?
DR. LONGO: Yes, we wanted to not interfere with the… you know, we wanted to be in tune with evolution, so not interfere with the starvation program, but at the same time allow people to eat and at the same time prevent the intake of the ingredients that are otherwise negative. So, yes, those are… and of course, we were very focused on safety. Can this be done by almost anybody, not almost anybody, but by the majority of people anywhere. That was all the considerations that went into the fasting mimicking diet.
HOWARD: So, what was that quest like? Did you sort of hit upon the outlines of the correct formula right away? Were there a lot of dead ends?
DR. LONGO: Um, we spent decades connecting nutrients with the genes, so we knew right away some of the fundamental things we had to do, but it took years to keep developing and keep testing first in mice and then in people to eventually have something that not only it gets the effects, and we learned the hard way, but it’s also about compliance. You can have everything perfect in your head and in your lab and even in a clinic if you check somebody in, but then what happens when they get out there. So, we also had to have some minor compromises on that I push myself, and my colleagues may say, “Well, if you’re trying to shut off this gene, why don’t you have less of that?” And my answer is because I want people to be able to do it. If people cannot do it, then it’s just… the whole thing is pointless. You know, eventually we might have like the perfect version for the hardcore ones, the ones that say, “I can do it however you give to me.” But I think for now, the technology is also there to make sure that people can do it a little bit easily, and it’s working, I think. We’re seeing, you know, tens of thousands of people doing it now, and so I think we are on the way to making this certainly an option for doctors but also for people that don’t need a doctor yet to handle at least some of the initial problems in each related dysfunction.
HOWARD: Hmm. So, what are the benefits of doing the FMD protocol? I guess you recommend that people who need to lose weight should do it once a month, five days once a month and then people who are at a healthy weight once every six months? What… Sell it. What would somebody get from doing this thing?
DR. LONGO: Well, first of all, I don’t want to sell it because you know, as I explain in the book, it’s there for people to do good, to improve within the… I know what you meant by selling it, but I don’t want people to misinterpret it.
HOWARD: Right.
DR. LONGO: I don’t make a penny out of this, but there is a company out there. I just thought that it was important to have a product just because to make it safe and to make it match the clinical results and to also please the doctors that really would never have embraced it if there wasn’t something there that was thoroughly tested clinically and after the clinical studies. But anyways, the fasting mimicking diet, what it does, what it was designed to do, is to push the body into breaking down many different damaged components and then turn on the repair and replacement systems including stem cells but also including intracellular repair modes that are then executed during the refeeding. So, the fasting mimicking diet really sets the body up, but it is the refeeding that regenerates and rebuilds and fixes the problems. I mean, it is the combination essentially, right? But of course, people are good at doing refeeding, and people are very bad at doing fasting, so that’s where the fasting mimicking diet operates… and again because of the way it is designed, it triggers all these different genetic changes that allow these repair, replacement, regenerative processes.
But the compliance in the clinical trial that we did here at USC, we showed that three cycles of the fasting mimicking diet reduce cholesterol, blood pressure, fasting glucose, triglyceride, IGF-1, which is a marker, a potential risk factor for cancer, C-reactive protein, a marker for systemic inflammation and a risk factor for cardiovascular disease. And as far as people that should use it, actually once a month is for someone who is obese and has at least two markers or risk factors that are elevated. So, somebody who is obese, has high cholesterol and high blood pressure, that’s once a month. If somebody is overweight with high cholesterol and high blood pressure, then maybe once every two months, and it just goes down from there all the way to, let’s say, a 35-year-old athlete that has a pescatarian diet and that has everything perfect, all the blood tests are perfect, so the person may want to consider twice a year and only if they are of normal weight.
HOWARD: Uh-huh. How important is the feeding between instances of the diet? Do you see big improvements even if people go back to their horrible Western diets between the FMD sessions?
DR. LONGO: Yes. Let me qualify this because people tend to attack me. Of course, in the book I talk about the pescatarian super healthy diet in between and that’s the best, right? And then eventually, you may get to the point where you would only need to do this twice a year because you have the pescatarian diet. The reality is that people don’t have a pescatarian diet, and we see the FMD working the best on those with the worst diet.
HOWARD: Hmm.
DR. LONGO: If somebody came in with fasting glucose in a clinical trial, people that have fasting glucose of 75 or 80, which is excellent, we saw no difference. I mean, it didn’t come down any more. Differently from chronic calorie restriction, you know, if you look at Walford’s studies, people that had 80 fasting glucose or low blood pressure, they came down more, right? That’s probably the distinction between the periodic fasting mimicking diet, at least one of them, and chronic calorie restriction. Chronic calorie restriction is pushing your body to more and more extreme, whether it’s good or bad for you. The fasting mimicking diet seems to be doing what probably is always there to do, at least what fasting tries to do but in a safe way, which is get rid of the problems, then return to normal, with a new set of cells or certainly with some level of rejuvenation.
I use the analogy in the book of a wood-burning train, and I basically say, if you have an old wood-burning train that doesn’t have enough fuel to make it to the next station, the engineer would go back and try to grab first the chairs and walls that are damaged and start burning those for fuel. Now, the train becomes lighter, and you have enough fuel to make it to the next station. And when you get to the next station, now you rebuild the chairs, you rebuild the walls that you used to obtain fuel, so now you may have… 20% of the train is brand new, and you make it to the station, right? That’s exactly what the body does. So, now if you start with your cells working properly, you are not really fixing anything much, and you don’t see a difference. That, of course, is very rare in the United States… maybe 10% of the people would be in that category, considering that 72% of Americans are either overweight or obese. But yeah, if you start with a problem, then the fasting mimicking diet seems to have a very powerful effect in fixing many of these problems. And we suspect that as we see in mice, the reason for this as we see in mice, which is multi-system regeneration. For example, in mice we can destroy completely, certainly destroy all the insulin-producing beta cells in the pancreas of a mouse, and then we start the fasting mimicking diet and we can show that within five cycles or so of the fasting mimicking diet, they start making normal levels of insulin again, and this is a permanent effect, meaning that we can stop the diet and they still… the insulin-producing beta cells are now functional long term, and the mouse now is back to normal.
HOWARD: So, you’re talking about in mice essentially the equivalent of reversing type 1 diabetes.
DR. LONGO: Yes, well, not the equivalent, yeah, reversing type 1 diabetes in a mouse model, and type 2, you know. So, it’s very effective. In mice, now we’re going to do clinical trials, of course, to see whether some of it is conserved in humans, but certainly the idea of taking bad cells and replacing them with good cells is clearly there also in humans. The question is, how far can it go, you know? Can it, like we’ve seen for people, can it regenerate insulin-producing beta cells and neurons and liver cells and etcetera, and if so, to what level? Of course, the clinical trials that we’ve published suggest that some of it are going on for sure, but the pathology treatment, we’re just starting to do. Well, some of it we’ve been doing for years, but we’re just starting to learn about how effective it can be.
HOWARD: Gotcha. I have taken up an hour of your time, so I’ll be conscious of not overstepping, but I do want to ask one more thing because a lot of the audience for this podcast are vegans or whole food plant-based eaters, so they will have been surprised so far to hear that fish and a fairly copious quantity of olive oil is recommended for longevity. When I look at say, the PREDIMED study from Spain, I interpret it fairly differently from what I read in the book and you discussed here. I don’t see any of those diets as being equivalent to, say Esselstyn’s or Ornish that reverse heart disease. I’m also real curious about olive oil versus which I teach people, which is oils are highly processed, artificial, calorically dense food. So, for the vegans who are listening, who are not going to eat fish at all, do you have thoughts or recommendations? Is there enough evidence to say that pescatarian is clearly superior to full-on vegan or are there other things they should do to sort of make up for the salmon deficiency or sardine deficiency in their diet as you see it?
DR. LONGO: Well, obviously, you can be vegan and you can be very healthy. As a whole, vegans are not necessarily doing that well compared to people that eat otherwise, right? That’s surprising, right, because you would expect vegans to do much better, so the suspicion is that you go from one problem to another. For example, many vegans that I talk to, I ask them what did you eat in the last 24 hours, and keep in mind that I am vegan maybe except two meals a week, so you’re talking to someone who is very close to a vegan, but if I ask the question, most of the times, they are protein deficient. It doesn’t mean that all vegans are protein deficient, but lots of them are because they don’t realize they need half a kilogram, a pound of garbanzo beans to have enough protein even if you only weigh 150 pounds. I have that many times a week, but most of the vegans I talk to don’t.
HOWARD: Right. So, you’re talking about vegan versus whole food plant-based, so vegans can just eat pasta and junk, right? As opposed to someone who is getting all of their calories from whole plant foods.
DR. LONGO: Yeah, of course, now I’m talking about vegans… yeah, they can eat whatever they want as long as it is plant-based, right? And now, if you get into the more careful category, we don’t know because there just aren’t enough people that do that to have epidemiological data. But for sure, you’re starting to get into… if you’re talking about the masses, you start to get into a difficult situation, meaning that if you eliminate fish, then you start eliminating also pasta, bread, and rice, or certainly have low levels, then you’re going to have a very little portion of the population being able to carry out. You’re also entering an area that is poorly understood, but what happens… so we know that a high carbohydrate diet over and over and over is the most beneficial one, I mean the one that comes up on top. So, if you eliminate starches, now all of a sudden, it becomes extremely difficult to have enough calories to get to the end of the day. Now, you’re even saying, let’s eliminate oils. Then, it becomes impossible to get to the end of the day, right? And I mean a few people, like one in a hundred, can do that. Most people are just going to struggle. We see this all the time, so this is why Esselstyn and Ornish, really the data doesn’t support low nuts and low olive oil. Now, there could be some olive oils that could contribute to inflammation, but overall, the data is very positive. Unless somebody is in a very advanced state of heart problems, I just don’t see, you know… the overwhelming majority of the results are positive in favor of the good fats.
Now, I’d love to look at the ones that are negative. But if you look at the Esselstyn data, I mean it’s very few patients that have actually been published, and I don’t think it’s ever been randomized versus the ester data, which is thousands of patients randomized. So, you know, I think we have to go with the pillars and the data. I mean, if Esselstyn and Ornish want to come up with data that show why that’s not true, you know, absolutely. But if you look at the recent data, mice that had even higher fat content live longer, so high-fat low-protein, they live longer than the mice put on a typical low-fat diet. So, again, multiple pillars are suggesting that good fats, and in their case, they’re even arguing that bad fats, but I don’t go in that direction because bad fats seem to kill mice early, so I always thought that it’s probably not a good idea. But healthy fats, salmon, nuts, and olive oil pretty consistently come up on the right side of things, and if you look at the Mediterranean diet, meta-analyses are showing a reduction of disease, not huge effects, but certainly better than the other diets, right? So, now, how would they perform if somebody had a plant-based diet, low-fat diet, etcetera, etcetera, I mean I don’t know, nobody knows. Certainly, it is a very tricky territory because nobody knows, right?
HOWARD: Um hmm. Right. So, the kind of study you’d like to see would be say, a randomized controlled trial with Esselstyn/Ornish versus a higher fat olive oil diet…
DR. LONGO: Well, no, no. For the regular population, I don’t even want to see that because nobody can do that diet. Right? Very few people can do that diet. I mean, the reality is when you spend time with thousands of thousands of people, you know, one in a hundred can do it, so I mean I am all for it if you have advanced cardiovascular disease, like the ones Esselstyn has been describing. It can work for you, sure. Obviously, if you can do it, do it. But when you’re talking to the masses, that’s an impossible diet to have, you know. I would never do it, and most people that I know would never do it. And so, you have to look at, you have to do a little compromise. First of all, it would be nice to show at least in a randomized study for the people that are in an advanced stage, you know. So, let’s take 500, 600 patients, randomize them and give them, you know, the Esselstyn/Ornish diet, and then randomize it to the same with good fats, right? That’s never been done. Let’s see that trial. Everybody that has ever looked at the data would say, they’re going to do as well, but you know, let’s see, maybe they’ll do worse. But we need to see it, but then I still think it will have to be confined to people that have a real problem and they may adopt this very severe Esselstyn diet because of where they are. When you are talking about the general population, I think it’s one of those directions that are not going to really help because it is so extreme that the great majority of people won’t do it.
HOWARD: See, you’ll have to come over. If you are ever in North Carolina, come over to my house, and I’ll try to change your mind with a meal.
DR. LONGO: No, no, I know, but I mean, don’t forget I was in Walford’s lab, right?
HOWARD: [laughs]
DR. LONGO: Walford’s crazy, crazy diet. If you could do it, then there’s a couple thousand people around the United States who could do it. But then they’re called cronies. But in the long run, they ended up doing worse than they thought, you know. Same thing for the monkey. I’m just saying something that looks very positive in the short run doesn’t necessarily mean it’s going to be very positive in the long run, especially when you get into this phases of life like over 65 when you start having immunosenescence, immune system starts changing, etcetera, etcetera, and there is also inflammatory problems like a lot of vegetables, whole grains, and vegetables can have strong pro-inflammatory effects, so now when you push somebody on particularly something that they have never had before, you can start seeing all kinds of problems, and this is person specific, right? People may do very well, but then some people may do very poorly on having whole grains, for example. So, that’s where the complexity starts, and I think that we need to keep that in mind, and I’m not saying it cannot work. I’m just saying it’s trickier than we think.
HOWARD: Gotcha. Well, I really appreciate your insights and this book. So, for my vegan friends who are getting a little excited, we’re talking about like a 95% vegan diet, maybe fish twice a week and not huge portions, either as....
DR. LONGO: And it’s not necessary, you know. It’s not necessary. They can stay vegan. I’m just saying that they have to match the two fish meals with vegan nutrition, so it’s not necessary to introduce animals. There could be ethical reasons for not doing it. That’s perfectly fine. I’m just saying, be careful at, you know, not paying attention being vegan because it can easily get into the malnourishment area.
HOWARD: Right. What I’m saying is in terms of your influence on the world, you know, in a world where a lot of scientists are embracing ketogenic, very high-protein diets, you know, you are not coming out of the plant-based or vegan camp, and you’re basically advocating a largely whole food plant-based diet with a couple of exceptions for fish and olive oil. If the world adopts the way you eat, we will all be a lot better off.
DR. LONGO: Yeah, I think so, and why is olive oil not part of the vegan diet? That part I didn’t…
HOWARD: Well, because… I mean, just in terms of in tune with evolution, it’s extremely processed food that we’ve probably only had for, you know, since we invented the press.
DR. LONGO: You mean in that sense. Yeah, absolutely, and this is why I think if you did not have the Italians, the Greeks, the Loma Linda people, and the clinical data and all of that, showing lots of nuts and lots of olive oil are actually associated with a longer lifespan, I would also eliminate it, but because people love it, because it gives you calories that you need, because it does push you a little bit in a ketogenic mode, and because of these data, you have to go with the facts and say, look, it’s probably the way to go because you have to eat something, and that’s the other thing. It’s difficult to have too many rules, you know, for most people.
HOWARD: Right. Although I would say, you know, that Blue Zone countries can get away with more olive oil because they are so much more active. They are walking and fishing and gardening, you know. I think there has to be a match to your movement and the amount… the richness of your diet, you know.
DR. LONGO: You know, most data would suggest that the higher fat induces, not just the good fat, even the bad fat, this is why the Atkins diet is so popular. Most data would suggest that you are going to lose weight, and not gain weight by having a high olive oil and nut diet. There’s very little data going against it. So, the caloric input is there obviously but it does not, particularly the good fat, there’s almost very little data suggesting that… Weight gain in most of the countries like southern Italy is definitely not due to olive oil, is due to the high-starch diet and of course, sweets and other things that they eat. There’s very, very little data suggesting that especially the good fats, even the bad fats, are contributing to… in fact, almost every paper… I mean, I’m very much against the Atkins diet, but almost every paper is showing weight loss. I mean without high bad-fat, a high-protein diet is showing weight loss, and I always tell people, look, you know, this is an illusion because eventually it’s going to hurt you, but just from the point of view of weight gain or loss, if you have a high fat diet, most of the studies will show weight loss.
HOWARD: Gotcha. One last question. Someone… I told him I was interviewing you, and he wanted to know is there a difference in the results of the fasting mimicking diet and longevity diet in men versus women and premenopausal versus postmenopausal women?
DR. LONGO: Well, no difference in men and women. We saw similar results in men and women. Pretty soon, now we’re trying to get the data for over 30,000 people. I mean, I don’t know how many we’re going to get, but certainly over 30,000 people have done it. Hopefully, we’ll get a couple of thousand feedbacks. Premenopausal and postmenopausal, we did not have that many women. They were postmenopausal. You know, at some people that’s something we’re going to look into. But yeah, we haven’t done that yet.
HOWARD: Gotcha. Finally, for people who want to try the fasting mimicking diet through the product that you scientifically validated and want to follow your work, where should they go?
DR. LONGO: Yeah, they go to… there is a website called ProlonFMD.com and take it from there. There is a questionnaire and some other qualificational questions, and they are either assigned to somebody that needs a doctor or somebody they can do it just by talking to a registered dietitian that I think the company provides.
HOWARD: Gotcha. Are you active? A website or a blog or a social media?
DR. LONGO: Yes, I have… well, first of all, I have a foundation called the Create Cures Foundation, and all the proceeds from my book go to the Create Cures Foundation. It’s CreateCures.org. Then I have a Facebook page where we post articles of studies that we think are well done and interesting to people, lots of vegan studies, and that’s Prof Valter Longo Facebook page. If they like the page, they just get the articles as we identify them, and now I think soon enough we’re going to start having some PhDs start writing articles because lots of times journalists may not completely get the point of papers, so for some things that I really care about like proteins and good vegetables and pro-inflammatory vegetables, we’re going to have a number of topics that I really love that I think it’d be good to have PhDs spend some time figuring out what’s real and what’s not.
HOWARD: That’s a GREAT service to eliminate the middleman of the science journalists, most of whom I find don’t really understand what they are reading.
DR. LONGO: Yeah, the problem is that most of them do not come from the medical or science background, and it’s very hard for journalists like that. It’s impossible to put it into context, right, to say, okay this group discovered this, but let’s look at 50 papers, right? What do they show? What is consistent? What are the pillars showing? I don’t want to blame them. Lots of them are doing a great job, but it’s just impossible to really explain it a way that can be useful to a reader. Well, what should I do now? You know, there’s a paper that came out recently showing that tomatoes are bad for you and in the same paper they had tomatoes are bad for you and then pizzas are good for you. [laughs] It’s an epidemiological data, right, so I was laughing because somebody reading this is going to say, what is this? What does it mean, you know? Well, you know, because they were talking about pro-inflammatory meat and vegetables and etcetera on colon cancer. The paper was very interesting, but it really needed somebody to say, okay, let’s look at the reality. For most people, tomatoes are fine. For few people, tomatoes might be bad. Same thing for gluten. So yeah, those are some of the examples where I think that… I just feel really bad because I’m thinking if I were just an average reader, I would be very confused. Now, I see all these data attacking vegetables.
HOWARD: Right, that’s just you know, people who are acting out of goodwill. We’re not even talking about all the industry marketing that’s deliberately trying to muddy the water for us.
DR. LONGO: You know, these were a top journal and a top research group, and probably the data… now, of course, we’re also very interested in trying to break it apart because it had red meat and tomatoes in the same group, right? So, of course, I was thinking, wait a minute, which one is contributing to what? Maybe tomatoes are contributing to a 0.3% increase in inflammation and the meat is contributing to 80% and they average out to 37, I think it was. So, you know, it’s very complex, and yeah, probably there was nothing wrong with the study, but there was probably something wrong with the way it gets in the news, it gets presented, and it gets used to argue, oh you see, vegetables are bad for you.
HOWARD: Right. So, I’ll include a link to the Facebook page and to ProlonFMD and to CreateCures.org in the show notes for today’s episode, and again, I really want to thank you. The work you are doing is phenomenal. I’m going to be bragging when you win the Nobel Prize that I got to interview you.
DR. LONGO: [laughs]
HOWARD: Thank you so much for taking the time.
DR. LONGO: Well, thank you, thank you, very nice interview.