Episode 352: Special Guest: Dr. Valter Longo, Fasting Mimicking, Nutritional Science, Cellular Rejuvenation, Reproduction & Lifespan, Calorie Restriction, Autophagy And More!
Welcome to Episode 352 of The Intermittent Fasting Podcast, hosted by Melanie Avalon, author of What When Wine Diet: Lose Weight And Feel Great With Paleo-Style Meals, Intermittent Fasting, And Wine and Vanessa Spina, author of Keto Essentials: 150 Ketogenic Recipes to Revitalize, Heal, and Shed Weight.
Today's episode of The Intermittent Fasting Podcast is brought to you by:
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SHOW NOTES
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The Melanie Avalon Biohacking Podcast Episode #115 - Valter Longo, Ph.D.
Valter's history
How animal studies compare to human studies
How the body regenerates itself
Pre-programmed cellular death
Timeline of reproduction within lifespan
Fasting & calorie restriction
Listener Q&A: Melanie - What level does he think is low protein? Does he think it is best to alway be low protein or is it ok to cycle between low and moderate or high protein diets?
Listener Q&A: Laura - Is there a way to mitigate muscle loss on an extended fast?
Listener Q&A: Shelley - Does the fasting mimicking diet really protect you from losing lean body mass? He says the glycerin drink that's included in the ProLon kit is supposed to protect you from losing lean body mass.
Listener Q&A: Heather - Have done several rounds of FMD. Wore a CGM and it spiked my glucose significantly - how is this mimicking fasting?
Calorie restriction & lifespan
FMD trials
The anti-cancer properties
Listener Q&A: Candice - What’s considered an extended fast—36 hrs, 48, etc? And what happens during each phase—like when does autophagy peak?
Stem cell regeneration
The differences in sexes
Listener Q&A: April - Am curious if his guidance differs for perimenopausal women vs. other groups but will see if he covers that in his book.
Listener Q&A: Tabitha - Do extended fasts or fasting mimicking diets affect women’s hormones and should they only be done at certain times of the monthly cycle? Curious to know especially during the perimenopause time of life?
Is ProLon appropriate for any age?
How ProLon works
Can you tweak the fasting mimicking diet?
Daily time restricted eating vs fasting mimicking diet
Breakfast skipping
Listener Q&A: Stephanie - How can I live to 180?
Our content does not constitute an attempt to practice medicine and does not establish a doctor-patient relationship. Please consult a qualified healthcare provider for medical advice and answers to personal health questions.
TRANSCRIPT
(Note: This is generated by AI with 98% accuracy. However, any errors may cause unintended changes in meaning.)
Melanie Avalon:
Welcome to Episode 352 of the Intermittent Fasting Podcast. If you want to burn fat, gain energy, and enhance your health by changing when you eat, not what you eat with no calorie counting, then this show is for you. I'm Melanie Avalon, biohacker, author of "What, When, Wine" and creator of the supplement line AvalonX. And I'm here with my co-host, Vanessa Spina, sports nutrition specialist, author of "Keto Essentials" and creator of the Tone Breath Ketone Analyzer and Tone Lux Red Light Therapy Bannals. For more on us, check out ifpodcast.com, melanieavalon.com, and ketogenicgirl.com. Please remember, the thoughts and opinions on this show do not constitute medical advice or treatment. To be featured on the show, email us your questions to questions@ifpodcast.com. We would love to hear from you. So pour yourself a mug of black coffee, a cup of tea, or even a glass of wine, if it's that time, and get ready for the Intermittent Fasting Podcast.
Melanie Avalon:
This is a very special episode today with Dr. Longo. We can't wait to hear what you guys think. If after listening, you would like to try the fasting mimicking diet, you can go to Prolonlife.com and use the coupon code IFPODCAST to get 10% off your order of the ProLon FMD.
So that is Prolonlife.com with the coupon code IFPODCAST for 10% off your order of ProLon. And then these show notes for today's episode, which will have a full transcript, will be available at ifpodcast.com/episode352.
So again, Prolonlife.com with the coupon code IFPODCAST for 10% off. All right, now enjoy the show.
Melanie Avalon:
Hi friends. Welcome back to the show. We have a very special episode of the intermittent fasting podcast today with a very special guest. This is somebody that we talk about on this show all the time. We get questions about all the time. We are here with a legend in the fasting world, Dr. Valter Longo, who actually is from USC, where went so it's personally, I'm very excited about this as well. Fight on. So listeners are probably familiar with Dr. Longo, but for those who are not, he is actually the Edna M. Jones professor of gerontology and biological sciences and director of the Longevity Institute at USC. I remember, actually, when I was at USC, I used to always pass that building and it looked very mysterious to me. I don't think I even knew what gerontology was at the time, which kind of shows how far things have come in my life. Dr. Longo, though he has received so many awards for his work from the NIH, he's been recognized by Time magazine. Just a laundry list of things which we will put in the show notes. He's also the author of an incredible book, which I have right here, the longevity diet. I highly recommend it. The subtitle is discover the new science behind stem cell activation and regeneration to slow aging, fight disease, and optimize weight. And Dr. Longo has actually been, he's been on my other show, the Melanie Avalon biohacking podcast, and he's actually been on this show like five years ago now. So it's been quite a while. And I know there's been a lot of developments and updates and so many things. So I have so many questions. Personally, I have a lot of questions from you guys because you had a lot of questions. So, Dr. Longo, thank you so much for being you.
Valter Longo:
Thank you.
Melanie Avalon:
So to start things off, just to get listeners a little bit familiar with your work, and for those who are not familiar, a little bit about your backstory, what made you so interested in aging calorie restriction fasting. I know in the book you talk about wanting to be a rock star when you were younger. So what led you to what you're doing today?
Valter Longo:
I was a music student, actually, in Texas. The University of North Texas had one of the best jazz programs in the nation. They asked me to direct a marching band. And so I said there is no way that I'm going to do that. I was a rock guitar player, so I wasn't going to be a marching band director, and I have nothing against marching band, by the way, but I wasn't going to direct it. So I thought maybe what I always wanted to do was aging. And it was always in my head. And so I was probably 19 years old, and I was sure that I wanted to study aging. So I went over to the biochemistry department, and of course they thought I was crazy because I'd never taken a biology course in my life. And they say that you're not going to last more than three months, but that's not the case. And so that's all I've ever done since. And then fasting came in mostly with Roy Walford at UCLA when I started my phd in 1992, a long time ago. And Roy at the time, was most famous person on the planet for nutrition and aging. And he was, not surprisingly, working on something called calorie restriction. So I started in his lab, but then I left his lab to go back to the biochemistry department and start working not on calorie restriction, but on starving bacteria and starving yeast. So I sort of got the sense from the very beginning, the starvation, real fasting, like water, only fasting was hiding something even more important than just calorie restriction. Calorie restriction just refers to just eating about 25% less calories than normal. But fasting, of course, is no calories at all. And so, yeah, since then, I've been focusing my laboratories both here and in Italy, I've been focusing on fasting.
Melanie Avalon:
I have so many questions already. Just to start with, the animal studies, how much of the aging pathways and everything in the animals, how appropriately do they apply to humans? Is it like a one to one thing, or is it more extrapolations, or what's the comparison there?
Valter Longo:
You mean in general, timing wise, when.
Melanie Avalon:
You find findings in rodents or yeast, how do we know how much that applies to humans?
Valter Longo:
This is why I started working. I went from humans and mice in Walford lab to bacteria and yeast at UCLI and the John Valentine's lab. And because I thought all these organisms have 3 billion years of history, and I thought in 3 billion years, all these organisms have been evolving in parallel. And so I thought there's going to be probably very fundamental laws for what's happening during fasting that apply to all organisms. Now, of course, there's a lot of differences, and you have to make sure you understand them and you apply them. And so that's what we do. So we run lots of clinical trials for that reason. But I think the fundamentals were going to be, I mean, at least that was my hypothesis. The fundamentals are going to be the same. So if you starve a yeast, a unicellular eukaryot, it's going to start shrinking, and then it's going to get into a low aging mode, and it's going to start eating its own components while it's shrinking. And then eventually you feed it again and it re expands. Right. So I thought this is probably something very much conserved all the way to humans. You shrink, you eat your own parts, essentially, while you're doing that, and pick the ones that are most damaged and then turn on programs that are very similar to the embryonic developmental programs. So the same programs that generate organs when you need to re expand. Right. It all makes sense. And that's what we now see in mice, in rats, and we're starting to see this in people. But really, a lot of that started in yeast and bacteria.
Melanie Avalon:
Okay, awesome. Yeah. Two thoughts from that really quickly. One, I think you were pointing out in your book that we clearly, as humans, when we create an embryo, we have the potential to create something that is not aged. It's really interesting that our bodies age, but we still harbor this seemingly inherent potential to create something that is completely young. So how do we apply that to our entire body? Is that just two different systems? Can that translate over? Is there something different that's going on when we're creating embryos versus our bodies aging?
Valter Longo:
Yeah, and this is the big difference between, I think, what we do and what a lot of my colleagues do. Right. So there's a lot of biohacking. And our point has been that the human body already knows how to go back to zero. Right, meaning age zero. But how do you do that? Right, so how do you make a liver or a muscle or a pancreas regenerate itself and go back to zero? And so we've shown that, in fact, you could do this with fasting, mimicking diets and do multiple shrinking, re expansion. Shrinking re expansion. And if you do it enough times, you'll see that actually these Yamanaka factors, these reprogramming, these markers of embryonic development, they turn down, right. And they start the process of regeneration. And then when you refeed, they actually start the process of re expansion and making new cells and more functional cells. For example, we've done it with pancreas. We take the mouse and we damage the pancreas to where it no longer makes insulin. And then we start with the fasting, making diet and refeeding cycles. And you see that the pancreatic cells begin to be reprogrammed, and then eventually they start making insulin again and they become functional again. So we went from a permanently non functional pancreas to a regenerated functional pancreas. So this is just some of the examples. Now, can you actually make it all the way to an organism that is completely young? That's much, much harder. But I think that we're on the right track. Right. And I don't know that we want to make people go back to being 15 years old, but certainly we can rejuvenate. We now know that we can make people younger. The question is, how much younger at.
Melanie Avalon:
The point of death? What do you think is happening there? Because what I'm thinking through in my head right now is the aging of all these different organs and the potential to, I don't know, independently anti age each individual organ, but the body as a whole. What do you think actually happens at the point of death? Is there a system wide message where it's just decided that everything has independently aged enough that we just have to stop all systems? Or what do you think is happening there?
Valter Longo:
We've been working also on the theoretical part, and we're not very busy on that, but we have. And there are two possibilities that we came up with, and one is that aging is actually programmed, right, which is very unlikely. We demonstrated for unicellular organisms. What does that mean? But nobody's ever demonstrated for mammals. So is it possible that there is actually a program to kill us, to get us out of the way so that new generations can have the space and the food and the resources to grow? The evolutionary biologists will say that's crazy talk. There is no way. And maybe it happens in microorganisms but nowhere else. But let's assume that that's not true, then the other part is really, there is something called the force of natural selection. And so what does that mean? Means that the evolution, as the job, is selective for organisms that are very protected, as long as they are still in a phase where they can contribute to the next generation. Right. So let's say for humans, let's say it's 40 to 50. After that, it will make sense. And we know that the force of natural selection goes down, meaning that the force that kept everything working in an almost perfect way is now weaker and weaker and weaker and weaker. So by the time you get to 70 or 80, that's almost gone.
Melanie Avalon:
Right.
Valter Longo:
There's no force anymore. And what does it mean? It means you're on your own and your organs are on your own. There is no help from evolution anymore because evolution doesn't care about that 73 year old person, and in fact, it might select against it, get out of the way. That's why then we die, because we've been on our own for 30 or 40, 50 years by then, and things go progressively wrong. Eventually the system stops it.
Melanie Avalon:
In all of the various animal species, does the timing of when they typically reproduce and the amount of time required to foster those children or the babies, does that correlate to the lifespan of the species pretty equally?
Valter Longo:
Yeah, very much, right? Very much. There was a great experiment done 40 years ago by Michael Rose at UC Irvine, I think. And he took flies, and he took the flies that were reproducing early, and then he took the flies that were reproducing late, right? And he selected them for many generations. Kind of like saying, imagine if we went out and took women that are having children very late in their mid 40s, right? And then we took women that had children very early, 1820 years old. And then for generation, we selected these two groups, right? And then they went back and looked at it. And the flies that were reproducing earlier, they had a shorter lifespan, a much shorter lifespan, and they were very good at reproducing, but they lived a lot shorter. And those that were reproducing until later time or at a later time were selected for reproducing later time. They were not as good early on. They were 80% as good at reproducing, but they were making offspring for a lot longer. And this has been shown in lots of different organisms. And so, yes, so the reproductive span is very much associated with the lifespan.
Melanie Avalon:
Oh, my goodness. Okay. I'm so excited right now because that question haunts me. Do you think that translates over to humans? And so, for example, this is just me being completely selfish. I don't really anticipate having children. Do you think women who don't have children, would that affect their lifespan at all?
Valter Longo:
That's actually been published in many studies. Right. So it's a little tricky because on one side there is an advantage, and then there is a disadvantage of having too many children, probably because people become very stressed out. Right. So I think in the end, there's probably not much of a difference. So that percent doesn't matter that much. And if there is a difference, it's probably a few years. But the point would be if we found a way to postpone making, let's say, women and men reproduce until much later, let's say that we found a way to allow women to reproduce until age 65, then most likely that group of women will live longer on average, or a lot longer on average.
Melanie Avalon:
So fascinating. Okay, one more last animal. Rabbit hole question. The antiaging or longevity programs or mechanisms in the immortal jellyfish, is that the same pathways, or do they have something else going on?
Valter Longo:
Well, the jellyfish, you can look at them a little bit as a colony of microorganisms, right? So if you look at a colony of yeast or bacteria, is the colony immortal? Yes, it is immortal, but does it really relate to us?
Melanie Avalon:
Right.
Valter Longo:
Well, yeah, in some ways, but it's going to be very difficult to translate that immortality of a colony. And so the jellyfish, in a sense, are like a colony that sticks together, right. And of course, it's a more complex organization. So it is closer to mammal than a colony of yeast. But let's say it's an in between situation, right? So you cut something off and it can regrow. Just like if you kill part of a colony of bacteria or yeast, it's going to regrow back. It doesn't really care that you kill some of it.
Melanie Avalon:
Right.
Valter Longo:
And the same is true for certain fungal colonies. Right. That have been discovered to be, I don't know, thousands of years old and been growing for thousands of years now, you could say, is that an organism or is it a group of organisms that simply keep expanding?
Melanie Avalon:
Okay, got you. That makes sense. Okay. Coming back to the calorie restriction and the fasting, a foundational question. I've always had these pathways that are activated, the effects of fasting, are they the same pathways as calorie restriction? Are they different? And also, if you are engaging in different modalities, like fasting and calorie restriction or fasting and protein restriction or all the various things that might be antiaging, do you think those effects are additive or do they cancel each other out? Like, if you're doing one, are you pretty much good, or does doing multiple things add more antiaging potential?
Valter Longo:
Well, I think that, of course, the risk is that if you start doing multiple things that are improvised, that could hurt you.
Melanie Avalon:
Right.
Valter Longo:
So already, calorie restriction, again refers to eating 25% less than normal. Not less than people eat, but less than normal.
Melanie Avalon:
Right.
Valter Longo:
So then a typical male would be, I'm fairly thin and I'm 170 pounds. If I were to be calorie restricted, I would be maybe 145, right? Yeah, it's already pretty extreme. Now, even that, it's not clear that that's going to be beneficial to anyone. I mean, the study Wisconsin, among mean, Wisconsin showed lifespan extension, but the one in the NIA did not show lifespan extension. And so then you will argue that maybe calorie restriction, chronic, color restriction, like the extreme and chronic, it's going to give you a lot of benefits, but not necessarily make you live longer. And in the process, it's probably going to slow down your metabolism and your hunger, et cetera. I would say that I think that the periodic fasting mimicking diet are starting. And protein restriction is another one that I like. And time resistant eating, what Sachin panda has been talking about for decades, those are the things that I like, and I think they are additive, meaning, like if you eat for, let's say, 12 hours a day, maybe a little bit less, 11 hours a day, and then you're protein restricted, but not excessively protein restricted, you got to be careful because you can go from one problem, which is too much protein, to the opposite problem, which is too little amino acids of certain kinds.
Melanie Avalon:
Right.
Valter Longo:
So then timers hit the eating, let's say eating for 1112 hours a day, plus protein, the correct type of protein restriction, the correct type of diet, say pescatarian, what I call the longevity diet, plus the periodic fasting making diet, plus the exercise, that's probably 20 extra years of life expectancy.
Melanie Avalon:
You've mentioned a lot of words that we did get a lot of questions from listeners about, so I'll start bringing some of them in. So on the protein front, I think listeners and even me and my co host Vanessa, when she's here, I think there's a lot of confusion surrounding protein intake. On the one hand, we talk all the time on this show about the importance of actually like, a moderate or high protein diet for muscle growth and just supporting body composition. And I recently interviewed Dr. Gabrielle Lyon all about the benefits of protein. But then, on the other hand, we see these benefits of low protein and how protein associates with aging and dietary protein restriction, the benefits of that. So we had a question. I know, my name is Melanie. This is from another melanie, not me. She wanted to know. She said, what level do you think is low protein? Do you think it is best to always be low protein? Or is it okay to cycle between low and moderate or high protein diets? So, protein, what can you share about this issue?
Valter Longo:
Yeah. Well, first of all, the 20 years of life expectancy that I mentioned earlier is compared to, let's say, a western diet, right? So not compared to somebody that might have another type of positive intervention. So the protein, everybody loves this oversimplification. High fat, low fat eye protein, low protein, high carb, low carb. I think we need to move away from this, right? And I know people like it simple, and I can understand that, but it's not simple. The human body is extremely complex. So the solution is not going to be simple.
Melanie Avalon:
Right?
Valter Longo:
So even protein, you could be on a high protein diet and have deficiency in lots of amino acids, right? So let's say that you are on 100% legume diet, very high protein. Let's say 25% of your calories come from protein. You're still going to be malnourished, right? Because all you eat is legumes. Why? Because legumes contain very low level of a number of amino acids, which are very central for muscle and lots of other. So my recommendation. So we started clinics in the US and Europe from the foundation, and these are nonprofit clinics. And so I recommend, it's called create cures. And I recommend that people consider either talking to people that are dietitians and nutritionists at the clinic or somebody that knows what they're doing. Unfortunately, this low or high is really meaningless. And it could be very damaging because people then may say, oh, I have very good protein intake every day, so I'm good to go, not realizing that they don't, because all they're eating is legumes. Or, I have a reasonable low protein, but it's all from red meat. I'm fine. And again, now you may not be fine just because, yes, you have, say, 17% protein of your calorie in protein intake, but it's all from red meat and you still might have a problem, right? And then it gets more, even more complicated than that because there is phases of life, right? So if you're zero to three is one level of protein, then three to ten, then ten to 18, then 18, all the way to, let's say maybe 25 to 65 70, a relatively low protein diet is good, mostly vegan, but not completely vegan. But then after 65 70, then you have to go higher and have more animal proteins because otherwise you're going to be deficient in certain amino acid.
Melanie Avalon:
Right.
Valter Longo:
So I know it's very confusing answer, but that's because it's extremely complicated and I'm just trying to summarize it in 1 minute. But it's almost impossible, right. To really give. And that's my message here, instead of having an answer is like, please do not think you can get a manual out of 1 hour with me or somebody else because it doesn't work like that.
Melanie Avalon:
You have so many studies published, it's overwhelming and amazing. And I was going down the rabbit hole reading a lot of your recent ones and going like just what you were saying about you can't summarize things in 1 minute, even with your studies. I'll read like one study and then I want to read all the references and there's just so much information. And I was even going on one rabbit hole because it was talking about in the case that they were looking at, I think it was in monkeys, the calorie restriction was actually protective against sarcopenia, which was kind of mind blowing. So it just kind of goes to show how complicated everything is and how many layers there are.
Valter Longo:
Yeah. So calorie restriction causes muscle loss. But then some studies suggest that the lower level of muscle now is more functional than the higher. But again, most people are not going to want to look like they're starving and have more functional muscle. Right. Even there, as you just pointed out, it's a complex answer and it's best handled by somebody that can follow the person and get them to where they want to be.
Melanie Avalon:
So the muscle itself, we got a few questions about that. Laura wanted to know, is there a way to mitigate muscle loss on an extended fast? And Shelly wanted to know, does the fasting mimicking diet really protect you from losing lean body mass? Dr. Longo says the glycerin drink that's included in the prolonged kit is supposed to protect you from losing lean body mass. So what have you seen in your studies and trials with the fasting mimicking diet and muscle loss?
Valter Longo:
Yeah, we've seen that four out of four trials now are showing we're looking at about maybe 300 patients, all ages, no lean body mass loss. Right. So there is a temporary lean body mass decrease during the fasting mimicking diet. I cannot talk about commercial products, but as it is in the box.
Melanie Avalon:
Right.
Valter Longo:
So people, sometimes they complain about all my sugar spiked. Well, that way we tested it is protecting, I guess, muscle loss and is increasing insulin sensitivity and is actually helping reverse diabetes.
Melanie Avalon:
Right.
Valter Longo:
So it works the way it is right.
Melanie Avalon:
Now.
Valter Longo:
If you change it or improvise at home, who knows, right? I don't know, but I can tell you. And some of these trials we didn't do, right. Other people have done, but it works very well the way has been designed. And I think not only it works very well in protecting lean body mass loss and in causing insulin sensitization, but also I think that we worked very hard in making sure that somebody could do this for 20 or 30 years. And it'd be hard to claim that problems come from this diet because we're saying you should probably do it only maybe three or four times a year and that's it, if not less. Right. Depending who you are. Yeah. So I think that we now know we can protect lean body mass. Now, when we combine it with diabetes drugs, that's when we see the lean body mass loss.
Melanie Avalon:
Right.
Valter Longo:
But of course, we don't see it with other diabetes drug. We see it in the diabetes drug. So we're presuming that it is the diabetes drug, it's not the fasting diet that is causing the lean body mass loss.
Melanie Avalon:
Oh, wow. So, like, when it's combined with metformin, people tend to lose in both the.
Valter Longo:
Trial, one was with metformin, one was all diabetes drugs. Then we see the lean body mass loss, but you also see it with the drugs alone.
Melanie Avalon:
Question about those findings and results. Are you finding that nobody's experiencing overall lean body mass in the end, or are? Some people are and some people aren't, and it averages out to them not. I'm just wondering if people respond differently individually or is it pretty consistent?
Valter Longo:
It's generally consistent, but some people, we'll have to look at the scattered plots, but some people probably, on average, they don't. But some people are probably going down and some people are going up in muscle mass. Right. If somebody was doing it and they clearly saw. But to know if you're losing muscle, you will have to get a daxa or something similar. Right. Because, well, there is some devices that can measure impedimentiometry. They can measure, but those are probably not very accurate. So if you get a Daxa, you'll know if you in fact lost muscle mass and bone density. If somebody was in that category and for whatever reason they think it's a fasting making diet, then that's something to keep in mind. But the issue is also, how frequently are you doing it? Because if somebody was to do like the trials that I just told you on, diabetes is once a month for six to twelve months.
Melanie Avalon:
Right.
Valter Longo:
So we're not recommending anybody else does that. So that means that you're doing it six times in six months or twelve times in twelve months. And that may also be why we see some lean body mass loss. My point being that if you do it once a month for three months and then you stop, then you have all the opportunities to regain your. Even if you wear among the small percentage for whom lean body mass is reduced, then you have an opportunity to regain it.
Melanie Avalon:
Is there a difference in people who are obese or overweight versus people who are normal weight with the muscle loss?
Valter Longo:
No, there isn't. So we looked at normal weight and we looked at at least two trials normal weight and two trials on overweight and obese. No lean body mass loss in the absence of other drugs. And in the one we just finished in Italy, there was even six cycles in six months and still we didn't see any muscle and lean body mass loss.
Melanie Avalon:
You said there is a temporary loss. How fast does that come back? Is it right after they stop within one week?
Valter Longo:
We measured that one week after and it's already back.
Melanie Avalon:
Wow. Okay. You were talking about how people were saying that it spiked their blood sugar and the implications of that. So maybe just to revisit it one more time, because Heather literally had that exact question. She said that she's done several rounds of the FMD diet, fasting, mimicking diet. She says, I wore a CGM on a recent round and the soup spiked my glucose significantly from around 70 to 160. How is this mimicking fasting when consuming soups causes a huge insulin spike. So that actually adds another question. Is that still fasting? If you're getting that high blood sugar response?
Valter Longo:
We're not trying to have an identical effect to water only fasting. That's not our purpose. Our purpose is to make people live longer, younger and healthier.
Melanie Avalon:
Right.
Valter Longo:
And so from all the trials we see, so if somebody sees the 160, they will say, okay, well, this is going to make me gain weight and this is going to make me insulin resistant. But yet trial after trial after trial, we see exactly the opposite. Right? And then even trials, like, know, completely independent of us. Or, you know, all these trials have been done by other people, by big universities, because people can say, oh, there is a product behind it and there is some attempt to. These are independent trials and that's what they found. Right. So then the spikes may actually be beneficial to maintain lean body mass and maybe even they may be beneficial to get this impressive sensitization to insulin. Right, that we see in a short time. Now, we are also going to try to test versions that have a lot lower starches and they have a lot lower carbohydrates. So we'll see. But I think we've been doing this for ten years in the clinical setting and it's going to take us a while to beat the effects that we see now. For example, Heidelberg saw a one c dropping from, I think, 8.1 to 6.7. Very impressive change in diabetic patients.
Melanie Avalon:
Right.
Valter Longo:
And I'm sure lots of them were getting the same spikes, as this person is saying. So again, I'm very worried. People are just going home and getting the continuous glucose monitor, seeing one piece of it and then concluding that this is bad for them, very dangerous. But I'm all for people checking themselves and that's good, but don't come to conclusions because that's not the way it works. We'll see. And I wouldn't be surprised if when we tested with lower glycemic spikes, that we start seeing less effects.
Melanie Avalon:
So, interesting. And actually, I was reading last night one of your. I think it was more recent, it was a study, it was called diet composition influences the metabolic benefits of short cycles of very low caloric intake. And it was looking at very low caloric intake with a standard laboratory chow in rats compared to plant based fasting mimicking diet. I'm just curious because it was saying that a long lasting metabolomic reprogramming in serum and liver is observed in mice on very low calorie intake cycles with standard diet, but not fasting mimicking diet. Do you know the diet that I'm referring to? I'm wondering if that was a. I.
Valter Longo:
Think I'm among the.
Melanie Avalon:
Yeah. Yes. Was that a beneficial metabolomic reprogramming with the standard chow?
Valter Longo:
This is a study by Rafa de Cabo, and this is the way, probably the graduate student that was working on it saw it. But now we have lots of mouse lifespan studies, even mice on a high fat and a high calorie diet. And this we published a few years ago. So it's taking that short window that you saw in the paper, and it's taking a lifelong.
Melanie Avalon:
Right.
Valter Longo:
And we're showing that, remarkably, it is a natural metabolism paper from two years ago. Remarkably, the fasting making diet only once a month is able to reverse all the problems caused by the high fat, high sugar, high calorie diet.
Melanie Avalon:
Right.
Valter Longo:
So the heart effects, the insulin sensitization, the insulin resistance, and the effects on cholesterol effects. Yeah. So I would say now we have lots of mouse, rat and human data. It's pretty consistent. It's almost like it's a little bit too good to be true. So I would now, hopefully, we're going to get some negative results, because so far it's been working even much better than we expected. I always think whenever I saw the Heidelberg study, they did something very similar to the paper you're referring to. They did five days of a mediterranean diet a month. Right. In diabetic patients. Five days of a mediterranean diet a month against five days of the FMD. And when I look at the paper, I think they probably did it to show that the FMD is pointless. The mediterranean diet is going to work. I mean, I don't know. Right. But I suspect that that's what they were trying to do. But sure enough, the mediterranean diet is worthless five days a month. And the FMD causes remarkable effect. And go look at it, because it's really impressive differences between this maybe a little bit calorie restricted, very healthy diet and the FMD.
Melanie Avalon:
So now I'm super curious, in your history of running all these trials, what was the biggest, surprising finding for you? Or it doesn't have to be the biggest, because that's a big question. But what was, like, a big, surprising finding for you maybe sometime where you thought you would find one thing and you found the opposite or. Yeah. What has been surprising in your FMD trials?
Valter Longo:
I think that the effects on cancer have been remarkable and thus far. And I think at the beginning, we will have expected kind of like what you see with the ketogenic diet. Right. So you see working against cancers, lots of cancers, but actually helping some cancers grow faster.
Melanie Avalon:
Right.
Valter Longo:
So the ketone bodies hurt a lot of cancers and help some. And I expected that from the fasting mixing diet. I truly did. And I'm surprised that after 20 years, we haven't seen that. Right. And I expect it. But really, like, another two papers were published just this week on the fasting McGinn diet and cyclic fasting. It just keeps on working in all the models that have been tested. So, for example, a paper that just came out in cancer research this week by a chinese group showing that the fasting mimicking diet is causing b cells to start attacking the cancer. So another novel colorectal cancer in this case, right, in mice. Yes. So I think that that's surprising, right, after all these labs and all these attempts, and nobody yet has come up with negative effects, but I'm sure it's going to happen. But it hasn't happened yet. So, very happy about that, but also very surprising.
Melanie Avalon:
Do you have a theory as to what the fasting mimicking diet might be circumventing or avoiding? That is the problem for why ketogenic diets sometimes support cancer.
Valter Longo:
My theory is the following. Is it possible the starvation for human beings represented an opportunity, kind of like sleep, right? So an opportunity to get rid of damage component. Right. Something that is under the force of natural selection that I mentioned earlier for the purpose of distinguishing good from bad. And so you only do it during fasting and not necessarily when you have a lot of food. Right. And why? Maybe because the bad becomes food for the person.
Melanie Avalon:
Right.
Valter Longo:
It's a lot of speculation, but is it possible because, let's say precancerous cells, cancer cell, autoimmune cell, insulin resistance cell, senescent cells. So imagine all of this is food, right? So you don't want to throw it away. So maybe because we starve so frequently, maybe that was left around to become food when we don't have any food coming from the outside.
Melanie Avalon:
Because I'm not sure exactly which cancers are supported by ketogenic diets. But do you know if they've done calorie restricted ketogenic diets in those situations?
Valter Longo:
No. These are normal calorie ketogenic diet, right?
Melanie Avalon:
Yeah.
Valter Longo:
So of course, the FMD is a calorie restricted ketogenic diet, but they've done usually normal calories, right? Yeah. So of course the normal calorie, if there was a program that was signaling go after the damaged cell because we're starving. So the normal calories now will prevent that, right. And say, well, we're not starving, we're just getting the calories from somewhere else. And so maybe that's why we see both. Because, yes, the ketone bodies may be part of the program to kill cancer cells, but the ketone Bodies may also be part of the fuel for certain cancers.
Melanie Avalon:
Okay. And then speaking of self eating and breaking down these things, so we do talk about autophagy a lot on this show. And that's another thing where I think it is so presented as black and white and autophagy is on, autophagy is off, when in reality, autophagy is probably occurring all the time to different levels, and it's probably way more complicated than the way it is often presented. So in your trials, can you actually measure autophagy? So do you guys measure autophagy? Candice wanted to know when autophagy peaks. She says she's seen charts online, but who knows what type of science that's based on.
Valter Longo:
Yeah. Now there are trials to look at the FMD and autophagy. We see it in mice after a few days and probably maybe by day three, that's when. And it also depends in which cells, in which organs. So it's going to take a while to know how much autophagy is going on in how many systems. But autophagy, I think is just a small part of what I was talking about earlier, this shrinking re expansion. So one of the components is autophagy, but there is probably also cellular killing, as I was mentioning earlier, and using cells for fuel, the reprogramming of cells, the stem cell activation, the stem cell cells renewal. So there's probably a big program to remove damaged components and then regenerate. And autophagy, I speculate maybe 20% of the whole operation.
Melanie Avalon:
Got you. For the stem cell piece. Do you find that it affects both the release of stem cells? Does it increase the amount of stem cells? How all, does it affect the stem cells in the body?
Valter Longo:
Yeah. So of course, in humans, we're just beginning to look at it, and we did have some initial evidence that we published on circulating stem cells. But in mice, for example, the metropoietic stem cells, those in the blood that give rise to all immune cells, they increase in number and then they increase in self renewal properties, meaning they start producing more of themselves.
Melanie Avalon:
Right.
Valter Longo:
So stem cells get activated and make more stem cells. And then this is associated then in the mouse with a rejuvenation of the immune system and a restoration of damaged immune system, more stem cells and more active stem cells. But in some other organs, we don't see the stem cells going up. We see the reprogramming of cells happening and the Yamanaka factors. So we think that it can go both ways. One way to achieve it, more stem cells, another way to achieve it, take a somatic cell, reprogram it into an embryonic like cell, and then do the job and then go back to a differentiated cell.
Melanie Avalon:
Wow. So fascinating. We got a lot of questions about women specifically. So I guess first, as a foundational question for me, when you're doing these, the majority of your studies are they split populations of male, female. Do you test in women specifically? So are there sex differences?
Valter Longo:
We haven't seen it yet. Now, we really tested the FMD on thousands of patients in informal clinical trials, right. At least over a thousand, probably between cancer, diabetes and all the other diseases, Alzheimer, et cetera. Probably, you know, maybe 1500. So far, there wasn't, there hasn't been anything that is so evident that it works in male, doesn't work in female, or vice versa. But I think as we have more bigger numbers for specific changes. So let's say, for example, a one c or fasting glucose or cholesterol, then at some point, I think once we have, let's say, 300 males and 300 females that have done, say, three to six cycles of the fasting making diet, then we can go and compare them and see is there actually a difference in the response of males and females? But clearly they both respond. And all the trials thus far have been mixed with males and females.
Melanie Avalon:
I'll read two of the questions I got about it specifically. So April, she said, great timing. She said, I just started his book today, and we'll do a round of prolonged when I'm done. I'm curious if his guidance differs for perimenopausal women versus other groups, but I'll see if he covers that in the book. And then Tabitha, she said, do extended fasts or fasting mimicking diets affect women's hormones? And should they only be done at certain times of the monthly cycle? Curious to know, especially during the perimenopause time of life. So do you have any guidance there?
Valter Longo:
Yeah. So lots of people are asking about this. We haven't got reports of, let's say, in the cycle. The FMD is done early on versus late. We haven't gotten reports from people saying it clearly works best in one part of the cycle or another. And so far, we haven't tested around menopause, before menopause and after menopause, but it's certainly been tested on women in all those stages. And thus far, we see pretty clear results in all stages. Also, because some of the trials might have had half of the women pre menopause and half of the woman postmenopause. And it works as a group. And so I think we will have seen problems if it was just specific for a stage of life. But again, as I was saying earlier, and I encourage people to write to us and say, I'm in this stage and this is not working for me. And you never know. This could motivate a clinical trial on a specific population, but thus far we haven't seen it, but it doesn't mean that it's not there. So it could be that something works a lot better in certain groups, but I think that the effect is so powerful that probably most people benefit regardless of the stage. But, yeah, maybe some will benefit more.
Melanie Avalon:
Okay, got you. Yeah, that'll be exciting to see future as you get more and more and more feedback with that. That actually made me think of another question. When you're talking about when to do it, age of onset of implementing fasting, mimicking diet, or really anything, but I guess I'll keep it specific to fasting, mimicking diet. Is there a difference in when people start implementing this as far as the potential benefits that they see, or is it pretty much whenever you start it, you'll be good?
Valter Longo:
Well, I think that it all depends, right. For most people, they're going to have some issue. It's going to be beneficial. Now, we see effects on cholesterol, some of it. A bunch of this has not been published yet, but let's say we see clear effects on an ldl, we see effects on blood pressure, a1c, we see effect on abdominal weight. Again, no loss of lean, body mass. So if you think about all those things and see reactive protein in multiple trials, it goes down, inflammation goes down. So I would say the great majority of people are going to have some issue in this arena. If you think about the Americans, people in America, 75% are overweight and obese, right? And maybe probably 85% have some weight issue. So that means that 85% of the people will clearly benefit. Now, we've been talking about, if you just think about the weight and nothing else, right? But probably 95% of people benefit if you think about the weight and all these risk factors for diseases. So we've been talking about 20 to 70 now. We just finished the Alzheimer's trial in people up to 85. And I think the results are surprising in a good way. We expect that people having problems, but we didn't see that and becoming frail and we didn't see that. And also we're doing trials in the very young one, down to six years of age, in the type one diabetes trial in Gaslini children's hospital. And so now we've been talking to people about the possibility of running a trial in the young, maybe not so young, but maybe like say 14 to 18. Is it possible that maybe this is a great way to give them these five days of a vegan diet? It's a great way to educate the brain of a younger individual without forcing them to eat less or change their diet. And so with the hope that they get there on their own. Right. That's another thing that we didn't talk about. But these five days of a vegan diet, low calorie fasting, mimicking vegan diet, they have such a beneficial effect on people that we see lots of people basically gravitating more towards vegan nutrition. Could it be that in children, in the teenagers, this is going to be a good way to train the brain to behave in a different way without imposing diets?
Melanie Avalon:
I imagine that's a lot harder to conduct those trials. Probably getting like consent, I guess, or getting it approved to do it in the younger populations.
Valter Longo:
It was not an issue. But in the Gaslini children's hospital in Genova, Italy, is inpatient. Right. So they have to check into the hospital. But these are very young, like down to six years of age and with type one diabetes.
Melanie Avalon:
Right.
Valter Longo:
So, yeah, I think that we've been talking here at Chla with different faculty doing in the 14 year old, 14 to 18. I think it should be pretty straightforward. I mean, they're still getting 800 to 1100 calories a day, so the risk is really minimal. But, yeah, of course, I love to go through their ethical committee approval as.
Melanie Avalon:
Far as actually doing the fasting and mimicking diet because I realized we kind of just jumped in. Could you just tell listeners briefly what the ProLon program looks like? And then I have a specific question about how it can be implemented. But in general, it's five days or. Yeah. Would you like to just tell listeners a little bit what they should expect?
Valter Longo:
The FMD that we've been testing in lots of trials, there is different version. There is a version for Alzheimer's. There's higher calorie. There's a version for cancer. It's a lot lower calories. There's a version for autoimmunities that it's a different composition. But let's say the one for normal people that's been tested so much, I cannot name commercial names, but let's say that one is 1100 calories or so on day one, and then it goes down to 800 calories on day 2345. It's a low calorie, low protein, high fat, plant based, and it's relatively high in carbohydrates, even though it's very low carbohydrate. But I mean, composition wise, it's relatively high, and that's by design. I did not want people to cycle between high ketogenic state and low ketogenic state. And it's maybe out of being over cautious, but that's the way I like it. So I was always worried that if you get to severe ketogenic states or very high ketone bodies and then back and you keep going back and forth enough times, that could eventually cause problems. And I don't have any evidence for that, but I was afraid of that. And that's why, by design, the FMD is relatively high in carbohydrates, even though, because it's so restricted, it's still a very low level of carbohydrates.
Melanie Avalon:
So that possibly sort of answered my question. My question was, so I personally do a one meal a day approach with intermittent fasting. I think I talked about this before, last time I had you on the show, but I eat like, very high protein and then I fast during the day. So with the fasting mimicking diet commercial version, would I be able to do it in a one meal a day approach and have all the meals at once, or it sounds like that would be the antithesis of what you were potentially nervous about happening.
Valter Longo:
Not necessarily because the FMD, again, let's say that you do it three times a year. That's not really going to. So you could do it either way, right? You could try to compress it. It'll be hard to do for you. But if you already do it like that, it is possibly doable in one meal a day, and this is only for five days, and then you go back to whatever it is that you do, right. So I think that it can be done like that, but it would not be easy, let's say, to have the two soups and the bars and all the other things that are in there all in one shot. But it's doable. But it's also not necessary, right. For those, say, 15 days a year, you could have your regular meals, say, morning, noon and evening.
Melanie Avalon:
So basically, the comparison between daily intermittent fasting all the time versus fasting mimicking diet however many times a year, but then not fasting the rest of the time. I mean, I don't know if it's a comparison where you're like, oh, this one's better, this one's not, but you're seeing similar benefits. I don't want to put words in your mouth. What are your thoughts on that comparison? Because a lot of the audience is doing daily intermittent fasting.
Valter Longo:
Yeah, I mean, the daily intermittent is not intermittent fasting. I think I like such impanda's time restricted eating, meaning like, eat within so many hours a day. And I think that's a very good practice in addition to the periodic fasting making diet. So I recommend 1112 hours of food consumption because as you get to the 16 hours, you start seeing gallstone issues. If you skip breakfast, you see this is associated with a shorter lifespan. So the breakfast keepers, they tend to live shorter than the non breakfast keeper. Now, of course, it could be that the breakfast keeper have a terrible lifestyle, et cetera, et cetera, but that's not a good start. And this is why I usually say, if you're going to skip, skip dinner and fast for 16 hours or whatever, probably better not to skip breakfast. Now, it doesn't mean that you cannot be a breakfast keeper and live to 100, but the epidemiological data suggests that in general, the breakfast keepers live shorter, have more cardiovascular disease, et cetera. They're compatible. So you could do, let's say eleven, let's say twelve or 13 to 16 hours of fasting per day regardless. Right? And then on top of that, as I was saying earlier, add, say, three times a year, fasting mimicking diet. So the two things are expected to be additive, if not even synergistic, potentially.
Melanie Avalon:
Okay, got you. Yeah. The breakfast thing is something where I just feel like it's so complicated. And with the epidemiological data, I just wonder if it's a lot of healthy user bias, like we've been told so long that skipping breakfast is bad. So are people who are breakfast skippers engaging in other lifestyle habits? And then a lot of the studies are funded by the breakfast cereal food industries.
Valter Longo:
No, they're not. They're. No. In fact, we did the same thing. We did the analysis and got scooped by a chinese group and we saw the same with the enhance the CDC database. Very clear effects. Don't forget that these epidemiological studies adjust for smokers and adjust for bad behavior. And on top of that, I always ask the question, why doesn't that, let's say they have bad behavior, some bad behavior, which we do not see. Why doesn't a good behavior, which would be the fasting, now, counterbalance the bad behavior? Right. Why don't we see them at least live normal? We see them live shorter.
Melanie Avalon:
Right.
Valter Longo:
And that's where you got to become concerned. Right? Let's say they have bad behavior. Well, 16 hours of fasting is clearly beneficial. There's nobody's arguing with that. Why doesn't that help them at least live normal?
Melanie Avalon:
I see what you're saying. So not necessarily fasting studies, but if there are studies on breakfast skippers, they are technically then fasting a certain amount of time. So technically they shouldn't see the issues. Yeah.
Valter Longo:
So most of them are going to be fasting for 1416, 18 hours a day. Right. Because they skip breakfast and they've made, I don't know what time they had dinner. I'm not saying that 16 hours is bad, but I'm saying this breakfast skipping is definitely not a good idea. And also there's papers that I actually wrote a little piece on about a year ago showing people started eating at 12:00, they were hospitalized and they either started eight or twelve, the same identical diet. Right. And those that started at twelve had a lower energy expenditure and they were increased hunger.
Melanie Avalon:
Right.
Valter Longo:
And so now we not only have epidemiological studies, now we have the second pillar, clinical studies showing why that could be a problem. Right. So start at twelve. Now you're going to be more hungrier and your metabolism slows.
Melanie Avalon:
Did they actually end up eating more still?
Valter Longo:
I don't think they. No, they were being fed the same exact food. They brought them to the hospital and they gave them the food. So then the very controlled study, right? Yeah. So then, of course, if somebody only eats once a day, like in your case, well, eventually you're going to be able to control it and still have benefits. But in the general population, just that change caused problems. Multiple problems.
Melanie Avalon:
I was thinking of the studies where they skip breakfast and they are hungrier, but they don't ultimately end up eating more because they can't literally compensate for that entire skipped meal by making it up later.
Valter Longo:
No, they knew exactly what they were eating because they did it in the hospital. Right? Yeah. So then this was very controlled. So it's very clear that the results and multiple trials actually were in the same issue. This cell metabolism from about a year ago, multiple trials were showing the same thing.
Melanie Avalon:
Very interesting. Okay, well, one more last topic. I want to be really respectful of your time. So many people just wanted to know, in general, your blanket recommendations for lifespan and longevity. So some rapid fire, just some quick questions. Stephanie wanted to know, how can I live to 100 or sorry, to 180?
Valter Longo:
Good luck. Tell me. If you find out, then tell me. But to 110, I would say read the book. All the profits go to, all. My part goes to the foundation so we can help people live longer. And so I don't make a penny out of it. But yeah, the longevity diet goes through it. But in general, number one pescatarian diet, fish plus vegan, maybe fish three times a week, high nourishment, low protein, let's say age 20 to 70, and then you go. Moderate protein intake, wash the amino acids, because if you have vegan, you cannot just have legumes. You have to have legumes, seeds, and nuts varieties so that you get the right amino acids. Then 12 hours a day of time. Recipe, eating maybe 13 hours a day of fasting. Say twelve to 13 hours a day of fasting. If you're overweight or obese, skip lunch like I do, Monday through Friday, and then you can have the normal three meals on Saturday and Sunday. Then 150 minutes a week of exercise, plus an hour a day of walking, and then three cycles of fasting. Five day fasting, making diet per year. Yes. So those are the major recommendations.
Melanie Avalon:
Awesome. Well, Dr. Longo, thank you so much for your time. Thank you for all the work that you're doing. I've just been forever grateful for so long, and I've been such a follower of your work. And like I said, I was overwhelmed looking at your list of studies. And I'm really excited to see everything that comes in the future. So just thank you. I will continue to follow your work. Hopefully we can bring you back on in the future.
Valter Longo:
Sounds good. Thanks a lot.
Melanie Avalon:
Thank you. Bye bye.
Melanie Avalon:
Thank you so much for listening to the Intimation Fasting Podcast. Please remember, everything we discussed on this show does not constitute medical advice and no patient-doctor relationship is formed. If you enjoyed the show, please consider writing a review on iTunes. We couldn't do this without our amazing team. Administration by Sharon Merriman, editing by Podcast Doctors, show notes and artwork by Brianna Joyner, and original theme composed by Leland Cox and recomposed by Steve Saunders.
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