In recent years, interest in fasting—and in diets that offer some of the same benefits as fasting—has surged. Dr. Valter Longo was ahead of the curve: he has been studying the secrets to longevity, including fasting and fasting-like diets, for over 20 years. Now he’s pioneered a new way to accrue many of the benefits of fasting without the potential long-term consequences of chronic calorie restriction. It’s called the Fasting Mimicking Diet and, in this podcast, Dr. Fitzgerald talks to Dr. Longo about the spectacular benefits of short-term fasting, the downsides of long-term fasting, and how practitioners and interested clients can use the Fasting Mimicking Diet to reap health benefits and increase their healthspan — and their lifespan.
In this podcast, you’ll hear:
- How Dr. Longo became interested in longevity
- About two of the key pro-aging pathways in the body and how they are influenced by foods and fasting
- About the potential long-term consequences of calorie restriction
- How calorie restriction affects estrogen and testosterone production
- What “calorie restriction” and “fasting” mean
- How a fasting mimicking diet can rejuvenate the immune system
- What constitutes a Fasting Mimicking Diet and how the active ingredients in the diet matter as much as the ingredients that aren’t in the diet
- Who should consider doing a fasting mimicking diet, and who shouldn’t, and how often it is safe
Professor Valter Longo is internationally recognized as a leader in the field of aging studies and related diseases. His discoveries include some of the major genetic pathways that regulate aging and life-threatening diseases and the identification of a genetic mutation that protects men from several common diseases.
He is a Professor of Gerontology and Biological Science and Director of the Longevity Institution at the School of Gerontology at the University of Southern California in Los Angeles, one of the leading centers devoted to teaching and research on ageing. He is also director of the Oncology Laboratory and longevity at the Institute of Molecular Oncology IFOM in Milan.
Professor Longo received the Nathan Shock Lecture Award from the National Institute on Ageing (NIA/NIH) in 2010 and in 2013 the Vincent Cristofalo ‘Rising Star’ Award for Research on Aging, and the 2016 Glenn Award for research in the Biology of Aging.
In 2015, after a number of his papers were among the most widely cited in the biomedical field, Time magazine called him a ‘guru of longevity’.
https://www.facebook.com/profvalterlongo/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899145/ – Paper on FMD and MS
https://www.ncbi.nlm.nih.gov/pubmed/27810402 – Paper on disease and FMD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755412/ – Paper on fasting and aging
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388543/ – Paper on fasting and circadian rhythm
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Dr. Kara Fitzgerald: Hi everybody, welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And today is no exception. I’m really excited to be talking to Dr. Valter Longo, out of USC, and specifically, the director of The Longevity Institute. You are likely familiar with his recently published book The Longevity Diet. He’s an internationally recognized leader in the field of aging studies and related diseases. His discoveries include some of the major genetic pathways that regulate aging and life-threatening diseases, and the identification of a genetic mutation that protects men from several common diseases. And we’ll ping him on what those are, exactly, in a minute.
Dr. Kara Fitzgerald: He’s professor of gerontology and biological sciences and director of the longevity institution of the school, gerontology, at the University of Southern California, in L.A., which is one of the leading centers devoted to teaching and research on aging.
Dr. Kara Fitzgerald: He’s also the director of the oncology laboratory and longevity at the Institute of Molecular Oncology, IFOM, in Milan. Dr. Longo received the Nathan Shock Lecture Award from the National Institute on Aging. In 2010, and in 2013, the Vincent Cristofalo Rising Star Award, for research in aging. And he also received the 2016 Glenn Award for research in the biology of aging. He has a number of really highly cited papers, and Time magazine called him, recently, the Guru of Longevity.
Dr. Kara Fitzgerald: Dr. Longo, welcome to New Frontiers.
Dr. Valter Longo: Thanks for having me.
Dr. Kara Fitzgerald: So, give me your background. How did you come to study longevity?
Dr. Valter Longo: That’s actually all I’ve ever done. I was a music student in my first year in college, in Texas, and that’s when I made the decision that I wanted to study aging. So from the very beginning, I switched to the biochemistry department and joined several labs that were focusing on aging research. And that’s all I’ve ever done. I just thought it was just a fantastic, at the time, a fantastic scientific field. I also realized that it was relevant to so many diseases, and I was just wondering why nobody was focusing on the underlying cause of so many of the human diseases, which is aging.
Dr. Kara Fitzgerald: Yeah, that’s extremely interesting. What instrument do you play?
Dr. Valter Longo: I was a guitar player.
Dr. Kara Fitzgerald: So how did you just randomly make the jump in to biochemistry? Were you pinged by a particular study or…
Dr. Valter Longo: No, I think that’s what I probably wanted to do all along, and in the book I talk about the fact that I was in the room when my grandfather died and I was five years old. And so, probably that just stuck in my head as a very major event. Usually you don’t get to see somebody die, personally. I didn’t connect it very much, maybe I’m connecting it more now and just thinking that, all of a sudden, at 19 I was sure I wanted to study aging. So I suspect that was probably the event that stuck in my head. This is a big problem, right? Also, my grandfather died fairly early, in his late 60s, so I think that that was probably also important for me making the decision.
Dr. Kara Fitzgerald: That’s pretty interesting, yeah, and a good decision, indeed. So, just thinking about your grandfather, the town that you grew up in, it’s a blue zone. Many folks there live a long time, correct?
Dr. Valter Longo: Yes, it has a record prevalence of centenarians. And, in fact, that’s something that I talk about in the book, is this comparison between my grandfather, and just a block away is Salvatore Caruzo, who was his friend, but the same age. And Salvatore just died a few years ago, so 40 years later, right? So then, I just always thought how amazing, and became one of the oldest person in the world, 110 years old. So I just thought how amazing it is that somebody could live 40 or 50 years longer or shorter, possibly based on the decisions made.
Dr. Kara Fitzgerald: Right. Yeah, that’s interesting. And your town in Italy is?
Dr. Valter Longo: It’s this little town, it’s called Molochio in Southern Italy, in the Aspromonte mountains.
Dr. Kara Fitzgerald: Okay. Well, I want to circle back and talk about what you guys grew up eating, and doing, and why there’s so many people there living a really long time. Just jumping into the juxtaposition between Salvatore and your grandfather. I’m sure that, at some level, motivated you to be looking at these genetic mutations. Identifying some that promote longevity, but also the ones that, when turned on, really push aging. Can you talk about those?
Dr. Valter Longo: Yes, so, eventually I made it to UCLA, to the pathology department. Roy Walford was one of the gurus of something called calorie restriction. And, at least in the early ’90s, that was recognized as the most powerful intervention for aging. But Roy, at the time, in fact, he was in Biosphere 2, he was doing the first human, he was a medical doctor. He was doing the first human trial on calorie restriction. So him, and other seven people were doing this study on themselves, essentially. And their results were phenomenal, but also it was clear that there were lots of side effects. And eventually Walford will die relatively early of Lou Gehrig’s Disease. The fact that it was due, in part, to this calorie restriction. But the point being that me and another small group of scientists around the United States realized that we couldn’t keep doing research in humans and mice, we had to move back to simple …
Dr. Kara Fitzgerald: Okay.
Dr. Valter Longo: Yeah, so we moved back to simple organisms. In my case, unicellular yeast, baker’s yeast, and others started studying worms and flies. And the gamble was, of course, that we would find genes that regulate aging, and those genes would be the same or similar to those that regulate aging in humans. So it actually worked out, believe it or not, everybody thought it was a very bad idea, but we were able to identify two sets of genes. One is called TOR-S6 kinase, and the other one Ras-PKA, which I call, respectively, the protein pro-aging pathway and the sugar pro-aging pathway. And eventually those were recognized, were validated by others. And I think, particularly, the TOR-S6 kinase pathway together with the IGF1 pathway discovered by Cynthia Kenyon and Tom Johnson, those are recognized as the two most important genetic pathways that accelerate aging and age-related diseases.
Dr. Kara Fitzgerald: Let me just say to the listeners, that you’ll see in the show notes, we’ll link to some of the papers where Dr. Longo is talking about these particular pathways. Okay.
Dr. Kara Fitzgerald: So TOR is related to sugar, and protein kinase A is, obviously, related to protein and accelerated-
Dr. Valter Longo: The other way around. So, amino acids in protein activate TOR and IGF1, and the sugar activates PKA in yeast, Ras PKA.
Dr. Kara Fitzgerald: Okay, okay. Hey, I just wanted to circle back to the Biosphere, and some of the side-effects. I’m just curious what they noticed doing calorie restriction.
Dr. Valter Longo: I think it’s pretty consistent, in fact, just a couple days ago I visited the University of Wisconsin, where they did the monkey study on calorie restriction. And so, you see pretty consistent similarities between the monkey study and the human study, which is tremendous effects on diabetes, cancer, cardiovascular disease, or the risk factors for them. But then, you see both the monkeys and the people being pushed to the limit, to almost anorexic levels. So, for example, in Biosphere 2, the BMI was something around, below 19, for males. So they were really pushed the limit, and of course they only stayed there two years, so when they came out, they looked terrible. But that was it.
In the monkeys, there was opportunity to see that, in the monkey study, believe it or not, lasted 25 years, if not 30 years. And so you see that, for example, diabetes is completely, or almost completely absent in the calorie restricted monkeys, and it represents about 60% of the monkeys on the control diet. Cardiovascular disease cut by 50%, cancer cut by 50%. Yet, if you look at the overall mortality, there is not that much difference. And so, for example, and I’m trying to get from them, and it’s been hard, but I’m trying to get from them the actual table, with all the side-effects. But some of the things I’ve heard, for example, pneumonia, the chance of dying because of an infectious disease. The ability to recover from anesthesia. So, little things that, in many different ways, end up killing the animal.
And so, I think that the side effects are many, but they don’t necessarily represent lots of people. So each person may get a variation of that, so maybe the sensitivity to a different infection. So people will come back and argue, and say, “Look, I tested the effect of a particular virus with calorie restriction, and I didn’t see a problem.” That’s not the point. You could be protected from 80% of the viruses, but you could be sensitive to 20%, and that still could get you killed if you get exposed to that 20%. So that’s, I think, some of the things that some of my colleagues are underestimating. You can be just sensitive to a minority of problems, and eventually that’s going to be enough to get you in trouble.
Dr. Kara Fitzgerald: Right, right. So there’s not going to be a single smoking-gun trigger increasing or limiting the improvement on mortality. It’s variable, I suppose, depending on a number of factors in the individual. But there’s changes to the immune system sufficient…
Dr. Valter Longo: The immune system can certainly, appears to be, lowered by the calorie restriction. For example, testosterone levels are lower, and there’s lot of changes, including IGF1 can change, depending on what diet you have. So these chronic interventions taught us a lot, but they’re clearly not the way to go.
Dr. Kara Fitzgerald: Right, right. I want to ask you one more question about that, and then jump over to your work, which actually shows improvement in hematopoiesis, and stem cells, and improvement in white blood cell count. It’s actually really, really cool. But, I’m just curious about the stress of calorie restriction and cortisol and HPA access changes. Any comment on that as being a piece of the driver, if the problems in calorie restriction?
Dr. Valter Longo: We don’t know. I think that the suspicion is that the body is able to switch to an alternative mode, that’s very clear with both fasting and calorie restriction. And the origin of that, probably, is fasting. So calorie restriction is tapping into the fasting response. But when you enter these alternative modes, you can have, obviously, lots of benefits, but the idea is not to stay there all the time. It was never the idea, because, keep in mind, if you’re calorie restricted, and calorie restriction refers to, say, 25, 30% of calorie intake below the normal level. Not the excess level. So when you’re calorie restricted, for example, fertility is going to be impaired, or blocked. So clearly the calorie restriction was never meant to be forever. It was meant to be for a period, food is not available, whether it’s the winter period or you happen to be in a area where there’s no food, fine. You can be restricted. But you gotta get outta there, and that’s, I think, the problem of applying something chronically that has never really been meant to be applied chronically. Yes, cortisol goes up, for example, during calorie restriction, and we know that increased cortisol levels, chronically, if it’s a temporary, acute effect, cortisol can be very beneficial, and we see that in fasting.
But, we know from the work of many scientists that that same cortisol, eventually, can cause lots of problems. So that’s just one example.
Dr. Kara Fitzgerald: Right, right. Yeah, that’s fascinating. I’m curious, we were just talking about the microbiome before we started the interview, and I’m sure there’s some pretty radical changes there. Actually, and in your model, as well.
Dr. Kara Fitzgerald: Okay, so you talk about increase risk of infectious disease in the calorie restriction population, but you actually showed hematopoietic stem cell-based regeneration, and reverse of immunosuppression in your program, looking in animals. I don’t know, do you just want to talk about that a little bit, and then we’ll get into the nuts and bolts of what you’re doing.
Dr. Valter Longo: Yeah, so, first of all, I think it’s important to clarify that calorie restriction, or fasting, are words that don’t mean anything. And I think, like with everything else, we need to start describing what it is that we’re talking about.
Dr. Kara Fitzgerald: Okay. Let’s start there.
Dr. Valter Longo: It’s like eating, doesn’t mean anything. You can eat very well or very poorly. Calorie restriction, again, refers to this 30% chronic reduction in calorie below the normal level. And fasting, it can go from a few hours to a few months, is a potential period for people. And fasting could be very good or very bad, just like calorie restriction. So what we’ve done, is to begin to identify the safe and effective modes of fasting, so how long do you do it for, and what do you have instead of water-only fasting, which we realized very early on, it was not a good idea, both because of compliance, people did not want to fast with just water, and also because of safety. There are all kind of concerns, and usually water-only fasting should be done only in a clinic that specializes in water-only fasting and that has medical personnel.
Then we identify, first in mice, and now we’re doing it in people, a period of fasting, well, first of all, we identified a Fasting Mimicking Diet. That is 800 to 1,100 calories per day and lasts about five days. And then we applied that to both mice and humans. And in mice, we were able to show that just four days of this Fasting Mimicking Diet, followed by 10 days or so of the normal diet, a high-nourishment diet, so this alternation was able to first kill, actually, white blood cells, and then activate stem cells, multiplicative stem cells, and during the refeeding, particularly, the stem cells now can give rise to newly generated white blood cells. And by this process, if you do it enough times, you can get immune system rejuvenation and rejuvenation not just of the immune system, but certainly the hematopoietic system is one of the ones that is clearly affected by these cycles.
Now it’s very different if you did calorie restriction or something similar, which could potentially have the opposite effects.
Dr. Kara Fitzgerald: Right, yeah, it’s fascinating. That’s really great that you’re going the distance to look at how it should be pulsed and so forth. And just jumping on this topic, too, your human trial, did you look at white blood cell counts or did you evaluate immune response in human population?
Dr. Valter Longo: Yes, yes. We did that and we haven’t published on that yet, we’re going to publish on that soon enough. But, keep in mind that our population in the trial we published last year, with 100 patients, that was relatively young population, so we didn’t start with people that have these immunosenescence, which would be more typical of the over 60 population.
Dr. Kara Fitzgerald: Right, okay. Well, we’ll look for that study, that’s pretty exciting.
Dr. Kara Fitzgerald: Okay, so talk to us about the Fasting Mimicking Diet, what’s it comprised of?
Dr. Valter Longo: The Fasting Mimicking Diet goes back to what we discussed earlier, the connection between proteins and TOR, and proteins and IGF1, and sugars and PKA. And so it takes advantage of this knowledge, not just this knowledge, much more than this, but this is just two major components, I think. And so it’s a low sugar, low certain type of amino acid diet, and it’s a high fat, but certain type of fats, everything is selected based on its activity on genes and the idea is to make people as happy as possible, as nourished as possible, and as full as possible. And at the same time, achieve all of the effects that we want to achieve that would be achieved by water-only fasting.
Now, in this new set of papers that we are about to publish, we’re going to, I think, also introduce the concept that it’s not just about removing things with the Fasting Mimicking Diet, there’s also active components. And I cannot discuss it now, but that’s also going to be the next wave of papers indicating that, it’s not just what you remove, but it’s also what you have in there that has active effects.
Dr. Kara Fitzgerald: Well, let me ask you about, you’re clear that some aminos are better than others. Can you mention some amino acids we want to emphasize in the diet?
Well, I just want to circle back to you talking about some amino acids are favorable, and some are negative. Can you speak, specifically to that?
Dr. Valter Longo: Yes, it’s not that the amino acids are favorable or negative, they’re just negative for the fasting response. So if you have lots of leucine, for example, and you have lots of methionine or cystine, you’re going to interfere with the fasting response. So those are just some of the examples of the amino acids that need to be lower, or low in the Fasting Mimicking Diet.
Dr. Kara Fitzgerald: Okay, alright. So they’re going to be more actively used in the TOR pathway?
Dr. Valter Longo: Well, they are TOR and IGF1 promoting, or inducing. And so if you have them in the diet, you can reverse, or partially reverse lots of the responses.
Dr. Kara Fitzgerald: Okay, alright. Your diet, it looks like it’s really high in plants, plant proteins, plant phytonutrients, and so forth.
Dr. Valter Longo: 100%, definitely.
Dr. Kara Fitzgerald: You recommend some fish.
Dr. Valter Longo: I wouldn’t mix the longevity diet, everyday diet, with the Fasting Mimicking diet.
Dr. Kara Fitzgerald: Okay, okay.
Dr. Valter Longo: The Fasting Mimicking Diet is just something that lasts five days. It comes in a box, and that’s it. It’s more like a medicine. The everyday diet is something very different, and it’s completely different from the Fasting Mimicking Diet.
Dr. Kara Fitzgerald: Can you talk about the constituents of the Fasting Mimicking Diet?
Dr. Valter Longo: Yeah, so the Fasting Mimicking Diet has, basically, bars that are made of certain type of nuts, again, selected for their fat content. And vegetable chips, soups that are, again, selected for their content. And everything is made to look reasonably normal, but, in fact, every single soup and every single component took years of development to get it to the point where it could be tasty for people, but It will also be acceptable from the point of view of promoting fasting response, and not just that, also adding to the fasting response.
Dr. Kara Fitzgerald: Okay, and we’ll link, actually, to the site where clinicians can access it. That people can access this program.
All right, so, talk to me about some of the biomarkers that you’ve been looking at. And I’m interested, specifically, in what you might recommend a clinician who’s working with patients with the Fasting Mimicking Diet, what they would look at. So what did you look at and research, and what would you recommend carry over into the clinical setting.
Dr. Valter Longo: In research, of course, now we’re starting lots of clinical trials, many we have on cancer, on Alzheimer’s, we’re about to start diabetes, Crohn’s, colitis, so we have many, many trials. Each one is completely different, with very different diets and different lengths and different calories. But for the time being, I think that what we recommend is basically what we’ve done for the clinical trial on normal subjects and maybe what the main changes were. So we showed that three cycles of the Fasting Mimicking Diet were able to reduce cholesterol, triglyceride, systolic and diastolic blood pressure, c reactive protein, CRP, fasting glucose, and also IGF1, in the subjects that appeared to have problems to begin with. So if somebody had low CRP, nothing happened. But if somebody had high CRP, in the great majority of cases, that was brought back to the normal level. So those are the things that I would test, a baseline, and after, probably three cycles of the diet. You’re not going to see lots of differences after one cycle. But after three cycles, many of these should be changing, particularly those that have a problem to begin with.
Then, of course, that depends on the use of the diet, we think it can be very effective against inflammatory conditions and diseases. This is why we’re about to start multiple trials on autoimmunities. So, of course, the doctor, in each case has to evaluate which markers they should be looking at.
Now, an interesting thing, at the beginning everybody said, “Oh, of course you see all these changes because of weight loss.” And so I had a colleague from Yale look at this, and in fact it turns out that these effects are not associated with weight loss. Of course, you lose weight, but when we analyzed the data, it did not show that those that lost the most weight, got most effects. In fact, in some cases, or in many cases, we had the effects with minimal weight loss. So suggesting that this is going to the core, or the heart of the problem, and not just simply making people leaner, and therefore, although it does make people leaner, but that’s not the reason why they become healthier.
Dr. Kara Fitzgerald: What about the ratio of fat to muscle?
Dr. Valter Longo: The ratio of fat to muscle was, and that’s another, I think, great, unique feature of the Fasting Mimicking Diet, that the relative lean to total body mass was actually increased after three cycles of the FMD. And the absolute lean body mass, this was a crossover trial, so we had two groups that went on the diet, and in one case, absolute lean body muscle mass was not affected, and in the other case it was just slightly affected, reduced, but again, with an increase in relative body mass. And the interesting thing is that if you look at patients at the end of the diet, you’ll actually see a decrease in lean body mass, even absolute. And then you look at them again a week after the end of the diet, and they regain that muscle mass and return to the normal level. And that’s what we think is really the advantage of this versus the great majority, if you’re just thinking about weight loss. The majority of diets out there is that refeeding period is really the moment where the muscle is being rebuilt, and so we are now doing a clinical trial at University of Verona in Italy, looking at muscle strength and a variety of tasks on the athletic performance.
Dr. Kara Fitzgerald: I would imagine that that ratio might’ve been moving towards a favorable ratio. It might’ve been a piece of why the weight loss, those that lost less weight, still had much of the other improvements that you’re talking about, in terms of inflammation and sugar and so forth.
Dr. Valter Longo: I think it goes much more to the core of aging, and we think that by causing intracellular, in-organ, regeneration, that’s where the effect is. So, autophagy is clearly occurring in all kinds of cell types, it’s not all of them, and also at the organ level and the system level, you have replenishment of cells and we suspect that the body is able to get rid of, as we’ve shown, in our autoimmune paper a couple years ago, the body can get rid of damaged cells and replace them with functional ones.
Dr. Kara Fitzgerald: So, I’m assuming that individuals are getting into some degree of ketosis. Are you measuring ketones in that population, or do you recommend it?
Dr. Valter Longo: Yeah, ketones is one of the four things we always measure. We measure IGF1, IGFBP1, ketone bodies, and glucose. And that’s a good way to look at compliance, but also look at response, so people should have lower, or much lower IGF1 by the end of the five days of the diet. Should have higher, or much higher IGFBP1. Should have much higher ketone bodies. And should have much lower glucose. So if you don’t see those, then there could be compliance issues, the patient didn’t follow the diet, but they could also be that the patient, for some reason, is a non-responder. We don’t see that very often, but it can happen and also you want to investigate whether they may have some metabolic genetic disorder, something that, for example, prevents gluconeogenesis, and that could put the patient at risk for hypoglycemia, et cetera.
Dr. Kara Fitzgerald: Yeah, that’s really interesting. Yeah, I’ll look forward to seeing what you find there. We use ketogenic diets in practice sometimes, therapeutically, and do see a similar resistance. So ketones themselves have been shown to inhibit, there was a really interesting paper out of Yale, the inflammasome 3, I think, specifically. Are you looking at the production of the ketone bodies themselves, are one of the drivers of the anti-inflammatory benefit? Or a strong driver?
Dr. Valter Longo: We haven’t looked at that particularly. So I’m glad that other people are looking at it. We’ve been so busy just looking at the effects of this Fasting Mimicking Diet, on so many diseases, and trying to get an idea of what the major player may be. And so, I think it’d be good to look forward to other groups actually looking at what different components, or results of the diet, can do. And the ketones and fatty acids are certainly one of them. So it’d be great to see, could some of the effects be explained by these. Now, of course, there is no doubt that the switch to a metabolic mode, in which ketone bodies are used, is important, or very important, in the effects that we see. So, that’s almost for sure. Now, whether the ketone bodies themselves are also having a, independently of metabolism, an effect on different cell types and responses, we don’t know. So I’m glad to see that others are looking at it.
Dr. Kara Fitzgerald: Yeah, it’s pretty interesting. I was taught that they were basically waste products, so the research on them being important in and of themselves, perhaps as signal molecules in some form is pretty interesting to me.
What would you say a healthy fasting blood sugar is, in your research? What kind of numbers?
Dr. Valter Longo: I think that you can go down as low as, probably, the 50s and still be okay. It depends, that the doctor has to make that evaluation on whether somebody should go that low or not. But that’s probably the strongest response that we see, and that we want to see. But some people may go down to the 70s, or 60s, and that’s probably the more common response that you see.
Dr. Kara Fitzgerald: What about IGF1?
Dr. Valter Longo: IGF1, same way. By day five you want to see, preferably a 30, 40% drop. So if somebody is starting with, say, 280, ideally you want to get down to 160, 170, or lower even by day five. But then, you’re not going to see that big of a drop after three cycles, after you return to the normal diet.
IGF1, I’ll just repeat the answer. So for IGF1, we want to usually try to get patients to maybe a 30, 40% reduction, temporarily. And then you may expect, at least based on our clinical work, about a 20% reduction, long-term. So if somebody starts with 280, they may go into the 150, 160 range, temporarily. And then, they return to maybe 220 or so, after they resume the normal diet. That would be considered a good response. Of course, this is in the absence of changing their everyday diet. Which I think is pretty remarkable.
Dr. Kara Fitzgerald: Oh, right, that is remarkable. So they would return to what they were eating prior to? And just toggle between the fasting-
Dr. Valter Longo: I guess what I’m saying is, somebody has a high protein diet. If somebody has a 280 IGF1 level, they probably have a high protein diet. So, if they do three cycles of the Fasting Mimicking Diet, even though they return to this high protein diet, they should expect their IGF1 to be lower, to maybe the 220s level. Which is starting to have a big effect. If you look at the epidemiological data, it could have tremendous effects on breast cancer, prostate cancer, colorectal cancer, where 280 is associated with a very high incidents of these tumors.
Dr. Kara Fitzgerald: So, you talk about the frequency of using the Fasting Mimicking Diet in healthy individuals, and you recommend twice a year. And then, increased frequency when you’re actually dealing with an active disease state. How did you come upon twice a year as being appropriate in healthy individuals? And what’s the frequency you would recommend otherwise?
Dr. Valter Longo: Yes, so the idea is to do it when you need to do it. And so, I will say, historically, and for all the reasons that we discussed, a couple times a year seems to be very, very safe. Particularly because it’s a Fasting Mimicking Diet, it’s not fasting. Now, keep in mind, for example, water-only fasting is associated with gall stone formation, hypoglycemia, et cetera, et cetera. So I want to warn people, because the fasting came around many times before in the last couple hundred years, and always disappeared. And the reason why it disappeared is because, eventually somebody got hurt from it, and doctors then turned against it. So, I think it’s very important to understand that, if we make the same mistake again, we’re going to end up with the same result.
So you’re going to end up with somebody coming out and showing that people who do water-only fasting, they get the gall stone, and they get gall bladder operation, and everybody’s going to say, “I don’t want to do this. It’s not worth it.” So, I think it’s important to keep in mind the potential in deciding the frequency, and the potential side effects.
So twice a year with the Fasting Mimicking Diet, there is really no evidence whatsoever that this 800 to 1,100 calorie diet, which is relatively high in fat, but it contains carbohydrates and proteins. So I think it’s a very safe approach.
Now, if somebody is obese and has high cholesterol, high blood pressure, now the minimal risk that could be associated with frequently doing a Fasting Mimicking Diet is clearly lower than that risk imposed by the obesity and the risk factors. So, then that person has to do it, I think, about once a month until they move to a different range. So if it works as it has worked in many, many, in thousands and thousands of patients that have done this, then you slowly can move into once every two months, every three months, every four months, and that’s probably the average frequency for a U.S. person. Once every four months, I think that is probably a good frequency for the average American.
Dr. Kara Fitzgerald: It’s a higher fat diet, what fats, in particular, are you emphasizing in it?
Dr. Valter Longo: These are all plant-based fats, so olive oil, and nuts. All the fats come from the two sources that are, over and over and over been associated with protection. So that’s the only source of fat.
Dr. Kara Fitzgerald: Any comments on medium chain triglycerides? We’re using them a lot in our field, and they seem to promote ketosis, because they’re burned so readily and absorbed rapidly.
Dr. Valter Longo: Yeah, medium chain fatty acids, they can be effective, there is data now suggesting that they can be effective in brain function, and potentially protective against cognitive decline. I will warn people against chronic diets that contain medium chain fatty acids because, again, we don’t know the long term consequences of, particularly if you have them together with the standard diet. So, for example, ketone bodies plus the standard diet, now, I always say big mistake, why is that? Well, it’s like taking a hybrid car, and trying to push the car, tweak it, so they can use electricity and gasoline power at the same time, even though it’s not designed to do that. You may get some benefits, it may run faster for a while. And then, eventually it’s going to break down. Now, of course, you could redesign it, but that’s not what people are doing.
Dr. Valter Longo: The danger of starting mixing chronically, things like that, is that you are now confusing the system. And if the system is confused for long enough, it could break down.
Dr. Kara Fitzgerald: So if you’re pushing ketone body production and you’re still ingesting sufficient simple carbohydrates for fuel, is that what you’re talking about, basically?
Dr. Valter Longo: Yes, so I’m saying that the body can be in a high nourishment mode, works on glucose mostly, or it can be in a starvation response mode, and now it can work on fatty acid, ketone bodies, and of course it still uses glucose. It understands that, it has been programmed to do that. Now, if you’re in a sugar mode, and then you start throwing in there ketone bodies, as some companies in silicon valley are doing, now all of a sudden, the body is not going to understand what’s happening. All of a sudden, you’re pushing the brain, particularly, but everything else, to try to have two modes at the same time, and the question is, okay, you could be great for five years, seven years, 10 years. What happens after 15, 20 years of doing this? My guess is you’re going to start seeing people with weird conditions in the doctor’s office. Some of them, potentially, very bad.
Dr. Kara Fitzgerald: Right, right. Well, if you look at the standard American diet, it’s extremely high fat, and extremely high simple carbohydrate, of course we’ve seen the fallout of that, very clearly. So yeah, I think that your point is really well taken.
So what about health span, life span. I know we don’t have long-term studies on calorie restriction in humans, but what are you thinking about with regard to your protocol?
Dr. Valter Longo: We have long-term studies on calorie restriction in monkeys, so I think that those are, together with the human studies on calorie restriction paint a pretty clear picture, which is, again, you’re going to get good and bad. But the good is extraordinary. So, the good is revolutionary for medicine, and that, to me, is just unbelievable that we don’t spend half of the funds at the NIH on this. Because, I guess, and that’s what we’ve been trying to do with the Fasting Mimicking Diet is what I’ve been trying to do for the past 25 years, since the Walford years. Clearly, calorie restriction can have tremendous effects on health span, the healthy longevity. But then it has these side effects. So if we could figure out, or remove the side effects, then I think that’s really a medical revolution and I think, I’m very biased, but I think this periodic Fasting Mimicking Diet is getting very close to that. As we’ve already demonstrated both in animal studies and in human studies.
Now, of course, we don’t have the long-term data. But we’re starting to get there, and the prolonged Fasting Mimicking Diet, and by the way, I should mention, I don’t make a penny out of this, everything I donate to a foundation called Create Cures Foundation, to keep funding research and efforts in this direction. But, the prolonged FMD now, has been done by over 50,000 people. And now there’s going to be an app collecting, where people can collect data and send it back in to the database. And so, I think, in a couple years, we may have a million people that for whom we’ll know the effects of multiple cycles, or many cycles of Fasting Mimicking Diet. So, I think, it’s going to be extraordinary, because in a few years, we may be able to say, “Hey, we’re now reducing, not just the risk factors for cardiovascular disease, diabetes, cancer, et cetera. We’re actually starting to reduce the incidents of these diseases.”
Dr. Kara Fitzgerald: Yeah, yeah, it’s extraordinary. That’s really cool. So, I did want to mention that, that you don’t receive any profit from the L-Nutra company that produces the ProLon products. Can you just give me the web site where people can access this? And when is this app going to be available?
Dr. Valter Longo: This app, I think, is already ready to go, or really, really close to being available to doctors and patients. And the site is prolonfmd.com. P-R-O-L-O-N-F-M-D.com. So then doctors and patients can find all the information about this on that web site.
Dr. Kara Fitzgerald: What kind of data are you interested in collecting from the people using the app?
Dr. Valter Longo: Everything. I think that weight, circumference, the cholesterol, the blood pressure, all the things that the diet has, inflammation, inflammatory markers, fasting glucose, et cetera, et cetera. So, for example, in the trial, we show very clear effects on pre-diabetes. So people that were pre-diabetic returned to the normal level. Right there would be extraordinary, now having, say, 50,000 people that are pre-diabetic, how many can we see returning back to the normal state, and what is the frequency. Maybe it turns out that you could do it every four months. And a pre-diabetic, by just doing this every four months, can return to the healthy state.
Dr. Kara Fitzgerald: Yeah, that’s very interesting.
Dr. Kara Fitzgerald: Now, you talk about exercise, appropriate exercise. You mention community in your book. What about the other lifestyle interventions that, are you recommending concurrently with the Fasting Mimicking Diet, or when they cycle off of it? Talk about some of those and what you think are most important.
Dr. Valter Longo: So the exercise, I have a chapter in the book. Obviously, very important, but, also, in the book I try to talk about five pillars of longevity, so not just looking at one study or two studies, but really looking at five different disciplines. And so, for exercise, if you look around, for example, if you look at the centenarians, they’re very active. They don’t really exercise. But in the book, I really look at the meta-analysis, so the studies of studies. What if you put all the exercise studies together, what is the effect on lifespan? And it turns out that about 150 minutes of exercise a week is ideal. If you go to 300 minutes, you don’t really see that many changes, that much additional improvement, and also, it looks from the data that, if you do about 10, 20% of that exercise, you push yourself. So, if you have, out of the 150 minutes, maybe 30 minutes in which you push yourself, not to the limit, but certainly to a higher level of exercise.
The exercise is 150 minutes, of which, maybe, 30 minutes should be at the strenuous level. It doesn’t mean that you have to push yourself to the limit, but certainly pushing yourself a little bit seems to be important. That’s basically, I said 30 minutes of exercise every other day, and then maybe a little bit more on the weekend, and that should be enough for most people to optimize their health span. Healthy longevity.
Dr. Kara Fitzgerald: What are you recommending when they’re on the FMD?
Dr. Valter Longo: When they’re on the FMD, no exercise. They can walk around, they can be fairly active, but they should stay away from any dangerous situation, at least until they know how it affects them, even driving, for some people, could be problematic. We really don’t see it, but we have to think about one in a thousand. We use to be one in a hundred, but now we’re really starting to think one in a thousand.
Dr. Valter Longo: And this allowed us, again, out of 50,000 people that have already done it, very, very few adverse events that were in the three or four level. So, for example, I think we had the one patient that went to the hospital, but then was released with no problems. So that’s very important, to not combine the FMD with anything like exercise, that could push you over the edge.
Dr. Kara Fitzgerald: Right. It seems, to me, in general, you want a physician or a clinician of some form monitoring an individual doing the program. Is that correct?
Dr. Valter Longo: Yeah, if you have any concern, if you have a disease, you need a physician to do the FMD. If you don’t have a disease, we recommend a physician, but some people decide that they just want to talk to a registered dietitian, and that’s fine. But, yeah, the recommendation is for a physician in all cases.
Dr. Kara Fitzgerald: All right, just a couple more questions, I just want to pick your brain. One of the interesting things I read about laboratory findings in the Biosphere, was thyroid production was down. It makes sense to me, because metabolism is ramped down in this population. Have you seen any changes like that in the FMD folks?
Dr. Valter Longo: I think there may be a temporary effect on thyroid production, but we’re now doing a clinical trial on Hashimoto syndrome, and the hope is that it can help, at least, with this autoimmune disorder. But, yeah, I think that those temporary effects on hormones and other factors are very much coordinated. So as long as they’re coordinated, meaning that, as long as they’re part of something that is evolved process, an evolved, adoptive response, people should be fine with it.
Again, if you start creating an artificial environment, then I think that, whether it’s thyroid hormone, or anything else, eventually it could cause problems. We haven’t seen anything thus far that appears to be a long-term hormonal, for example, testosterone, estrogen, were not affected by the cycles. Now, testosterone and estrogen are affected by calorie restriction, for example. They’re both lowered. So it’s also an interesting difference, the periodic FMD seems to be able to not drive things down the same way the chronic calorie restriction has been know to do.
Dr. Valter Longo: For example, chronic calorie restriction drives fasting glucose level lower and lower and lower and lower. So let’s say that somebody has a fasting glucose of 75, it’s very healthy already, right? You wouldn’t want him to go down any more. But, after chronic calorie restriction you see that. After cycle of the FMD, you don’t see that. If they started with 75, they continue with 75. They might go up to 78, so it’s very, very important that the system recognizes what’s broken and what’s not. And it doesn’t necessarily continue to lower hormones or factors that might be at the right level.
Dr. Kara Fitzgerald: One of the things I wondered about calorie restriction, especially in light of the lowered output of T3 and T4, and was also a possibility of a decreased mitochondrial density, and then a subsequent reduction in oxidant stress. And therefore influencing less inflammation, and perhaps, anyway, any comments on that? On reducing oxidant stress and free radical activity in the calorie restriction versus the FMD?
Dr. Valter Longo: Obviously calorie restriction is very beneficial for lots of things. Whether it’s inflammation or mitochondrial functions, and there’s a recent study showing, in people, that it reduces oxidative stress. So, there is no doubt that calorie restriction can be very beneficial, again, the problem is the other side. For example, a recent study showed that it reduces metabolic rates. Well, what happens is that most people that undergo long-term restriction of calorie eventually can no longer sustain that. Then they go back to the normal diet, and if your metabolism is slowed, and in some cases, it can be slow for years. So now you return to the normal diet and now what’s been observed over and over and over, you regain all the weight and more. Why? Because now your body is gone into a thrifty response, it’s trying to save energy, but yet, now you’re back eating normally. So these are some of the things that are important.
It’s important to learn from calorie restriction, tremendous amount of data for the last hundred years, including great work recently in humans, but it’s also clear, to also the people that are doing it, that this is not the way to go, the periodic intervention seems to be a much better way to go. Together with the daily intervention, for example, in the book I talk about 12 hour time restricted feeding. That’s a very good practice. And I talk about two meals a day if you’re overweight. So there is things you can do every day, but the intervention, the revolutionize your diet should probably be only periodic, also because of compliance. People we know already, cannot do major changes to their diet for very long periods.
Dr. Kara Fitzgerald: Right, yeah, absolutely.Listen, I just want to thank you so much for joining me today, and just being willing to go on this journey and answer all these questions. It’s been useful and illuminating for me. And I think my audience, likewise, is going to glean a lot out of this. So thank you so much for your time today, Dr. Longo.
Dr. Valter Longo: Oh, you’re very welcome, thank you.
Dr. Kara Fitzgerald: And we’ll just make sure we link to your site. I’ll throw up some of the key publications that you’ve authored with your team, and we’ll make it available.
Dr. Valter Longo: And I also have a Facebook page, where I just update people on the new studies that I think are relevant and, yeah, so…
Dr. Kara Fitzgerald: Okay, we’ll link over to Facebook as well. Thanks again.
Dr. Valter Longo: Okay, thank you.