Health Longevity Secrets

Is Fasting Healthy?

• Robert Lufkin MD • Episode 179

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This week we look at the secrets to a longer, healthier life in our exclusive conversation with Dr. Walter Longo, a pioneer in longevity and healthy eating! Embark on Dr. Longo's incredible journey, from his transformative experiences with Dr. Roy Walford at UCLA to his groundbreaking research on fasting. Discover how periodic fasting and fasting-mimicking diets can reset your metabolism, and learn about his innovative "summer mode" and "winter mode" eating patterns that can revolutionize your diet.

Ever wondered how fasting stacks up against the ketogenic diet, especially in the fight against cancer? Dr. Longo shares fascinating insights on the metabolic wonders of fasting, the challenges of water-only fasting trials, and the development of the fasting-mimicking diet. 

Get the lowdown on the fasting-mimicking diet (FMD) and its impressive health benefits without the extreme effects of ketosis. Learn about its meticulously designed macronutrient composition and its role in clinical trials for conditions like diabetes, cancer, and autoimmunity. Dr. Longo’s commitment to health, longevity, and charitable causes shines through as he underscores the potential of these dietary strategies to transform lives. Don't miss this enlightening episode filled with actionable insights for a healthier future!

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Speaker 1:

Welcome back to the event. Our guest today will be speaking on all things fasting. You're going to learn how fasting can significantly improve our chronic diseases and also dramatically affect our longevity when you stay to the end. So our presenter for this discussion is Dr Walter Longo. He has over 30 years experience in the field of longevity and healthy eating and is one of the world's experts in the field. Following the footsteps of his mentor and head, roy Walford. Pioneer of studies concerning health longevity, walter Longo is currently professor of biogerontology and biological sciences and director of the Institute of Longevity at the School of Gerontology at USC Los Angeles. He's also director of oncology and the longevity program in Milan. Professor Longo is also the scientific director of the Create Cures Foundation and the Walter Longo Foundation.

Speaker 1:

Now let's jump right in. Hi Walter, thanks for coming on the program. Well, thanks for having me. I apologize, my voice is a little hoarse today, but fortunately my throat's not sore. But I'm so excited about today talking about all things with caloric restriction and fasting and the benefits of it and how we can approach it. But before we do that, I thought I'd reference a little bit of your origin story. I think we both worked with Dr Roy Walford at UCLA. Our paths crossed there. Maybe you could tell us a little bit about that.

Speaker 2:

Yes, so I actually started my PhD in Roy's lab at UCLA. He was in the pathology department and so I joined the pathology. I was first in biochemistry, then I switched to pathology and spent two years in Roy's lab and when I first joined he actually was in Biosphere 2. He was doing the first human clinical study on color restriction, and him and other seven people in Biosphere 2, which was this enclosed environment in Arizona, in the Arizona desert, and so yeah, so that was a very interesting experience that I ended up only staying two years and then moving back to the biochemistry department, because I think you know we it was the explosion of the genetics of aging era and Roy wasn't really, it was not very molecular lab, and so I think, back in the biochemistry lab, I think we got a lot more accomplished in the genetics of aging at least. But I learned a lot with Roy and his team and they were all focused on calorie restriction and the effect of calorie restriction on aging and health.

Speaker 1:

So what is it? Dr Walford was an expert on caloric restriction and you've continued that work on and expanded it to become one of the leading authorities in your own right in this area. So what is it about? Caloric restriction that's healthy, I would think you know. If you stop eating and don't have calories, that's bad, because you starve to death. So what's going on there?

Speaker 2:

Yeah, so actually Walford Roy was working in the whole lab on calorie restriction, and calorie restriction refers to for humans, about 20 percent reduction in calories below the normal level, and uh, but since I, I was at the biosphere too when they came out and they look terrible and uh, you know. So I think that was the day where I thought I'm never going to work on calorie restriction. Right, everybody thinks I work on calorie restriction, but I never worked on calorie restriction and I always thought, I always thought, always thought, how do we get this without this obvious restriction, this very severe restriction, which nobody's going to do? And so first the genetics made sense, and so we keep still working on the genetics of aging, so eventually we can target the genes. But then it was also you know what, if we just fast for a brief period, right, and then go back to the normal diet for a long period, right, so a long period of normal diet in a brief period on a totally fasted state, and that's what I worked on, and so I somewhat pioneered that.

Speaker 2:

You know, people were before me were doing before what we do in the lab. We were doing like long fasting periods, like weeks, right, or they were doing calorie restriction or they were doing this, you know, 14 hours, 16 hours of daily fast, right? So I just introduced this idea of what if you, you know, once a month, once every four months or six months, have this brief four, five, six, seven days of fasting, first started with water only fasting, and then moved to fasting, mimicking diets, and so I mean, and then you know, as you start doing science, you realize that fasting means nothing and calorie restriction means nothing. And it's about what exactly are you doing and to whom, right? And so the same thing, you know, could be very beneficial to somebody and very bad for somebody else, right? So I think that's what I like, to sort of like fuse the FDA mentality with the Walford mentality and say, okay, how do we come up with things that actually can make it to mainstream medicine and be respected and you know, and be standardized, uh, and help people, still using some of the ideas that roy had, which is plant-based, you know diet, right? You know like a plant-based diet. So, yeah, can you, can we use a plant-based diet to then, let's say, coming from the longevity zones of the world, and you combine it with fasting to help people and standardize it and do clinical trials, randomized clinical trials and then to help people stay healthy longer? Yeah, and so sorry for the long answer, but I thought that I had to sort of introduce this idea because otherwise, you know, we just use words that are meaningless.

Speaker 2:

Yeah, so in this particular use of fasting and fasting making diet, what's happening? Two clear things are happening. One is resetting metabolism and the metabolic state of a person, right, why? Well, probably we come from a long history of what I call summer mode and winter mode. So in the summer mode you eat a lot of fruit and you eat a lot of honey and nuts and whatever is available and you become insulin resistant and potentially even become obese, right? This still happens for the emperor penguins or the salt pole. So you get all this fat, you accumulate it because at some point you're gonna face the winter, uh, where you're gonna switch from insulin resistance to insulin sensitivity, and then you burn that fat. So that's one thing, that clearly the fasting, these days of fasting and it's necessary to undergo days of fasting that's one thing that it does Switch from this summer mode to the winter mode Fat accumulating, insulin resistant, fat burning, insulin sensitive Then clearly it takes several days for autophagy and all this multi-system.

Speaker 2:

It's not just autophagy, autophagy is just one of the many things that are occurring, but it's shrinking. So individuals the Ensel keys back in the days, had done these experiments on humans showing that people in semi-starvation, eventually they shrink right and all the organs shrink and then when they refeed they re-expand right. So that that's uh, this shrinking part is associated with a lot of clearing of cells and junk material, and so that's another important thing. And then three is what we see is, you know, turning on of stem cells and then in multiple systems and we see this very clearly, mice and rats, and we're pretty sure it's happening also in people and then reprogramming of cells into a more. You see these Yamanaka factors, these factors that are involved in sort of resetting the youth of a cell right and making it in an embryonic-like stem cell. So we see this Yamanaka factor go up, different Yamanaka factors in different cell types, and then the stem cell get activated right. So these are some of the things that we see during this particular fasting, mimicking, diet intervention.

Speaker 1:

So let me see if I get this right then. So the caloric restriction which Dr Walford was working on is cutting down the number of calories you eat, you know, to 1600 or whatever, and it's arguably one of the most powerful longevity interventions of all time over. You know, historically it really works. The problem is nobody can sustain it and you, you know you look terrible. It's very difficult to do Right.

Speaker 2:

So I will argue yes and no. Right so, based on data, right? So if you look at the mice, eventually somebody did the experiment, right, right? So they took mice that were outbred and all kinds of genetic mixing and they showed that a third of the mice lived longer on calorie restriction, a third of the mice were not affected and a third of the mice lived shorter than calorie restriction.

Speaker 2:

If you look at the monkey study, the monkey study shows that the NIA study after 25 years show no effects on lifespan at all from calorie restriction.

Speaker 2:

The Wisconsin study show an effect on lifespan, but a minor effect, because they seem to be a big effect on diseases like diabetes and insulin resistance, cardiovascular disease, cancer, but then overall the lifespan extension was fairly minor, right, and yeah. So I think the reality is different from the stories that we've heard and the reality is, yes, some people are going to probably benefit a lot from calorie restriction, some people are going to be probably neutral to it and some people are going to be hurt by calorie restriction. So, yeah, so that's probably, and we also saw it in the monkey study. So I would say that that's probably a good way to look at, and so, but the important thing about calorie restriction. It tells us there is something about calorie restriction that can have a big effect on disease and lifespan, and so I mean our quest has been how do we get all of this without having the problems right? How do we get all the mice to live longer, or all the rats and eventually all the people to live longer?

Speaker 1:

So, instead of getting some live longer, some live shorter with calorie restriction. Getting some live longer, some live shorter with calorie restriction. Instead, you've taken the approach of fasting, where you go to essentially zero or low calories for a short period of time, you know, five days, seven days, something like that. And now what are the benefits of fasting? Is it the same as caloric restriction, the same types of things you talked about on a molecular level?

Speaker 2:

Yeah, as I was saying, the ones that I listed, you know, the switch of metabolism, the autophagy, the stem cell, the Yamanaka factors, the shrinking re-expansion, all of that is from fasting and fasting mimicking diets. You know we used to do water-only fasting and we still do some of it. But even the mice struggle with it. And so we, when we did that many years ago, the first trial at USC and Norris Cancer Center with water-only fasting, I think eventually we had to stop that trial because it took so long I think it went on for 10 years.

Speaker 2:

Right, it was so difficult to recruit people on water-only fasting because most of the cancer patients, even though we thought they would be very motivated, they would do it and the oncologists would go for it and of course the oncologists you know, debbie Quinn and Tanya Dorff, et cetera, they were very supportive but still the reality was it was very difficult to recruit people. Patient did not want to do water-only fasting, they felt cheated by it. And so you know that really gave us the motivation to apply and get funded by the NIA and the NCI National Cancer Institute for the fasting-mimicking diet, right, so, and that's almost exclusively what we've been working on, and that's almost exclusively what we've been working on, and it's not necessarily. I mean it's 50 to 70% calorie restricted. That's what it is, and it's only for, let's say, four to seven days. Most of the times it's five days.

Speaker 1:

Now, when people fast for four to seven days, their metabolism switches. Our audience has heard about this before, but they switch from burning glucose to primarily burning ketones. They go into what's called ketosis as a sort of healthy response to that. Now what are the benefits of fasting versus the benefits of? Some people go into ketosis through fasting, but some people go into ketosis through a ketogenic diet where they have low carbs and they turn mTOR down and AMP kinase up with ketogenic diet. Are there additional benefits? If someone's on a ketogenic diet, are there additional benefits for them to fast also, or are they the same thing or similar effects? Rather, they're not the same thing, but do they have similar health benefits?

Speaker 2:

Well, the ketogenic diet, you know, if you think about the very low carbohydrates say less than 10% or the calories coming from carbohydrates, the short-term data is very good that's what we were talking about earlier right, it's very good, right? So, lots of benefits. The long-term data is terrible, right? So, both in mice and humans, right? So if you look at the meta-analysis on ketogenic diet and longevity I think it was a Lancet study, but there's several it shows that it's better to have an 80% carbohydrate diet than a ketogenic diet, than a low carbohydrate ketogenic diet. And so I think that we're mixing short-term benefits with long-term benefits.

Speaker 2:

And I also say I like to look at pillars of longevity, like epidemiological studies, clinical studies, basic research, et cetera, and you know so, centenarians are one of the pillars actually. So if you look at epidemiology, the ketogenic diet is associated with a shorter lifespan. And if you look at centenarians I never met a centenarian on the ketogenic diet is associated with a shorter lifespan. And if you look at centenarians, I never met a centenarian on a ketogenic diet. So I think that you know, you start putting it together. And even in the mice if you look at the Simpson work with mice, the mice on a low-carbohydrate diet did terrible, longevity-wise right.

Speaker 2:

So I think, in general, low-carb, high-protein, right, and that's what a lot of people that do ketogenic diets have because you have to get the calories from somewhere, right. So there are some ketogenic that are low-protein, very high-fat, you know. So those are. You can argue they could be more beneficial, but I mean yeah, in general. Yeah, the longevity diet is not positive for ketogenic diets. It doesn't mean that people cannot benefit from doing short periods of ketogenic diet, but overall, I think you know, relatively, at least 40% of calories should come from carbohydrates and yeah, so those, if it's mostly plant-based, those seem to be the ideal diets.

Speaker 1:

Yeah, I could see where if you increase the protein on going a ketogenic diet and you lower the carbs and replace it with proteins, there'd be problems with the protein. But are you saying also with people who basically keep proteins constant but lower the carbs, increase the ketones and fats? That's also problematic for long-term survival in a ketogenic diet.

Speaker 2:

Yeah, I'm saying that the overall animal-based ketogenic diet that's going to have high protein or very high protein animal-based, and very low carbs, it's going to have tremendous benefits because you're going to see and that's a problem with the Atkins and all of that you know for decades that people do it and they have benefits, uh, short term and they fall for it and then, most of the times, they regain. It's very difficult to to continue and they regain the weight and and and the problems, but but they get the short-term benefits and that's why it, after 50 years, is still around because, uh, it has a tremendous, uh short-term benefit. Most people will have a high protein, high animal-based proteins, and then I think they fall into what the epidemiology is showing, which is you're probably not going to live very long. It's not clear why you're not going to live very long or are you going to live shorter, but that seems to be pretty consistent. Also, looking at the animal data and what Simpson has done and, by the way, simpson is the Australian lab when you look at this, they look at all kinds of dietary combination, right. So, high protein, low protein, high carb, low carb they did not have an opinion. They looked at like over a thousand mice and lots of groups, and then they say, well, let's see, let's see which one lived the longest, and it turned out to be high carb, low protein.

Speaker 1:

And so what is it about fasting that has so many benefits to not only longevity but chronic disease? We're seeing the fasting and turning down mTOR and you know some of these are in ketosis, I guess, with the fasting. But they get benefits of cardiovascular disease, of course, type two diabetes and you know things like cancer and even Alzheimer's disease. What's the unifying factor? Is it the things you mentioned already, the autophagy and all the benefits with fasting?

Speaker 2:

I think it's all of the above right? So if you look at, we've done 15 years of studies on cancer and that's one of my lab in Italy is actually focused on cancer and usually a cycle of fasting or fasting-mimicking diet is as good as a cycle of chemotherapy against the cancer cell, right? Almost in every study we've done. I mean, it's not going to cure any mouse, but just like chemotherapy, it's not going to cure the mouse, but it's going to slow down the cancer progression, right? So now, yeah, so just thinking about that is in our hands, at least in most cancers, a cycle of fasting-mimicking diet is as powerful as a cycle of chemo, with the difference that is helping the normal cells, it's killing the cancer cells, helping the normal cells, whereas the chemotherapy is damaging everything. So, yeah, so that's just one of the many things that fasting does, and I think the biggest thing is the ability, especially this longer fasting mimicking diet, to distinguish between damaged cells and healthy cells. And it would not be surprising if this was an evolved role for fasting, right? So let's use fasting to determine which are the rebel cells and which are the functional ones, right? So if I fast, a human being, if you're not responding to fasting. You are not normal, and so the immune system can attack you. And that's exactly what we see, right, the fasting promoting T cell dependent attack of the cancer cells. And. But exactly what we see, right, the fasting promoting T cell dependent attack of the cancer cells. And.

Speaker 2:

But it's very sophisticated. And that's why you think about an evolved process, because when you look at autoimmunity, the opposite happens, right. So it's like, if you think about cancer, the immune system becomes stronger, recognizes the cancer cell and attacks it, and if you think about autoimmunity, the immune system gets weaker or not generally weaker, but the cells that are attacking self are being killed preferentially, right. And then you have to say well, I don't know how to do this. It seems very sophisticated, it cannot be coincidental, right? So, yes, that's why we haven't proven it yet. It's difficult to prove that this is an evolved process, but it may be an evolved ability to go after dysfunctional components, whether it's a cell that is not working properly, do autophagy, or you kill it, you turn on the stem cell and make a new one, right? So so you have all kinds of tools to rejuvenate. And this is why we just published on two clinical trials showing 2.5 years of biological age reduction after three cycles of the fasting mimicking diet.

Speaker 1:

And so you mentioned the fasting mimicking diet a little bit maybe before. What exactly is that? It's a diet that mimics the effects of fasts. Could you explain that?

Speaker 2:

Yeah, so the lab was always focused on, since my years at UCLA with bacteria and yeast, always focused on the connection between nutrients and signaling pathways, right? So, understanding what glucose does, what each amino acid does, et cetera, et cetera, and what fat does. And we came up with a fasting vegan diet which is a low calorie, low sugar, low protein, high fat diet and that was designed and developed to match the effects of water-only fasting on several markers of what we call starvation response, right, igf-1, igf-bp1, glucose and ketone bodies. That's what we were trying to match those changes up and down of those four. And then, when we match it, then we consider that to be a fasting-making diet. What does it mean? It just allows you to eat, not a lot, but it allows you to be a fasting-making diet. What does it mean? It just it allows you to eat, not allowed, but it allows you to eat about half of what you normally eat, and but it does so in a quit, a composition that tricks the system and and allows it to enter a fasting response mode.

Speaker 1:

Yeah, so to be clear, it's different from a ketogenic diet in that it is low hypocaloric, right, so you're not zero calories, but it's a little bit of caloric restriction. So, people who are on a ketogenic diet, it's not the same as a fasting, mimicking diet. If you want to do that, you need to drop your calories down. Am I getting that right?

Speaker 2:

Well, it's much more than that. First of all, it's a relatively high carb diet, right, the fast-treating vegan diet is about 45% of the calories. It's heavily restricted in calories, but then it's about 45% carbs, 45% fats and 10% protein, so it's very low protein. It's all plant-based protein, so extremely low levels of certain amino acids. So it's it's truly designed as what we call a nutrient technology.

Speaker 2:

Then we want for people to just be food, but it's not just food to us, right? So to us is trying to achieve very exact changes in the blood, in in the markers in the blood. And uh, yeah, so it's got nothing to do with the ketogenic diet, although both the ketogenic diet and the fast-treatment diet cause elevated ketone bodies, and in our case, we did not want these ketone bodies to get too high. So we don't want the seven millimolar levels of ketone bodies because we are afraid about this yo-yo ketogenesis. Right, it continues up and down, right, so maybe it's being over-careful, but that's how I think about the FMD. The fast-dermatogen diet, is something that should never hurt anybody, and you know even one person, and maybe this is impossible, but that's the way we look at it, right, you know, it should be so carefully designed and implemented that, it'd be difficult to imagine how it could hurt anybody.

Speaker 1:

Yeah, and this fasting mimicking diet is available not only for for consumers any, anybody can purchase it, correct? It's also available for certain. There are variations of it. Now that you're I know you're working with some insurance companies to get reimbursement for it for certain diseases as a treatment or a supplement for that. Is that correct?

Speaker 2:

correct? Yeah, I don't, you know, I'm just speaking as a long ago of you.

Speaker 1:

Okay, yeah.

Speaker 2:

So there is a company, I started a company. I'm not, you know, I'm not hiding it I give everything to charity. I don't take consulting from the company. I don't take, you know, anything from the company and you know all the, the, the, the shares of the company. If it goes public, eventually it'll be donated to charity. Shares of the company If it goes public, eventually it'll be donated to charity.

Speaker 2:

But yeah, I always thought it was very important to have the company and 15 years later, I'm glad I did it because otherwise we have so many clinical trials right now and the company has been instrumental also in providing the kit to any hospital in the world that asked for it and, without asking too many questions, just say, go and do it, do what you want to do and do it independently, and then, hey, let's hope that it's positive.

Speaker 2:

But you know, and that's been what I really pushed very hard for and it's working out right. So now we have trials on diabetes from University of Heidelberg, trials on diabetes from University of Leiden, cancer trials from many different cancer centers around the world. Stanford now is working on autoimmunity and, yeah, so it's been. I don't know, maybe over 25 trials and many more going on, and I think that without the company, that would not be possible, and without the company, I think it would have been very difficult to then get the product out to the people in a fairly inexpensive way, right? So, yeah, so I'm happy that this happened, but I'm out of it, right, meaning like I don't have any commercial role or the company's run by the CEO, and yeah, so they do what they do.

Speaker 1:

Absolutely, and I respect that. We'll have somebody else, we'll invite someone from the company to talk on a program and they can go into that. But it's really amazing work that you've done and it's being done. And how can people follow you on social media or what's your website falter if they want to hear more about the work you're doing?

Speaker 2:

yeah, so we have two foundations, uh, one with my name and one is called create cures, and then I'm on instagram and I don't run. I mean, I, I'm involved, but I but the foundations run them. And Instagram and Facebook, those are the major two social outlets that we run.

Speaker 1:

Great. Well, thank you so much, walter, for spending time with us and sharing your experiences on this, and thank you so much for the great work you're doing.

Speaker 2:

Thanks, thanks and best wishes with your summit.

Speaker 1:

Wow, we've learned about what calorie restriction is compared to fasting, and how fasting itself is different than a ketogenic diet, and how all of these things can actually benefit not only our longevity, but a host of chronic diseases. I want to thank Dr Walter Longo for joining us today and sharing his amazing knowledge. Remember that Dr Longo is giving a bonus to our VIP Pass members, so if you haven't claimed your VIP pass or access to recordings, transcripts, mp3s and, of course, our must-have bonus package, you can get it now by clicking the button on this page to upgrade before it's too late. Remember that when the event is over, the recordings and all the bonuses go away. So make sure you claim your VIP pass before it's too late.