Episode 549: Dr. Valter Longo: What 30 Years of Longevity & Fasting Study Reveals About The GLP-1 Trend

Summary

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Habits and Hustle – Episode 549: Dr. Valter Longo: What 30 Years of Longevity & Fasting Study Reveals About The GLP-1 Trend

Date: April 28, 2026
Host: Jennifer Cohen
Guest: Dr. Valter Longo

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Episode Overview

Jennifer Cohen sits down with Dr. Valter Longo, renowned longevity scientist, director of the USC Longevity Institute, and creator of the Fasting Mimicking Diet (FMD). With over 30 years of research and 40+ clinical trials, Dr. Longo shares deep, research-backed insights on what truly works (and doesn’t) for extending lifespan and healthspan. This episode explores:

• The science and nuance of fasting and time-restricted eating
• The role and risks of high-protein diets
• The clinical data behind FMD for cancer, Alzheimer’s, and metabolic health
• Why ultra-popular GLP-1 drugs (like Ozempic) are not the ultimate solution
• Dr. Longo’s personal routines and philosophies for healthy aging

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Key Discussion Points & Insights

Dr. Valter Longo’s Credentials & Approach

• Dr. Longo holds a PhD in biochemistry (UCLA), postdoc in neurobiology, and decades of cross-discipline training (oncology, endocrinology, gastroenterology) ([01:45]).
• Clear about being a scientist, not a practicing MD, he’s led numerous clinical trials on human health, cancer, and aging.

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The Longevity Diet vs. Fasting Mimicking Diet (FMD)

Longevity Diet:

• Everyday diet, primarily pescetarian/“pesco-vegetarian” (fish + plant-based), aiming to optimize both length and quality of life ([07:19]).
• Core structure: 12 hours eating, 12 hours fasting each day, favoring safety, feasibility, and long-term results over extreme or trendy restrictions ([07:28]) (“We picked 12 hours because of safety, feasibility. People can do it … it can be very effective without the problems that the 16 hours causes.” – Longo, [08:43]).
• Includes whole grains, legumes, nuts, olive oil, minimal animal protein and dairy.

Fasting Mimicking Diet (FMD):

• Not everyday, but periodic (e.g., 5 days a month or a few cycles per year).
• Plant-based, low in protein, sugar, and calories, higher in healthy fats ([05:42], [19:27]), designed to mimic the molecular effects of water fasting but safer and more tolerable.
• Shows preservation of lean mass and metabolic health, unlike blunt calorie restriction or GLP-1 drugs ([06:05]).
• Suitable for disease prevention and adjunctive therapy (cancer, Alzheimer’s, diabetes).

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Deep Dive: Fasting, Time-Restricted Eating, and Metabolic Flexibility

• Why 12-Hour Fast?

  • Data show longer fasts (16-18h) linked to higher cardiovascular risk and gallstone complications ([10:33]).
  • Skipping breakfast correlates with poorer health outcomes; the key might be fasting duration, not the meal skipped.

• Body’s "Set Point" and Overcoming Weight Plateaus:

  • Longo describes body’s tendency to defend established weight, but FMD cycles can help “unlock” stubborn plateaus ([14:10])—“probably what happens is that people are locked in that weight modality until there is a very strong signal to switch” ([15:57]).
  • Too long restriction can backfire (“thrifty mode”) – the body saves energy and stubbornly clings to fat ([16:47]).

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FMD: Disease-Specific Variations ([27:44])

• Cancer:
  • Stricter calorie restriction (~600 kcal/day), tightly timed with chemo or other treatments ([28:05]).
  • Data in triple-negative breast cancer: FMD + chemo nearly doubled 4-year survival rates vs. chemo alone ([33:28]), and improved progression-free survival.
• Alzheimer’s:
  • More calories (up to 1,400 kcal/day), additional healthy fats, supplements like caffeine and ketogenic nutrients to support cognition ([29:49]).
• Other chronic diseases:
  • Clinical trials for diabetes, Crohn’s, ulcerative colitis, olfactory dysfunction; results pending but promising.

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Protein: Friend, Foe, or Both? ([35:26], [37:59])

• Lower protein (especially animal-based) is associated with longer lifespan in animal models and supporting epidemiology.
• Muscle gain possible at lower intake (0.8g/kg/day) with good amino acid mix and resistance training. High (>1.2g/kg) protein not needed for most ([100:05]).
• “If you want to live longer and age better, stop eating so much protein.” – Longo ([38:05]).
• Vegan diets are possible but require careful amino acid balance; eggs/dairy/fish can add nutritional robustness.
• “Eggs and dairy are neutral at best. Red meat is always very negative; white meat is negative to neutral.” ([40:38])

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GLP-1 Drugs (Ozempic, etc): Promise and Pitfalls ([53:01] onward)

• Short-term benefits: Weight loss, reduced cardiovascular risk (~10%), some anti-inflammatory effect.
• Major caveats:
  • Most users regain weight (often plus extra) after stopping, often regain only fat while losing muscle ([55:24]).
  • High discontinuation rates: 70%+ abandon within 2 years due to side effects, cost, or perceived “completion” ([59:58], [62:01]).
  • Side effects: GI disturbances, possible depression/anxiety, suicide risk, rare but severe complications (optic nerve ischemia) ([60:21]).
  • Drugs “push one button” in body’s complex symphony; unlikely to sustainably coordinate long-term health ([63:01]).
• Best use: For those who have failed every other approach, under medical supervision ([57:45]).
• Dietary interventions like FMD/Mediterranean diet offer greater risk-reduction, no side effects, and long-term health gains.

“Don’t show off the GLP-1’s 10% effect when the Mediterranean diet is showing 30%.” – Longo ([54:31])
“The drugs are really dumb, because you’re pushing the same button all the time, while the human body is this perfect orchestra.” ([63:01])

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Supplements and Peptides

• Most “targeted” supplements or peptides are minor players compared to master regulators (e.g., rapamycin, metformin have some data; others less so) ([77:00]).
• Dr. Longo takes: Multivitamin, vitamin D, B12, omega 3s (algal & fish oil mix), on an alternating schedule ([89:49]-[90:47]).

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Exercise vs. Nutrition for Longevity

• Nutrition/fasting = “85% of the impact”; exercise (including resistance training) = “maybe 15%” but crucial for mood, quality of life, and cancer outcomes ([92:02]).
• Excess/precarious exercise in youth can lead to orthopedic issues; sustainability is key ([95:19]-[96:27]).

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Dr. Longo’s Own Regimen ([45:28])

• Morning: Whole grains, almond spread, fruit (from Southern Italy).
• Often skips lunch (not for everyone, but works for him and helps with weight control).
• Dinner: Big minestrone with legumes, vegetables, olive oil, small pasta portion.
• Balances starches with “much more nourishment” (legumes, vegetables), not the reverse.

“People make the mistake of having a lot of starch and little nourishment—you have to turn it around.” ([46:08])

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Practical Takeaways & Action Steps

For Lifelong Health & Longevity:

• Longevity Diet: Plant-based foundation, fish/eggs in moderation, 12/12 eating window, low added sugar, healthy fats (esp. olive oil, nuts), rotate food sources to minimize toxins ([82:22]).
• FMD Cycles: Most benefit shown from 3-4 five-day cycles per year (can be as little as 2 for healthy, up to monthly for disease states) ([47:59]–[48:34]).
• Protein: 0.8g/kg/day enough for most; up to 1.1-1.2g/kg if focusing on muscle building ([100:05]); mix between plant and some animal for amino acid coverage.
• Exercise: Regular, not excessive; strength training and aerobic activity both valuable.
• Supplements (if vegan/very low animal product): Vitamin B12, D, omega 3; alternate, avoid excess.
• Major emphasis: Real food, sustainable habits, simplicity, no extremes.

“If you combine the longevity diet, 12-hour eating window, good sleep, and a couple FMD cycles a year, you’re stacking the deck to give yourself 15-20 years more healthy life expectancy.” – Longo ([85:39])

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Notable Quotes & Memorable Moments

• On diet feasibility:
  “From the very beginning, we say 12 hours, because … the 16 hours [fasting] causes problems, and it’s not feasible for most people.” ([08:43])

• On GLP-1 drugs:
  “It’s really condemning you to be stuck. It’s a little bit like addictive drugs or foods.” ([55:59])
  “People are just walking through a minefield.” ([61:40])

• On FMD’s regeneration effect:
  “It’s hard to believe — you take a kidney or pancreas that is completely, irreversibly damaged, and then restore its normal function.” ([84:19])

• On protein myths:
  “If you want to live longer and age better, stop eating so much protein — but have enough, and have good quality.” ([38:05])

• On the science vs. trends:
  “Most diets chase the newest study, but science shows everything and its opposite every day. That way, you go crazy.” ([10:33])

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Timestamps for Key Segments

• [01:45] – Dr. Longo’s background & introduction
• [03:38] – The Longevity Diet and FMD: Origins and philosophy
• [07:19] – Longevity Diet vs. FMD: What’s the difference?
• [08:43] – Why not 16:8 fasting? The case for 12:12
• [14:10] – Why people regain lost weight & how FMD helps “unlock” plateaus
• [19:27] – What’s included in the FMD?
• [27:44] – Disease-specific FMD protocols (cancer, Alzheimer’s, metabolic)
• [33:28] – FMD nearly doubles survival in triple-negative breast cancer
• [35:26] – The protein debate: How much, what kind, and the real risks
• [53:01] – GLP-1 drugs: myths, risks, and the reality behind the trend
• [77:00] – Peptides, supplements, and what actually works
• [89:49] – Dr. Longo’s own supplement and meal regimen
• [92:02] – Nutrition versus exercise: What the data really say

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Conclusion

Dr. Longo makes a clear, compelling case for longevity being driven by nutrition, metabolic flexibility, smart fasting, and realistic, moderate exercise—not by drugs, extremes, or unsustainable trends. His real-world advice is as attainable as it is powerfully evidence-based.

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For more:

• Books: The Longevity Diet, Fasting Cancer
• Online: Instagram/Facebook @professorvalterlongo
• Non-profit: Create Cures Foundation (Los Angeles)

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Transcript

[A]

Hi guys, it's Tony Robbins. You're listening to Habits and Hustle. Crush it.

[B]

Welcome to Habits and Hustle with me, Jen Cohen, where we break down the mindsets and strategies behind extraordinary lives. Today I'm joined by Valter Longo, one of the world's leading voices in longevity science. He's a biochemist, director of the USC Longevity Institute, and the creator of the Fasting Mimicking diet backed by over 40 clinical trials. For more than 30 years, he studied what actually helps people live longer and healthier. Not trends, not hype, but what the science consistently proves and what he's found challenges a lot of what you're hearing right now. From intermittent fasting to high protein diets to GLP1 drugs. In this episode we break down what really works, what doesn't. And the simple science backed approach your body, body is designed to respond to. He also shares how he lives himself. No shortcuts and no extremes. This one will change how you think about aging and your body's ability to heal. So let's get into it. We today have a very special guest on Habits and Hustle. We have someone that I've been wanting to have on the podcast for probably like three or so years. I've heard exceptional things about him and I'm sure you guys have already heard of him. His name is Dr. Valter Longo. He is a doctor and he's going to actually, you know, before I'm not even going to tell you, he's going to tell you himself. Dr. Longo, what kind of doctor would you say you are? You obviously do a lot of longevity cancer research, right?

[A]

Yeah. So I have a PhD in biochemistry from UCLA next door here and undergraduate degree in biochemistry in what's called postdoc in neurobiology. Right. So it's a training that you do after the Ph.D. in, in neurobiology. But, but I've actually been trained in a lot of different disciplines, you know, from endocrinology to oncology to, you know, gastroenterology or at least, you know, the clinical research part of that. Right. I'm not, I don't, I'm not a medical doctor, I don't practice medicine, but I certainly do a lot of clinical trials, human clinical trials on all these topics.

[B]

Well, I got familiar with you well, a little bit before, but you wrote the book Fasting Cancer.

[A]

This is my latest book.

[B]

That's your latest book?

[A]

My first book was the Longevity diet. Which is 2018.

[B]

Yeah, like seven or eight years ago. But when did you write Fasting Cancer? When did it come out?

[A]

Fasting cancer came out very recently, like six months ago. Yeah, so.

[B]

So I was familiar with you, of course, before that, but that was the book that really kind of struck my. Like the whole idea of cancer to me is the most, the scariest thing in the world, right.

[A]

To most people.

[B]

To most people, it's like the biggest fear of everybody. And so that when I saw the title, I was like, oh my God, like, I need to like delve into all of the stuff that, all the research. Because you've been doing so much research on longevity and obviously aging and fasting. I mean, the. Can you tell people? Just, let's start with the, the thing that you're most known for, right, which is the fast mimicking diet. Longevity diet. What is kind of your whole hypothesis that we should be fasting? It's what should we be doing in terms of like, how do we live the longest and healthiest, Right.

[A]

So that's really my focus and the focus of the institute that I started at USC is how do we make people live as long as possible, as healthy as possible? That's what we've been working on for 30 years. And even before then, when I was at UCLA, I was a student, Roy Walford. And Roy at the time was the most famous person in the world. He was a medical doctor at ucla. And he was focused on how do you make people live longer, healthier and. Yeah, so I think that after all these years, when we came up with, I came up with something called the longevity diet, and then I came up with something called the fasting mimicking diet. And so these were also. We were also thinking about things that are feasible, right, that people can actually do and not just something that's very beneficial. For example, we can go into it if you want GLP1, right. Receptor agonist. Most people abandon them, you know, within a couple of years. And you, for those to be effective, you need to do it permanently, right? Or certainly very, very long term. So. So to us that's not feasible, right? That's not a good idea. It may work, you may get very good effects short term. But then what did they achieve? Maybe I achieved that, I gave you side effects and then now you regained all the weight and you as even unhealthier than when you started. Yeah, but so the longevity diet is the. What do you do every day, right? And, and the, and the fasting making diet instead is what do you, what can you do once in a while, right? Is it possible that you can just do in this Case five days of a vegan diet that mimics fasting. Right. So then the idea was first developed in simple organism, then in mice and then in people. Can you eat but get the same responses molecularly as if you were water only fasting. And that's what a fasting making diet is. So it's a low calorie, low protein, low sugar, high fat, plant based diet that does all these things depth water only fasting does. But as advantages because of course it has salts, it has carbon sources, meaning it has energy backups. Right.

[B]

So glycerin, I saw it has, doesn't have glycerin or.

[A]

Yes, glycerol. Yeah. And the glycerol, the jaboglycerol is for example, people going back to GLP1. Right. So GLP1 receptor agonist. Most of these drugs you lose 2 to 1 or 3 to 1 parts of fat for lean mass. Right?

[B]

Yeah.

[A]

So you're losing a lot of muscle essentially while you're doing this. And so with the fasting mimicking diet, we don't see that. Right. And one of the reason is because it's an evolved process that has the job of just making you lose the fat. You know, you don't want to lose. If you think about history and you're fasting, you do not want that organism to be losing muscle.

[B]

Right, Right.

[A]

You want to have it so that the muscle is protected. And one of the ways the muscle is protected is glycerol.

[B]

Right.

[A]

So the fat is broken down and glycerol now can be used to make sugar for the brain. And instead of taking muscle to make sugar through what's called gluconeogenesis. So now the glycerol is used to feed the brain instead of the muscle being used to feed the brain or certainly the amino acids released from the muscle.

[B]

Okay.

[A]

Used to feed the brain. Right. So this is just one of the many tricks that we have in the fasting making diet to make, make sure that we get lots of benefits and, and, and no side effects or very little side effects.

[B]

So let me start from the beginning. Okay, so the long. So you first write this book in 201718 the Longevity Diet. Now is the longevity diet. Is the diet, the fast mimicking diet, are they one and the same?

[A]

No, the longevity diet is, is everything, including the fasting Mickey diet. Okay. So the longevity diet is for example, a pescetarian diet.

[B]

Okay.

[A]

So fish plus vegan or fish plus vegetarian actually probably. And those seem to optimize longevity but also minimize frailty. Right. So people can live long, but can live long frail. For example, the southern Italians are famous for many having a lot of centenarians. But the southern Italians are also some of the most frail people in Europe. Right. So you don't want to have, you want to live until 100 and be sick for 30, 40 years or even be frail. I mean, you know, you cannot go up the stairs or you cannot go for a walk or you cannot do lots of things that you want to do. Yeah, so that, that's what this longevity everyday diet is. And then it has all the components, for example, 12 hours of eating and 12 hours of fasting per day. Right. So we're staying away from the 16 hour, 18 hour fasting for lots of reason which we can discuss. But we picked the 12 hours because of safety, feasibility. People can do it, but also because of it just takes longer for it to be effective. But in the end it can be very effective without the problems that the 16 hours causes it.

[B]

Well, it's funny because actually not funny. I mean fasting for a long time was very trendy, a very trendy, like the intermittent fasting, the water fasting. And I feel lately it hasn't been as like, it hasn't been as popular. Right. Because people are coming back and saying it's not something that people like to do, whatever. And I was noticing that the people that were like super into fasting, they were like shortening their windows from like a four hour window. Like it went from like the 16 hour window to the eight, like to the. There's other people, they're only eating within a four hour window.

[A]

You're within a two hour.

[B]

I was gonna say some are even in a two hour window or not eating at all for five days with the water fast. Why did, when did you realize and what are the, what are the benefits of or what, why now have you noticed that doing 12 hours is just even better than doing a 16 or these long stretches of diet?

[A]

I mean the longevity diet is based on five pillars, Right, but meaning that it's not just a lot of diets are based on epidemiological data. Right? You look at these big studies of wheats this, wheats that, and how do they compare? The longevity diet is based also on centenarians. What did the centenarians all over the world, Okinawa, Loma Linda, California and Sardinia, et cetera, et cetera, what did they eat? And then how do you make a mouse live longer? How do you make a rat live longer? How do you make a monkey live Longer. How do you make a. And so those are all important, in addition to the, to the epidemiological data, to come up with something that it's less likely to be affected by the new study. Right. Somebody's every day something new comes out, and if you do that, you're going to go crazy, because then each, if you, if you look at any study, they're always going to prove everything and everything against it. Right?

[B]

Yeah.

[A]

And the opposite. So from the very beginning, we say 12 hours. I say 12 hours because, for example, I was noticing there was old data, but very good data. They were saying if you skip breakfast, you live shorter with twice or much higher levels of cardiovascular disease. Right. And so I say, then I started thinking, this is really strange. Is it just about the breakfast or is it about the 16, 18 hours of fasting?

[B]

Right, right.

[A]

And then, you know, there were also data showing that after 12 hours, your cholesterol, your circulating cholesterol level go up, the LDL levels go up, and they keep going up the longer you fast. And then I was looking at data, and this is like 10 years ago, or gallstone and gallbladder operations, women that were fasting for 14, 16 hours, they were twice as likely to need people with gallbladder disease, twice as likely to need an operation. So, yeah. So all of that from the very beginning, and then the feasibility. Right. I was a student of Roy Walford back in the 90s, and, and he was talking about something called calorie restriction, which is what if you severely restrict your calorie all every day of the year? And then I was noticing that nobody was doing that. Right. And so I always thought, you know, it may be good for the lab, but that's not good for people. Right. Because, you know, to do calorie restriction, you have to be losing a lot of weight. I'm already pretty thin. Imagine me minus 30 pounds. Right. That's what calorie restriction looks like. Yeah. So I thought it cannot be something that pushes people all the time to the edge. And, you know, so the 12 hours made sense scientifically, clinically, and also made sense feasibility wise. It's just easier and most people can do it. And I think I got it right. You know, and now we're starting to see the data indicating it may not just be skipping breakfast, it may be any 16 hours. And there is a study published last year indicating that any time you do 16 hours, you are putting yourself at twice as much, twice as higher, twice higher risk for cardiovascular disease, and also overall mortality increase, overall Mortality, really?

[B]

What about. Is it. How about the fact that you just end up eating more? Because when, for me, when I skip, let's say breakfast, let's just go with the breakfast thing. When I don't eat breakfast, I'll just end up eating those calories anyway later on during the day because I'm just like, I'm making up for it. Like, my body also has a. Don't. What do you believe in, like, baseline. Like, do you feel like everyone has a baseline weight that you can only modify so much where it gets to be uncomfortable? Or do you think that we can all. Or is it not about that at all? I mean, I know you take it from a health perspective, but for the weight piece of it, because a lot of people are doing the fast for weight as well, Right?

[A]

Right. Yeah. So first of all, the breakfast keepers, there was no other information. It was just people that skip breakfast, they do worse, Right. There was no reason. And for a long time the idea was, oh, they do worse because they have bad behavior. But it doesn't look like that, right? It doesn't look like that's what it is. Yeah. So I think that it probably is about fasting, right. For so long. Right. It's just too long. And somehow the body is. Particularly if it involves, if it's 16 hours that involves skipping breakfast, the body, you know, has negative responses, right? It does. It. It turns into a modality. Maybe it's the cholesterol, maybe something else, but something is negative about it.

[B]

Right.

[A]

And then, you know, the, your second question about the weight, it's. Yeah, the body likes to go back to a weight at which you were stable. Right. So if somebody's overweight 30 pounds, and you stay in this 30 pounds overweight long enough, the body likes that because it understands that that's a good situation. Right. It may not be modern in modern time, a good situation, but it was for the history. For 100,000 years, you know, Homo sapiens have been around. So it tries to keep you there. It tries to keep you there. But that's where the fasting, mimicking diet kicks in. Right. So for example, in the documentary, it's going to be shown very soon and the premier is going to be shown in the documentary, we're showing that the body likes to go back to a certain weight where it's stable. And so if you try to move it. And so in the documentary, we were showing a doctor, right? In this doctor, we were overweight, obese, hypertense for a long time. And so we Put him on the longevity diet and the everyday longevity diet. And the doctor, after nine months doesn't change at all. It loses a couple of maybe 3 or 4 pounds, but doesn't change at all. Then we started the fasting Mickey diet. So again he had been at about maybe 90 kilogram in a, in a very steady way. And so the, the longevity diet, this like maybe Mediterranean diet, but taken to even more extreme, doesn't do anything, right? So now we put him on the fasting making diet. So in about six months, the following six months, eight months, he does three cycles of the fasting Mickey diet. Then you see his weight comes down, his glycemia comes down, his blood pressure comes down. Now he gets rid of, he was on Ozempic and other drugs, he gets rid of drugs and he gets rid of not just the glycemia drug, the diabetes drug, he gets rid of the hypertension drugs and his weight goes back to normal, right? So probably what happens is that we are locked, people are locked in that, you know, in the weight modality until there is a very strong message switch, right? Get out of it, right? Get out of it. Because, you know, now, you know, you kept the, the fat and now the three cycles of fasting, making that come around and it just pushes you to, to start burning fat versus accumulating fat, right? So, so yeah, so people are stuck, but they can get out of it. The fasting diet is certainly a good way to do it.

[B]

So the fat, so the fast mimicking diet can actually trigger you out of that baseline diet that you've been stuck with.

[A]

Yeah, the first thing you can, I can do that. But now I think it's important for people to understand that if you go too long, right? If, if the restriction is too long, and these are studies that have been done for a long, long time now you can get into something called the thrifty mode, right? And the thrifty mode now is, tries to save energy as much as possible, right? So if you fast for too long, that doesn't happen. The body doesn't switch into a catabolic, into burning fat. If you fast, if you fast for too short, if you fast for too long now the body starts being worried about I may have to save energy because I may die like this, right? So if I don't start putting away, keeping the fat, then I'm going to be in trouble. And so now you enter this thrifty mode. In this thrifty mode, we are worried that maybe epigenetic and that may be why so hard for people once they get into this fat saving mode, it may be so hard for people to get out of it because basically everything tells you eat and go maybe in a lower energy expenditure mode. And that's what it was shown. Meaning you are burning less calories.

[B]

Right, right, right, yeah.

[A]

If you enter that, then you, you get a problem, you get the opposite problem, you know, so if you do too short, you don't enter the catabolic mode. If you do too long, you enter the energy saving mode, you. And this is why people underestimate the power of understanding the science and understanding that you have to do it just right. So then you unlock it and you can keep going and then you can go to a different weight. Right. Which could be £30 lower than you.

[B]

Right. It's a very delicate balance. It sounds like.

[A]

Well, it's a delicate balance because it is a program that is there to protect you from starving to death, but it's also, you know, there to protect you from a. Maybe it's a good, it's good to keep saving fat. Right. And in the majority of the history of human beings, and not just human beings, any organism, you know, starving, it was a real possibility. Right, right. And so, you know, and there is no more pressure, natural selection pressure, than starving to death. Meaning that evolution is very much aware of the danger that could kill you and then it wants to eliminate those as much as possible. And certainly starving to death is probably one of the most common ways that people have died in the last 100,000 years.

[B]

Wow. So can you just give us a very brief description? And when people who don't know and they're not familiar with what the fast mimicking diet is, what does it contain? Like if someone to say, hey, Dr. Longo, what is this fast mimicking? What do you mean by this?

[A]

Yeah, yeah. So the fasting mimicking diet, the, the, when I first developed it, like 20 years ago, I started developing it, the idea was to first make it fasting mimicking. Right. And so, and then you use a lot of, again, low protein, low sugar, relatively low carb, but not too low.

[B]

So your body just interrupt you so people understand. So when you say fast mimicking, it's basically your body fast thinks it's in fast mode, but you're, you're basically giving people little things to eat and drink, to supplement so they don't feel that like ravenous feeling and deprivation of a normal fast. Would that be con.

[A]

Yeah, the deprivation. But also I think that it's very important to. The deprivation Also includes just the opportunity to stop and have a meal. Right. So people, I think there is a problem with, you know, you need to have a certain amount of foods and calories, but also the routine of having breakfast, of having lunch.

[B]

Right. Psychologically.

[A]

Yeah, psychologically that's very important. And then of course, lots of other things that, that need to be in there. Like I mentioned, you know, the, the salts and all of that. Yeah. So then the fasting making diet as the, I mean the molecularly and without going to the details, there is to four markers. You know, IGF1, insulin, like growth factor one has to go down, glucose has to go down. And then something called IGF BP1, which is an inhibitor of the growth factor, has to go up. And then ketone bodies, they have to go up. Right. So ketone bodies are the, these byproducts or fat breakdown. And so this is where ketogenesis, the word ketogenesis come from.

[B]

Right.

[A]

So now the, the, this diet that I just described, lots of vegetables, lots of nuts, lots of oils, olive oil, they have the job of changing those markers. And of course, you know, the fasting Mickey diet theoretically could be made with lard, for example. Right. You know, theoretically even lard will make it a fasting mimicking diet, but it wouldn't make it necessarily a healthy fasting mimicking.

[B]

Right, right, right. Okay. Yes.

[A]

So then, then, then the idea was let's match the fasting mimicking properties with the very healthy ingredients of the, you know, of the longevity diet, let's say. Right. So what did the. Can we take ingredients from Okinawa, from Loma Linda, from, from Italy and then use those to make the fasting, the fmd.

[B]

So is there like a, so when you do a fat like you basically, was it a lot of trial and error to figure out the exact. Like you had like, like to kind of figure out what to do, like the balance, like 20 years ago, how were you kind of figuring this out? Like what was your team doing? Were they trying different foods? Were they incorporating? Were you trying it in rats? Like how did you kind of figure out this, this ratio of salt or glycerol or whatever you put in that thing, like to figure out that perfect balance of how your body doesn't feel deprived or it's not burning lean muscle? Because that was the other concern. Right. Like people don't want to burn lean muscle. So that's another thing. How did you kind of figure out the, the measurements? Like how did you get the recipe, so to speak?

[A]

Yeah, I mean, we've always Focused on the genetics of longevity and the genetics also of weight loss and weight gain. So we already started from understanding the connection between ingredients and the consequence of having that ingredient. Right. So then it was just a matter of testing it out. So for example, you know, we knew that we had to have low protein in the diet. Now people shouldn't mix the longevity diet with the fasting making diet. You know, the longevity diet is normal protein. The fasting making diet is very low protein. Right. But it's not just the protein but the amino acid content. So meaning that you could have a relatively low protein content, but if it comes from one source, especially animal source, the amino acid that we want to have very low and usually there what's called essential amino acids, the amino acids are high, are too high. Right. So it's not just protein level, but then protein type. And even between two vegetable sources, you can have a two, three fold difference in the content of certain amino acids. Right. So then that's why, you know, you want to have. So we were more thinking about amino acid level, right? So yeah, and then we're picking protein sources, just to give you an example, with the, with the, with the amino acids, protein sources that will contain low levels or, or higher levels of those amino acids. Yeah. So then everything in the FMD goes through that reasoning, whether it's fat. And so you could have any fat, but then you have olive oil and it's got monounsaturated fats. And so each ingredient was tested in mice. And then we were looking for the effects in mice. Then first you look at the short term effects, right? What happens in a couple of weeks. But then eventually we started doing the lifelong studies, right. And that's really. Those are the very expensive ones and they're the ones that you need to then have a chance to make somebody live longer, healthier, right? So for example, a few years ago, first we did it in normal mice and then we did that in mice that were fed a very bad diet. Right. So we wanted to test both. Right. And you know, for example, the mice that had a very bad diet, this was published a few years ago. We show that, you know, they get very big, right? And they get very unhealthy. And it's really remarkable how unhealthy they become because I thought, what's some western diet going to do to a mouse, right? I thought maybe make a little, a little bit shorter. It almost cuts their lifespan in health, right. And it just completely messes up cholesterol level, heart function, inflammation, you know, Insulin resistance. So okay, so this is a bad diet, right? Fine. And the mice become very big. Then we start with the fasting making diet once a month for five days. And we thought it's probably going to make him a little bit better, right? We thought just mice on the normal diet and mice on this really bad diet. And the mice and the, and the bad diet for 25 days a month and a good diet for five days a month. They're going to be in between. They were not. They were like identical to the mice on the good diet. And so that was very surprising to us. Right, so just five days a month of this FMD. How can it be 25 days? It's five times as much bad diet than good diet. And yet the five days were enough to bring everything back. Cholesterol, heart function, glycemia, insulin resistance, you know, name it. So now we just finished a 500 people trial in southern Italy with overweight and obese people. I cannot talk about the results, but the.

[B]

Why.

[A]

But yeah, because it's not published yet. But the.

[B]

Are they good?

[A]

Well, we'll see. But, but the idea is, is it possible that, you know, it's not really about good food and bad food is about the role of the bad food. So we, we think of bad food as something that every day does a little bit of damage to you. Right. But that studies show that it's not true. Right. Because otherwise I, you know, you got 25 days of damage every month.

[B]

Right.

[A]

So then you don't come back from that with five days. And so, you know, either is there is a regenerative process that brings you back or maybe the food is just pushing you into a modality which then accelerates the aging process. So it's not doing damage, but it's just pushing you, let's say in insulin resistant modality, in an inflammatory modality, et cetera, et cetera. And that eventually if you don't unlock it every month, right. Then that that makes you age faster.

[B]

So okay, so a couple. You said a few things. So one question I have is how have you revamped the diet from 20 years ago to now? Like what are some of the findings that you have kind of revised that you know now that you didn't know back then?

[A]

Well, I mean, 20 years ago it was the mouse version. Right. So Right. And we use it for cancer. You know, now there is a lot of fasting making that is one for Alzheimer's, that is very different from the one for everyday people, is very different from the One in cancer. Cancer is much lower calories.

[B]

So let's talk about that. I'd love to. So you basically took the diet and kind of tailored it to disease specific. So there's a, there's a specific fast mimicking diet for an Alzheimer's patient versus a cancer patient versus autoimmunities.

[A]

Yeah. Versus diabetes versus prediabetes. Wow.

[B]

I think about that. I'd like to know the difference. How much, how much different can they all be?

[A]

Well, I mean, for example, the cancer one is much lower calories, 600 kilocalories. Because with the cancer we need to get quick, quickly in and out, meaning that the cancer patient gets chemo and the chemo is gone within a few days. Let's say it gets chemo, it could be getting chemo, it could be getting immunotherapy kinase inhibitor and lots of different therapies. So, so we need to try to achieve these changes in IGF1, et cetera that I talked about before. Quickly. Right. And so because you know, we don't have the time to get there more slowly. But for Alzheimer's, for example, is the opposite. We have high calorie, we add an extra 3 or 400 kilo calories per day because now we're dealing, we just finished a trial in Italy. We're dealing with people that may be as old as 85, 90 and we cannot give them a 600 kilo calorie, which is what we. So for normal people is 800 to 1100 kilocalories per day for cancer is 600 and for Alzheimer is 1400. Right. So yeah, because we don't want to push somebody who's 85 to a very restricted diet. And you know, that was probably a good idea because so far we've had very little, you know, high grade toxicity, meaning like the type of toxicity that makes the doctor worry. Right. So it's minor things like a little bit of a headache and things like that. But you really don't see the, we haven't seen very much of the grade three, grade four toxicity, which makes worry, makes clinicians worry.

[B]

So what do you do in the Alzheimer's fast mimicking diet, like besides adding more calories, are you just adding bigger portions? What are you adding? Any specific ingredients?

[A]

And we're adding lots of, I mean in the Alzheimer's is not just calories, it's also other things. So we add caffeine and it's a ketogenic supplement that we actually give, give patients between the cycles. Right. So, so they did the Cycle and then all day, 25 days in between cycles, they got these three 400 kilo calorie ketogenic supplements. So high fat, very healthy, most of it from nuts and olive oil. But there was also caffeine and some, some other things in there that have been associated with protection from, from cognitive decline. So, you know, Alzheimer's a little bit special because there's really nothing out there that works. Right. And so we felt let's just go all the way, which we usually don't do because then if you put all these things in there, you don't know what worked.

[B]

Right.

[A]

But we thought, especially because we were talking to neurologists, I remember six or seven years ago, and they were telling us, you know, good luck. Right. Because by the time somebody's got an early Alzheimer's, I mean their brain is so damaged that it's going to take a miracle for anything to bring it back. Right. That's when we started thinking, okay, let's just go with everything we can and yeah, we'll see. But in mice works very well. But, but you know, I think it's, it's a lot rougher because in mice we start early. Right?

[B]

Right.

[A]

Yeah. If you start in an 82 year old patient that is already being diagnosed with Alzheimer's, it's not helping you. We don't have high hopes.

[B]

Yeah, it's, you're right past the point. I'm also asking because my mother was diagnosed with Alzheimer's recently, a year ago. And I'm looking. Thank you. And I'm looking for anything. And the truth of the matter is like once you've kind of hit some a place, there's nothing that you can really reverse. Yeah.

[A]

I mean it's, everything is possible, but it's extremely complicated compared to other diseases. Right. Once the nervous system is badly damaged and you know, your brain undergoes atrophy and a lot of the brain cells are lost. So yeah, it takes, it would take like some remarkable regenerative process to do it. Yeah. To bring it back and bring it back without doing damage to the very delicate nervous system. Right. So it's not just you gotta bring it back, but you know, you also have to save what's left that is still working.

[B]

Exactly.

[A]

Alzheimer's patient can still function relatively normal physically. Right. Not all of them, but many of them can. And so you have to preserve all of that. You cannot add to it. And then, you know, you have to restore learning and memory. But it's just, it's a rough, you know, enterprise.

[B]

It Is what's interesting though. People who have been diagnosed with cancer have been prescribed fast mimicking diet. It's been, it's been kind of known and researched to have had pretty remarkable results on cancer patients.

[A]

Yeah. So there are many trials now on fasting, mimicking diets and cancer. And the one that is most studied is triple negative breast cancer. For good reason. Right. The triple negative is much more aggressive. Mortality is very high at five years. Right. And that's one of the most common cancers in the planet. So the multiple trials now are showing patients that did chemotherapy alone versus, I mean patient did fasting, making diet plus chemotherapy versus chemotherapy alone to do much better. Right. Survival wise.

[B]

How much? How much? What's the percentage?

[A]

Four years, about three and a half, four years. It was about, nearly twice as high the survival in the FMD plus chemo versus chemo alone.

[B]

Oh wow.

[A]

Yeah. And then the new study which is published by the Vernieri group is showing progression free survival, which is not overall survival, but it's like how long you live without the cancer progressing. Right.

[B]

Okay.

[A]

So they're showing improvement in that and also improvement in what's called complete pathological response, which basically is what they call a surrogate for overall survival. Right. And so this is much higher in the patients that do a fasting mimicking diet compared to the, you know, what they normally expect from, from the database. Right. So, so yeah. So then multiple trials are now showing that with some of the most metastatic, in the metastatic cancer, the most aggressive, the, the initial trials are, are very promising. Now for the earlier type of cancer, somebody is going to receive, let's say surgery, that's a different story. Right. So we're trying to be, maybe more careful and we're saying, you know, if you have a 98% percent chance of being cured, maybe leave it alone. Right. You know, just, just take your 98% and don't. So the foundation that I started, so they follow lots of cancer patients every year and usually they put them on a longevity diet, 12 hour time restricted eating and lots of other things, you know, muscle training and, and aerobic exercise. But they don't. We usually in the early stage cancer patients, we don't. Not that we have any evidence that it's not good for you, but you know, certainly it makes a big difference for mice and cancer. But we're just saying until there's a trial that is showing superiority versus the therapy alone, we don't, we just don't feel like, you know, we should recommend.

[B]

What about protein because in the, you said like the longevity diet, A, you said it has five pillars. We talked about the centurion pillar, we didn't talk about the other four. But that has fish in that. It's a, you said he has fish in that diet. Fast mimicking. It's vegan, like you said. What is your take on protein? Because do you like, do you believe that too much protein can actually age you quicker?

[A]

Yeah, I'm, I'm writing a review now on proteins. Right. And, and it's interesting, right, because if you look at overall all the science that has ever been done, if you, you know, proteins color, what's called calorie, what I was talking about earlier, which is you just read normal calories, you reduce it by to say 20%, 25%. Right. That's the most successful anti aging method ever done. Right. If you look at, you know, thousands of studies, right.

[B]

By reducing your calories by 20%, reducing not below excess.

[A]

I mean reducing it is normal calorie intake, let's say whatever, 3,000 kcal and you reduce it by 25%. Right.

[B]

And that's the best aging, that's the best way to.

[A]

Yeah. If you slow down aging, that would beat any other intervention because there are literally thousands of of studies, including human studies showing remarkable effects. Right. And so if you think about the second one is probably protein restriction or if you think about it, the only one that doesn't require you to eat less is protein restriction. Mice, rats, you know, and the monkeys, they live longer. They were calorie restricted but also protein restricted. Yeah. So I think if you look at all the studies, the indication would be that it is sufficient. But low protein diet that is mostly plant based is going to make you live longer or a lot longer. Now if you look at the epidemiological data only, which is what most of my, you know, the most of the podcasters let's say out there talk about, then you know, it's a lube. You could get lots of different answers, right. You could get high protein is good for you. Mid protein is good for you.

[B]

That's interesting. Yeah. So especially in the fitness and wellness world, right. We're all told that we need to be eating like a lot of protein, especially in midlife. Right. Like to keep, you know, lean muscle on. Like all you hear now is protein, protein, protein, creatine, creatine, creatine, like anything to kind of increase your protein.

[A]

Yeah.

[B]

So you're saying the opposite. You're saying if you want to live longer and Age better. Stop eating so much protein.

[A]

Yes, for sure. Stop eating so much protein, but have enough protein and have proteins that, you know, include proteins, let's say two thirds of very good quality amino acid profile. Right. So for example, if all your proteins coming from legumes in your law, you're going to have a problem.

[B]

Right.

[A]

Yeah. So, so and I think the vegans, you could be vegan and very healthy, but you need to pay attention to what you're eating because otherwise you're going to end up being malnourished. Right. So it's a lot easier. And this is probably why the doctor is always recommended. Yeah. Eat a little bit of everything.

[B]

Yeah.

[A]

Because it's much less likely that somebody eats meat once a week and fish two or three times a week and chicken. Those are going to do pretty well. You know. Now they're not going to do as well maybe as those that are vegetarian and they have a more restricted diet, but they're generally going to do pretty well. So, so then you have to, you know, you have to look at what you're trying to achieve. So if you're trying to achieve a long lifespan and you know, but you also want the strength. I think it's, it's probably good to, I go back to the pescetarian diet, like pescatarian, Pesco. Vegetarian, let's say.

[B]

Right. Like fish.

[A]

Fish, but also some eggs, maybe up to three a week. Three eggs a week?

[B]

Only three eggs a week. What if you eat three eggs a day?

[A]

Well, I mean the, the data indicates that, you know, after three eggs a week, you know, in general, I mean, let's put it this way, they're not. Lots of. We're going back to epidemiological studies. Lots of studies say it's fine.

[B]

Right, right.

[A]

If you have, if you don't have too many eggs. But some of the biggest one are showing that past three eggs a week, you're starting to see a mortality increase. Right. Now, you know, it's a, it's an association. It doesn't mean the eggs were causing it. But that's not a good start. Right. If you start seeing, you know, this particular food is not eggs are normally not associated with living long meaning like, you know, legumes are and whole grain wheat is and you know, nuts are, and olive oil is. And while the eggs, you don't see it. So it's either neutral or negative. That's usually where you see them. Now red meat is always very negative and then white meat, it's negative to neutral and Eggs and dairy is usually, you know, neutral to bad. Yeah. So I think that probably okay for most people, like, if somebody has to have lots of eggs, it's probably okay. But, you know, maybe not.

[B]

Maybe not. If you're saying like maybe not, it's neutral at best.

[A]

Is neutral at best.

[B]

At best.

[A]

Yeah.

[B]

So. But okay, so dairy, like Greek yogurt, would that be neutral?

[A]

Generally, lots of the data will put them in the center. Right. Neither good for you. So, for example, this is very nice work done at Harvard, looking at what are the ingredients that are going to get you to 70 or 75 healthy? And you have the, in this case, fruits. I'm not. I think it should be more limited because if people hear fruit is at the top, then it can, you know, eat too much fruit.

[B]

That's, that's me.

[A]

But, but I say, you know, vegetable and, and fruit and nuts and legumes and whole grain were at the top. And then, you know, the red meat and the processed meat was at the bottom.

[B]

Right.

[A]

And then, you know, and the. Lots of the, the eggs and the dairies and the yogurt and in the center. Right. So probably, you know, if you're not looking for a record, you know, if you. Most people are not looking to get the record longevity and they're basically, it's not a bad compromise to eat yogurt. And of course, it's very high nourishment. Right. So then certainly as you get to 65 or older or 60 older, those are probably the type of ingredients that might help you not become frail. So then there is also the idea of different stages of life for different foods for different food and food quantities. Right. So once you get to a certain age, then most people start losing weight, and that weight loss is usually associated with living shorter.

[B]

Right, Right.

[A]

So that's why when you get to 65, and for somebody, it could be 60, for somebody else could be 70. Right. Chronologically, chronological age. So when you get to that point, you want to stay there and stay strong.

[B]

Right, Right.

[A]

And so, yeah, so to stay there, stay strong, some people might have to have, you know, yogurt and, and, and eggs or more eggs and more yogurt. Some people may not.

[B]

Yeah, I guess you're right. You got to think about all the different, like, there's so many different benchmarks that you're like or like different variables that you're looking at. Right. To like, what, what will make someone healthy. But you're saying that, which fish. Do you say fish is neutral?

[A]

No, no, fish is Positive neutrals or positive meaning neutral or positive? Yeah.

[B]

Okay.

[A]

The pescatarian, the pesco vegetarian better than everybody else. Right.

[B]

What about salmon that's farm raised though? Like fish that's farm raised, is that still neutral to positive?

[A]

We don't know that. Right. So we know there, there are toxins associated with it. And, and so usually the recommendation is maybe eat it once a week. Right. So if you have a farm raised salmon. Yeah, once a week. So you limit whatever toxins that are associated with the fats in the salmon. And because if you think about so many food, so much food.

[B]

Yeah.

[A]

It's got toxin in it, right.

[B]

So much.

[A]

Yeah. And so if you went around and analyzed. So for example, I tell people, most people don't, don't know that brown rice has got arsenic.

[B]

Yeah, arsenic, for sure.

[A]

Yeah. So. So I mean in a, you know, and the mercury and the, so there's, and the acrylamide and so, and a lot of it is in vegetables. Right. And, and so yeah, So I think that, so would you say you also have to say I gotta eat something, so maybe rotate a lot. Right. Then don't eat the same foods all the time and only salmon. The same farm raised salmon three times a week or the same tuna twice a week because you know, the mercury, mercury poisoning is a reality. And so. Yeah. So then instead of scaring people with, you know, don't eat anything. It's because then people go into the modality and say well I can, you know, I cannot have anything. But. Yeah, you can but try to, you know, if it's salmon farm raised, make it once a week. Yeah.

[B]

So what about you? Because you said, you said that brown rice does have arsenic, which some of us know. Do you recommend to people to have white rice then and stay away from brown rice because of that poison.

[A]

I mean it's a poison. Right. But you know, if you had it, let's say once a month, it's got maybe twice as high as some of the white rice rice or two or three times. It's not like 20 times higher. Right? Yeah. So. So I think that the bigger problem comes in when somebody and you, I, I meet these people all the time, they say I eat it three times a week.

[B]

Right.

[A]

That's when you're going to get in trouble. Right?

[B]

That's when you get in trouble and

[A]

that's when you may get, end up with arsenic poisoning like mercury. Right. So if you, if you start having swordfish and, and, and tuna three or four times a week, that's Going to be a problem if you have tuna once a month, you're probably going to be okay.

[B]

You'll be okay.

[A]

And what do you eat?

[B]

What does your diet look like?

[A]

Yeah, my diet is, is really everything that I preach, right. So I have a lot of whole grains in the morning, for example. Then I have like an almond spread. Both of those I get from southern Italy and I, I store them and then, you know, I have some fruit and then I skip lunch and I, you know, and it's not necessarily a good thing, Right. But, but that's an example of a compromise, right? So for me, whenever I don't skip, I've been doing it for 20 years and that's the only way, together with the fasting making diet, that I can keep the weight that I, that I want.

[B]

That you want.

[A]

Yeah. So going back to your question earlier, you know, my, my weight is probably sat like 20, 25 pounds higher than I am. But you changed it to keep it there. I have to do a lunch and I have to do the FMD and I have to do the longevity diet. Right. So then at night I have these big, you know, minestrones with the legumes and lots of vegetables and olive oil and pasta. But, you know, I have maybe 75 grams, 80 grams of pasta and not, you know, so the mistake people make is to have a lot of these starches and little nourishment, right? And you gotta turn around. You have to have a lot of vegetables and legumes and little pasta or rice, right. White rice or brown rice and. Yeah, those are the ideal combination, right. And that's how people used to do it because they were poor and that's all they had. The minestrone is all over Italy, right? Because you have the Genovese in Liguria, you have the Genovese minestrone in the south. They have the. And what it was is people were poor and at certain point they were running out of food and they were like just grabbing anything they had and put it in, right. So that you get an extra meal. So that's gone now. Right. Even in Italy, nobody does that anymore. And now you have these big rice dishes and pasta dishes and whatever else. Right. The starches that, that, you know, of course you're going to make you gain weight and they're going to make you insulin resistant.

[B]

Yeah.

[A]

And they're going to make you die earlier.

[B]

So how did you, so how often would you suggest people even doing fast, mimicking diets? Like, what would be the, what's the most optimal. To get optimal results, to live the longest and healthiest. How often?

[A]

Yeah, I think that it depends. Right. So, for example, in the diabetes trials, it's every month for either six cycles or 12 cycles. Right. These are patients that have diabetes. But the case that I told you earlier, this doctor only did three times. Right. In six months and it still worked. Right. So I think that, yeah, you can start. The doctor, in the case of a diabetes patient could start with every month and then move to once every two months and then every three months and take it from there. You know, for everybody else, I think maybe like three times a year.

[B]

Three times a year?

[A]

Yeah, maybe even two. Maybe I do once or twice. Right. But I skip lunch, you know, and I do the longevity diet and I do everything else. So. So, yeah, to me is not as I don't need as many, but, you know, most people are overweight and obese and. And they have lots of other issues. And so as those issues come around. So, for example, Stanford just published on. On Crohn's disease. The University of Miami published on the FMD and ulcerative colitis, and universal Rome published on FMD and hyposmia, the loss of olfactory function, smell and taste. Right. And the ability of the FMD to restore taste, smell loss. So, yeah, meaning every. Every different people have or don't have different problems, and then they have to decide how to use the FMD based on where they start from, based on baseline. Right. Where their starting point.

[B]

What about fasting in women? Because there's a lot of chatter about fasting not being great for women, hormones, especially as women are in middle age.

[A]

Yeah, I mean, fasting again is good, bad and neutral. It doesn't mean anything. We just mentioned like 16 hours, 18 hours, probably not good, 12 hours, probably very good. And yeah, so I think that probably is very good for women. And, you know, at least 50% of the patients in the many 40 clinical trials that are being completed now with the fasting making diet, I would say the majority are women and they did very well in the great majority of the trials. So, yeah, it's working very well for women. I think what we still need to define. So, for example, we just finished a trial on polycystic ovarian syndrome and one on endometriosis, and we're going to be publishing those soon. And yeah, I think the timing is still, you know, somebody's period, for example, when is the best time to do it.

[B]

Right.

[A]

You know, so. So we were talking to endocrinologists and some of the female and specialized endocrinologists saying, you know, maybe there is a period where it's not going to work very well. Right. So I think soon enough we're, we're going to start publishing, you know, don't do it in this moment, you know, but, but yeah, beside maybe that one week a month where may not be ideal to, to, to do it, I would say that the, the, the effects have been remarkably positive.

[B]

Can fasting help prevent cancer? Or can it help when you. Only when you've already been diagnosed and help potentially with the diagnosis?

[A]

Yeah. So there is no doubt that diet prevents cancer. Meaning, like if you have the perfect diet versus the bad diet. And now in mice we were able to show about a 45% in female mice, 45% reduction in tumors lifelong. So big, big effect. But also it looked like not only there was a 45% reduction, but many of the tumors were benign versus malignant. Oh yeah. So it's a dual effect. And they were, they happened later. They were benign and, and they were much lower like overall. But yeah, then you know, whereas with some of the diets, like Mediterranean diet, we know there is about like a 7% lower cancer risk. Right. More cancer mortality risk lifelong, which is not a lot, but you know, better than nothing. It's better than nothing. And yeah, so for, for these newer diets and more, you know, at least scientifically, diets that have expectation to be much stronger, like fasting making diet, longevity diet, we need to do a lot more work. Right. So, so now we're starting to do the first trials with, you know, for example, the Calabria trial that we just finished. I also had an arm that was doing both the longevity diet and the fasting making diet. Right.

[B]

Yeah.

[A]

So, so now, you know, we're about to publish several studies in mice that where we do the longevity diet, you know, for the entire life. So we'll see now what they show on cancer prevention. But yeah, the expectation is cancer will be lower or much lower or certainly it'll happen later and it'll be, you know, some of the malignant cancers will show up as benign tumors. Yeah.

[B]

So let's Talk about the GLP1s we touched upon at the beginning of the conversation. Do you think there's any potential side effects to GLP1s? Like could, do you think a GLP1 could possibly show it's a cancer causing medication peptide later down the road? Because people don't know. Right. They, they've been using it for diabetes for so long or for many years.

[A]

Yeah.

[B]

People don't know. Everyone and their dog is using it for weight loss, right?

[A]

Yeah, people don't know. And everything is possible. It's also possible that it's going to reduce cancer. Right, so. So that would be the expectation based on.

[B]

Because it does help with inflammation.

[A]

It may help a little bit with inflammation, but it just lowers your risk factor for cancer, which is obesity and diabetes.

[B]

Right, Right.

[A]

So those are risk factor for cancer. And so if you reduce that, you know, then it could potentially, for example, cardiovascular disease. Now, we know that GLP1, at least the initial data, it reduces above 10%. Right. So people and GLP1 have about 10% cardiovascular disease reduce risk. Now, you know, in my new book, which is not in English yet, it's called the Weight of Longevity, you know, I'm comparing it to just a Mediterranean diet. And I'm saying the Mediterranean diet seems to have a 30% decrease in cardiovascular disease. Right. So now don't show off, please don't show off the GLP1.10% effect.

[B]

Yeah.

[A]

When the Mediterranean diet is showing 30%.

[B]

Right, right.

[A]

And it doesn't have any side effects. And now we're saying that we could probably do much better than the Mediterranean diet. But even if you just use the Mediterranean diet, it's so much better. Right. You say you get the weight loss and you get the. And you get lots of. Lots of benefits. Yeah. So. So I think that there is a long list of side effects of GLP1. And now the new studies are showing something very scary, which is you do it, you're gonna need to continue doing it. If you stop, you're gonna regain the weight. And when you regain the weight after you stop, you regain the weight much quicker or quicker than people that have lost the weight with diet. Right. So, and, and the, at least the, the potential mechanism that I saw was that you're not making your own GLP1 because, you know, you're getting the drug.

[B]

It's like when you take testosterone, your body stops taking testosterone. So it could be the same thing.

[A]

It could be the same thing. Right. So this is what the scientists that published a paper, I think speculated, or they have some evidence for it, but either way, it was clear that they regain weight more quickly and probably because they were no longer functional. Right. So it's really condemning you to be stuck. It's a little bit like addiction, addictive drugs or, you know, addictive foods. Right. So all of a sudden, now I give you something that you can never get away from.

[B]

100%. Also, though, it's. If you're. If you're burning a third muscle. Right. So. Right. So you're burning some muscle off your body, your metabolism will obviously slow down. So when you get off of them, your body doesn't have the same accelerated metabolism or whatever metabolism you have because you don't have as much muscle to burn.

[A]

Not only that, but now what you regain is fat.

[B]

Right, Right.

[A]

So we're not even counting that you regain the fat more quickly.

[B]

Yeah.

[A]

But you're not regaining the muscle or you're getting a lot less muscle. Right, yeah. So that, that really may condemn you to be stuck on this drug that has got so many side effects for the rest of your life.

[B]

I know.

[A]

Certainly for decades.

[B]

And it's really.

[A]

Yeah. Scary. And, you know, I think what's problematic, very problematic, is that the physicians are not saying this. Right. The physicians are now saying, well, you know, and I can see that when somebody has tried, I mean, so if you, if you, if you look at our foundation, you know, sometimes we have Doctors, we have PhDs, we have nutritionists, sometimes they cannot do it. Right. So they could take somebody, and for most people, great. They do very well, and they, they become better and they become healthy, but some people cannot. So I think it's, it's fair to say, hey, I tried everything. We've been trying for three or four years, and it takes two to three years. As. As that happened for the doctor that I was talking about earlier, it. It took them two years to get back to normal. Right. From diabetes, hypertension, obesity to a normal person.

[B]

Right, right.

[A]

And so, so if the team, let's say in this case, worked on him for three years.

[B]

Right.

[A]

And after three years, he's just still stuck on all these problems, then I think it's okay to be on GLP1. Right, right. And I think it's okay to.

[B]

If you tried everything.

[A]

I tried everything, but not the way it is now. You go to the doctor and the doctor, you know, says, you know, I don't know if you want spend the money and go to a dietitian.

[B]

Right, right, right, right.

[A]

The system is not really there to, to provide what we provide as a foundation, which is. Or the, the, the clinicians provide the foundation, which is. I'm going to follow you. You know, I'm gonna be your friend for the next two or three years. Right. So that we find a way to get you back to, to full health. That. That's not reimbursed. That doesn't exist. Right. And so either you have the money to pay for it or you don't get it. And what you get reimbursed is the drug. Right. So the doctor says, come on, you know, I don't know anything about nutrition and I cannot follow you every couple weeks and to see how you're doing, I cannot be your friend. Right. You know, so I'm just gonna give you a drug to begin with. That's what the. That's a big problem. Right. Then I'm just really surprised that the media are not talking about more and the doctors are not talking about it more. Say, hey, you know, please reimburse the rest. Right. Because once the rest is reimbursed, then it's a fair game to say, hey, you need GLP1, right? Because at least get that 10% lower cardiovascular.

[B]

Right.

[A]

Because you're not going to be able to do the Mediterranean diet, you're not going to be able to do the longevity diet, you're not going to be able to do the FMD or whatever. And yeah, so then, then we do the second best. And the drug is certainly valuable in that sense.

[B]

Well, no, I've seen myself with friends of mine who are on it, and they lost a lot of weight and they looked great. And then when they got off, they thought, they thought, oh, great, you know, now I'm at my lower than my, my goal weight. And they gained the weight plus more within a month. Within a month, people were gaining like 40 or 50 pounds in a month. Yeah, that's scary.

[A]

But even more scarier scary is what is the chance that somebody can stay on it for five or 10 years.

[B]

I know, exactly.

[A]

Is that. Because I think it's over 70% abandoned within two years. Right. But what about five years or 10 years? Because if the answer is 95% are going to abandon, then, you know, then you're making a big mistake.

[B]

Right, right. Because everyone's going to be overweight again.

[A]

Everybody's going to be overweight, but with all the side effects that come with those five years of, of the drugs. Right.

[B]

What are the side effects that you've seen?

[A]

Well, for example, neon. So this is ischemia, optic nerve ischemia. And then there is, you know, certainly studies showing both things, but certainly multiple studies showing depression, anxiety. Some studies are showing positive effects, but some studies are showing very bad negative, like doubling of suicide rate. And so now who's right? I don't know. But certainly it's not good when you see all those, you know, studies in major journals indicating twice as high, you Know, anxiety and depression and suicide rates. So. Yeah, so then I'm not saying they're, they're, you know, conclusive, meaning that all we know that. But that's not, you know, a good association to, to see those type of studies. And so, yeah, then we just say the muscle loss, potentially bone density, although that, that doesn't, you know, again, the muscle is very clear, the bone density is not very clear. Some studies are showing no, no loss of bone density. But then again, it's pretty short term. Right. So what if you did for 10 years, you know, then are we going to see then the bone density loss?

[B]

Exactly.

[A]

See osteoporosis increase?

[B]

Sure.

[A]

Somebody that has been on it for 20, 30 years. Yeah. So it's just a minefield and I think people are just walking through it.

[B]

Walking through it. What about the fact that like you said, people get off of it or abandon it, as you put it, within two years. Why is two years the point where the people are just getting off of it?

[A]

Yeah. The papers that I saw, multiple papers, they don't show why. So it could be that you're satisfied with what.

[B]

Right. You think you got it, you think

[A]

you got under control, or it could be that you're depressed or it could be that, that you have big side effects. Right. So, you know, the doctor, for example, that we followed had major side effects. Right. So, yeah, so there is a lot of gastrointestinal side effects and, and lots of issues. So. Yeah, but for all the reasons combined that over 70% were no longer doing it.

[B]

What about the fat? What did you think, or have you heard that after a time period, people's bodies tend to acclimate on the drug because, like, people can eat through their appetite. Like, you know, like, I have a lot of people, I know who. It worked great for a year, year and a half, even two years, and now they're just eating back to where they were because they've, they've like their body became so acclimated to the drug. So unless you keep on increasing it and increasing the dose, you're kind of screwed.

[A]

Yeah, I mean, that's certainly, you know, in need of more studies. But also, if you think about drugs, GLP1 is one case, but also statins, right? They're really. We think of drugs as very sophisticated. Right. So there's a lot of studies behind it. And you know, now you have a molecular target and this is going after this receptor of GLP1. But the drugs are really dumb, right? Because now you have the human body and this is like this perfect orchestra with every moving part. You know, there is three and a half billion years in the making, right? Three and a half billion years of evolution. And so now you have that. And what we were saying earlier, right. The fasting response and the fat is broken down and it's preserving. It's making glycerol. So the glycerol now is preserving the muscle. So this is very sophisticated. And now you're replacing it with keep pushing the same button. Right. Okay. So you. Somebody sitting there and pushing GLP1 button all the time. Right. If you think about it, it just doesn't look good, right. Compared to this sophistication of the human body that now you have somebody pushing the button. So in the great majority of the cases, it's just a matter of time before you're going to get bad results from somebody pushing the same button ten times a day for the rest of your life.

[B]

Right, right.

[A]

So, yeah, well, they keep on coming

[B]

out with a new. Like it was first the GLP one. Now there's like, it works on two receptors with frasepatide, now it works on three receptors.

[A]

But the more you do that.

[B]

Yeah.

[A]

The more you do that, probably you have now a potentially synergistic trouble zone. Right. Because if one drug can cause problem now, two drugs may cause five times more problems. Right. Or at least have the potential. We don't know. Because now you're interfering with two pathways. Right. And then if you have three now you probably, you know, there's probably. I don't know, I'm speculating and, you know, but, you know, now, as you imagine, let's take a car.

[B]

Yeah, Right.

[A]

And let's take, I mean, a good example is that, you know, you. You take a laser that is. That is very powerful, Right. And you start using the laser running through your engine and every part of your car until the car goes a little bit faster. Right? Okay. And then you say, okay, oh, wow, you know, now I found a point where the laser, it makes the car go faster. So let me keep doing that. Right. And now you're gonna do another laser, another hole through your car. So that goes a little bit faster. Right. Well, I guess what's probably going to happen, if you ask any mechanic, well, by the time you have poked three or four holes in my car, it might go faster, but it's going to break down.

[B]

Yeah, yeah, yeah.

[A]

So. So, so you can think of this as the same way, Right. You know, it's really putting a hole. I mean. Yeah, it can achieve an effect like weight loss, but it's really not coordinated with the rest of the trillion cells in the human body.

[B]

Yeah.

[A]

It's just on its own and it's just, you know, I put a hole in there and that's not the way you want to make a car go, like longer. Yeah. So you're sending your car up for breaking down. Right. And so, yeah, so I think at the theoretical level now, and hey, I'm saying at the theoretical level, but yet we know drug out there eventually. So in the new data, for example, and statin shows that people that have less than 170 or so in LDL don't live longer, you know, don't have a decrease in mortality if they take statins. Right. So, so I think that, and these are like jama, New England Journal Medicine, you know, meta analysis. Right. This is not like one study. These are studies that are looking at all the studies.

[B]

Right.

[A]

And they put it together and say, hmm, that's really interesting. People that have, you know, LDL, 160 LDL, not total cholesterol, they seem to do better than people that have very low cholesterol. So how do you explain that? Right. And so, yeah, so I think at the beginning you get the story, oh, you know, this should be in the water. Like statin should be in the water. They're so good for you. And then 20, 30 years later, you get the story. It's like, no, the meta analysis show maybe you shouldn't have taken it. So, yeah, so I think that again, I'll go to the glp, one thing, if you need it, you need it. Right? So, so some people, yeah. For example, the studies, I think it was New England, it was showing that for people that already had cardiovascular event, there is no doubt the statins were good.

[B]

Right, Right.

[A]

It reduce your, your mortality by 10%, no doubt. So there was very clear, even after 20 years, but there was the only group that seemed to be benefiting from the, from the statins. And yeah, so I think that we need to have a system that is, that can help you do it the right way. And then with all the tools, like including the FMD, the 12 hours and lots of other things, you know, that can help you because, you know, if it's not feasible, if you're asking people to do something like Italians in the Mediterranean diet, you know, probably less than 10% of Italians are doing the Mediterranean diet. Why? It's just people don't like to be told what to eat. Right. And, and that includes me Telling them what to eat. This. But this is why we're saying, okay, yeah, you can have the longevity diet and this is what we do in the clinic, or you can have the fmd, right. And look at the mouse and look at the people. Right. You know, they, they have a crazy diet and, and at least they do the fmd. Right.

[B]

So let's talk about a mouse for a second. Right? Like, has there been any, like, data, anything talking about that, how a, does a mouse correlate to a human? Because I've seen studies that say that doing tests on mice doesn't necessarily correlate to how a human will behave or perform.

[A]

You know, it correlates. It doesn't necessarily mean that humans are going to behave the same, respond the same way. Right. So, so yeah, so most of the drugs that you see out there have been tested in mice first. Right. So immunotherapy, chemotherapy, just name it, cancer drug, diabetes drug, G1, everything goes to the mouse. And usually that's how it starts. Right. It starts with, oh, it works for the mouse. And then let's come up with a drug that'll do the same in people. Yeah. So the mouse is a very good model.

[B]

And what else can you test on?

[A]

Well, you could test that in rabbits, you can test it in rats, you can test that. In some cases they require monkey studies because it is so dangerous for a person. And so they may require a primate model. Yeah, but those are, you know, expensive. And ethically, you know, the medical field is trying to move away from that, from, you know, from using monkeys to.

[B]

But as a mouse and a rat, the same thing, I would imagine.

[A]

No, no, the rat for certain things is a better model. Right. And, and the mouse is a better model for all the things. It's easier to work with mice. But I think that, for example, we have shown the FMD cycles being able to cause reprogramming and stem cell dependent regeneration in mice. Right. In multiple, so the pancreas, the gut and different systems. And so a year ago we published for kidney, we published it in the rat. And so we now show that we can damage the rat kidney and then start the fasting, making diet cycles, and the red kidney goes back to being functional after six FMD cycles. So that was particularly important for us because it's just unlikely that you now tested in two different rodent models and you're gaining very similar effects. So that makes it much, your case, much stronger. Moving to people. Of course, we already done 40 human clinical trials, but in fact, in that Trial. We had a small human trial for chronic kidney disease patients. And it worked, right? It worked very well for them too. Right. So it's preliminary, but it worked. So yeah, I think that having studies in mice and rats and then in humans is the best way to go.

[B]

Wow. Okay, what about like you have these labs both in USC and in Italy right now?

[A]

The lab in is still open. I probably closed by the end of this year, but there's too much. But yeah, the Italian lab was focused on oncology, molecular oncology, so cancer. And the US Lab here at USC is instead focused on aging and regeneration and, you know, fasting and longevity diet, et cetera.

[B]

What other findings have you found in all of your work beyond fasting that help with aging backwards or slowing down the aging process?

[A]

Yeah, so yeah, the longevity diet. So now we're going to publish several papers on that. And then, you know, protein restriction has always been one of the things that we worked on. For example, some years ago we use an Alzheimer mice. They have this genetic mutation that give people Alzheimer early. And so it's called triple transgenic mouse. It's got three bad mutations that make this mouse develop this bad learning and memory. And then we use the. In the first paper we used, we alternated one week of a very severe protein restriction and one week of normal proteins. Right. We just kept going back and forth and. And it made a lot of. It wasn't as good as. As the fasting mimicking diet, but it was very good, you know, very good effects. Right. So just alternating very low protein diet with normal protein diet, week, one week on, one week off. That made a big difference. Yeah.

[B]

So how much of a difference? Like 20%.

[A]

Oh, you know, we looked at lots of different things, but you know, in some of the cognitive testing, it made a big difference, you know, really?

[B]

But how much. Can you give me an example? Like, give me a data point.

[A]

Well, you know, usually we look at restoration of normal function. Right. So in some cases it was bringing it back to normal, right? Oh, yeah. So now you see a big effect of the genetic mutations. And then what you want to see, you have a control mouse and you have a genetically modified mouse that's got this cognitive impairment. And then you do the alternate protein restriction and then many of the, at least several of these changes went back to normal or close to normal or, you know, no longer as bad. Right. So a range of effects.

[B]

What do you. What's your take on all these supplements like, or peptides even? You know, everyone's taking all these peptides for longevity. Right. You have so many. Do you, what's your, do you have any info like do you have an opinion on all these things?

[A]

Yeah, I think it goes back to what I said earlier, which is the, the, the sophistication of the system versus the something comes in.

[B]

Yes. So it's like a GLP one.

[A]

Yeah. So it's the same argument. Right. The exception would be like in the case of rapamycin. Right. So rapamycin is a drug that blocks a particular pathway which we and others have described as being pro aging or aging accelerating. So if the peptide or whatever or the drug goes after a master regulator, then I think it could be triggering this sophistication. Right. But those are very rare. So most things you do are gonna, you know, act downstream somewhere. Meaning, like they're blocking something that is down there. Right. It's, it's not the master regular up here. Right. So, so if a peptide change, for example, growth hormone or IGF1, these very high level master regulators, then it's got a chance. Right. Because you know, it could be telling the body don't go in mode A, which is be. Which would be for example, high reproductive mode, high growth. Right. So a certain age we're not reproducing and we're not growing.

[B]

Right, Right.

[A]

So why is it that we're putting all this energy into reproduction and growth pathways? Right. It makes no sense. Right. So then a lot of organisms, we know that, for example, 30 years ago we made unicellular eukaryotes, unicellular organism, live 10 times longer. Right?

[B]

Ten times, yeah.

[A]

And so you do that by. We did it by fasting them and by imposing two genetic mutations which push them to be in this what we call maintenance modes. Right. So don't worry about growth, stop growing and you know, and stop reproducing.

[B]

Right, Right.

[A]

Just focus on yourself. Right. So interesting, right? Yeah. So if there are master regulator and there seem like all organisms that have been tested there are, if you turn on the switch to stop focusing on the next generation and then focus on yourself, that can make a big difference. Right. So yes, there could be peptides that are, that eventually hit that switch. Right, right. If they hit that switch, mean the science fiction switch will be one that doesn't affect metabolism, it doesn't affect performance, it just affects your. You're not growing and you don't need to grow and you're not reproducing and you know, and you can stop it when you want to reproduce. Right. So you can say okay. You know, you know, I'm. Whatever. I use it until I'm 34, and then at 34, I stop for a year, I reproduce, and then go back on the. And the peptide. Or, you know, it could be a dietary intervention or both. Yeah.

[B]

Or about. About just even the fact that people. A lot of people are taking, you know, NAD is really. Is really important. Popular. Nad. Metformin is very popular. You're saying the only one that can maybe move the needle is repromycin?

[A]

Well, metformin is also a little bit of a master regulator. Right?

[B]

Yeah. Okay.

[A]

Yeah, But. But the data, if you look at metformin effects in mice, it doesn't make even a mouse live longer, as far as I remember. Rapamycin does and does in a very consistent way. Right? Yeah. So that.

[B]

Should we be taking that, then?

[A]

You know, if you made the mouse live longer by whatever peptide, you made the rat live longer. Like, say 20% longer or something like that, at least. Right. If you made the mouse live 20 longer, you made the rat live 20 longer. Okay. Then it starts, and then it's very safe. Like.

[B]

Right.

[A]

Let's say metformin, then I think it'll be a good candidate. Right. But, you know, we. We don't have anything like that right now. And rapamycin is probably the only one.

[B]

Should we take that? Should everybody be taking it?

[A]

No, no, no. Because rapamycin also causes hyperglycemia, and. Yeah, yeah, it's not good. And so, you know, and that's where maybe it might be good for a mouse and not necessarily for a person. Right. So. Yeah, but that tells you that the potential is there for some drugs to go after master switches. And then eventually we're gonna say, hey, this is really safe. But of course, the FMD is already there. Right. The FMD may be done three times a year. It's already doing all of this with no safety issues.

[B]

FMD also takes out all the senescent cells. Right. Isn't that, like, a benefit that people get?

[A]

Yeah, well, four things, right? One, autophagy, Right. So you need three, four, five days, probably the whole five days for autophagy. So the cells start eating themselves. Right. And that's one then clearly is doing stem cell activation. And now we're seeing it in multiple human clinical trials. We've seen major increase in either stem or progenitor cells and then reprogramming of cellular level, like, so, you know, now the hardest thing in aging research is how can you take an old cell and make it young again? Right. And it's called, you know, cellular reprogramming and epigenetic cellular reprogramming. But now we're shown over and over and over the FMD refeeding cycles do that in a very amazing and coordinated way. And then metabolic reprogramming. Right. What I said earlier, the fasting, mimicking, diet, refeeding, are now metabolically rewiring your system. And it's not a cellular process necessarily, but it's more. It could be cellular somewhere, maybe in adipocytes, but it's basically telling your body, stop accumulating fat, start using fat. And the beauty if you look at our work in mice, rats and humans, is that it keeps on going. Right. So it's not that you do the fasting, mimicking diet and then a week later it's all gone. You do the fasting, making diet, and then for months, actually in the first trial we did the USC, three months later, 60% of the effects were still there. Right. So after three FMD cycles, once a month we stopped. And then we look at three months later, and then you see about 60% of the changes that are still there. Right, so. So yeah, so I think drugs are okay, but I would say that we probably haven't been as loud as others in advertising. I think the people that do some of these peptides and pills have been louder than us in claiming and over claiming. And also the companies involved, I think they're being more. Stick to the data. Stick what? You know, don't, don't over claim. And, and maybe that's why some of these other things are more popular than the fmd.

[B]

I think they're both. I mean, I think that people who know, know. I know, like the community of doctors I know who, who prescribe the fast mimicking diet to patients just for their overall health, never mind for like, you know, longevity or for cancer, it's pretty extraordinary. Like, I think people who know the research, I mean, I think it kind of speaks for itself. It's just more about people who know. No, and if you don't know, you don't know. Right, so.

[A]

Right, right. Yeah. But. But I think, you know, now there is soon enough an opportunity to make it mainstream. Right?

[B]

Yeah.

[A]

And it should be mainstream. Right. Because of all the things we say, you know, it's going after Crohn's and colitis and cognition and, and inflammation, and it's going after cancer cells and it's doing it in a safe way. I don't think too many people are arguing if you do this Three times a year.

[B]

Right, right, right. Three times a year.

[A]

That, that you know, not, you're not going to find too many doctors say oh no, this is going to cause problem in the long run.

[B]

You're not saying every day. You're not like restricting so you're not into calorie restricting every day. You're not into yo yo dieting. You're actually not even necessarily into vegan every day. You're not. So you're like saying long. The longevity diet, it's eating pest, like you know, eating fish, you know, more like a meditation. A Mediterranean diet.

[A]

I say in a Mediterranean is for Mediterranean people. Right. So if you're genes are from Norway or from Sweden or from Japan, you shouldn't have a Mediterranean diet. You should have a longevity diet that is, you know, that is personalized for you. Right.

[B]

And it's, which is about fish typically,

[A]

which is still going to be about low mercury fish and low toxin fish. And it's going to be about legumes of different kinds. Right. It's going to be about whole grains, it's going to be about oils and maybe there's a few different ones. The olive oil is different, definitely good, but doesn't mean it's the only one. So if you have, if you come from there are older vegetable oils that are good and then what? Well, there are some, you know, I, I, I, I haven't investigated as much as I done for, for olive oil but you know, there's some like maybe sunflower or some of these vegetable oils that have good data behind it. But, but you know, I don't want to, I've never spent the time because I'm so happy with the results of the olive oil and it just covers so much of the world population that you know, can, can do deal with that, that, that you know, and, and then I think the nuts and the dark chocolate and so there is a lot of sources of, of, of healthy fats that are fairly confirmed to be healthy or very healthy for you that you know, we never investigate it, but it doesn't mean there are not other oils, for example, or fats sources that you know eventually could be as good as olive oil.

[B]

Okay, but you're basically just saying though that for 15 days of the year, five days, you know, maybe even every quarter is a good chance, it can give you a fighting chance, so to speak, to really live longer and healthier.

[A]

Yeah, I wouldn't call it a fighting chance. I mean the data is just spectacular.

[B]

I know.

[A]

No, no, I mean, you know like

[B]

if you're saying it's a good. Oh yeah, I'm saying. Yeah, yeah. Like so basically, let me, let me recap, let me re. Say that then.

[A]

Yeah.

[B]

Basically you're saying that if someone does fast mimicking at least every quarter, let's say for five days, the chances of them living longer and healthier are spectacular.

[A]

Based on your research going too far on the other side. I mean, I think the results have been spectacular. Especially mice, especially in rats, I mean, really unbelievable. Right. You know, they've taken a kidney or pancreas that is completely, you know, damaged irreversibly and then restoring in its normal function. Right. I mean, it's hard to believe.

[B]

It's pretty amazing.

[A]

Yeah. Right.

[B]

So that is spectacular though.

[A]

Dr. Yeah, yeah, that's what I was saying. That part is spectacular. But it's in mice and rats. Now, the 40 clinical trials are showing really remarkable results with insulin resistance, you know, glycemia and inflammatory markers and cholesterol and blood pressure and you know, over and over and over in very consistent way clinically.

[B]

Right, yeah.

[A]

So those are very good. Yeah. So I think that it's not a fighting chance because a, if it's making your cholesterol lower, if it's making your blood pressure lower, if it's making your glycemia lower, it's making your biological age younger by two and a half years at least based on a number of factors and the measurement, the number of factors, I mean, it's hard to imagine how you would die in the same time. Everything is much, much better. But you're still going to die in the same day. Yeah. So much, much less likely. There's no guarantee.

[B]

But you're stacking the deck.

[A]

Yeah.

[B]

So you're stacking the deck for you.

[A]

You're doing all the right things. You know, if you combine the longevity diet and you combine the sleep and the 12 hour timers eating and you combine it and put the two, three cycles a year of fasting, making diet. I think, you know, you're getting into this 15, 20 years of life expectancy increase range. Right. Based on lots of data. And also if you look at the Harvard studies, you know, the chance of getting to 75 without needing drugs with cognitively being cognitively functional and healthy. You know, Only less than 10% of the US population is in that group. Right?

[B]

Yeah, that's.

[A]

So you have one chance in 10 right now with the way, you know, if you look at the general behavior of the population now, if you do all the right things that Study show that you're doubling your chance of making it to 70. So now all of a sudden it could be, you know, 20, 30 million people.

[B]

That's amazing.

[A]

Then all of a sudden are getting to 70 or 75 healthy just by making those changes. Yeah, but, and this is not even counting the fasting, making diet. This is just changing your everyday diet and, you know, and, and following a few things that everybody can follow. Yeah. So I think that, you know, that, that, that that's the way to go. There's four or five things you can do and hey, you know, if you can do them all, do them all.

[B]

Right. It's amazing. What, what is the documentary really going to be focusing on? This?

[A]

All of this.

[B]

All of it.

[A]

All of this, yeah.

[B]

That's amazing.

[A]

Cancer, diabetes that I talked about is in there. He talks.

[B]

Oh, yeah.

[A]

He'll tell the story. There's cancer patients that are basically saying, you know, I was in trouble, and then I came out of it. But I think that what we also done, which was very important and compared to lots of other documentaries, I pushed the director and the producer to put in the clinical trials. Right. I said, you know, don't make it about our case. Case is irrelevant. Right. But make it a. Tell the story with the case, but then let's show the three or four clinical trials that have been completed on that. Right? Yeah. So I think that that's what's special about this documentary, is that do it right science wise, but also have the emotional part. But don't be too focused and maybe doesn't make it as entertaining, but it certainly makes it, you know, very convincing. I think that, that you have, you know, multiple clinical trials backing up the story.

[B]

And when you talk about your lab in Italy that's focusing on cancer, what are a couple of findings that maybe we don't, we haven't heard of that you've kind of brought to the surface.

[A]

Yeah. The, the exciting new findings are what we call starvation escape pathways targeting. So, meaning that we can we, we take the fasting mimicking diet and now we're starting to do this in, in patients. Right. We take the fasting. In the old days it was like, okay, let's combine chemotherapy plus fmd, immunotherapy plus fmd. Fine. And it works so much better together than, as I would say there. Now we're saying, okay, what if we instead look at how the cancer changes after we give them the fasting making diet. Right. And you see rewiring, meaning the, the metabolic pathways and not just metabolic the the cell changes completely its modality to adjust to a fast speaking diet. Then we can learn. We do something called RNA seq. We can learn how they change and why they change, and then we can use drugs that are already available to target those. And this works extremely well and it can go pretty fast. So we're very excited about this. Can be used for any cancer because, you know, it doesn't matter. You expose them to the fasting diet, you look at how it changes, and you do this computational analysis and eventually we're going to do it with artificial intelligence. And then it tells you, okay, these are the drugs you need to kill them all. Right. And yeah, so I think that we're very excited about this and hoping to get a lot more funds to keep it going because it's got a lot of potential.

[B]

Do you take any other supplements just for your health?

[A]

I take multivitamin and then I alternate between like D, vitamin D and vitamin B12. You alternate and omega 3? Yeah, yeah, I alternate because, you know, probably don't need each all the time. I don't think it's good to get overloaded with supplements, but I alternate. Yeah. So every four day? Every four day or so I'll get.

[B]

Take a break.

[A]

One or the other. Yeah.

[B]

Oh, wait, so you take vitamin D once every four days or four days on one day off?

[A]

No, no, I will take it every four days. Every, say three days.

[B]

Okay, three days.

[A]

And then I'll switch to B12 because a lot of my diet is vegan, vegetarian. And then I'll have, let's say a, you know, Omega 3. Usually I mix algal oil and fish oil.

[B]

What about exercise? Have you done any type of research on the effects of exercise for longevity, aging, well, health span? Yeah, exercise in addition to the fasting?

[A]

Yeah. I'll say something that is not going to give me a lot of friends first. And then your exercise, whether it's in animal studies or in human studies, does not fare very very. Does not compete with nutrition and fasting. Right. It's very far. And so I was just in Italy and this Rossetti group was showing the data in sick days or the number of sick days in your life. And it was a sevenfold between the effects of lack of exercise versus a bad diet. Right. Sevenfold difference in how impactful is a bad diet and, you know, how sick you're gonna be in your life versus how is no exercise you're gonna be. Now that said, I think exercise is very important. Right. You know, so I said that extra thing that. Right.

[B]

Because nutrition is 80% of it, at least. You're saying it's 100%.

[A]

No, no, I'm saying it may, you know, these data suggests they may be 85%. Right? Yeah, 85% of the lifespan extension and the health span extension that you get is going to come from nutrition and fasting or nutritional intervention and then the extra 15%. But I think that, you know, exercise is very important mentally. And so, I mean, I'm all 100% behind exercise, say, you know, 150 to 300 minutes a week, muscle training and all of that. I think it's, it's very important. So.

[B]

But why is it important? If you've seen, if you've seen the data that says it's not as important, not important for.

[A]

Well, that's not important for how sick you are. Right. But for your men, I mean. Yeah, it doesn't mean that you're not going to be happier.

[B]

Mood.

[A]

Yeah. Serotonin and lots of other things that happen when you, when you exercise. And so. Yeah, so I think that, and that 15% is not, it's not, you know, it's not insignificant. Right. So having a 15% extra benefit is very important. Right. So. And you never know. Right. So, you know, as part of my classes, I also show the effects of exercise and some of the really remarkable effects are on cancer patients. Right. And you'll see these results where they're showing people that are exercising regularly and they have cancer and they do so much better if they're exercising versus not exercising.

[B]

Right, right.

[A]

And you're thinking, is it possible that. So I don't know if it's a motivation thing or if it's the actual physiological effect, but the ones that exercise, they tend to do so much better in progression and survival and lots of other things. Yeah.

[B]

So get the mood and the mental elements of it. Right.

[A]

It could be mental, it could be that helps them fight, you know, their fighters, and they're going to do it with all different things. But some of these, some of these trials are randomized. Right. So it's not like you pick the ones that are more motivated.

[B]

Right.

[A]

You take 100 people and you divide them by two and you say you exercise and you don't, and then maybe you cross it over. Right. So some of this data is real. It's not about selection of, of motivated patients, but some of it might be affected by, by bias.

[B]

Wow. Gosh, you're right. You, you didn't make a lot of friends with that one. No, I'm Just kidding. No, but I. I think I. I mean, people know more or less that it's also with like, weight loss, right? Like, you can exercise until the cows come home, but if you're not eating properly or eating the right foods, you're going to gain weight. It's just. It is what it is, you know,

[A]

and there is a bigger problem that, you know, exercise. And there was a paper, actually they came out of, you know, there was the bigger loser, biggest loser. Right. But then ended up in being a real paper. Right?

[B]

Yeah.

[A]

And the real paper went and followed and I forgetting what journal it was, and it went and followed. And most of them, I think they were doing like hours a day of exercise, right? Yeah, yeah, yeah. So I think when the camera is on and the show is on, right. Whatever your show may be, you could do that. Eventually you're gonna be upset, you know, and you got problems and you don't have time, what are you gonna do then?

[B]

Right, right.

[A]

And that's. You're still gonna eat, and you can still eat the right food, but are you gonna take the. Forget the six hours, but are you gonna take the one hour a day and go exercise every day? Most people don't. Right. In the long run, as you get older and as you get more things to worry about, you may say, you know what? I don't feel like, oh, it's raining outside, or it's too hot or it's too cold, you know? Yeah. So it's a lot of. So the compliance and the feasibility that I was talking about before with the Mediterranean diet, eventually you're gonna have it also for the heavy exercises, right? And then you're gonna have like my brother and my sister, for example, right. My. My brother was a soccer player, and I told. And I was a soccer player and I told my brother, you gotta stop. Right? Ah, no, no, no, no, no. And now he's limping, right?

[B]

Because he's limp.

[A]

Right. And my sister was a triathlon runner and now she has a hip replacement.

[B]

Right, Right.

[A]

So.

[B]

So, you know, much of anything is not good.

[A]

Well, it wasn't even too much. They weren't professional. They were not professional.

[B]

Yeah.

[A]

But it was like they enjoyed it and they did it all the time, Right. Until they could get surgery. Right. And so.

[B]

So I see your point. So now they have to stop exercising, but they have to be eating right to keep the. Have the right. They have to learn the discipline of eating properly.

[A]

And yeah, they're both eating the longevity diet. Of course they are, because they're not doing soccer anymore. They can't. And they're not doing triathlons anymore. And I mean, it's just we're three and. And I'm the only one that, you know, I played until I was 45. Right. You know, played.

[B]

How old are you now?

[A]

58. Yeah. Yeah, so. So I played.

[B]

Whoa, whoa, you're 58?

[A]

Yeah. Yeah.

[B]

And this is. Okay. And like this. And this is. You haven't done anything to you because you look really young.

[A]

No, no, I haven't done anything yet. Yeah, no. God forbid.

[B]

Yeah, yeah. And so this is all just doing the fast mimicking diet, living a certain

[A]

lifestyle, longevity diet, fasting making diet. And.

[B]

Yeah, and I was gonna say longevity diet too. Just your, Your diet, I should say.

[A]

Yeah, yeah.

[B]

And. And, and habits. Daily habits. But you're saying. Because you didn't really. You exercise, you played soccer. Sorry, you played soccer, but then you didn't play after a while. But after 45.

[A]

Yeah, after 45, I stopped. Right Then I started doing biking and things that at age I started. My hip is still my hip and I still don't have any problems. Right. So, yeah, to me it was very important. I mean, somebody else could say, and there was a case of my brother and my sister. I don't care. I'm just going to keep doing. Okay, fine, but keep in mind, I mean, it's okay, but then keep in mind what the consequences could be. So in my case, I said, you know, I don't want to be. I don't want to be 60 and needing a hip replacement.

[B]

Yeah.

[A]

And so far, you're okay? Yeah, I'm good. Right. So I can still do my bike, you know, every. Every other day.

[B]

Yeah.

[A]

And lots of other things. And, and, you know, they don't put me at risk for, for, you know, inflammatory conditions, you know.

[B]

Yeah, absolutely. Is there anything we haven't covered, Dr. Longo, that's important for people to know about?

[A]

No, I think, I think we pretty much covered it. Yeah.

[B]

Are you sure? Because you're here right now. I want to make sure.

[A]

Yeah, yeah.

[B]

That I got everything done with you.

[A]

Yeah. I think with the diseases we talked about, cancer, Alzheimer's. Yeah, I think we covered the. A lot of ground.

[B]

I like factoids. Like, there's. Is there any, like, like, facts that we can like, like that you can, like, share that maybe we haven't, like, any kind of data points that we haven't covered?

[A]

No, I think, you know, one thing that I was gonna say then, I. I didn't Say was we're now going through, you know, I mean, I'm doing this review on proteins, but it's more like longevity diseases. Right. And, and so you know that, and that's consistent with what we've been saying. The other thing I'm having my team at the foundation do is the, the muscle part, right? Yeah. So, so then we're looking at hundreds of papers on, you know, plant supplements, plant protein supplements and, and animal. Yeah. And so I think that what we're going to conclude is that probably what we already concluded before, 0.8 grams plus training, plus muscle training. 0.8 grams per kilogram or 0,37 grams per pound of body weight is enough for the majority of people, even if you want to build muscle. Right. But in fact, if you look at all these hundreds of papers, you know, those that are in the 1 to 1.2, they tend to have an easier time building muscle. Right. So. So I would say don't do it. But if you care so much about muscle. Oh, okay, then, then I think the 1.1 to 1.2 a good quality amino acids, like some animal proteins and some.

[B]

Oh, I know. I was going to ask you. Okay, so wait, so you're just saying that like you're, if you can have 0.8 grams of protein, it's, it's. You don't need to have one. One. Because the whole thing is one gram. One. Yeah.

[A]

Well, now people are advertising.

[B]

Right, right, right.

[A]

So they, they're muscle for muscle. Yeah, for muscle. And so now for sure, what we're concluding is 2 grams, 1.6 grams is not needed. You know, it's very little difference. You know, very few papers are showing if you have 1.6 versus 1.2, you do better. 1.6. Very few. Most of them show no effects at all. And also most of the papers show if it's animal based, it's not superior to plant based. As long as it's a good mix of plant based supplements. Right. A lot of them are actually. They're showing total protein intake. They can also come from supplements. Yeah.

[B]

Okay, you said something, you said it a few times. With amino acids. What if you just take a nine, like, like a, like nine essential aminos. Like a, like.

[A]

Yeah, like the data, you know, we don't know what the consequences are, I think. You know, but that way you're not

[B]

eating as much protein, but you're having the, the, the building blocks to protein.

[A]

Yeah, no, no, I mean theoretically I think it can work, but it wouldn't be you know, those essential amino acids are going to be the one driving the aging process. Right. So if you look at the studies in mice and rats, always essential amino acids. Right. The one that accelerate the aging. Essential. Right. So brain chain amino acids, methionine, you know, so almost exclusively, if you look at the non essential, they're the only one, like glycine, that seem to be doing good if supplemented. Right.

[B]

Really?

[A]

So restriction, if you look at the restrictions are all on essential amino acids. They work making rodents longer lived and healthier. Much healthier. Right. If you look at the few cases of supplementation with amino acids and living longer is glycine, which is a non essential amino acid.

[B]

Non essential.

[A]

Non essential. Right. So, yeah, so then what you. You said, yeah, it's just like, then you might as well eat proteins. Right. And that's okay. Right. In fact, it may be better to eat proteins because now you have the non essential, including glycine. They may be beneficial. Yeah. Because it turns out that glycine is an inhibitor of methionine. Of methionine. It facilitates methionine decomposition. Right, yeah. So the higher the glycine, the less metanine you're gonna have in the system. And so it's going back to probably. It's going back to the essential amino acids. Lowering essential amino acids.

[B]

Lowering essential amino acids. Okay. Wow. Dr. Longo, thank you so much for being on my podcast.

[A]

Oh, you're very welcome.

[B]

It's been, it's been a long time awaiting for me, so I appreciate this. And where do people find. I mean, they can buy your book Fasting Cancer or the Longevity diet book from 2018, but they want to know more about you or where can they find you?

[A]

Yeah. So Facebook. Professor Valter Longo. Facebook and Instagram.

[B]

Okay.

[A]

Yeah. Most USC faculty now have Facebook. I know Instagram. So most professors anywhere. Yeah. So Instagram is the same. Professor Valter Longo. And then the Foundation Create Cures foundation is here in Los Angeles and we help lots of people and, you know, including those that cannot afford it.

[B]

That's great. Well, thank you again for being on the show.

[A]

Thanks a lot.