USC Longevity Scientist Dr. Valter Longo: Why Growth Hormone Peptides Age You Faster opens a useful window into growth hormone signaling through a longevity lens. The conversation is not a shortcut or a spectacle. It is a reminder that healthspan is built through signals the body can understand and repeat.
I'm not sure if you're you're fully aware, but right now there's this huge craze and enthusiasm about peptides. And some of these peptides are regulated and approved, like the GLP-1 receptor agonists. And then I think there there are a lot of other peptides that are not approved and and unregulated that are kind of riding the coattails, I think, of of the GLP-1 receptor agonists that have become very popular. And [snorts] in particular a kind of class of these peptides to my understanding are essentially telling the body to produce more growth hormone. And I know that growth hormone and IGF-1 has been really central to to your work over the last 20-plus years in thinking about aging and improving health span and longevity. So, I wanted to get you on to kind of dive into these peptides and what they're doing to human biology and and whether there are any things that we should be concerned by or thinking about before ordering them often from a forum and and these these compounds are being sent from China. And then people mixing bacteriostatic water with the powder assuming they're pure and injecting them into into themselves hoping that they're just all positive. So, firstly are you as a scientist in longevity, are you aware of this this craze and this conversation that's happening right now? If I can start with GLP-1, right? Because it's such a important one, right? And so recently I I spent a lot of time um looking at the GLP-1, right? And what it does, I mean and we're going to keep talking about this, but there is a Uh, people are looking at the short-term effects of these and they're just completely
these and they're just completely ignoring the long-term effects, right? So, GLP-1, for example, short-term effect, clearly, people lose a lot of fat. But, I also lose a lot of lean body mass, right? And then, if you look at the 3 years data, uh, you see that about 92% at least according to a large study, 92% of people quit. Only 8% continue, right? And then, if you look at the recent study that just came out, most people will regain the weight, but now probably or most likely the natural GLP-1 and this relates then to the the rest of the discussion. The natural GLP-1 is now lowered, right? So, you're making less of your your natural GLP-1. Similar to if if you inject testosterone and then stop. Exactly, right. Your your body gets used to this new source of of a hormone and now it doesn't produce as much, right? Uh, and so the result is that if you lost weight with nutrition or dietary changes, you gain you regain weight slowly, but if you lost it with GLP-1, you regain it fast, right? So, then the net result and and then I asked ChatGPT to you know, put it Can you put it all together? What does based on the data? Uh, and the result was 11 lbs of I think it was 10 or 11 lbs of fat loss if you weighed 100 kg, let's say 11 kg of fat loss, and then you regain eight, I think, and then but then you you have a net loss of 2 kg of lean body mass, right? So, eventually in 3 or 4 years, you've basically lost 3 kg of fat if you weigh 100 kg, so whatever, 220 lbs, you lost 3 kg of fat and and lost 2 kg of lean mass, right? And that could be a mixture of bone and muscle and other lean mass. right. So all of it together. So, think that could be mitigated if people were exercising more though?
were exercising more though? During it while they're taking that drug. I think, you know, my point is if you can, don't take the drug, right? If you can, you know, and we can talk about it later FMD and other intervention like 12-hour time restricted eating, but there are it's not necessary to revolutionize your life and your lifestyle and run 5 hours a day to lose weight, right? It just takes some tricks and you can do it in a good way and then keep it keep So, I have Foundation Clinics both in Europe and the United States and we follow thousands of people. Most people we can get them there in the long run and and they never, at least not everybody, but most people don't regain the weight, right? So I think that uh rather than trying to say, "Well, let me find a way to block the GLP-1 side effects on on muscle and and etc." I would rather say, "You know, come to the Foundation Clinics or go to somebody that knows what they're doing and just do it the right way, lose the weight, and keep them lean body mass." And for example, the fasting mimicking diet, we see no lean body mass loss and now this trial number five or six. So, it's very clear that if you intervene for brief periods of of fasting mimicking diets, um you get the fat loss, but you don't get the lean body mass loss. It's just an example. I'm not saying, you know, it's the only way to do it, but certainly that's one of the few interventions that I think don't that don't require a revolution of of your lifestyle, which most people clearly cannot do because otherwise we wouldn't be in this GLP-1. My understanding is at least the the proper prescription of a GLP-1 is meant to be for people who are considerably overweight that have tried to lose weight multiple times, but haven't been successful. So, are you of the view that the the common or typical way that people are trying to lose weight with nutrition is not adequate? No, I'm saying now everybody is going to GLP-1 as the solution because I think the
as the solution because I think the medical community is making the mistake of of making it sound like, "Oh, this is the perfect drug, right?" And it's not the perfect drug. Now, it is a drug that is important should you have experts like I just described and they fail, right? They have a couple of years and this is the way American Diabetes Association and everybody will want it to have it, right? So, have professionals that can get the lifestyle changes so that you can get there. If they fail, then do do the GLP-1, right? That's kind of where I was trying to get to. I think a lot of the people that are taking them not not necessarily everyone, but a lot of people will say, "I've tried the diet thing and it failed." Because they've tried to go to a doctor, they may have had two courses two, you know, lectures on nutrition and and of course, if you don't have the experts, right? And so, what I've been talking about for the last 5 or 10 years is that we need to train so you have now the physician and then you have a registered dietitian, right? And and we I started a program a registered dietitian at USC and they're great, but it's just not enough training for for registered dietitian to be at the level of a doctor, right? So, we just need a new category of professional healthcare professionals that are just focused on getting you back to full health. We don't have it. We never trained them, right? So, of course, then if if you don't have them, it's not easy to get you there and then you turn to the drugs, right? So, yeah, I agree a lot of people are in that category, but because they've never been exposed to the right type of healthcare professional who can get them there like we do, you know, with dozens of patients uh every year. Do you see the kind of, I guess, {quote} {unquote} GLP-1s that are that have come down? Some of them have been approved, like the the GIP agonist and then the glucagon agonist that have come out after drugs like Ozempic. Are they superior in
Ozempic. Are they superior in terms of what we're seeing for weight loss and and that lean mass preservation? The idea that they have is they come up with a drug, you know, you have two one drug, then you have two drugs, and then you have another drug that takes care of the side effects of the first two drugs, right? That's just a problem, right? In general, because the body is this perfect harmony, let's say, right? Then and then then you're interfering with drugs that disrupt this harmony, right? So So, I think that yes, you can have a second drug, of course, the two drugs now are better than the one alone, right? And then the third drug might be getting you to have more muscle mass or not lose muscle mass and maybe help you with the bone density, but the the problem is eventually, what are these three drugs, all of which were basically, if you think about GLP-1 receptor agonist, it just keeps on pushing this receptor, right? This is not good, right? This is not how we were designed. And this is going to come back when we talk about the growth hormone, the secretagogues, right? So, we're not designed to have something keep pushing a receptor like that all the time, right? And so, eventually if you think about a car, right? Let's say you take a you know, a hybrid car, right? And it is designed to alternate between gasoline and electric, right? So, let's say now you push the both at the same time, eventually it's going to break down, right? It's not designed to It's designed to alternate. It's not designed to have a both, right? You could say, well, if I have a from maybe I have a car going faster, and you know, and performing better. Yes, of course, you may very well get there if if you had an engineer that does that. How long is that car going to last? It's going to break down, most likely. It's not designed to have that that push in in from both directions, you know. I think what you're saying, I think most people rationally would agree that if you can make changes through lifestyle and healthy nutrition and lose the
and healthy nutrition and lose the weight in a sustainable way, that's going to be superior to not making any dietary changes and just taking these drugs. But, I imagine that some people here, if we were to kind of steel man that position, and what would the pushback be? I imagine some people that are kind of prescribing these drugs would say, "Okay, yes, I understand, you know, evolution and what we're designed for, but our environment has shifted dramatically. And in this environment, let's say, instead of comparing the person who's obese to the person who is obese that loses weight sustainably with diet, let's just compare the person who's obese that stays obese for the rest of their life versus that person who's obese that takes these drugs and becomes normal body weight. Have they likely improved their healthspan and longevity? The data suggests about a 10% reduction in overall mortality and in cardiovascular mortality. Uh the problem is what will have happened if you just switch them to the Mediterranean diet. Now, you'll have about 25% reduction Mediterranean diet. I'm not saying anything crazy, so I would say that that's uh that's not good, right? This is not good to to think like that because and this is exactly the the what the doctors are doing now. They're saying, "Well, it's better that better than nothing, right?" Great. Uh if you really fail if you put him expose him to the right professional and they failed, then fine, it's better than 10% than nothing. I agree, right? And that's is I was saying earlier, right? But But I think we shouldn't think like that. We should think about let's train the professional. Like I always mention the exercise in the' 60s, right? In the' 60s, nobody exercised, right? And we had this idea in the' 50s and the' 60s that that's just not something anybody's going to do. Who's going to go around running around? That's just a stupid thing, right? This is what they thought in the' 50s, right? Uh well, now half of the US adults and European adults about, right? They regularly exercise, right?
right? They regularly exercise, right? So, now something that was viewed as stupid and impossible, half of the population is actually embracing it, right? And and not complaining. I I would say that most people that exercise will tell you, "This I don't want to quit. I don't want to exercise pill, right?" Let's Let's say that right now we have the exercise pill. Most of these people will say, "I don't want it, right? I'd rather exercise." It's exactly the same with with nutrition and fasting mimicking diet and 12-hour time restricted eating. You you need to have the professional expose you to it. Eventually, you're going to say, "This is great. I don't want to change." Of course, you don't want to do the fasting mimicking diet every 2 weeks, right? But if we're starting If you say every 4 months, can you take 5 days and be vegan and do a fasting mimicking diet? I think that's like exercise. Eventually, you could get You're not going to get 100% of the people, but you're going to get 50%. And And I want to give you an an example another thing from from our mouse data and then our human data. So, we took uh the worst possible and I remember we talked about it in in the last time, but I don't think we did. So, we took the worst possible Western diet, right? High fat, high sugar, high calorie, and we gave it to mice. And they become huge. Uh and then we gave them a fasting mimicking diet once a month thinking it's probably just going to make it a little bit better, right? The maybe if we're lucky half, all right, half of the way, right? Uh Uh it completely I mean, almost everything we looked at, whether it's heart function, cholesterol level, weight, it completely reversed it, right? Just 5 days a month, even though they continue this bad diet lifelong, right? So, now we've done that study for people. And, you know, most of the studies already indicate uh this is the case, right? If So, if you have a really bad lifestyle, if you intervene with the FMD, the especially if you have a bad lifestyle, because people that have a very good lifestyle, they don't get as much
lifestyle, they don't get as much benefits as people that have a bad lifestyle. So I would argue that, you know, things like this, and again, it's not the only one, but things like this are missing. Nobody's I mean, very few people are doing it. So, those are the one that can really solve the problem, because of they're also respectful of the evolution of where we come from, and of the fact that people are not willing to change their lifestyle, and, you know, and exercise for 3 hours a day, and and eat the perfect longevity diet, right? Yeah, I like that example of exercise because I do think there is with this incredible enthusiasm towards these weight loss drugs, there is almost a sense of nihilism. Like, we can't do anything else, everything has has failed. But, that's a good example of of culture and society adopting something new, and what I'm sensing from you is some optimism here. Absolutely. Yeah. I think but we they need people need help. And it doesn't need to be somebody a doctor that, you know, calls you once a day. Just enough, you know, let's say an hour a month, right? An hour a month of somebody that knows what they're doing, and telling you, "Okay, this is not working. Let's try this. Let's Let's shift that." And then eventually get you to the place where, you know, you can make the change and keep it. But, sorry. I moved away from your question. So, yeah. So, the secretagogues mimicking growth hormone releasing hormone, right? So, this is basically are peptides or drugs that are taking the place of a natural hormone, you know, growth hormone releasing hormone. And so, the pituitary in in the human brain produces growth hormone. And so, these drugs or secretagogues can either act just like the growth hormone releasing hormone, or they can act similarly by different pathway. They don't necessarily go through the growth hormone releasing hormone receptor, but
hormone releasing hormone receptor, but they can, but they don't have to, right? But, the result the major result that that people that are injecting with this uh drugs or peptides these are like just so people are are kind of understanding what we're talking about, like the ipamorelin or tesamorelin or CJC these types of peptides. Yes. And most of these actually come from drug company research in the' 90s or or, you know, in in the last, let's say, 30, 40 years. And uh you know, eventually they went off patent. I'm imagining I don't know all the details. And so, now they're uh free to use. But, if you think about it, this is not new, right? So, people they're years ago, 40 years ago, they used to inject themselves with growth hormone, right? So, this was a lot of people were doing that. And They're actually with with growth hormone itself. right? So, this a lot of people they did that. I don't know if that was legal. Uh although, it can be legal A doctor can prescribe growth hormone to people that may be in need of growth hormone. And that was because at the time people were under the impression that would help them stay youthful. Uh I think a lot of people that were using it, let's say, in the' 90s was muscle, right? Okay. So, they were in, you know, the bodybuilders, right? So, this was very common. This and others, right? So it was very common to inject growth hormone because it works, right? It It actually helps you build muscle. And and so, there is a lot of data on that. And so, I think that now, for whatever reason, these peptides are are legal or maybe legal or are pseudo legal, I don't know, right? I'm I'm not an expert on the legality of all of this, but but basically, they're doing what what you know, the muscle builders have always done, but now they're they I think are talking us about aging and and health and longevity, right? And then and of course, the problem is that 100
and of course, the problem is that 100 years of research in the aging field shows exactly exactly the opposite, right? It shows that if you think about a mouse and or even a worm or or a fly, I mean, you can take your pick, right? All of them that have record longevity extension have mutations in the growth hormone, IGF-1, insulin signaling pathways, right? So, if you like the mouse, the two mice that have the three mice that have record longevity, record longevity extension, right? One is called Snell dwarf. One is called Ames dwarf, and one is called Laron dwarf, right? And all what I just said is they're dwarf, right? Why? They're lacking growth hormone. And uh completely lacking growth hormone, right? So now the pituitary, the Snell and Ames dwarf in the pituitary is no longer able to make growth hormone. And uh and they have they live about 40% longer. All three, and this is you know, this is so solid that is, you know, in textbooks now. So, this is the work of of Andre Bartke and John Kopchick, right? So um but the more importantly, not only they live 40% longer, half of these mice or different type of mice don't get diseases or there is no evidence of chronic conditions or diseases, right? So, they they live 40% longer and yet you don't see in half of them versus less than 10% of the controls, right? So, the the typical mouse like a typical person 90 over 90% will develop some chronic disease in in their lives. In these mice, now half of them never develop anything, right? And now you can say, "Oh, it's just mice." It's not, right? So, we've been following the human equivalent. Of course, we started our work many years ago with yeast that not surprisingly had mutation record longevity. They could live up to 10 times longer than normal. Mutation in the growth signaling pathways, right? So, the
signaling pathways, right? So, the pathway for growth and for for longevity with this is the same pathway and the outcome of whether it's it's someone's someone's optimize or getting growth or they're getting a prolonged life depends on how often and how much that pathway's activated. Right. It's not just a pathway, right? It's what we call a axis, right? Because pathway usually refers to intracellular in inside of a cell, but this is a axis, so it starts let's say in the brain with growth hormone releasing hormone hypothalamus, then growth hormone in the pituitary, then growth IGF-1 in the liver, right? So, the the growth hormone travels to the liver, activates the growth hormone receptor IGF-1 insulin-like growth factor one is released. Now, insulin-like growth factor one IGF-1 can go and activate the pathways inside lots of cells and that includes TOR, that includes S6K1, that includes lots of things. And those are that's the growth axis, right? Then there are other There's another we consider the major Uh, another one that has nothing to do with growth. It has to do with sugars, but you know, we have to discuss it now, but so yeah. So if someone is is let's say going to the forum, buying any of these kind of growth hormone mimetics or compounds that increase release of growth hormone from the pituitary gland and so presumably they're elevating their IGF-1 levels in doing that? Yeah, so so there's lots of studies showing that that the the IGF-1 levels are elevated. You know, not all of them have maybe cause major elevation, but in general that's the effect that people are trying to get, right? Cuz that IGF-1 is the one that helps the muscle building, helps with the bone building, etc. People might experience some benefits in the short term and that's through activation of TOR and S6 kinase and those those pathways. This whole axis and network, right? There is a network that responds to that. And so of course
that responds to that. And so of course then you have lots of benefits, right? In in the short run, uh, you know, you might feel uh, reinvigorated, uh, you may build muscle and and the data is out there. I mean it is quantified. Some of it is major muscle. Some of the studies are showing major muscle acquisition, right? So that's true. Uh, but that's that was also true if you think about weight loss for cigarettes, right? So cigarettes was one of the the most uh, adopted weight loss uh, practices, right? Uh, so so people could smoke a pack a day and use it to maintain a a lower weight, right? And everybody knows, right? You quit smoking, you gain weight, right? So but that's a fact, right? There's a lot of data from back in the the' 50s and earlier showing the the role of cigarette smoking in uh, in protect in in decreasing body weight. So then, you know, it took 50 years to figure out that uh, maybe this is not such a good idea, right? And it took a lot of lawsuits and it took you know, a lot of people and yeah, so now you know, imagine that, right? Imagine if somebody said, oh, take cigarettes because look at the the effect that it has for you in 6 months, right? So, but you know, jumping to humans, so we start following people 20 years ago, right? They have don't have the growth hormone receptor, right? Or at least have a mutation that makes it almost as if they had no growth hormone. And that's a monogenic type mutation, that's not affecting other things other than growth hormone. Uh this is just affecting the response to growth hormone. So, it's like you had no growth hormone coming from the pituitary, right? So, the opposite of this secretagogues, right? The opposite, but the severely opposite. Just like the mice, right? The mice live 40% longer they have very low IGF-1 levels circulating. But now the trick is that the IGF-1 that that are circulating kind
the IGF-1 that that are circulating kind comes from the liver. But most cells in the body can make their own IGF-1, so locally they can still make they don't need the liver one, right? So, you get rid of the liver because if you get rid of the IGF-1 everywhere, you probably going to die, right? So lots of cells in the body can make their own IGF-1, but the liver is not making it. That seems to be really good actually. Kind of like cholesterol actually, right? Cuz most cells throughout the body produce their own cholesterol, but people that have very low cholesterol have lower risk of cardiovascular disease. Right. Yeah. Then the people that that we followed, they have high growth hormone, but that's not working because the growth hormone receptor is blocked, right? And so, in the IGF-1, the growth the central growth factor that that make people grow is very low. So, in fact, this this group is This is in Ecuador. This is about you know, whatever, 3 and 1 / 2 ft tall, right? And but um they don't they really get cancer. They are um rarely get diabetes. They get it, but very different from the people having the same overweight or obesity. Um And so yeah, and then cognitively we actually brought them to Los Angeles to do functional MRIs and lots of tests. And cognitively they show the profile of a 20 years younger individual. So we had them and the relatives. And so the relatives look a little bit older than their age cognitively. And the Laron's, which is this growth hormone receptor deficient group, they show a cognitive ability that was typical of much younger people, right? And uh yeah, so so and if you look at the mice and humans with that mutation with this IGF-1 growth hormone receptor deficiency, very similar, right? Almost everything that I said for humans is true for for mice. What's the natural kind of change to levels of growth hormone as as someone ages? Is it similar to like testosterone that goes
similar to like testosterone that goes down as a man ages or estrogen as woman ages? So IGF-1 is is very high when you're very young and then it it just collapses eventually to to very low levels, right? Cuz I imagine an argument that people may have for supplementing with growth hormone or one of these growth hormone secretagogues is similar [snorts] to say estrogen for a postmenopausal woman. You know, maybe they would say okay, it's it's normal for growth hormone to kind of go down as we age, but evolution doesn't care about how vital and fit you are. So replacing it is actually optimal in a similar way to I guess what we've seen in some of the studies looking at hormone replacement for women. Everything is possible, right? But that's not what the data is showing, right? So, it is possible that if you replace something that is missing, um things will get better. But it's like, you know, imagine I I always use the analogy of an old car, right? So, let's imagine you take an old car and you put a brand new powerful engine in it, right? And you take it around the Let's say that you take a racetrack, right? And you just push it a little bit. Uh what do you think is going to happen? The other parts Parts of the car are probably going to Yeah, it's it's going to be a problem, right? So yeah, you can push it, uh but the data in humans and you can take epidemiological data, you can take mouse data, you can take a human genetics data, it consistently shows that's not true, right? I like acromegalic people that have high growth hormone or mice that have high growth hormone, they die much earlier. They have all kinds of cardiovascular problems, they have all kinds of metabolic problems. So, there's people all you know, there's a drug, multiple drugs in the United States that are blocking growth hormone receptor or the growth hormone pathway in acromegalic people, people that have gigantism, right? So, they just
gigantism, right? So, they just naturally may have a overactive pituitary, so they make tons of growth hormone. So, by that argument, right? Then you should say, "Okay, these are supplemented if equivalent to people that are doing these growth hormone injections or secretagogue injections all the time and they die much shorter. I mean, in the mice you see like a tremendous shortening of lifespan and very sick mice and rats. And in people, same thing to the point that they give them these drugs to bring the IGF-1 down as much as possible, right? So, yeah, so I think that no matter how you look at it, the reality is that the growth hormone receptor and IGF-1 deficient mice do much better in middle age and in old age, right? And the people or mice have excess of this growth hormone, they do worse at all the time. Now, is there a a way to solve this? I think there is, right? Meaning like, well, why is IGF-1 so low in the 80-year - old? Could we somehow, you know, replace that IGF-1 so we can stimulate, you know, in a way that doesn't cause more problems than than solutions? I think it's possible, but it's certainly not injecting yourself with secretagogues. I think it's it's going to be, you know, lots of research, you know, for example, so what we're working on in my own lab, right? So, is it possible that you can have growth hormone very high, right? Or or very Or you get growth hormone to be very high and and GLP-1 to be high naturally and something called FGF-21 be high, right? These are all protective, but yet have IGF-1 be moderate in the 120 to 160 range, right? That's what we're working on. And it's not easy, right? So, I think so
And it's not easy, right? So, I think so there is a potential solution, but you have to keep in mind not disrupting the um you know, the factors and trying to go along with what we were built to do, but maybe uh tweak the master regulator so we can be better even at old age, right? So, it is possible, extremely difficult, extremely delicate, and, you know, and it's certainly not I'm going to take something coming out of China and inject myself with it. Uh that's almost for sure going to cause problems. And I imagine to prove that that's going to take long-term placebo-controlled trials of some sort. Well, it's going to take epidemiology, right? So, now the the those that are injecting themselves are I guess are doing epidemiologists a favor, right? Cuz eventually, you get to ask a million people or you get to follow a million people. And and so, we the epidemiologists are going to get to see what happens to them, right? And so, um it may be there is a subgroup of people that have done certain things like they injected regularly with uh the secretagogues, but they also did something else. And they are living longer with less diseases, right? Okay. Now, it's epidemiological data, and now you can start doing long-term trials. And so, yeah, all of that together eventually could bring us to people, uh you know, living longer healthier. Absolutely, right? So, I think is that's why why I was saying high growth hormone, high GLP-1, or you know, cycling GLP-1, cycling high growth hormone. FGF-21, but moderate IGF-1, which right now you wouldn't have because, you know, you increase growth hormone, you're going to increase IGF-1 as a consequence, and you're going to decrease FGF-21, which is also a key protective uh factor. Um anti-aging protective factor, right? So, if you look at traditional Japan, traditional Mediterranean, traditional the population that
traditional the population that historically had the life expectancy records, right? The number one in the world, number two, number three. So, those places usually had two to one, if not three to one, plant-based to animal-based proteins, right? So, now, if you look at most of them have one to one, but they're still relatively low protein. So, they're still around 0. 8, 0. 9, but they're 50 / Now, what people are doing and what a lot of the entertainment now is proposing go to two to three times as much and make it largely animal, right? Really bad, right? Because now you're starting to push probably those IGF-1 levels above 200, but you're now entering this domain where lots of data from all directions is suggesting you're going to die early and you're going to have lots of diseases that you would not otherwise have. I switched my light morning coffee to Non Drowsy a while back and honestly, I couldn't be happier. No mid-morning spike followed by the crash that tells you that second coffee was not the greatest of ideas. Non Drowsy is Pique's coffee alternative, pronounced Non Drowsy, which took me an embarrassingly long time to get right. It's built around a full spectrum reishi, the fruiting body and spore powder, which is a more concentrated form than you typically see. There's actually some pre-clinical research on reishi's beta glucans and some human trial data on immune markers, NK cell activity in particular. The energy comes from 82 mg of slow release caffeine from fermented pu-erh tea paired with L-theanine for calm, sustained focus, more of a sustained lift than a jolt. Plus, ceremonial grade cacao. Get your Non Drowsy today and save 20% by going to piquelife. com / simon. Is cancer the disease state that you're most worried about for people that are injecting these growth hormone secretagogues? Uh not,
growth hormone secretagogues? Uh not, because the acromegaly might people, cancer is increased but not a lot, right? Uh probably because they die of something else earlier. It's a cardiovascular disease uh seems to be uh one of the problems and uh um also insulin resistance, right? So, the the growth hormone uh high growth hormone uh controls insulin resistance and uh um and in the long run, you're probably going to get the opposite effect that you may get in the short run which is get weight weight gain instead of weight loss. In the long run you're probably going to get weight you're going to get insulin resistance and this is human data, right? Insulin resistance, gain weight weight gain and then with that the cardiovascular disease and and lots of other problems. What would you say I'm I'm trying to think of the the rebuttals right now from from people in this space. What would you say to someone who says exercise increases IGF-1. So is it possible that kind of taking these peptides periodically or like pulsing it is just mimicking that and is in fact not just driving IGF-1 at all times and therefore may not be a risk. This is like in the 50s saying is it possible that cigarette smoking uh you know is just going to be yeah, there's some smoke that you inhale, but you know, you look at the weight loss effect. It's very solid and people enjoy it, right? Great, it's a great combination, right? Cigarettes and nicotine and weight loss. What better could you ask for, right? So everything is possible, but but that's why I was saying you need the data, right? You need the epidemiological before you start going out and recommending to millions or hundreds of millions of people potentially cuz you know, this is what the peptide this is a world world wide
the peptide this is a world world wide phenomenon, right? So people are starting to look in like GLP-1, right? But at least GLP-1 is FDA approved for diabetes and obesity, right? It went through a lot of scrutiny and doctors are involved. Here you're talking about very little scrutiny and no doctors in most cases, right? So so yeah, so I think is there a a version like a pulsatile version, you know, you inject yourself and then you you know, IGF 1 maybe goes up temporarily and then it comes down and is that possible that it's going to just give you benefits and not problems? Yes, I would not count on it because overwhelmingly the data is negative. And so I think it's going to take better than wishful thinking, right? Then say, okay, let me try that, right? Let me try injecting myself with something that clearly has been shown to accelerate aging even in humans and then hope for the best, right? Yes, very similar to the cigarette argument, right? It's very it's DIY medicine. Yeah, it's very experimental. right? But but I think that people are not thinking about the ugly ugly reality of having all the problems that is going to cause in the long run, right? And so you know, and I would suggest that people search acromegalic acromegaly, right? Just just do Google or AI and and look it up, right? Look look at what happens when you have lots of growth hormone all the time, right? Now you can argue, yeah, that's lots of growth hormone all the time. Fine, right? But this is really bad for acromegalic. So is it just going to be a little bit bad for you? Yeah, that's what I will argue. That's exactly what I will argue. The lower the injection, the the less bad it's going to be. But good, I just don't see it.
to be. But good, I just don't see it. Good, yeah, temporarily, obviously we all know that, right? Yeah, you're going to get some muscle, you're going to get some some benefits, but yeah, again, I'll go to the cigarette argument, you know. As a scientist yourself and also watching how GLP-1s have kind of played out over the last 5 years, why do you think a lot of these GH secretagogues, they were being studied in the 1990s, but they never kind of made their way to, at least in my understanding, to like phase three clinical trials testing them against a placebo. So, if someone's wondering about that kind of gap in the research and why that doesn't exist, do you have any kind of views on that? I think it's probably because the the data was so negative, right? And the pharmaceutical companies probably thought, this is not good, right? This is not a good direction. So, pharmaceutical companies want something that is not associated with lots of problems to begin with, right? So, obviously they were paying attention. You know, I give talks all the time for big pharma. They know, right? And so, uh yeah, so it's probably not a good idea to get into something that is already associated with aging acceleration and cancer and lots of other problems, right? In some cases you can argue, but I mean in general nobody argues that that the acromegalics die a lot earlier and have lots of problems, right? So, they probably thought this is not a good uh direction to go in. You know, let's go to GLP-1, which, you know, is, at least commercially, a good direction. And And I think the side effects they discovered later, but they're not what we're talking about, right? Nobody's arguing that GLP-1 is accelerating aging, right. So yeah, so I think they were paying attention to the science, probably, and they didn't go in that direction. Then, I think they went off patent, right? So eventually, you know, they had a 20-years patent shelf life,
patent shelf life, and um and that expired, right? And then that's where and now anybody can make it and there's no regulations of it, right? So I think probably around maybe 2015, that's when a lot of these patents, I'm assuming, I don't know, I'm just speculating here. Right. Patent expired, and then now anybody can make it. And it seems like the craze to me seems, if I think about the human psyche, I think firstly we all fear aging and we want to be youthful. So, there's a fear component which is leading to kind of over-indexing on the short-term benefits that are claimed and under-indexing on potential long-term disease risk that could come with this experimental drug. Yeah, absolutely. And I don't know that you call it a potential because in the case of GLP-1 is potential, right? Because it is fairly rare. A lot of this, I mean, beside the lean body mass loss, but a lot of the bad side effects like neon and you know, the going blind, right? They're they're fairly rare. Um here you're talking about pretty good evidence that you're going to have a problem. You know, the more you do it, you're going to have a problem, right? The very few acromegalics, if they don't take drugs that lower the growth hormone uh levels and IGF-1 levels, you know, very few of the acromegalics will uh will be able to have a normal life. I don't think people understand this. I think this is going to hit people really hard to hear this information because no one's talking about it. Yeah, but that's you know, that's that's the world we live in, you know, so so yeah. So, I think you know, all of a sudden I think this is a way to not having to go to the doctor to get growth hormone and you just can do it um you know, because it's just available and that's what people are doing, right? But you clearly feel there's
But you clearly feel there's going to be a lot of regrets. Yes. What would you say if you had a loved one or a family member that was either thinking about using these or already using them. I will show them the data. Yeah. Just show them, you know, the the problems in mice and the rats, humans, genetic data, the acromegalic data. Uh just we you know, it could come from 20 different directions. Like very consistent, And also we'll say, "Hey, we're not arguing that you're going to gain muscle." Yeah, absolutely. I'm not arguing that you're going to lose weight with cigarettes. I want to kind of flip from the pharmacological side to nutrition and and things that people can do that will kind of activate these pathways in a certain way to actually improve their long-term disease outcomes. And you mentioned earlier, you mentioned TOR and S6K. So perhaps for listeners that are not really familiar with those pathways. We've gone over them a little bit previously. But perhaps we can start there and then use that as a basis to start talking about nutrients and nutrition and and how that plays into these different growth pathways. Yes. So the TOR S6K pathway, if you think about aging research, um beside the blockade of the insulin IGF-1 signaling, uh it's considered the blockade of the blocking the TOR S6K is considered uh the most powerful anti-aging intervention, right? Um so it it and I think This started in my lab with the in yeast many many years ago, the identification of S6K being the most powerful. So mutation like if you stop that signaling, the yeast lives a lot longer. And that's downstream of the liver producing IGF-1. It is downstream of IGF-1, right? So the liver produces IGF-1, IGF-1 circulates,
liver produces IGF-1, IGF-1 circulates, and not just IGF-1, also insulin, right? So growth hormone controls both IGF-1 and insulin, right? And and growth hormone, there's data also that controls TOR directly, right? So, the growth hormone can go through the growth hormone receptor mostly, can go in multiple direction, right? So, it can it control not just IGF-1, but also TOR directly and insulin. So, yeah, so So, now um all of them a lot of these pathways converge into the the TOR signaling, which is central in cellular growth and organismal growth. There was a publication uh in um where they gave rapamycin to middle-aged mice, and this was done in three different universities, University of Michigan, uh Texas, and Jackson Laboratories. And that's where then this idea of rapamycin exploded because three different labs all said, you know, this is first drug we could get in all the doesn't matter who does it, you get a lifespan extension extension, and healthspan extension. Uh even if you start in middle age, right? So, yeah, so I think that that now most people view that as the most powerful pro-aging pathway, right? And whether it's it's human Of course, the human data is still just beginning. But I say everything else is really developed, right? So, Do you think rapamycin through that action is promoting longevity? Well, rapamycin is promoting longevity, but rapamycin also causes hyperglycemia, right? Insulin resistance. And so, I think now you know, at least for humans, that's a good and a bad, right? And And that's why I think most people will say probably not a good idea uh to to go in that direction. We need to find out find maybe a smarter drug that My argument would be that drug needs to be upstream, right? More of a master
be upstream, right? More of a master regulator, because TOR is is too central for the life of a cell, right? And the function of a cell. So, I think interfering with that, yes, it can give you benefits, but it can give you problems, right? So, yes, so I would argue probably we need to act upstream, like growth hormone receptor level. And uh because of what I said earlier, right? You know, it just does it all, right? Rather than TOR does only one. And uh surprisingly the lifespan extension caused by the growth hormone receptor mutation or growth hormone mutation is much larger than the one caused by uh rapamycin, right? TOR inhibition. Of course, one is a drug and one is a mutation, so it may be that the mutation is more powerful cuz it's just completely lacking uh the the production of of growth hormone or or the activity of growth hormone. But, yeah, so it looks like growth hormone is uh you know, the secretagogue uh uh induced hormone uh is at the center is the master pro-aging factor, right? But, what you're saying is if you're interested in remaining youthful and avoiding chronic disease, you would in fact want the opposite of what these peptides are doing, which is elevating growth hormone. Yes. Yep, exactly. And would that potentially come at any consequence in terms of short-term vitality and how much muscle someone has and how vital they feel? It may um if you do it in older individuals um I think, you know, we've been following 100 Larons uh in Ecuador for 20 years. Guevara, Dr. Guevara is an endocrinologist has been following them for 50 years. They're very vital. They have almost no IGF-1, right? And they're very vital and they uh they produce less insulin,
and they uh they produce less insulin, but that insulin works very well, right? They're funny, they're sharp, they're mentally uh very active, they um they're cognitively younger than their biological age or their chronological age. Yes, so I think they, you know, whether you look at a mouse, a rat without growth hormone, or a person, we just don't see it, right? Now, it's considered they're born with that, right? So, then you could argue, if you always had a ton of growth hormone, and all of a sudden I get rid of it, could it be a problem? Yeah, it could be for what we were saying earlier, right? So, now you've always had a ton of growth hormone because you ate a lot of proteins, and you had a bad diet, um and so all of a sudden now you go down, could that person now be in trouble? Yes, because um you know, uh now it might take a certain level of growth hormone for to maintain normal function. You're really flipping the script here, though. On the current conversation around growth hormone and longevity, at least in the peptide space. Yeah, I mean, of course, this is my world, right? So, it doesn't matter how you do a secretagogue or growth hormone injection or growth hormone releasing hormone injection, um it's uh the result is the same, right? You can activate uh um IGF-1, you're going to increase IGF-1, you're probably going to increase insulin, you're going to increase insulin resistance, uh you're going to increase mTOR, uh you're going to do all of that. Yes, you're going to get benefits, no doubt. And then you're going to get problems, you know, and then, of course, not everybody's going to get problems. I don't know, you know, it depends how much you're injection injecting, how how effective that is, but let's say that you get a major increase in in IGF-1, let's say from the ideal one I just wrote um I recently wrote a a meta-analysis on on IGF-1 levels and it was 120 to 160 seems to be the range that minimized
range that minimized mortality, right? So, yeah, so now you can get, you know, from 160 to 250 and and a lot of people in the US and Europe have that 250 to 280 and that I think I forget what the cutoff for make acromegaly is, but I think it's around 300, right. So, at 300 the endocrinologist will potentially, and I don't call it, but uh will potentially start prescribing you uh growth hormone lowering drugs. And I mean, IGF-1 lowering drugs. Remind us how nutrition affects growth hormone and IGF-1 levels and what we've learned about optimal nutrition to perhaps help someone maintain IGF-1 in that range that you just mentioned between 120 and 160, what that would look like. Yeah, so the proteins, but not just the protein, I think also the calories, right? Calories and protein level uh control largely control. There's other factors, of course, like you mentioned exercise can increase IGF-1. Um yeah, so so um then the the ideal um is 0. 8 g per kilogram. I think it's 0. 37 g per pound of body weight um and that's what every medical association in the world of the majority of them recommend, right? And um now if you look at the the entertainment um you know, you're you're seeing two to three times recommendation of of protein intake, right? So, we actually took the time to go through hundreds of papers recently and and just to focus on muscle, right? And and it turned out that you know, so 0. 8 clearly and and what I call the longevity diet, right? So and I wrote a book on this, so people can um can pick it up if they want. I don't make a penny, everything goes to my foundations. But you know, the longevity
foundations. But you know, the longevity diet is, you know, mostly vegan uh pescetarian actually, some fish plus vegan diet, low protein, which I just described. Lots of nuts, legumes uh uh lots of vegetables, some fruit, not high fruit, not fruit and vegetable uh vegetable and some fruit. So that's the longevity diet and maybe uh omega-3 fish once or twice a week and then uh uh yeah, fish again two or three times a week. Uh so that gets you not only the 0. 8, but it gets you the uh what we think is an ideal, if you look at old Okinawa, old Japan, uh traditional Japan, traditional Mediterranean, traditional Okinawa, the one that the population that uh historically had the life expectancy records, right? The number one in the world, number two, number three. So those places usually had two to one uh or if not three to one plant-based to animal-based proteins, right? So now if you look at most of them have one to one, right? But they're still relatively low protein. So they're still around 0. 8, 0. 9, but they're 50 / Now what people are doing and what a lot of the entertainment now is proposing, go to two to three times as much and make it largely animal, right? Really bad, right? Because now you're starting to push that probably that those IGF-1 levels above 200, but you're now entering this domain for where lots of data from all directions is suggesting you're going to die early and you're going to have lots of diseases that you would not otherwise have, right? So the high animal protein diet, you you in when you get to the uh you know, 1. 5 g per kilogram or let's say 0. 7 uh uh yeah, 0. 7 g per pound, right? 0. 7 g per pound. If you get to those levels, you're going to see lots of problems. Now, we took the as I was saying, I took
Now, we took the as I was saying, I took the time to go through the muscle. Guys will say, "Okay, fine. People say, I don't care. I want to gain muscle." And and it turned out that between 0. 8 and 1. 2 very little difference, right? Uh grams per kilogram, right? So, say 0. 37, I have to convert to 0. 5, right? Grams five, right? Grams per pound, right? If you go from 0. 37 g per pound to 0. 5 g per pound or 0. 6 even close, little difference. As you go higher, yeah, you started to see more difference on muscle building if it is combined with resistance training, right? So, not a huge effect. And now we're trying to get the exact numbers, but the interesting thing is it still makes very little difference if you're not training, right? And they also shows that the training is making a huge difference. The protein is making a little difference, right? So, training makes a big difference. And then And now And you got to have enough protein, right? You cannot be 0. 5 or the 0. 18 g per pound and think you're going to build muscle by training. So, training made a big difference. It was clear that you needed the minimum, but then yeah, if you added the lots of proteins you had a small additional effect that is pretty consistent, but not worth it, right? Definitely not worth it unless for some reason you must have that extra kilogram of lean body mass, right? So, Do you think that the protein source, did you look at that in the analysis of of plant versus animal? Yeah, we look at the protein sources. I usually the I mean, if you look at at plant-based, the majority of the plant-based are pretty good source of branched-chain amino acids and pretty good source of methionine. These are the ones the
methionine. These are the ones the essential amino acid that count the most, you know. So, the only exception for methionine is legumes, right? So, if your diet is mostly legumes, then yeah, you're going to have very low methionine, right? Which is a good thing from in terms of activation of these pathways you're talking about? Which is a very good thing well, it's good and bad, right? It's good like low protein, but you don't want to get to too low protein as I just mentioned, right? So, low methionine but sufficient methionine is good. Too low methionine and you're going to get you to frailty, right? So that's So, you you have to have a low but not too low, right? I guess what the question I'm I'm wondering is let's say you're getting above the RDA, let's say like 1. 2 g per kilogram, which I would say is like moderate. So, you got 0. 8 50% up. Yeah. And then you have above that, you have like bodybuilder levels at like 1 g per pound, right? So, somewhere in the middle, let's say 1. 2 g per kilogram, but it's mostly coming from plant protein with lots of legumes in there. If you have too much legumes, you might struggle with the muscle building. So, I will have it maybe the legumes no more than half, right? Maybe even a third to a half. If you're trying to build muscle, you probably don't want to have it mostly legumes. You probably want to have it let's say 50% uh or less legumes, and then nuts, uh whole grains, and uh you know, um and and seeds, right? Seeds also are good good source of Most people are probably not just eating legumes, hopefully. Right, yeah. So So, that's not Yeah, that's a small group. Yeah. I will start with the same Harvard studies over and over showing low carbohydrate diet, especially if it's high in animal fats and proteins,
it's high in animal fats and proteins, higher cardiovascular disease, higher cardiovascular mortality, higher cancer mortality, higher overall mortality. And the Lancet study indicates the same, better to have an 80% carbohydrate diet than a 20% carbohydrate diet. So, the data is pretty clear that low carbohydrate diets, yes, they can have an advantage short-term, like we discussed for the other topics. And if you look at the Okinawans, they had 85% carbohydrate diet. The Japanese always had high carb. The Italians, they live long, they've always had a very high carbohydrate diet. Loma Linda is a high carbohydrate diet. Everything is possible, we just don't see it, and the data is clearly strongly against the low carb diets. One thing I've been thinking about more lately, as I get older, is brain health, staying sharp, maintaining focus, and protecting cognitive function long-term. My days involve constantly shifting between screens, emails, social media, phone calls, recording podcasts. All of this requires a lot of cognitive processing power and cognitive reserve. And there are stretches where I feel absolutely dialed in, and there are other times where the fog creeps in. And what I've come to appreciate is that there are biomarkers that you can measure that act as a window into your brain health. Things like inflammation, blood sugar regulation, nutrient levels, and hormonal health all influence how your brain performs today and over time. If we're not measuring those systems, we're making assumptions that what we're doing is working. That's one of the reasons I use Function. It gives you over 160 lab tests each year, so you can see what's happening beneath the surface. For me, tracking things like inflammatory markers and markers of metabolic health like triglycerides and HBO1C has directly informed how I train, how I eat, and how I recover. Rather than just doing things blindly, I have data to help guide the lifestyle choices that I'm making and where I may or may not need to pay more attention. Own your health for $ 365 a year. That's a dollar a day. Learn more and join using my link functionhealth. com / simonhill
functionhealth. com / simonhill and use the gift code Simon 25 for a $ 25 credit towards your membership. I had Andrew Glennon yesterday. I'm not sure if you know her. She's a researcher at Harvard. And they did a an interesting analysis on three cohorts, the typical ones that that Harvard looks at like the Nurses' Health, Nurses' Health 2, and Health Professionals Follow-up. And it was a I'll send you this publish with with them, right? Oh, you published with them. So In fact, our paper was I mean, I was middle author, but it was a collaborative paper with Giovannucci and Giovannucci where we looked at plant a high plant-based diet protein diet versus a high animal-based protein diet. This is highly cited paper back from like what, 7 or 8 years ago. Uh where the group that had high plant-based proteins were doing better, but the one with high animal-based protein was doing worse or or a lot worse, yeah. But but it turns out that the the devil is in the detail. So, it turns out in the Harvard studies, and now we have a follow-up study publication with with Frank Hu um following the study. It turns out that this was really something that the the world got confused cuz that's how popular this these papers were, right? So, it got confused, why? Because the the If you look at the the group with a high plant-based protein that was doing well, it doesn't actually have more proteins, and it probably has less essential amino acid compared to the low group that was doing worse. Meaning, they said, "High High animal protein, bad for you, okay? High plant-based protein, good for you." But that's not what it was in the study. I mean, they were not misleading, but people understood it the wrong way. They understood that people were eating lots of plant-based proteins, and people eating low plant-based protein, but low overall protein in general, were doing
overall protein in general, were doing better, right? So, people that had more protein, but they were plant-based, did better. That's not the case. They just had a proportion of protein that was higher. But in fact, they had less essential amino acid, right? So, because of what I said earlier, the composition of the amino acids is very different in some sources In In general, in the plant protein and in their study. So, that meaning that by by in decreasing the animal protein and increasing the plant protein, you're you're changing amino acid profile, right? And really, my point in the future is we have to move away, now that we have artificial intelligence and that we have apps, we're going to very soon have to move away from the idea of protein. It's irrelevant, right? Protein is irrelevant. You can have a threefold difference between methionine between uh legume and a uh and a chicken, right? So, threefold, right? So, then, if you had 10 g of legume proteins, as far as methionine is concerned, is equivalent to uh 3 g of a uh chicken uh uh serving, right? The study that that I saw on cardiovascular mortality, which they published looking at the the ratio of plant animal and then also protein density. Which I thought was interesting cuz they looked at both. It found clearly when you had a higher plant animal protein ratio, lower lower cardiovascular mortality. It was like super clear. And that was for stroke, it was for heart disease, and combined cardiovascular disease. It didn't This paper didn't look at total mortality. [snorts] But what I found interesting was then they looked at protein density. And in the people that had a high plant animal ratio, the ones who had higher protein density had lower cardiovascular mortality than those who had low protein density. And that was like the first paper I think that I saw that had analyzed that and it interests me cuz when I kind of
and it interests me cuz when I kind of they didn't actually say specifically what percentage of calories were coming from protein, but I I kind of calculated based on their BMIs and what the typical calorie consumption would be. It worked out that the the protein dense group at the lowest risk of of cardiovascular mortality were getting like 18 to 19% of calories from protein. But it was mostly from plants. From plant, yeah. So, again, it's the amino acid that counts. So, I like the fact that in this case they look at proportion, right? It's a better way to present it because it's basically saying it's not a higher protein group, but it's a group that has higher proportion of plant-based protein, right? Yeah. So again, that makes sense because now in that group with the mostly plant-based protein, you could have a lot less methionine, less branched-chain amino acid, etc. And now, of course, there are also other benefits of the plant-based diet, right? So, they're gaining the the benefits of the plant-based diet, uh which are difficult to calculate because there's probably lots of them, plus they probably have the same or lower level of the amino acids that accelerate the aging process. We actually calculated not for the for that study but for the same group, right? For the three groups, right? Yeah, and the high plant-based group has lower essential the same or lower essential amino acid compared to the low plant-based group, yeah. And so inside a cell, if we come back to those pathways, is the cell the cells just kind of sensing these amino acids as they're coming in and based on certain thresholds or concentrations, it's like it's activating those pathways or not? Is it as simple as that? The amino acids are acting the different level. They can act at the level at the nervous system level. They can act in the liver. They can act directly to the cells, right? So so you can have a let's say leucine directly activating TOR
TOR TOR in a muscle cell. You can have then methionine act affect liver production you know, liver metabolism and production of lots of things. And then you can have the amino acids also affecting the hypothalamus. A signaling to the hypothalamus, you know, shall I release growth hormone releasing hormone or not, right? So yeah, so It's a cascade. These amino acids are regulating everything as they should, right? Because the body is trying to make decisions what should I do next, right? Do I have enough methionine and and to build things, right? Do I have enough leucine? So it it understands that if you have uh this level of methionine, maybe you can do certain things and if you don't, For example, reproduction, right? And that's really key in all these, right? Because it's evolutionary theories and the idea is the most powerful way to live long, right? So So if you think about we are always stuck in a growth and reproductive mode, right? So we are ready to reproduce all the time, right? And we are ready and we're you you IGF-1 growth factors all the time. But in fact, we reproduce only you know, for some two or three times in a life, right? And and so, if you look at evolutionary theories, it will say, "This is not a good investment, right?" So, don't try to be in a high reproductive, high growth mode all the time when you're not reproducing. Switch to a highly protective maintenance mode, right? And just sit there until you want to switch back. And then now, that modality, like we see for fasting, is not necessarily a low metabolic phase, right? Because when you're starving, something we see very clearly, mice, for example, are looking much more active. They're they're more active, right? So, they're not less active. So, you know, if you get in the right modality, now you can have very high, you know, protective pressure, so the whole system is now Right. as the job of
whole system is now Right. as the job of protect age as slow as possible. Make you age as slow as possible. And yet, get the be very active and be very, you know, sharp, right? Because that's another thing we see, that not only they're very active, they're looking for food, so they remember things much better, right? So, and there's something that we're starting to see also in the clinical trials. That makes sense from a survival point of view that if calories and food is scarce, you need to have good cognition. Yeah, but you don't want to invest in reproductive systems. You don't want to invest in lots of things that are like There's a trade-off. Why would you do that? And this is why if you go below a certain level of calories, the cycle in women stops, right? So, it's taking you out of the game, right? It's saying, "Okay, let's let's focus on protecting you and not on reproducing cuz it's clearly you don't have enough calories, right?" So, of course, the message shouldn't be, you know, go into an anorexic state, but the but but the point is how can you get there and sit there and in very active, very sharp, right way or modality and then, okay, when you need it for those couple times a year in a lifetime, exit. And you know and and reproduce. Which has really been, you know, a lot of your life's work working out how do you manipulate the diet. I want to get into that because you mentioned FMD and we we should redefine that and the longevity diet and how this kind of feeds into everything we're talking about here. Before we get to those dietary methods, you mentioned insulin before and there is a whole community of people out there who I think should strongly advocate for a ketogenic or very low carbohydrate diet for the one of the primary rationales being you lower insulin. And that's going to promote longevity. What are your thoughts on that that approach before we get into yours?
approach before we get into yours? Well, I will start with the same Harvard study that you mentioned, right? So over and over showing low carbohydrate diet, especially if it's high in animal fats and proteins, higher cardiovascular disease, higher cardiovascular mortality, higher cancer mortality, higher overall mortality, right? And and the Lancet study indicates the the same better to have an 80% carbohydrate diet than a 20% carbohydrate diet. So the data is pretty clear that low carbohydrate diets, yes, they can have an advantage short-term, like we discussed for for the other topics, but in the long run, uh you know, and if you look at the Okinawans, they had you know, 85% carbohydrate diet. The Japanese always had high carb. The the you know, the Italians, they live long, they've always had a very high carbohydrate diet. Loma Linda is a high carbohydrate diet. Uh you name it, right. It's Yeah, you you know, everything is possible. We just don't see it and the data is clearly strongly against the the low carb diets. Yeah. So, those those populations without realizing it are kind of living in that preservation mode because of their nutrition. Yeah, if you look at Okinawa, 39 g of proteins per day, right? 70% of their calories coming from uh purple sweet potatoes uh at least in the' 50s. And um calories around 1, 800, right? So, they were calorie restricted. And the Japanese actually they were not that far away. Higher protein intake, it was more in the like 60 g, right? Uh, but those are the Japanese that now are still, you know, top top of the world or or some of the top countries for life expectancy, right? So, yeah, so I think that if you look at the population that historically had lots of plant-based and either low protein intake or moderate moderately low, let's say, 60 g 65 g.
low, let's say, 60 g 65 g. That's what the Japanese had. Uh, yeah, those are the ones that are performing forget the the zones like the blue zones which you know, then are like exceptions and you know, but even if you just look at the countries and the life expect like Japan for 25 years was number one in life expectancy, right? And if you look at at least among the the large countries. And um and if you look at the historical you know, nutrition data consistently low protein even now I think they have maybe 13% protein diet and I think it's now a 50 / 50 plant and animal. So, if you had to go high, I would say that's that's as high as you should should go, right? 50 13% you know. But I think it's better now to talk about grams, right? Because uh per kilogram or grams per pound because everything that you buy, it tells you how many proteins you have. So, I I think it's, you know, percentage is is something a technical, but how do people translate that into a what do I do? But people can count how many proteins they had about during the day with applications now. You know, of course, yeah, application will also turn into percentage, but I think it's probably better to go with with plant-based versus animal-based grams of proteins per day. When you talk about preservation, if we come back to like what's happening inside of of a cell, if you're kind of dialing down the activation of of TOR, remind me what's happening with AMPK and and how is the cell kind of shifting in terms of going from build to repair mode? Like what does that kind of look like and what are the benefits of that? Let's say when you fast, right? When when you fast or you do the fasting mimicking diet, uh, now you have AMPK is activated and then you have a network of genes and proteins and, you know, they they can go in opposite direction, right? So, you have the bad ones like TOR versus kinase go down and the AMPK
TOR versus kinase go down and the AMPK go up and then downstream of that, you have usually transcription factors, right? And that's what you want to have up, right? So, you want to have up the the uh, FOXO, for example, transcription factor. And these FOXO transcription factors, I like to see them as captains, right? So, if you think about, you know, you have to get things done. The captain has to be there and say, "Okay, I have 200 people under me, 200 soldiers and and I can give jobs, right? So, the job of the transcription factors is to, for example, antioxidants like superoxide dismutase, catalase, glutathione, um, or heat shock proteins. Okay, let's activate these proteins that have the job of you know, protecting the cell uh, and uh, Um, know, protecting the cells against damage, heat damage, but lots of different type of damage. And uh yeah, so then you can have let say DNA repair genes, right? So, they have the job of um um you know, uh making decisions about shall I repair this? How should I repair it? How much effort should I put into it, right? So, you know, if you think about the disposable soma theory, that there is only so much energy that we can put towards protection, right? Why? Because in in evolution just then then force of natural selection had a job of keeping you healthy enough to reproduce and then it's okay if you get out of the way, right? They we're not There's no force of natural selection trying to keep us alive forever. So, that means that a certain amount of damage was allowed, unless one exception, if you're starving, right? If you're starving, that's not allowed because you're not reproducing. I got to get you You haven't produced the offsprings yet that I want from you. So, I got to get you there, right? And that's why this is three and a half I I call it three and a half billion years of R & D, right? This has been going on this bacteria had a stationary phase. Yeast had that, right? Now, yeast have three phases. One, life
Now, yeast have three phases. One, life in the fast lane, then you have something called stationary phase and they live two to three times longer. Then you have something called spore, they live a hundred times longer, right? So, if you get in the spore, of course, that the spore state is a very low metabolic state, right? Almost dormant. Um, but um but yeah, so evolution has learned out already learned out of you know, switch you back to all these different modality. And that's why I was saying if we can now find a way to be non-reproductive, highly highly mentally active and physically active, that is going to be way more powerful than anything you've ever seen, right? Until of course, now there's a lot of work we're working on that and lots of groups are working on the reprogramming stem cells and all of that. So, there is a biohacking world that is coming, too, but but I it's going to take a while to get there. And there's a lot that we can do with nutrition, which is really your focus with the FMD and and your books. If if we think about that, is it okay to think about it as a switch? Like AMPK sort of switches on and mTOR switches down. That's getting the cell operating in this kind of preservation mode that we're talking about. You have two things. I think the longevity diet is more about the preservation mode, right? What I talked about earlier, right? The what you do every day, right? So, 12 hours of time restricted eating. So, eat for 12 hours only. Um you know, the and all the things we already discussed. Sleep well, right? So, that's that's a continuous preservation mode, right? Uh and everybody should do as much of that as possible, right? But the fasting mimicking diet and fasting is very different game, right? Why? Because now and now we published many papers on this. But but the first one was in 2014 when we did it with uh chemotherapy, right? So, we give mice chemotherapy, and we damage the blood system, right? So, they're they're just really uh not able to, you know, the white blood cells and the immune system is is dysfunctional, right? Then we start the fasting cycles, and now we're starting to see
to see um you know, the white blood cells going back to normal uh even though we had chemotherapy, right? And uh and so, we couldn't explain it. So, it turns, you know, long story short, the fasting is now activating the self-renewing stem cells in the bone marrow. And now is making a much better at at producing a renewed immune system, right? In fact, we irradiated mice, so we wipe out their their immune system, and then we just take the bone marrow cells from the fasted mice, right? Much more powerful than than the recipient, the one uh the one from mice that were not fasted, right? Yeah, so then on one side, the fasting is activating stem cells. Not just the the just bone marrow was an example, but now it turns out we see neural stem cell activation, we see muscle stem cell activation, we see these stem cells activate everywhere. Why? It's very simple. The system is shrinking a little bit, right? As you fast, and then it needs to re-expand, right? And to re-expand is going back to the embryonic developmental programs. So, it's using stem cells. The other thing that it uses is autophagy, right? So, before it can rebuild, it has to break it down. And I forgot we talked about it last time, but yeah, so you want to have a very sophisticated process of breaking things down, right? It's It's like sending your best construction crew, say, "I I get rid of this and this. Keep that. That looks good, right?" Yeah, so very sophisticated system breakdown. Then you activate the stem cells. And then the thing that, you know, really surprised us in 2017 in a paper with the pancreas. So, we damaged the pancreas of the mouse. And then, you know, it's a permanent damage, so they become type 1 diabetic. They cannot make insulin anymore, right? Then we start the fasting mimicking diet cycles, and you start seeing the reprogramming of cells, right? So, the cells go from non-functional beta cells, which make insulin, to a weird cell which is called
insulin, to a weird cell which is called non-alpha non-beta. And then they sit there for a while. And then when you refeed the mice, they go back into a beta a working beta cell, right? So, now the body has the ability of turn And I guess how they do it. Yamanaka factors. It's just turning on all these embryonic developmental factors. They make all cells young. It's turning them on. But each organs, so for example, in their case was Oct4 and Sox2, right? And also a gene called Nanog. And so these are reprogram embryonic reprogramming factors. Then we more recently looked at the kidney of a rat, right? We said, "Let's go to a different organism and let's see if it keeps working." So, we did this exactly the same thing. We damaged the kidney, right? And and now my collaborator Laura Perin said, "There's no way the podocytes are going to regenerate, right?" Because adult kidney cells don't regenerate. And but sure enough, you start seeing them turning on different in this case is Myc, different Yamanaka factors, and they they're going from a completely dysfunctional disrupted modality to a functioning and and if you look at what we call we did something called spatial transcriptomics. So, we look at how all the cells work in the kidney. We just slice the kidney and we look at all the different cells. And you see that the this is completely this pattern is completely disrupted, right? By by a chemical by a toxin. And then you give them the six cycles of the fasting mimicking diet and it just returns to its original state, right? Which is really unbelievable. Has that been translated into humans or is that the next step or like In the paper we had small but two seven patient and six patients, right? 13 patient at University of Rome clinical trial chronic kidney disease patient. So, we gave them three cycles of the fasting mimicking diet and not only proteinuria came down. Now, we cannot, you know, go and take the kidney cells and and know if Yamanaka factors are turned on. But something interesting
turned on. But something interesting happened, which is not only the proteinuria, which is a measure of kidney damage, came back down to nearly normal in in all 13 patients, but a year later it was still down, right? So, and and then when we look at circulating progenitor cells and stem cells, they were tripled in the blood of the kidney of the patients, right? So, are they it's it's strange, right? Why all of a sudden chronic kidney patients are tripling the level of progenitor cells in circulation as the kidney is now becoming more functional. Is it possible that they know exactly what to do, right? So, they're now bringing in the stem cells, Yamanaka factors, and autophagy, and from the three different sides, it's fixing the kidney, right? So, That's exciting, exciting work. Yeah. Could you do the GLP-1 oral, right? Stop after day two or three, finish together with the fasting mimicking diet, and then you're good to go until next month, and then you do it again. So, you now minimize the side effects of the GLP-1, but utilize the temporary hunger management effects of GLP-1. I get asked a lot about how to make investing in your health a bit lighter on the wallet because the tools that genuinely move the needle, fitness equipment, important supplements, sleep support, they all add up placing pressure on our bank balance. That's why we recently integrated Truemed on our 38 TARA website. For qualified customers, it means that thousands of our American customers are now saving on their monthly orders by putting pre-tax HSA or FSA dollars toward their purchase. Products that qualify as medical expenses under IRS guidelines. While it varies depending on how much HSA FSA funds you have, on average, using Truemed provides a 30% saving. The same applies across Truemed's wider partner network. You fill out a short clinical intake form, and Truemed handles the documentation and receipts for reimbursement. It's super simple to set
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see that in perhaps in in humans who have newly been diagnosed with type 1 diabetes. Yeah, we started that trial, right, actually in children in in Italy. And unfortunately, because they had to be hospitalized cuz we were worried about, you know, them being too young to be doing the FMD the fasting mimicking diet outside. Uh we have to stop, right? But we started already seeing evidence in multiple patients of insulin coming back up, right? So, yes, so now we I agree we need to do a maybe in adults instead of children. Uh and see if we can uh you know, if we can see the the production of beta cells or functioning beta cells. The problem with type 1 diabetes is it's an autoimmune disorder. So, the the risk is that you intervene, uh you you regenerate, and then the immune system is going to attack again, you know. Right. You mentioned FMD cycle. If someone's not familiar with what that means in these studies, the human ones in particular, what what are the subjects eating during that 5-day period? Yeah, so this comes in a box, right? This this diet comes in a box, and in but it's a low calories, it's about 770 to 1, 100 kcal per day, 5 days. It's mostly it's all plant-based, um and lots of vegetable soups, and lots of fats from from uh nuts and olive oil, and it's a high-fat, relatively high-fat diet, uh and low sugar, and low protein. Uh 100% plant-based. And And the idea when I developed it a a long time ago, 20 years ago, uh the idea was to make it very I could have made it fasting mimicking with lard or or you know, giving lots of different sources of fats. Uh but I um I think I had the good idea of of making it plant-based and very healthy, right? So, picking lots of very healthy ingredients, and um and and that turned out to be a good idea. For example, in the Crohn's disease uh models, mouse models, we compared
models, mouse models, we compared water-only fasting with the fasting mimicking diet, and the fasting mimicking diet was doing better than water-only fasting because the fasting mimicking diet was changing the microbiota. It was feeding the the prebiotics to the gut of the mice. And so the mice with receiving fasting mimicking diet cycles, they were much better at reversing this gastrointestinal autoimmunity. How often would you recommend someone does or what does the science show in terms of when someone may want to consider doing FMD? Is it for someone with disease, someone that's healthy, and and how frequently would you recommend doing it kind of outside of eating a diet that's that's in line with your longevity diet? So now we we're done we just finished a large trial of 500 patients in southern Italy. And this for the first time we went every 3 months. Um so we've we'll we'll see what the data shows, but but I think that um probably, you know, let's say three or four times a year uh is a good general advice, right? If you if you're overweight or obese, if you have inflammatory issues. Or now Stanford just published a very nice study in Nature Medicine. Three cycles of the fasting mimicking diet, you know, having a remarkable effect together with standard of care on Crohn's disease patients, and in many cases causing remission. And now, University of Miami published a smaller study with colitis ulcerative colitis. Um and so yes, so in those cases when you have diabetes or you have a disease, then of course you have to talk to the doctor. But I think that uh at the beginning you might want to start like once a month until you improve. And then you can go once every 2 months, and then once every 3 months, and eventually maybe as little as once every 6 months if you get to perfect health. I was
if you get to perfect health. I was surprised. I saw a paper and and you can expand on this looking at healthy adults that did FMD. I think it was a few cycles and looking at biological age. Yeah. So, we we looked at the two different trials, right? We And so, using this Morgan Levine and Morgan now is at Altos Labs, but she was at Yale. So, she developed something called BioAge that where we can use blood markers to calculate biological age. And so, in both trials we saw after three cycles of FMD the same result, which is 2 and 1 / 2 years reduced biological age. I really like Morgan's BioAge clock because it is based on markers that most physicians around the world will will say is no doubt that these if these are becoming lower, for example, cholesterol, blood pressure. I think I forgot all the markers, but but it's the markers are widely recognized as risk factors for diseases. Right. And so, she used that, but she used the enhanced the CDC database to then show the pattern predict ability to predict mortality in however many years following. So it's it's very clever cuz it's using highly you know, markers that labs will measure very carefully and very well. So, and [clears throat] then using markers that are clearly accepted by the medical community as disease risk factor. And so, if that you know, even if you argue with the validity of of the biological clock, you cannot argue with the validity of of making all these risk factors lower. So either way, yeah, 2 and 1 / 2 years of biological age reduction. So, that specific kind of nutrition formulation still has benefits for someone that's that doesn't need to lose weight. Sure, right. This is why I was saying, you know, this has now been tested for
you know, this has now been tested for for Crohn's disease and colitis and lots of other things. There's a lot of trials on cancer. Yeah, so I think that um the um what I was saying before, the Yamanaka factors, the stem cells, and the autophagy, uh all of that it's going to work on on everybody. And you know, of course, again, mechanistically, we know this very clearly in mice and now rats. Is it the same in in people? We don't know, but certainly we are seeing the results of that, right? That what you would expect if the Yamanaka factors were in fact activated, if the stem cells were activated. Oh, they are, right? Because now we're we're in multiple trials, we measure stem cells in circulating. They're they're up now awfully. You know, we're with the new technique technologies, we'll be able to measure more stem cells, you know, do we see lots of different stem cells circulating um being higher or much higher? We'll see, but uh the idea is that it's it's affecting aging first. Right. How frequently do you kind of cycle off the longevity diet and do a do an FMD? I do it I do something that I'm not supposed to do, which is I combine it when I'm sick, and I don't feel like eating, right? I'm not advising people because it could be dangerous, uh but that's how I've been doing it, and um and uh um you know, and now also, of course, the company is starting to think about um can we combine it with GLP-1, maybe like short-acting? That's a trial that we're interested in doing. So, going back to what you were asking before, which is, you know, a lot of people just have a difficult time, they're hungry, and they're like, "Well, I don't want to do 5 days of restriction." So, then, is it possible to have a short-acting GLP-1 or just having a GLP-1 pill for just a couple days, get through the FMD, stop the pill, get rid don't have the the lean body mass, because that's the thing, right? We don't see any lean body mass loss with the FMD cycles, right? And and now lots of trials are all showing the same
lots of trials are all showing the same thing. So, yeah, could you do the GLP-1 oral, right? Stop after day two or three, finish the together with the fasting-mimicking diet, finish the fasting-mimicking diet, and then you're good to go until next month, and then you do it again until, you know, so you now minimize the side effects of the GLP-1 and but utilize the temporary uh hunger uh management uh effects of GLP-1, right? So, that's an interesting trial that we're now thinking of of uh doing. How would you describe the the FMD established safety profile? And in particular, maybe we can go back to the earlier part of our conversation, how would you looking at the total body of evidence, how would you compare that to something like the the growth hormone secretagogues? Uh come on, you cannot ask me that that question, right? It's another another category, right? Uh yeah, I mean, you know, we the FMD has now been done by probably over a million people. Um and um very little great Some people did have great three, great four uh side effects, temporary, and then they're back and uh 47 clinical trials, you know, I would say out of the 47 like 43 positive. Most of them uh done not by the company or any or even right? Done by Stanford decided to do a Crohn's study and and Miami did the I'm not even the paper of the University of Miami uh paper. Um yeah, so that's that's very good, right? It's not the company, you know, finding some group that is willing to show what they want, but it's more like Stanford said, "This looks very promising. I like Walter's mouse study. Let me do it." And Stanford raised two and a half million dollars to do their own trial, their own trial on Crohn's disease, right? So, they will have, you know, believe me, they would have said, "This is bad, Don't don't
"This is bad, Don't don't Look at our patients. They did terrible." But, you know, the the data spectacular. So, that's what I think people want to look at. You know, look at the those that are doing trials, but look at those the trials done by independent university that you know, they have no influence on this, you know, so I wasn't a stand-for - paper, but I was like one of the 30 authors that definitely no chance in the world for me to even, you know, affect the way they did it and I mean, I certainly helped them, you know, build the trial, but so I think that's another category, I would say, right? But but yeah, I'm I'm not saying that the secretagogues are not powerful. They're powerful, like growth hormone is powerful, right? So, don't misunderstand me. I'm not arguing with the power of it. I'm arguing with the long-term consequences and you know, the ability to get to 110 healthy. That's a completely different game and also the ability in 7 years from now avoiding kidney disease, avoiding cancer, avoiding No, it doesn't need You don't You cannot just think about 110. Say, "Oh, if you're 40, you have to think about what's what's going to happen to you when you're 49, right? Are you going to get a heart attack?" Those are the problems. In acromegalics, you know, you see the heart mass growing and and um and you know, some of the effects that the problems you see might very well be related to you know, to to the growth the pro-growth effects on on uh heart cells, yeah, I know that that seemed like an obvious answer to that question, but I just wanted people to really appreciate that. Even though you've been talking about animal studies looking at FMD, you're also very much thinking about the total evidence, the totality of evidence and triangulating data from epidemiology and randomized control trials to the 47 clinical trials and so I think it's important for people cuz sometimes it can be a false equivalence. Oh, there's an animal study here and an animal study here. Right.
here. Right. but but that's that's not the case here. The the actual overall weight of evidence for an intervention like FMD cannot even be considered in the same bucket as something like a growth hormone secretagogue. I don't think so, right? That from from all direction, right? So and absolutely, right? So epidemiological studies animal studies, but not just animal, also yeast and worms and flies, you know, understand the science behind evolutionary biology and then, you know, studies of population, right? Whether it's genetic people the genetic studies in Ecuador or is following the Okinawans or looking at the historical diet of the Okinawans and what the proportion of proteins and where they came from. Yeah, so all of that I think goes. And you know, to me the competition comes from from Claude, right? It comes from it because now, you know, AI AI is is, you know, starting to do the same thing. Hey, this is a good way to go, right? Why not? Why would you have all this data and use only the epidemiological data? This is what journalists and and, you know, and influencers have done in the past, right? You look at epidemiological data, you look only a subgroup of studies and you make a decision based on that. Now AI is saying, hey, I can go and grab everything, right? And so so I think that that's where the competition is going to come from, but okay, right? So so I think eventually AI is going to say things that are fairly similar to what we're saying, right? Because it's it's going to quickly be able to go it just now it's just too low level, right? It's not sophisticated enough to do that, but but I think eventually it's going to get trained and we're training it. We're doing our own, you know, our own apps, right? So, and in fact, you know, soon enough we'll we'll probably have a free app that that has all of this in there. And and the people can use so yeah, so I think that that's going to make life easy because, you know, we're talking
easy because, you know, we're talking about a lot of, you know, mechanistic things and and people can say, "How the hell do I put it all together, right?" So, I think the the a free app would be be a good thing for people. Also, how you prompt it somewhat determines the information it gives you back. So, you could I'm sure you can prompt it in a way where it gives you a very evidence-based, objective, rational view of growth hormone secretagogues or potentially a view that is more biased towards, you know, the information it thinks you want. Yeah, exactly, right? So, beware also because a lot of these AIs are are trying to please you. So, we test them out a little bit, right? And and they tend to try to please you, right? To understand who you are and they seem to be yeah, telling you what you want to hear. So, if you are somebody that is taking the secretagogues and and AI knows that, it's going to probably tell you it's not so bad, right? Versus if it knows I'm asking the question and it might say, "Oh, yeah, absolutely, right? This is really bad." Yeah. Coming back quickly to the longevity diet, so thinking more about the everyday maintenance style diet that that we're adopting. You mentioned before that that sugar is another nutrient outside of amino acids that that affects these these pathways and that got me thinking. I know the longevity populations like Okinawans had a high carbohydrate diet uh low animal protein. But do you think is there any merit in the idea or possibility that perhaps a high fiber low animal protein diet that has plant protein in it but is also lower in carbs, let's say like Mediterranean style level of carbs as opposed to Okinawan, might actually be
opposed to Okinawan, might actually be superior for long term? Yeah, there is evidence. And this comes from the Harvard studies, right? So the Harvard studies um you know, the nurses and and physicians studies they showed that the ideal those that had a a relatively low carb diet uh but it there was rich in animal proteins and fats uh that was the best. But I think it was around like 47% carbs, right? So it may be that the ideal diet and you know, I don't know for sure because a lot of the data comes from the 60% around 60%. Those usually do very well. But but those studies indicated that maybe if you can be if you can have a very healthy diet and you can lower it a little bit to let's say around 45 50 uh that may be the the perfect spot, right? That that could be the perfect diet, right? So it's low protein. It's mostly plant-based. It is, you know say 48% of energy coming from from carbohydrates that could be the ideal diet, yeah. And is that where most people would land if they followed a let's say traditional Mediterranean or the longevity diet, is that typically where most people would would fall? The longevity diet is about 60% but but it also it gives you guidelines to reduce starches should you start gaining weight, right? So yeah, so it might for most people end up being 50% like because most people are going to be in the I'm either gaining weight, I'm overweight or obese, right? So, it's that's like 90% of all people in the United States, right? So, you're one of the three categories. So, if one of those three, then the longevity diet will say, in fact, I tell you I do this. I I don't eat lunch, right? So, why? Because if I eat lunch, even with the FMD and even I gain weight, right? So I do breakfast, I do a snack at 5: 00, I do
breakfast, I do a snack at 5: 00, I do dinner, but I don't do lunch, right? So, but that lunch would probably have had carbohydrates, right? And, you know, let's say they used to have rice or or pasta or whatever, a sandwich. Well, that's carbohydrate. So, now I just change and that's not really good carbohydrates, starches. So, I just got a dose of of sugar, essentially, right? People That's another thing, people don't think People think demonizing sugar, but they don't demonize white rice or bread, white bread is very close to sugar, right? And even in the speed that it gets to circulation. So, yeah. So, I think that absolutely uh using starches, you have to be careful with, right? Because starches can get you in trouble because starches more than sugar Sugar is obvious. People should know, "Oh, this is full of sugar." But, most people I talked to I just had a bowl of rice and they think, "I did not just have a bowl of sugar." Well, you had spoons of sugar, right? Exactly like, you know, the the same speed blood it arriving in the blood and very close glycemic index, not close to not 100, but like 75, 80, some of them even higher, right? And uh but the bowl of rice for some reason it's with vegetable, they think uh it's somehow now pure it's now no longer sugar, right? No longer bad for you, you know. So, how does that make you feel about a bowl of pasta as an Italian? Well, I don't have bowl of pasta, right? So, but I have everyday I have about 80 g of pasta, 75 g, sorry. Pasta now is lower glycemic index and it's got some proteins and it's got some vegetable protein. So, pasta is actually a you know, if you keep it like that, it's very, you know, we have this recommendation in the lots of people that we follow in the longevity clinics of the foundation. Yeah, make them eat pasta, that's okay, right? And rice too is okay, right? You just cannot have the bowl, right? You just got to have a little bit of rice like say 80 g and then have a big bowl
like say 80 g and then have a big bowl of vegetables and legumes and and lots of things that are highly nourishing. And the tricky the interesting thing is eventually you're going to like them more than the bowl they used to eat, right? Eventually you're going to be happier with that because the taste is an explosion of taste rather than sugar because that's when you eat white rice, you're having sugar. Now you have, you know, brown rice better, but now you have arsenic, right? So, but that's another podcast. So, in order to get sort of roughly half of your calories from good sources of carbohydrate and then moderating protein, that means you do need a good amount of these healthy unsaturated fats from nuts and seeds and olive oil and those sorts of foods. Yeah, nuts, [clears throat] seed, olive oil, but also, you know, yeah, then then of course the uh the vegetables, the legumes, yeah. So, and the thing, you know, every everybody that I talk to is like of here's Walter, he's going to tell you to eat less. And I always said I always tell you eat more, right? And what I'm talking about and I had it in my book, it's big dishes, right? It's it's a lot of food, right? It's not it's the opposite, right? So, yeah, the calorie restriction comes two or three times or say two to four times a year with the FMD, but the rest of the time I'm actually telling you eat more. And And we're about to publish a study. So, I'll just tell you a little bit about it. But, one thing is extraordinary is that it's not just the volume of food, it's also the calories, right? Which is like really remarkable, right? But, that you'll have to wait until the next podcast because in this paper we show the mechanism, you know, we show why is it that, you know, you can eat more calories and lose weight, right? So, Well, I think that's a good place to land the plane here today. And you can come back and join us anytime. Well, thank you. Yeah, we really value your contribution
Yeah, we really value your contribution to science and and just helping us kind of decipher the the confusion that's out there, particularly around peptides at the moment. Yep. Great. Thank you so much. There you have it, friends. I hope you enjoyed this episode. If you did and want to stay up-to - date with future episodes, be sure to hit that subscribe button on YouTube and follow on Apple or Spotify. Finally, thank you for showing up and [music] the effort that you're making to take control of your health. I look forward to hanging out with you again in the next episode.
Transcript auto-generated by YouTube. Verbatim — duplicates intentionally preserved.
Growth hormone and IGF-1 can support development and tissue growth, but longevity science asks a different question. A body held in constant growth mode may lose some of the repair signals associated with cellular maintenance.
Dr. Valter Longo’s caution sits on a broad body of work around growth pathways, fasting, TOR, and IGF-1. Some claims around peptides move faster than human outcome data. That distinction matters.
Periods of nourishment and strength training have their place. So do periods where the body shifts toward cleanup, metabolic flexibility, and restraint. Longevity is less about amplifying one signal and more about restoring rhythm.
"The body changes when the signal is clear, repeated, and followed by recovery."
Treat peptide claims with caution, especially when they promise youth or longevity.
Separate body-composition goals from lifespan and healthspan evidence.
Prioritize food quality, resistance training, sleep, and medically guided care before experimental shortcuts.
The strongest idea running through this conversation is restraint. Longevity is not built by chasing every new lever. It is built by understanding which signals matter, applying them deliberately, and allowing the body enough calm to adapt.
