Fasting For Longevity: Valter Longo, PhD Shares Cutting-Edge Fasting Science & Optimal Nutrition Protocols For Lifespan Extension & Disease Prevention

29:32And on the other side is probably metabolic switches. What does that mean? It means that people and all kinds of organisms, they can be in a fat storing mode or energy storing mode or an energy burning mode. So if it's summer and you have plenty of food, you have excess food, you wanna put it away, right? And if it's winter and you don't have any food or food that is scarce, then you will start using those reserves. That's the other big effect of the fasting-making diet is unlocking that. But very importantly, and I don't remember if we talked about it before, without getting the organism into a thrifty mode, right?

30:17So because if you go long enough, now we know from calorie restriction studies and lots of human studies, that eventually if you starve or restrict the system of a human body for long enough, it'll go into an energy saving mode. And so you wanna trigger this metabolic switch from the fat storage to the fat burning, but don't get into the thrifty mode, which now is gonna try to save anything that it can. So lower energy expenditure and save it because the system is worried about running out of fuel. Right, so it's very tricky, right? Then this is why the five days of the fasting-vaking diet and then go back because, and that's why also eating is probably important, right?

31:01So you're eating, but you're restricting for five days. And the message is, okay, get out of the energy saving mode, burn the fat. And we see the ketone bodies go up and the fat burning clearly going up, but don't enter this energy saving mode because we're okay. We're not gonna starve. Right. So from a lay person's perspective, that would mean an emergency state in which the body is essentially saying like, slow the metabolism down. Like we got to conserve everything because we don't know when we're gonna get our next meal and everything kind of goes into low power mode. Yes, and that low power mode could last years, right?

31:44This is why sometimes you hear people saying, I don't know what happened. I'm not eating anything and I cannot lose weight, right? And this is a big problem, right? And this is what people understand. The devil is in the detail. If you get into that, it could be epigenetically regulated. What does it mean? It means that the DNA can get modified to impose this thrifty mode, right? Impose that energy expenditure should be the lowest, as low as possible, because that's my biggest problem that you're gonna starve to death. And so for a couple of years, I'll keep you in this energy saving mode, and then we'll see things are consistently better.

32:21Maybe I'll get you out of it, right? So yeah, so I think that a lot of that is happening And very few clinics that are dealing with people that are overweight and obese understand this. And so without this understanding and intervening, it's very difficult to get the person out of this potentially epigenetic lack that makes them just hungry all the time and with low energy expenditure. So making it impossible. Yeah, I think that's a sort of common but under-discussed thing that happens with people who are sort of chronically overweight and they've gone on a lot of extreme diets over the years and restricted their eating, et cetera, and are in that state where now they'll say, like, it doesn't matter what I do.

33:06I can't lose weight. It doesn't matter how much I exercise and I'm doing all the right things. And I'm kind of in this place where I just maintain the same overweight status forever. My energy levels are low, et cetera. all of that. So for somebody who is experiencing that or is listening to this and is relating to that, what is that long road out of that? Like how do they, you know, where should they kind of direct their attention to, you know, claw out of that hole? Yeah. So, I mean, so the Create Cures Foundation that I started has dietitians that are specialized in this. It's a nonprofit that's here in Los Angeles, but they can follow anybody anywhere.

33:45and we usually apply four things. We apply the longevity diet is pescetarian, low protein, mostly plant-based diet, the fasting mimicking diet and the 12 hour time rest of the eating and then the exercise, right? And this, a combination of this, and some people say, I don't wanna do the fasting mimicking diet. And so people say, I don't wanna do the longevity diet. But most people say, okay, I can do three out of four or two out of four. And I would say that it takes about one to two years to get somebody back to where they need to be and just comfortable with this new diet. And a lot of times we try to minimize the changes, right?

34:25We really focus on not giving you, here's a diet that you should have. It's more, well, what is your diet? And what are the problems that you're having? Can we change this? and can we minimize the changes that you have as long as you think you can keep them for the rest of your life, right? So that's really the important thing because, and I'm sure we discussed it before, if you start doing this yo-yo, then you're in trouble, right? Then it's worse than having done anything at all, right? So it's better to just keep the weight and keep the problems rather than lose it and regain it. That's what the great majority of people do.

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40:25It's one thing to talk about fasting in the context of weight loss. I mean, let's be honest, that's probably what gets most people interested in this world to begin with. Another thing to talk about it in the context of chronic lifestyle disease prevention, But certainly, you know, if it helps you to lose weight, then you're at a lower risk for, you know, kind of being afflicted by many of those diseases. And then another thing altogether to talk about disease reversal, which you already sort of touched on. What was the lightning bolt moment for you where you began to see like, oh, my Lord, like this actually has an impact on reversing conditions that people have, like serious conditions?

41:07Well, of course, we've been working on cancer for a long time. But as far as multisystem regeneration, I think the first one was our work on chemotherapy and the immune system, right? And the blood and the immune system. So, you know, the mice would get chemotherapy and there would be dramatic or drastic negative effects, of course, on the immune system and the white blood cells and they will come down and stay down. And this is a problem that a lot of cancer patients have, right? And so then we started doing the fasting, making that cycle or the fasting cycle back then, we were not, it was more than 10 years ago, we were not even working with the FMD.

41:46We were working with just water only fasting in mice. And we saw that the stem cell, we saw the white blood cells. So the immune cells will come back up only in the mice that were giving chemotherapy plus fasting cycles, right? And so we said, how is it possible? They come down. So the fasting was not protecting the lowering of the white blood cells. It was just making them come back up to normal within a couple of months. And so it turned out to be, it was stem cells. So the FMD cycles were turning on the bone marrow stem cells. And the bone marrow stem cells, it took a couple of months to regenerate healthy white blood cells and repopulate the normal immune system.

42:29So really remarkable effect. And then we had a follow-up paper with the pancreas where we completely damaged the pancreas in animals. So completely blocked insulin production by the pancreas permanently. And then we started the FMD cycles. And then you see that again, this two Yamanaka factors being turned down in the pancreatic cells, in the beta cells of the pancreas. And then after a couple of weeks, insulin will get back to normal. And so this was showing that the pancreas can fix itself and can go back to normal insulin production. So essentially treating type 1 diabetes, right? And so those are the two papers that I think one stem cells and the other one reprogramming in a very sophisticated way.

43:23So I'm always entertained by the sort of pharmaceutical point of view that drugs are sophisticated and what could nutrition possibly do? And instead, I think you see evidence for nutrition starting something that is so sophisticated and it's so old, it's billions of years old and has evolved for the purpose of fixing lots of things in a way that it would be unimaginable with any cocktail of drugs or intervention that you could think of for now, right? Maybe 20, 30 years from now, we'll have artificial intelligence driven repair systems and it'd be another world. But I think that it's gonna be hard for a while to beat that extremely sophisticated, you know, 3 billion year old system that has the job of identifying a problem and coming up with a solution.

44:24Yeah, it's been designed through evolution over so many years to work in a way that the blunt instrumentation of pharmaceuticals can't. They're directed at one thing very bluntly and then there's all sorts of downstream implications and side effects from that that you don't see with the nutrition intervention, right? Or you can see it with the nutrition intervention if you misapply, right? If you don't understand mechanisms, you could cause problems, right? It's very powerful. And so if you don't understand how it works, then you could do a lot of damage. I'll give you an example. There was a paper recently.

44:59So for the longest time, we've been saying, if you give chemotherapy to a mouse or a person, don't refeed the mouse or the person while the chemotherapy is still high in the system, right? Because the refeeding means the growth factors go way up and now you have a very quick proliferation of cells while there's a lot of chemotherapy in the system, right? And so a year ago, somebody published an intermittent fasting, like I think it was alternate day fasting showing that the opposite of what we have shown for long-term fasting by using everyday fasting. So they give chemotherapy and then they cycled normal food fasting, normal food fasting.

45:41So now you have high levels of chemotherapy together with the refeeding. It's a very bad combination, right? And as we had predicted, the cardiotoxicity went up instead of down, right? So the two different methods of fasting, one causes really remarkable protection of the heart. The other one causes remarkable damage to the heart and both of them are called fasting. So this is why it's very important to standardize it, make food as medicine, test it very carefully, understand the mechanism. And then and only then it would beat, I think there are lots of drug-based approaches. Yeah. Some of the remarkable study results come from rats and mice.

46:23You talked about the kidney and the pancreas, et cetera. How much of that can we sort of extrapolate to apply to humans? Obviously, you can't study humans in the same way. Like, I'm always confused about, you know, how much we can read into these animal studies in terms of their applicability to human biology. I think that, I mean, of course, so we're running trials, right? But we, I mean, lots of universities and a lot of these trials are independent of us, meaning we just help them do the trial. So a lot of them have been demonstrated now in the clinic, like diabetes type two, and there are a number of papers, clinical papers on cancer.

47:06And so most likely the mechanisms are similar, right? So we've shown it in mice, we've shown it in rats, and now we've seen the effects on our human disease. Likely, it's the same mechanism, but we don't know, right? So, for example, the paper we just published on kidney damage in the rat, mouse and rat, mice and rats. So very powerful, the FMD cycles in fixing the damage. But then in people, it was a small trial, but it was six patients and then seven patients in is called a randomized crossover trial, right? So first six patients and then we control diet and then the control diet group goes into the FMD, right?

47:49And in both cases, remarkable effect on what's called proteinuria. So the protein in the urine is evidence of kidney damage, right? So not only the proteinuria was reduced right after three fasting-immimmunic diacycles in the kidney disease patients, but a year later, and the great majority of them still maintain that benefit, right? And interestingly, when we look at this mesenchymal stem cells in the blood, kidney mesenchymal stem, so they're like progenitor cells for kidney regeneration, they tripled in the blood of patients, right? So we don't know, right? Is it, are they being released to go to the kidneys?

48:34Are they being released in the bloodstream to go to the kidney and fix the problem? Or are they increasing the kidney and leaked in the blood? But it's really remarkable because you see a threefold increase in these progenitor cells that are clearly mostly used to repair kidney damage or generate kidney tissue, right? So, yeah, so in a lot of the trials, we see something very much consistent with what we see in the animal work. And of course, proving it is much more complicated, but in some cases, we may not need to prove it, right? So right now, do we need to prove, you know, the effect of the FMD and reversing diabetes?

49:20It'd be nice in humans. So we know how it works in mice. Do we need to prove the mechanisms in humans? No, we just need to prove that it works. It is feasible. And, but yes, it will be nice eventually to show that, for example, Harvard is interested in looking at pancreatic in the type two patients, looking at where their beta cell regeneration process that we've shown in mice is also occurring in the patient, in the type two diabetes patients that are receiving fasting-making diacycles. So there are ways I think to look into is reprogramming stem cell-based regeneration, et cetera, happening in people, it just takes a lot longer.

50:07What is the receptivity in the traditional medical community amongst general practitioners or nutritionists and dieticians with respect to the work that you do, fasting in general, the fasting mimicking diet, because when you, you know, we could talk about longevity all day long and, you know, are we gonna live to 120? But meanwhile, like something like between 30 and 40 % of Americans are suffering from type two diabetes or are pre-diabetic. Obesity rates are through the roof. Childhood obesity rates are through the roof. Heart disease is our number one. Like this is what's killing people, right?

50:44And this is kind of where everybody should be focused in terms of constructing a lifestyle to avoid these chronic lifestyle ailments. And your work and everything you talk about in your books, et cetera, seems to say pretty clearly and loudly like that this is a way out of that kind of death sentence that visits millions of people unnecessarily every year. Yeah, and I think the two things are very much connected, right? So if you look at the major risk factors for diabetes, cancer, Alzheimer, and cardiovascular disease is aging, right? So if you just wanna intervene on one thing, it's better to intervene on aging than intervene on obesity, right?

51:30So even obesity compare is dwarfed by the effects of 30 years of aging on any of these diseases, right? Meaning it's very small effect. Of course, it's got a big effect. So, but it's very small compared to aging. at least 30 years of age, right? So let's say that you could make people 30 years younger. That'd be the best way to go, right? Just make them younger and they can even be overweight, right? But of course, you know, the best way to go would be to do both, right? And this is what, you know, the fasting making diet, the longevity diet do. And by the way, unlike what we see with the GLP-1 agonist, so far when we don't use drugs, we don't see lean body mass loss.

52:15It's very clear, trial after trial after trial, no lean body mass loss. We just don't see the bad thus far, right? Of course, yeah, you could say when you have millions of people, maybe we'll start seeing some bad, but it's a very coordinated, it's very different, right? Then blocking an agonist, a GLP-1 receptor agonist. This is very coordinated response. And so there is not really a theoretical reason why there should be problems, right? And again, we don't see, in fact, in mice, we see bone density increase compared to the control. So if you take mice middle age and we give them the FMD all lifelong, and we look at bone density, it's higher than in the controls, right?

52:57So that means that maybe there is even, you know, bone regenerative, we don't know. I mean, I'm not claiming that there is, but there may be. But certainly in both mice and humans, we don't see muscle loss. after even many cycles. And in fact, we did the trial with women with breast cancer. And even after many cycles of the FMD, if they had a good healthy Mediterranean diet in between, they actually increased lean body mass, right? The muscle absolute weight increased and also the muscle function was increased. So this is, you know, by what's called impedance geometry method. So we don't know that part, we don't know how carefully was measured, but certainly in general, there seemed to be protection of muscle mass in these women, even after many cycles of the fasting-migging diet.

53:53So that's very important to get the reverse, the adiposity, so the fat storage, probably reduce the inflammation. And we clearly see these anti-inflammatory effects of the fasting-migging diet. Go after the aging process. So for example, IGF-1 and all these aging markers are reduced and they're reduced long-term. You don't just see the insulin-like growth factor one being reduced temporarily and then go back up. Laptin and IGF-1, they are reduced long-term. And this is shown many trials, right? So yeah, so it's going after the adiposity, it's going after the aging acceleration or their aging rate.

54:35and is doing so because it's guided, right? And we developed a lot of this with those problems in mind is not affecting the healthy tissues, including bone and muscle. Is there a use case for somebody who is severely obese to go on a GLP-1 and during that period of time adopt the FMD until it becomes rote. Like it becomes like easy to do that. They're not, you know, kind of, they don't have the hunger pangs that they normally would have. And because, you know, your house is on fire, you gotta put the fire out before you can do anything else, right? Like to take a person through that for however many months and then wean them off of it and then kind of monitor their adherence on a longevity diet.

55:30Like in your mind, is that like a good way to go? Like if somebody is really like in a, you know, like a really acute unhealthy state. Yeah, no, in my mind, that's option B, right? In my mind, option A, and I hope that, you know, eventually the government will also understand that we need professionals that are specialized in nutrition and they know what to do and they know how to do this carefully. and this probably involved molecular biologists, physicians and dieticians, right? That team and maybe psychologists, right? None of this is reimbursed or just the doctor part is reimbursed, but even the doctor part, not clear that it's reimbursed for giving nutritional and lifestyle advises, right?

56:15So I would say, that would be the way that should be done. The way we do it at the Cure's Foundation is take your time, take a couple of years and take the patient by the hand and say, okay, we're gonna get there, don't worry about it. We'll address the hunger, we'll address all of it, right? It's a 360 approach and we'll get you there. There's no hurry, we'll get you there. In the absence of this, yes. So there's, for example, a physician in Dr. Baccarin in Brazil who's been doing exactly what you just said, right? So she gives liraglutide, which is a short, it's a GLP-1 agonist that less than the new versions, right?

57:01And so she combines the fasting-mimicking diet with the liraglutide. And then eventually she gets the patient off liraglutide and keeps them on there. And yeah, so the hunger was her main problem. And she said, well, I just have an easier time with the patient by combining because then at some point the patient say, okay, I don't need the drug anymore. I'm good. And I can see the effects of the FMD. And I'm just, then I continue with the FMD. And the liraglutide is like a lower dose or less intense version of Ozempic or semilaglutide. It's a shorter lasting, something that I think you have to give every day to the patient, right?

57:46So the health life is much shorter. It means that there is also less concerns because of course these GLP-1 agonists are causing insulin production, right? And the fasting-vigging diet cause insulin sensitization. So it means that it makes insulin work better. So now if you increase the insulin on one side and you make insulin work better, a lot better on the other side, you could have a problem because now you could get the blood sugar level very low, right, very quickly. And so, yeah, that's why a continuous glucose monitor would be a very good idea. and a physician that really paying attention.

58:22Because for example, we've done a trial on type one diabetes in children in Italy. This was the first use of the FMD in children. And we were very concerned about justice, right? Insulin injection and FMD. And the fact that maybe the nurses would not expect that the child all of a sudden with the same level of insulin would be much more responsive in controlling glucose. And so we saw problems, you know, luckily we were prepared and everybody was wearing continuous glucose monitors, but we caught it on time. But we had some issues, even though I was very paranoid at the beginning, but they were not taking me very seriously.

59:04It's like, ah, don't worry about it. We do this all the time. But sure enough, we ended up in that situation, at least with one child. And so, yeah, so that was very, very good to think of the worst, right? I think of the worst when you combine drugs and fasting, this is why option A, I like it much more because we don't see muscle loss. And it's also, I just wrote an article on this, is that we are more and more underestimating the importance of the effort, right? So the effort of doing it like you did it, it's hard. I understand you can maybe do it on your own, but you got the professionals around you, they're helping you, put the effort in.

59:50People don't wanna hear that, Walter. Yeah, no, I understand that. But people have to hear that because, you know, I wrote in the article, I talked about exercise and now in the 50s, nobody exercised. And then some, I forget the doctor came around and said, you know, people should exercise every day and people didn't know what that was. What is that? Why? And I remember I read some of his interviews in the 60s and people were like, oh, people are gonna die if they're gonna exercise this much every day, right? And then eventually the health of the world, and hey, that's tough, right? That's much tougher than what I'm talking about to have to exercise regularly, right?

1:00:27So, but people do it. So I think that that's really the solution. Also mentally, psychologically, in that article that I wrote, I said, of course you cannot tell everybody do 50 miles a week of exercise or running, right? Nobody's gonna do it. But if you make it reasonable, let's say 150 minutes, and that's what people do now, right? In Europe and the United States, 150 minutes a week, a lot of people do it. It's not easy, but people manage and I think it makes them happier, right? Then when they exercise, so. Yeah, I think it's a broader conversation around our relationship with discomfort, right?

1:01:08And all good things are on the other side of the kind of uncomfortable things that you're avoiding, whether it's food, nutrition, exercise, or any other goal that you set for yourself. But the byproduct of kind of grappling with that is well beyond like achieving the goal that you've set for yourself because you've made this investment in yourself. You did the hard thing. You feel good about yourself. And suddenly you're more emotionally connected with your own wellbeing. And that spills over into like, not just your external outlook on the world in your own life, but like how you think about the decisions that you make, food, exercise, et cetera, but, you know, the people you surround yourself with, everything.

1:01:50And all of that, you know, all of those things are fundamental to well-being. Yeah, but I agree with you. Let's say 50, maybe 60 % of the population is not gonna accept that short term, right? I think for exercise, it took decades for the US and then the world, because this followed all over the world, right? I think an American idea, it took decades, maybe 20 or 30 years to have a significant portion of the population actually saying, I'm gonna go jogging. I'm gonna go and take a bike and do 50K. So yeah, so I think that before that happens, yes, we need to have methods that are maybe including drugs for some, for a percentage, but certainly methods like the FMD.

1:02:37And that's what I was saying earlier, We're testing it in Southern Italy, in one of the worst areas of the... either one of the worst or the worst in Europe, right? Yeah, we think of Italy as sort of this, you know, giant blue zone, but it's not really that. Not at all. I mean, if you look at Calabria and Campania. Yeah, so Calabria and Campania have surpassed the United States as far as overweight portion in children, right? So it's a big problem. And so the way we addressed it was, what about if we give an FMD for five days every three months? And everybody thought it's crazy, never going to work.

1:03:15We haven't published it yet, but let's say that it's looking good so far, right? That's cool. Yeah, so now it gets down to very little, right? The five days every 90 days that you have to dedicate to this program in a box, essentially a medicine in a box. Yeah. Since we last spoke, I would say that there's been an explosion in interest in healthspan extension, longevity medicine, this field in which you've invested your career and have been in for many, many years. a lot of energy right now. And everybody has their own kind of specific lane, whether it's AI technology, sort of the sophistication of scanning equipment, like all of these developments that are making healthspan extension more and more plausible.

1:04:04And I think among this group of people you share, there's many things, principles, ideas that you share in common, there are differences as well. And I think one of the key ones with respect to diet is this emphasis on protein. So somebody like Peter Attia, Rhonda Patrick, they're always pushing protein, talking about the importance of protein, particularly after a certain age, certainly after age 65, when you really need to be eating more protein than you might think to maintain your muscle mass and the kind of critical role that muscle mass plays in terms of how you're aging up. Your fasting mimicking diet and much of what you speak about kind of goes in the other direction.

1:04:52Maybe it's different when you reach a certain age, but at least on the FMD, this is a pretty low protein protocol and it's not entirely vegan. It can be entirely vegan or pescetarian. What's entirely vegan? What's that? Entirely vegan. Right. I mean, I've heard you talk about fish, two or three times a week on the longevity diet. So maybe kind of state your case or your perspective on this controversial macronutrient. Yeah, so first let's take out the FMD, the fasting making diet, because it's just five days. Sure, longevity diet, sorry. Three times a year and so it's completely irrelevant. So sometimes I've heard that argument that then maybe Peter made it, but I don't understand it because we're saying, you know, this is 15 days in a year.

1:05:41So even if you go zero protein, it will have no effect whatsoever on your muscle, right? No effect. And we've shown this clinically in 10 different trials. In fact, in a new trial, we're actually showing increasing muscle mass after six cycles of the fasting-making diet, right? And even not just relative, but absolute lean body mass, right? So that's clinically demonstrated to be false. If anybody's saying the FMD is causing reduction of muscle mass, it's the opposite, right? So far it's the opposite. The only time we see some lean body mass loss is in combination in the diabetes trials in combination with drugs.

1:06:23That's the only time so far we've seen lean body mass loss. Then the longevity diet is very different. What about every day, right? So, yeah. So I think that it is a big problem when we are using like a one or two pillar system to look at things, right? So let's say epidemiology. A lot of people love to use epidemiology. Studies are big population, right? But even if you look at epidemiology, we've done that and we've done that, you know, in a study published in JAMA with Harvard, we've done it in our own study. it's pretty clear that you don't need a lot of proteins, right? And it's pretty clear from many, many studies that the people that do the best are mostly vegan, low but sufficient proteins.

1:07:10And then in our own paper, and we were the first one publishing on that, the 65 was the switch moment, right? So at 65, we did not see, so people reporting a low protein diet, whether it was overall mortality or was cancer mortality, people reporting a low protein or very low protein diet did the best up to age 65, and then did not do so well after 65. So if an 80 year old said I have a very low protein diet, it did not do very well either for cancer or for overall mortality. So, and then the Harvard study with Giovannucci in the JAMA paper, I think that he showed, or we showed, cause I was a co-author that plant-based protein, high animal protein was not good, but high plant-based protein was associated with improvements, right?

1:08:02And that's where the devil in the detail comes in because there can be such a big difference, as I mentioned earlier, in amino acid levels in the plant-based proteins versus the animal-based protein that is not even clear what the meaning of protein is anymore. Meaning that it's irrelevant because it's really about 20 amino acids, right? So we should be talking about amino acid level and amino acid patterns. And that probably explains. So meaning that probably it's very clear that a low but sufficient amino acid intake is what you want up to a certain age. And by the way, the age should be biological age.

1:08:46It should not be chronological. So it could be 65 to somebody, but it could be 45 to somebody else and 72 to somebody else. So at some point, and you see the population weight, instead of going up, it comes down. That's a point where we see this switch in mortality prediction. Yeah, so then it's about amino acids. And again, epidemiology is one pillar, but then you have clinical studies, you have basic research. So how do you make a mouse live longer? Well, over and over and over and over for almost 50 years, low protein, low-methyne in diet, right? Just in rats, in mice, and no matter who did it.

1:09:29And so, yeah, so then that's like another pillar. And then the centenarians, whether you look at Okinawa had a 9 % protein diet, right? And for the longest time had record longevity. So I will encourage my colleagues to just expand from one pillar science to five pillar and the fifth is complex system. But let's say, even if you just go for four pillars, and if you go for four pillars, you see the devil is in the detail. It's about amino acids and it's about having sufficient and protect the immune system, protect the muscle, protect the bones, but reduce as much as possible the aging rate. Because again, what dominates is aging.

1:10:11so that if you can make somebody younger, they will live longer, they will be much healthier. And again, there is a 10 to 34 difference between obesity and aging and 30 years of aging as a risk factor for Alzheimer, cancer, cardiovascular disease, diabetes, et cetera. So yeah, it's about aging. The proteins are driving the growth factor, which are clearly at the center of the aging process in all organisms. And this is why our work with the Ecuadorians come in, right? So the Ecuadorians have growth hormone receptor deficiency and that's the protein pathway, right? So either mice, mice that have a growth hormone receptor or growth hormone deficiency are the ones that live the longest, live 40 % longer with the lowest disease profile, right?

1:11:00This has been known, John Kopchik, Andre Barkey worked for decades. Now, surprisingly in yeast, the 10 fold lifespan extension comes from the protein pathway, mostly from the protein pathway. So you block the protein pathway and the yeast now are reprogrammed to the living 10 times longer. And then our work in Ecuador with people, sure enough, people that have growth hormone receptor deficiency are protected in spite of a terrible diet, are protected from diabetes, they're protected from cancer, they're protected from cognitive decline. They seem to have, and we brought them to LA to do a functional MRI test on their brain.

1:11:38that had the function of a much younger person cognitively. And now we just publish on a neutral to positive effect on cardiovascular disease, which really surprised us that the plucks were lower or much lower in the pathway that response to protein intake is blocked, right? The most damning part is the Harvard study showing a 40 % increase in three different studies. in this Frank whose work, three different studies, 40 % increase in the diabetes risk in subjects eating high protein diet, right? Compared to the lowest, I think it was quintile. So the lowest quintile versus the highest quintile.

1:12:21Those that were in the highest quintile protein intake in three different studies, almost identical results, right? So, yeah, so I think that it's really hard to imagine how you could conclude from all of these studies. And we were talking about hundreds and hundreds of studies that a high protein diet is good for you. I mean, it should be sufficient and was sufficient plus muscle training, right? That's very important. And a lot of studies indicate that the protein intake you need per meal is very low, it's around 30 grams per training session, right? If you have 30 grams of good quality protein with enough leucine and that stimulates TOR activation, you're going to get maximized effects on muscle building.

1:13:11And that's probably all. I mean, and you could say even if you did it twice a day, you still be in 60 grams, you still be in a relatively normal to low protein diet. But beyond that is not to your benefit for reasons related to growth factor. I would presume that that would be offset for somebody who is extremely active, regardless of age, if they're like in the gym and do it like the negative implications of a higher protein diet would be abated by that very active person. Yeah? Not necessarily. No? Not necessarily. No, because the growth factor, it could accelerate or is known to accelerate the aging process independently.

1:13:57So your active lifestyle could certainly help you in other ways, live longer. But you're still, if you're accelerating your aging, your pro-aging pathways, that still can cause damage, right? That is still driving a faster aging rate in all your organs. Yeah, and then the exercise helps and maybe they could cancel out, but that's not what you want, right? You wanna maximize, reduce the aging rate and while increasing the functionality. So we're about to publish a couple of papers on that in mice, but also in using the Harvard databases. And so, yeah, I cannot discuss it, but certainly it's very consistent with what I'm saying, The data is that, first of all, you need to really understand mechanism.

1:14:51How is each amino acid affecting which genes, which are affecting what processes? For example, we talk about stem cells and we talk about reprogramming. We see protein as the major blocker of both of those, right? Stem cell activation or self-renewal and reprogramming the Yamanaka factor, the reprogramming factor. It seems like if you wanna stop that process, high protein. And it makes sense, right? And does it matter if it's animal versus plant? Yes, because it's about amino acids. That's why I think eventually, I think very soon we should begin to move away from even using the word protein intake because it's completely irrelevant, right?

1:15:30Because if it was a 20, 30 % difference between let's say legumes and red meat, you could say, okay, 20, 30%. I mean, legumes and let's say soy, right? or legume and seeds, seeds and nuts, right? So seeds and nuts, the amino acid profile between a seed protein and not protein and a legume is huge, right? Then it's even bigger if you got red meat or even white meat, right? And sometimes it's up to 10 fold. So that's when it's irrelevant because you could have 100 grams of protein which are providing 10 % or 20 % of that amino acid. And that amino acid may be the one that is making the big difference.

1:16:14Yeah, I understand. And it's complicated. It's always more complicated than you think it's gonna be, right? Yeah. But it's not complicated in terms of how you implement it, right? So if you have a mostly plant-based diet, you just need to, and this is what I preach, let's say that you're a vegan, then you should mix about a third, a third, a third plant, I mean, legumes, seeds, and nuts, right? If you have that, then you're good to go, right? So, you know, practically it's very simple, right? But if you only have legumes and you have already, so if you have a low protein intake and then it's all legumes, you're gonna have a problem, right?

1:16:53Because you're missing essential amino acids. It is so low. Because by focusing on one thing. Yeah, I mean, I think people, when I said complicated, I meant like, you know, the sort of physiological pathways and, you know, the science of it. I mean, the practicalities of it, as somebody who's been plant-based, I've been plant-based for a very long time. Like people think that it's this complicated, time-consuming thing. But if you're just kind of grazing on a wide variety of plant foods, it really takes care of itself. Like evolution has sort of, you know, figured it out. Like I've just never really had a problem with this and have been confused by people who seem to kind of obsess on protein intake.

1:17:32Like it's just, it's never really been an issue for me. Right, right. But some people, let's say, you know, the Okinawans, you know, historically and the Southern Italians, and maybe this is why they were so long lived, right? But they were very frail. That's interesting, right? So if you look at Southern Italy, the same regions that have record longevity, because they used to have mostly legume diets, you know, yeah, the seeds and the nuts were there, but not in the type of quantities that, so the legumes were very much available and the rest of it was maybe less available. And not surprisingly, you see a frailty level that is almost twice as high as Central and Northern Europe.

1:18:15So a lot of the Mediterranean countries are very frail, long lived by frail. So I think that in your case, you probably had the muscle training and all of that and enough variety, but to a lot of people, it could become a problem, right? So if you say five times a week, your proteins are all coming from legumes, then they might not be so easy to, if it's low protein and mostly from legumes, then it might be difficult to keep the muscle mass.

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1:20:35Are you familiar with this guy, Brian Johnson? Yes, yes. And his blueprint protocol? Yeah. I mean, I don't know the blueprint protocol. I know the 100 supplements and all that. Lots of supplements, basically putting a lot of time and resources and energy into trying to crack wide open this anti-aging equation. But part of it entails his diet, which is an entirely plant-based diet limited to 2 ,250 calories, I think, something like that. It's very dialed in. His last meal of the day is at 11 a.m. So this is a fasting protocol. I think he goes to bed around 8.30 or 9 at night. He eats within, I don't know, 30 minutes of waking up in the morning, probably around 6 a.m.

1:21:23or something like that. And I think he has three meals throughout the day, small meals. Have you looked at this? Do you have thoughts on kind of what he's doing here? Yeah. All his biomarkers seem to be fantastic. Yeah, yeah. Well, the short-term effects may be completely irrelevant compared to the long-term effects, right? So a good example is, let's say, the breakfast keepers, right? The breakfast keepers, you know, if you look at short-term, they may be actually very beneficial, right? And people argue that the breakfast keepers have a worse lifestyle and all that. But let's say that new clinical data suggests that it's not that, right?

1:22:06If you start eating later, you're going to have problems. But it may be difficult to see what's going to happen 20 years later, right? And you're going to get surprised. And the ketogenic diet could be another example, right? So if you look at the ketogenic diet, very beneficial, it makes you impressive results. but in the long run, people on a low carb diet, and there's lots of Harvard studies, they live short or much shorter, much higher mortality, especially if it's low carb, mostly animal based diet, right? So yeah, so I would say that when you enter a lot of territories, the a hundred supplements and eating within three hour window, each one of them is a gamble, is a big gamble, right?

1:22:55And then if you put four or five together, now it's a very bad gamble, right? So you're exiting the territory of the five pillars in multiple ways, right? So these centenarians eat in four hours and no. Is there any data from mice? Yes, there is some data from mice that show that that's beneficial or potentially eating within a smaller window is beneficial. So you have mixed data in lots of things that he's doing, but a lot of it, I think is gonna be negative, right? So it's gonna be, or not done before, right? So could it be positive? Yes, but it could also be negative or very negative. And so the surprise could come after 25 years and it could be a big surprise, right?

1:23:40It could be a big surprise. And now that is causing a big problem. If people don't realize you just need, like for example, ketogenic diet. Well, everybody talks about the ketogenic diet and cancer as a positive thing. And it can be, right? And there's a lot of animal studies now, some clinical trials that are suggesting, this is also in my book, that are suggesting that the ketogenic diet can be beneficial. But people don't talk about the cancers that are fed by ketone bodies, right? There's some cancers that grow much faster. And there's some cancers whose incidence goes up tenfold in people that have a high ketone body level.

1:24:20So yeah, so then very healthy short term, not so healthy for lifespan, and now associated with a much higher level of certain cancers. So this could be the surprise right now, all of a sudden, whatever you're doing, that is not within the domains of what's been tested for a hundred years. And all you need is one of, let's say, a hundred supplements, or even 10 supplements. People don't realize, I just looked it up the other day. And in Italy, drugs, just in Italy, drugs kill about 40 ,000 people every year. Drugs, right? Drug interaction. Not like recreational drugs. No, no, no. Prescribe drug.

1:25:00Prescription drugs. Prescription drugs. It's 40 ,000 people a year. And in the US, it's a huge number. I don't remember. I just looked up the Italian number for some reason and not the US, but it's a huge number, right? So you combine lots of drugs. they start interacting in ways that you cannot predict. And so now if you take 10 supplements, 20 supplements, 30 supplements, the higher the number, the more certainty, almost certainty that it's going to cause a problem. It might take one year, five years, 10 years, but sooner or later, that's going to cause a problem. For every additional supplement that you add into your routine, the complexity of how all of these things are interacting with each other, kind of increases exponentially, basically, is what you're saying.

1:25:45And we don't know. Even AI wouldn't be able to handle it for at least 20 or 30 years. That's so complex that you will need 20 or 30 years of data fed into AI to say, okay, now the only AI understands that maybe that's gonna cause a problem. But yeah, so right now we're very far away being able to handle, because you need big data, right? So how is the selenium that you're taking interacting with, kind of the mega dosing of vitamin D, for example, or something like that. Yeah. Because then the two are gonna change the host metabolism or the host response. And now the new host response, so it's not just how the two interact, it's how the two change the body.

1:26:34And now the two plus the body change affect the third one that you're gonna add, right? And our react. So all of a sudden, let's say your ferritin goes up, right? And now if you have a high ferritin and now you add some other supplement, now you have a recipe for disaster, maybe iron overload, because now you just have a deterred supplement that is making the ferritin work less well, right? For example. I see. You know, if you were counsel to Brian Johnson, you know, what would your advice be? I mean, I know I'm setting you up a little bit because you would have to know everything that he's doing, but kind of from a bird's eye view, general principle perspective.

1:27:14Well, I mean, of course, I mean, the only thing that I will add to all the things that we discussed before, so time versus the eating, the fasting-making diet, the longevity diet, I will add personalization, right? So you will wanna know everything about him and personalize all of it to him. I think he would say that he probably has that dialed in. Like I think he experimented with lots of different eating stuff with a big team of people who are weighing in and taking his blood markers like every day. If that was the case, he wouldn't be eating in three or four hour window, right? I think he's underestimating the uncertainty of doing something that nobody's ever done before, right?

1:27:55If you just think about the short-term effects and this is the overestimation everybody's making, you have diagnostics and you think that because, you know, so I had big experts. in the field tell me, you know, I have extremely low fat, you know, like 5 % fat. Well, you know, data suggests that if you have a little bit higher fat levels, you may live longer, right? So short term, you could say, you know, I have 5 % fat, I'm going to live forever. But the data is actually showing that those that live forever might be more in the BMI 25 range, right? Yeah. So then that's this acute response and this idea that, you know, if you have a very low fat, that makes you very healthy is misguided, right?

1:28:43Because that's not the case if you're trying to get to 110 healthy. And I don't mean just 110 frail, like the Southern Italians or maybe the Occhianawans. I mean, 110 healthy. So then, you know, you have to have the five pillars or more than five pillars. And those speak very, very clearly, right? And so then on top of the five pillars, then you need the diagnostics, right? Then you need to say, okay, I'm using the five pillars. I came up with all these things and now my cholesterol is still very high, right? Well, okay, that's not enough then. We need to intervene and make sure that cholesterol goes back to normal.

1:29:21And so, yeah, so I would say that, again, if you look at the longevity records, it comes from mutations that do lots of weird things like growth hormone receptor knockout, right? It makes mice and people very short, right? So it's very counterintuitive, let's say, because a lot of people inject themselves with testosterone or growth hormone to live longer. And yet, clearly after a hundred years of research, high growth hormone is making mice and probably people live the shortest. Right. Speaking of people who are short, I came across that CNN article about Lahren syndrome. and people who are genetically very small, like four feet and under, who really don't get lifestyle disease or cancer or heart disease as readily as we do.

1:30:12And I know you've done some work with this community, right? Yeah, so this is what I was just talking about, right? So the growth hormone, the little people that you're referring to have a mutation in the growth hormone receptor, right? So this is what I was saying. People are now, millions of people around the world are using growth hormone injections to become younger, right? And so if you look at them short term, you probably conclude that they are younger or they're functioning better, let's say, right? And so, but the mouse and the human data suggest exactly the opposite, right? So the little people, it's like, if you inject them with growth hormone, they'll have absolutely no effect, right?

1:30:54Because the receptors don't. They're missing the receptor. You have the key, but you don't have the keyhole. So worthless key, right? And so those mice and people that have the blockade in the growth hormone pathway are the ones that by far are doing the best, right? By far. I mean, if you look at mice, there is nothing that even comes close to this growth hormone and growth hormone receptor. And that's nice because it can be that the mice are lacking growth hormone or lacking the growth hormone receptor. Either way, they have record longevity and record health. And this has been shown, we work with this mice, but lots of laboratories.

1:31:33So there's really no doubt about it, right? So yeah, so that's why this genetics data is so important. And it's part of the, I put it in the centenary and the people that have lived with that change for a hundred years, right? So now we have the data both for the Larons, but also for the Okinawans and for the centenarians of southern Italy or Loma Linda. So your research and your latest book, Fasting Cancer, appear to support the thesis that the fasting mimicking diet in conjunction with traditional treatments for cancer seem to have a beneficial impact in terms of recovery and remission rates in general, right?

1:32:25Within the context of a very complicated field. I mean, differently from diabetes, cancer is really a hundred different diseases, maybe a thousand different treatments. So I would say that in general, especially for those that have advanced stage cancer, let's say stage three, stage four, the ones that are in trouble. A lot of the clinical studies are now showing that it seems to have a big effect, right? Making the whatever, especially chemotherapy thus far better, right? So one of the nicest ones that I mentioned in the book is the triple negative breast cancer, very aggressive women with metastatic cancer.

1:33:08The fasting-beaking diet now is nearly doubling overall survival. in the first study by Vernieri and colleagues. And then they just published a follow-up paper, which is not in the book, showing either chemotherapy alone, chemotherapy plus fasting-mimicking diet or chemotherapy plus fasting-mimicking diet plus metformin. And again, nearly a doubling compared to the expected survival of what's called PCR, complete pathologic response. These are just a few trials, but there's lots of them. that are indicating that the fasting-making diet is making survival better, making also the pathological response better.

1:33:53So if you look at the masses, the cancer masses after the treatment, they seem to have less active cancer cells. Now, there's also an argument, and this is why we say be careful. As I mentioned earlier, if you misuse it, let's say you say, oh, fasting is good, and so I'm gonna go to chemo, and then I'm going to refeed at the same time, that could cause problems and not solution. And the other thing is, you know, fasting mimicking diet has a very powerful effect on stem cells. And so, you know, we've looked at cancer stem cells and we've shown that in breast cancer, it reduces cancer stem cells.

1:34:32But others have indicated that in some cases, it could increase cancer stem cells, right? So in the early stages of the disease, right? So we don't know enough about it. We really haven't seen that. But I would say if it's early stage and the treatment is likely to be very effective, stick with just the treatment and don't try anything else. Maybe the longevity diet, maybe the 12-hour time restate of eating. And this is what we do in the clinics. We say if it's early stage and you have a 98 % chance of being cured by it, just leave it alone. Now, it could be that it will have helped you a lot, even in these early stages, but it could be that there's something that we don't know yet.

1:35:19And so I know people think we're paranoid, but I think it's a good way to look at it. And unfortunately, a lot of people don't look at it that way. So essentially, it's going to be case dependent, depending upon what type of cancer and how advanced that cancer is. more advanced cancers and certain types of cancers seem to indicate that traditional therapy, i.e. chemotherapy, in conjunction with a fasting mimicking diet seems to have a beneficial effect that outweighs chemotherapy alone. Well, I mean, if you look at the animal studies, right, then it's just overwhelming with all kinds of cancer, you know, colorectal, lung and breast and name it, right?

1:36:10And fasting mimicking diet plus chemo, immunotherapy, hormone therapy, kinase inhibitor. I mean, just phenomenal effects, right? And I mean, turning cancers that are clearly, so we published a paper a few years ago, they're showing hormone therapy, for example, right? Hormone therapy, so palbociclib, fulvestrant. This is in mice, right? And we also had the clinical trial, but in mice it's very conclusive. You use the standard of care, Palbosyclib and Fulvestrant. And the tumor is kept in check just like it is in people for a while. And then it starts adapting and it starts growing, right? You had the fast-imicking diet cycles and now you see the tumor going in the opposite direction until it goes to zero, right?

1:36:52So it's just over and over and over. The animal data is remarkable and really almost surprisingly, And it's not just my data, it's now a lot of labs that are looking at it. For example, in mice, we published two papers and some Spanish groups have done the same. Immunotherapy in mice does almost in some of these models for, let's say, breast cancer and even melanoma, that's very little. And the fasting-mimicking diet alone does more than immunotherapy, right? so so i would say the potential is huge in in all the different cancers and in all the different stages but because there is a system and the system should be respected and we don't know yet we haven't tested it for a lot of in clinically we haven't tested mice we tested it but not clinically you know that needs to be done before somebody and this is why my comment about definitely if you're stage four and nothing else is working, go for it, right?

1:37:51Because the animal data is phenomenal. But if you're stage one and you already know that, you know, what's been done for 20 years is working very well, then I don't think you wanna take a chance, right? Stick with the standard of care and then God forbid you get to the next level, then yes, then consider it. Yeah, I think that you're very, you know, kind of circumspect in the way that you talk about, in the way that you just did, you know, throughout the book. Like, hey, listen, I'm not like here to tell you like this is some panacea, right? Like, here's what we're seeing right now. Here's what I'd like to see.

1:38:30Here's some research that still needs to get done. I'm not telling you to not, you know, pursue every traditional therapeutic modality there is. I'm just saying, you know, in my lab and in other people's research, this is what we're seeing right now. There's something interesting happening here. I think it's worth pursuing and investigating, you know, more thoroughly. Right, right. But in some cases, the clinical trial, like for triple negative breast cancer and even for hormone therapy, I mean, for triple negative breast cancer, you're starting to see randomized trials showing a big difference, right?

1:39:04From what you expect or from what the control arm has, right? And this is in patients. So, yeah, for those, I would say, probably talk to your oncologist and say, hey, what about these three or four papers? It's looking good. How up to speed are the oncologists in this field? Some are up to speed and a lot of them are not. And a lot of them are going to wait for an FDA approval, which may or may not come. So, it's very expensive. hundreds of millions of dollars to get an FDA approval. The FDA looks at fasting-making diet is very complicated. So we talked to the FDA to make it feasible or to make it appropriate for the FDA, you probably need to take the 60 ingredients or so in the fasting-making diet and make it into six or seven, which will make it very difficult to do and very difficult for the patient, right?

1:40:03So it may or may not end up in FDA approval. And so I think the way to go is for the oncologist to be informed and to follow. And there's going to be a point where there's going to be enough trials and there is enough standardization of the diet that the oncologist could say, hey, this has been tested in seven or eight trials. It looks very good and I'm going to recommend it. Is breast cancer the form of cancer in which you're seeing the most kind of optimistic positive indications? No, in the animal studies, it's working very well with all kinds of cancers. In humans though? Yeah. In humans, it's breast cancer just being tested a lot more.

1:40:46It's not that we tested the others and it didn't work. It's more that - We know this disease better. Well, there is more effort dedicated clinically to breast cancer. So, you know, for whatever number of reasons, but there's more studies, More clinicians come to us and say, I would like to do a trial on hormone therapy and breast cancer or chemotherapy and breast cancer or immunotherapy and breast cancer. But now that we're starting, they're starting our trials on colorectal cancer, we finish one on prostate cancer. Eventually, hopefully we'll have a lot more, but yeah, there just hasn't been And there are many trials in any other cancer other than breast cancer.

1:41:36There's one randomized study that you talk about in the book with respect to breast cancer. 131 patients showed very promising results in the context of the fasting mimicking diet being kind of woven into their treatment protocol. 90 to 100 % tumor-free masses were seen in only 8 % of patients who completed chemotherapy without any FMD. 29 % with one cycle of the fasting-mimicking diet. 33 % with three or four cycles. And 53 % with all chemotherapy cycles combined with a fasting-mimicking diet. I mean, 131 patients, not the biggest population, but not insignificant either. Like that's a considerable result.

1:42:28Yeah. Yeah. And this is being confirmed by the Vernieri paper that we just published very recently in Cell Metabolism. But I think that I like, I'm a little worried, you know, that that's too early because that that trial was in women that were to receive the surgery. So early stage about to receive surgery. So I think that we'll see, but it falls into the category of too early to try it until there's more clinical data. But whereas in the metastatic setting, where we've seen the same exact results with the very similar to what you just described, But now in patients that have metastatic cancer, yeah, then I think that that's a very different scenario.

1:43:20It's working very well. And that's where we see the overall survival difference, at least in the early trials. So I'm more optimistic and excited about the metastatic one than the early one, because the early one in that trial is not enough to make conclusions about long-term survival. and it's very, very early before surgery. So yeah, I don't know. I don't wanna make that category of breast cancer patients too excited about, oh, I'll do this because again, I'm worried about the cancer stem cells and other things that could be affected in different ways. Now, yeah, I don't have that worry for the metastatic because again, it's been tested now more and we see no evidence of, and we see the overall survival improvement.

1:44:16And so, yeah, so I think that definitely a wild card, I will call it that, a wild card for any cancer patients, you know, of course, after a discussion with the oncologist for any cancer patient that is in the situation where this is not working, right? And then the oncologist says, you know, doesn't look good. That's it. You know, two to six months, there's not much more. Not just that, it can be stage four, you know, three to four years, but it's not working very well and we're concerned, right? So yeah, that's the, if the oncologist comes back with, okay, this didn't work, but we have this and this could work extremely well, right?

1:44:57And we're very confident. Okay, then try that. but at the point where the oncologist comes back and say there's really nothing left. And yeah, you could still live seven or eight years but we just don't have anything right now. That's when I would definitely talk to them and this is what the clinic, the foundation clinics do working with the oncologist and saying, okay, this is a good time to give it a shot, right? So, and see what happens. Hey, and in the book is full of stories and this is why I make sure or I don't make the stories into a reality. And there's people that like, you know, Vernieri published five cases of, you know, stage four colorectal lung cancer.

1:45:41And in fact, the lung cancer patient that - Yeah, Maggie Jones. I mean, that was like the most impactful story in the book, I thought. No, Maggie, yeah. But then in the Vernieri, I didn't talk about it a lot, but in the Vernieri study that is published in European, I think, Cancer Journal, You know, there's five cases and one of them is lung cancer. And the person was a friend of the oncologist, right? A good friend of the oncologist. And, you know, the oncologist thought, yeah, there's nothing we can do. You know, lung cancer stage four, the person went into remission, which shocked so much all the oncologists at the Italian National Cancer Institute that they publish a paper on this because they say, we never seen five patients out of a single trial with stage four going into remission, right?

1:46:27And so, yeah, so they were so surprised that they decided to publish a paper saying, okay, we don't know, it could be a crazy coincidence, but that's a little strange, right? That we're seeing all this essentially, I don't know if I want to call it that sentence, but certainly there's not much hope left, right? And then seeing, in one case, I think it was the colorectal, the cancer came back after three or four years, but there was already, and then the same treatment and the same result. So, yeah, so I think the hope that there is something that could make a big difference, right? That's, I think, what we got right now.

1:47:07And, you know, hopefully we'll have the demonstration of it in big clinical trials, you know. From a mechanistic point of view, the way you describe it in the most basic sort of layperson manner in order that, you know, normal people can kind of understand what you're getting at is that you use this analogy of cancer cells as these sort of food stealing thieves, right? The FMD is sort of an attempt to starve them. In other words, like close the grocery stores, right? That at the same time don't impact normal healthy cells in the same way they impact cancer cells. And through autophagy, like they can kind of, you know, kind of regenerate themselves, regenerate healthy cells.

1:47:51Is that... Yeah, I think the normal cells have been trained for 3 billion years, right? So they know exactly what to do. Bacteria, if you starve them, they know exactly what to do. Yeast and all organisms on earth, most organisms on earth, by the way, are in starvation, are starving right now, right? If you look at microorganism. So the normal cells, they know exactly what to do. The cancer cells have evolved with excess food, right? They only understand a lot of food and they don't understand how to make their own food. they understand that, hey, I got to get it from the bloodstream, right? So if you just do fasting or fasting-mimicking diet, they're not happy, you know, but we see over and over kind of like a cycle of chemotherapy.

1:48:35It's about the equivalent. So if you just do fasting-mimicking diet cycles, it'll have the slowing down effect of cycles of chemotherapy. But then when you combine it with chemo and we combine it then with immunotherapy, when you combine it with hormone therapy, et cetera, et cetera, that's where you see in a lot of cases, we actually can drive the cancer down to zero or really stop it, stop its growth for a very long time. So I think, yeah, the cancer cells are confused. And now we have this technology that I talk about in the book, which we call starvation escape pathways, black aid, right? So basically we use technology to say, I start the system with the fasting-micking diet, but then I take the cancer cells and I look at how they rewire using this RNA-seq technology, right?

1:49:29So I can show, I can see very rapidly and potentially now even using cells from the blood that I just collect. And so hopefully soon we'll do that in people. So I can see how they rewired and I can use drugs that are available to block that particular highway, right? So I know what the highway you're gonna take, basically, and I just block it, right? And that's really, we publish, it's got incredible effects, right? So alone does, yeah, it delays a little bit. Then we identify the escape pathways and we block it and the tumor comes down and stays down, either for a long time or permanently. So what is the message that you're trying to convey in this book?

1:50:12Because there is a sort of caution, like, okay, don't get too excited. You know, I'm talking about a very, you know, specific set of circumstances in which, you know, kind of what I understand would apply. So, you know, who's the reader for this and what is it that you want people to kind of get from it? Well, first of all, everybody in the cancer prevention settings, right? So treat aging, prevent cancer. And that could have a remarkable, you know, whether it's a fasting-making diet or the longevity diet or the time-restricted eating or the, you know, other things that are in there. So prevent cancer.

1:50:47Then if you're unlucky enough and you get cancer, at the beginning, you can still do lots of things like longevity diet, time-respected eating different. So now a time-respected eating, we go to 14 hours from 12. If you are a cancer patient, right? So we increase it to 14 hours. And longevity diet, we have to work on making sure that you don't lose muscle, your immune system doesn't get weaker. And so that's an everyday diet. Then the fasting-imicking diet is only, I think, for patients that need to do it, right? So if you're early stage and everything is, you know, you're having low levels of side effects and everything is smooth, I would say just do the longevity diet and time-rificity eating and do lots of other things that we talk about in the book, but that's it, you know.

1:51:37If you are metastatic or the oncologist says, nothing is working here, even though you're not metastatic, Yes, then I think I will consider the fasting-making diet and then I will talk to the oncologist and see what he or she has to say about using it. What is your sense of the impact that AI is having or will soon have on your specific field of study? Yeah, I mean, what I just said, I think eventually AI will make that process of identifying the escape pathways and the drugs very quickly, almost immediate, right? And I'm not talking about 20 years. I'm talking about two or three years. So in two or three years, I think we can probably, if we had enough money now, if the NIH is shut down, maybe we won't.

1:52:28But I think in two or three years of enough funding, we'll be able to use AI to very quickly get to the escape pathways, you know? And so then the idea would be, I use the FMD as a wild card and I use the AI to tell me what the other drugs are. And then I use FDA, already FDA approved drugs to block it, right? And so it's a little bit of a science fiction world. I call them cancer antibiotics, right? So I see that with enough funding in the next 10 years, we might have this sophistication to say, kind of like antibiotic, you go to the doctor and say, oh, you have an infection, so we'll give you this antibiotic.

1:53:07Let's see if it works. So I think, and maybe I'm optimistic with the time, but I think with the right funding, this could happen in the next 10 years where you get your cancer antibiotics, you have very low toxicity, kind of like FMD++ +, very low toxicity drugs that you can just take and let's see if the cancer goes away. And if it doesn't go away, then we'll try something else. But yeah, I think that's clearly theoretically, but also using the animal data. This is very close, right? But yeah, so sometimes it could be very close. Three years, it could be very close, 30 years. It's hard to know.

1:53:44But I think, you know, with the right funding, it could be within 10 years. And outside of the cancer context, are you among the techno optimists in terms of how AI is going to impact health span extension in, you know, a wide variety of ways, you know, kind of beyond your area of expertise specifically? Yeah, I'm very scared of AI. So I don't like it at all. Well, here's, sorry to interrupt, but I'll just say one thing. I've said this before on the podcast, but like, you know, I've had you've all Noah Harari on the podcast and he's, you know, sounding the alarm about like, you know, the sort of end of democratic systems and humanity at large.

1:54:25But we were both at the Google Zeitgeist conference and it's just, you know, Pollyanna all day long in terms of like how amazing it's going to be. Yeah, yeah. Very scary, right? Very scary. Yeah, you know, I think to see how scary it is, you have to look at evolution, right? Right. Systems evolve. Right. And it doesn't really matter whether that system happens to be, you know, derived from single cells or from a programmer. That's a scary part that I think everybody is underestimating. You know, if every system can evolve, it can find its way. Right. And so that's a scary part. And now for the first time ever, we have a system that evolves and is based on a program.

1:55:13And it can learn and eventually, where can it end up? So that's what sets a stage for, it's just a matter of time before it's gonna evolve. And it's gonna find its way. And the question is, what way is it gonna find? Well, if you look at the past, right, and dinosaurs and all kinds of organisms, you can see that some of the evolution could end up in the wrong place for humanity, right, as an antagonist. So, yeah, that's what I'm worried about. Of course, I agree with all the benefits. I just talked about one, but it's not something that we couldn't do computationally anyways, right? So I think that, I mean, I don't know, maybe there's nothing we can do, right?

1:56:05We cannot block AI. So I think we could regulate it, right? And begin regulating it in a planet wide manner. So that's probably the thing that we need to do very quickly. That would be my suggestion as somebody that works in evolutionary biology. We need to use its power, but also understand its power and regulate it as soon as possible. And I don't really see any, because everybody's thinking about making money using it, right? This is really entertaining, right? That, you know, imagine generating a dinosaur and thinking about how much money you're gonna make in Jurassic Park, right? Well, this is happening.

1:56:49The woolly mammoth is underway. That company just raised like some crazy amount of money and like it's gonna, that's what is happening. Yeah, we have more problems than AI then I guess. But yeah, so I think that we, I don't understand. I mean, maybe it's just the obsession with making money that is driving this irrational exuberance that has very little worst case scenarios. right? You know, what's the worst case scenario? Well, if the worst case scenario is really bad for human beings, then probably not a good idea to not regulate it, right? So. We talk about regulating it, but not really. You know, I mean, I think there are a lot of smart people who are thinking deeply about this, but the momentum behind this just moving forward is too great at this point.

1:57:48And I think, yes, like money is central to the whole thing. But I think beyond that, it sort of just speaks to the ingrained nature of the human animal. Like, you know, we're nothing, if not a creature that is just going to keep doing the thing and we'll like deal with the circumstances in the aftermath. And yeah, we'll give lip service. We better be careful, but we're bowling forward no matter what. And that's what I see happening. And I think in the short term, certainly there's incredible implications for this that are going to benefit humankind specifically in the healthcare context. I think these tools are going to be remarkable in terms of identifying diseases at the earliest stages and figuring out ways to circumvent them and cure them and prevent them.

1:58:35All of that, I think, is something to celebrate, but there is the kind of larger looming existential questions that are a little bit harder to kind of grapple with and determine solutions. But I think we lack the adequate humility to really respect the gravity of what we're doing. And I think we think we might know what the implications are, but I don't think we really do at all. Yeah. And I mean, if you look at nuclear power, right, so some of the same arguments were made. And right now we're in a situation that we probably rather not be in, right? Somebody goes crazy, it just wipes out the entire planet.

1:59:14So this is much worse, right? I mean, compared to the AI, I think the danger of nuclear power is very small, right? That's why it's particularly surprising that we don't see it for how powerful it can be and it will be. I mean, it's not it can be, it will be what happens then, right? So I don't know if we went back and in the nuclear science, we had made the same choices, if we had the choice at some point back in the past, right? I mean, I don't know right now that, everybody would like to be in a world where everything could be wiped out by just an event that goes in the wrong direction, right?

2:00:00So, yeah, so there's a lot of benefits, but maybe it wasn't worth having those benefits available to us considering where we are right now. Yeah, so in AI, I think it takes it to another level. Well, we're gonna find out. And since you're on a track to living between 120 and 130 years, hopefully we have it figured out so that you can live a long and fruitful life. And you're gonna have a baby soon, yeah? Yeah, yeah. So you're probably thinking about things more philosophically. Yeah, that's what makes me worry, right? So, yeah. Yeah. Well, I appreciate the work that you do. It's a service to humanity.

2:00:43And I just wanna acknowledge you for that service and appreciate you coming here and sharing with us. And you're always welcome here. The new book is Fasting Cancer. And if people wanna learn more about your work specifically, Volter, where should they go in addition to checking out? Instagram, I think Professor Walter Longo on Instagram and also the Create Cures Foundation. That's, you know, createcures.org, I think. Yeah, excellent. Thanks a lot, Rich. Great talking to you. Peace. Peace. Peace.

2:01:34That's it for today. Thank you for listening. I truly hope you enjoyed the conversation. To learn more about today's guest, including links and resources related to everything discussed today, visit the episode page at richroll.com, where you can find the entire podcast archive, my books, Finding Ultra, Voicing Change in the Plant Power Way, as well as the Plant Power Meal Planner at meals.richroll.com. If you'd like to support the podcast, the easiest and most impactful thing you can do is to subscribe to the show on Apple Podcasts, on Spotify, and on YouTube and leave a review and or comment.

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2:03:26Thank you.