Protein, Fasting, Cancer, and Longevity - with Valter Longo, PhD | The Proof Podcast EP 237

I think that there is nothing wrong with having proteins and of course building muscle but the amount that you need to get there is much lower than what people think don't forget though acute versus 110 healthy right two different worlds I can inject you insulin and I can show you lots of benefits and I can publish a thousand papers it doesn't remove the insulin resistance later on and the diabetes that you're gonna get eventually so our job is to make people live to 110. somebody's job is to prepare somebody for the Olympics that's a different job welcome to the proof podcast a space for science-based conversation exploring the Health and Longevity benefits that come with mastering nutrition physical exercise mindfulness recovery sleep and alignment facts nuance and trustworthy recommendations minus the hyperbole Dr Longo welcome to the show it's uh great to be able to connect again thanks for having me been very excited to get you back on we were just chatting I believe it was four or five years ago that we caught up in LA and did our first episode together which was a huge hit and over the years I've had many many requests to get you back on and I know that you you've you've done a lot of research since then and uh so there's plenty to to explore and over the past month or so just to give you a bit of of context I've had a bunch of conversations with the likes of Stuart Phillips Christopher Gardner Don Layman Sachin Panda and plenty of others and it's it's become clear to me that while there's a great deal of agreement on certain areas of nutrition Health span and Longevity there's also some specific areas where folks within the scientific Community have formed slightly different positions and I think one notable area in this conversation is is protein and specific amino acids and and whether or not higher intakes which seem to be beneficial at least on paper for certain outcomes like strength and Bone mineral density whether at this high protein intake is deleterious or not when it comes to the development of diseases such as cancer and cardiovascular disease and uh and our lifespan things that you talk about a lot so this is really what I want to focus this episode on with you today zooming in on things like igf-1 and mtor kind of buzzwords that I feel a lot of people are talking about but I'm not sure if everyone fully appreciates what they mean protein soils protein amount cancer and then if we get time some of your research looking at fasting as a sort of adjunct therapy during immunotherapy for people with certain forms of cancer why don't we kind of start here with your sort of very high level position on on nutrition protein disease and and Longevity and sort of where you've landed uh based based on all of your research that you've done over decades now yeah so um I I wrote an article recently with Rosalind Anderson of University of Wisconsin uh in cell for the journal scientific journal cell and those that are you know technically oriented let's say you can get a copy it's free you can just download it and and and it's the title is about nutrition for longevity so uh what are what are all the the complexities uh for someone to make it to um you know 100 or 110 but more so what are the complexity to make it there healthy and and relatively strong right so uh what emerges is a fairly uh complex um type of nutrition that um that um has uh you know of course intervenes and on the igf-1 and the growth factors and all of that but also is done in a way that um does not lead to Frailty uh it does not require for example calorie restriction color restriction refers to is famous very old intervention very simple which is what happens if you take a person um and you reduce the calories by 25 then you don't change the dietary composition um and what happens at least in the monkeys and the uh the monkeys do extremely well and um and they have very low cholesterol very low blood pressure etc etc but then the monkeys are pushed to a limit and you can argue over the limit and um and they look very frail so they're very thin the muscle mass is very low they could be not necessarily the muscle strength could be relatively good but uh they're pushed to the edge and so and then the monkeys don't leave them as as long as you would think right so yes they have all these incredible markers or levels of these markers but then they just live a little bit longer than those that had a you know the exactly same diet about 25 more calories um yeah so then then I think that uh if you look at everything you come up with you know pescatarian um diet nutrition um up to say age between age 20 and 65 I think that should change between 0 and 20. um I wrote a book in Italy which hopefully soon will be translated into English um and so the probably the Mediterranean diet seems to be best for the 0-20 and the 72 you know maybe 90 range but in between 20 to 70 let's say that what we what I call the longevity diet I think it's a a better choice and it's uh you know a pescatarian diet low protein High nourishment High you know moderate levels of unsaturated fats the olive oil the the the the um nuts Etc and um um and then you know whole grains um and um you know and completely uh avoiding Meats uh red meat and white meat now you know some people might seem think of this as extreme uh but in fact as you know I talk about Five Pillars so I don't not too much of this is my opinion right I mean of course I put it together that's my job and we do the research that it's missing but if you put it together so if you think about basic research like how do you make a mouse live longer if you think about well what happens if you put two groups of people clinical randomized clinical trials uh if you you know have diet and a A or Diet versus Diet B then what happens um in in epidemiology what if you look at millions and millions of people um and eating different patterns now to a lot of people the epidemiology is the only pillar right and that's where I think a lot of these controversy comes in right so a lot of my colleagues unfortunately and I mean not all of my colleagues but certainly a lot of my colleagues a lot of colleagues in the food World they rely heavily heavily on epidemiology and I've done a number of epidemiological studies myself and I can tell you that in epidemiology it's incredible pillar but it's also you can get a lot of answers right you can get anything in the opposite based on how you select the population that you you choose to compare um yeah then then also the centenarians you know what about sentence what are people that that have made it to 100 or 110 or 115 you know what is there something that uh is there a common denominator between all of these that that we feel uh it's hard to argue with and that's what we we've been focusing on okay you mentioned there that you've you've kind of got this framework where the the amount of protein that might be sort of you know say optimal for someone at different stages of their life may vary and you spoke about kind of low protein in adulthood up to 65 70. I know you wrote a paper on this with Morgan Levine which I I want to come to I have some questions um and then once you get to 6570 there might be some benefit in slightly increasing that protein I'm based on my understanding and reading of your work and hearing you speak much of that comes back to or seems to these sort of growth Pathways of of mtor and igf-1 particularly this idea of sort of through through at least the the midlife having a low protein consumption and if if someone's hearing this for the first time these keywords of mtor and igf-1 and let's say you meet someone at a dinner party of alter and they say Dr Longo you're speaking another language um slow down what what are these abbreviations actually mean and and for the the sort of layperson out there you know where are these Pathways found in the body and why are they important what is their purpose yeah so igf-1 refers to insulin like growth factor one and so not surprisingly is the main um factor in the blood making us grow right so we follow these little people in Ecuador and they have extremely low igf-1 and there are about three feet tall usually right so they're they're born with this growth hormone receptor deficiency in in the result of that so grotomon basically regulates the levels of insulin like growth factor one so if you have a logarithm receptor you have low igf one and the other one that you mentioned is store Target of rapamycin and so this is a x Downstream but also somewhat parallel to igf-1 um in sotor is also at the center of growth and and this is how we identify the tour assistant pathway over 20 years ago its role in aging because we saw that when we mutated very simple organisms the ones that lived the longest were dwarf it was they became much smaller but they we could make at least you know three five fold longer than the regular ones and so and that was a mutation in the Taurus his canes pathway meaning we inactivated Tauruses can A's and all of a sudden this little microorganisms they could live a lot longer so yeah that's a targeted robomycin robomycin then now surprisingly is a drug that uh and that I've been demonstrated to extend the lifespan of mice uh and in a way that uh I think most people will say it's more is superior than anything else we've seen um in history right so um there seems like blocking rapamycin especially if you started in middle age uh works better than anything we've ever seen um yeah so that those are Thor and agf one and um and so we and many many other in fact I almost 10 years ago I organized a conference where we brought all the top geneticists and experts in in biology of aging from all over the world and we asked a question what is the best Target for to extend human lifespan Health span and the consensus was the growth hormone igf-1 uh was the very top this is the one that got most votes it didn't the didn't get everybody's fault but certainly get most votes and in that paper we wrote a paper about that and then in the paper we actually put the votes you know we we wrote down who was president all the president were authors of the paper and uh and then yeah so then I think that the yeah not the consensus but certainly the most votes go to growth hormone receptor igf-1 are these Pathways in all tissues of the body or that are they only found in in certain cells like muscle cells or where you find sort of mtor and these kind of growth Pathways throughout old tissues the door is uh um everywhere and and so is I would say the igf-1 is in the great majority of cells um probably not all of them but let's say the great majority uh now they uh in different cells and different tissues they can have very very different effects right so some some cells in some moments have the job of making glucose you know like liver and some cells have the job at the same time of using glucose right so you can imagine now the brain cell and a liver cell during a starvation period uh would do something very very different yeah one is trying to deal with fasting and one is trying to do its job of functioning normal as normal as possible right so yeah but then just to tell you this this genes and and proteins are everywhere but they can have quite different jobs depending on the state and I mean I I feel like there's a some kind of General fear out there around these Pathways but from from my understanding and and reading your work and others is that these are very very important and they're critical but are we talking about sort of when they become hyperactive uh overactive that we see deleterious effects in physiology yes I think a good example is insulin right so if you think about 50 years ago and you think of insulin and you think of insulin as a very very positive um hormone and then but then it took a while right to realize that uh if you had too much insulin all the time then you become insulin resistant and um and then you have diabetes right so it's the same or similar with these growth factors uh that um they um you have to have the right amount and um and there is probably um you know at some point in some tissues we might develop resistance to these growth factors but you also might develop hyperactivity of these factors leading to all kinds of problems and so um in cancer certainly lots of epidemiological studies and our own studies and mouse studies and so there's a lot of different type of studies including the genetics one suggesting there is a a title linked between the levels of igf-1 and cancer but also the levels of igf-1 and lots of other problems so meaning that if you have a lot of it all the time um you're probably not going to do very well and not surprisingly people that have acromegaly so they're born with very high levels of agf1 they have a short lifespan um and they die fairly early from all kinds of problems I want to come back to a couple of of things there but just to kind of continue to kind of frame um everything that we're discussing here if someone's thinking well what causes igf-1 to get elevated my understanding is that it's it's uh the pituitary pituitary gland produces growth hormone which then stimulates the liver to reduce igf-1 or a lot of it anyway is that where most of igf-1 comes from in our body or is is it also influenced by you know hormones that are in our food no no most of the igf-1 comes from from the liver and uh um and the circulating now igf-1 lots of cells in the body can respond to growth hormone or even with aggro thermal and generate igf-1 but this circulating igf-1 the the great majority comes from the liver in response to growth hormone from the pituitary making it to the liver and cause in its release and so what influences how much growth hormone we produce well proteins are not surprisingly are the influence number one so if you take a group of people as has it been done it has been done if you say if you take a group of people and you put them on a low protein diet for long enough um you're gonna see the the igf-1 uh in response to different Cycles or cycling of growth hormone um you're gonna see a geophone go down down and um and also if you do fasting like in our clinical trials um many clinical trials now if you do fasting by day three or four fasting you'll see igf one go down and I think that it was [Music] um the uh there was a study where they did that and then they just fed proteins and that was enough to bring the igf-1 back up yeah the igf-1 levels are typically lower in people following sort of plant-based dietary patterns like pescetarian diets and vegetarian diets right uh not necessarily um the um there have been studies I mean lots of vegetarians and even vegans uh they know that at least the the ones that are are worried about their health they know that the levels of certain amino acids and proteins are low um in the in their diet and so they overeat they overeat proteins and so um the um a lot of the vegans and vegetarians have normal igf-1 because they have so much protein now that doesn't mean all of them some of them are probably very much igf-1 deficient but in studies that have been carried out um the the vegans had the Nara statistically significant difference in agf1 compared to the controls unless they also were protein restricted because you know being aware of the problems with proteins they I think they were over 20 percent of their calories came from proteins yeah which which brings me to you mentioned before sort of chronic elevations being a problem so how do we kind of differentiate between acute changes in igf-1 say after you do resistance training or have a one high protein meal versus chronic elevations and I guess if we were to think about this with a different biomarker perhaps we could think about blood pressure if you do a workout your blood pressure will can go up acutely if we were just to look at that in isolation we might say that exercise might not be that great for our cardiovascular health but we know long term it has a different effect on blood pressure or typically does how do we how do we kind of think about that here with igf-1 yes well first of all in the studies that looked at muscle synthesis the um the protein level needed to optimize it was not that high right it was around 30 35 grams from where I remember and um you know this was per meal so you could argue that if you win twice as much and you did you did two workouts with two meals you could get to 60. but that those studies and it wasn't just one suggested that 60 grams let's say of good quality proteins having the the right amino acid profile uh uh I mean that study suggested 30 grams but let's say even go twice as much uh there will still be fairly low protein level right for for most people and um so yeah so I I think that um that there is nothing wrong with having proteins and and of course building muscle but um the the amount that you need to to get there is much lower than what people think and um and so our recommendation we have two Foundation clinics one in Los Angeles and One Milan and our recommendation is to say establish what type of muscle mass and get somebody to measure it what muscle mass are you happy with and then um you know go down in process until you actually start losing that right so uh go to the I mean don't go below let's say 0.7 grams per kilogram of body weight per day but you know as long as you stay above 0.7 and your muscle is fine then you're good to go you know and you could also argue that you're now you know igf-1 and Insulin actually are very similar a very similar receptors right so you could like it's possible it's not very well established but it's possible that you could be doing the opposite you could be maintaining the igf-1 receptor more sensitive right by keeping it lower like you keep your insulin receptor more sensitive by keeping insulin all the time and then you know of course insulin goes up with a meal and now the insulin receptors are very sensitive and that's what you want right um you want to have low levels of insulin but then spike it have insulin do its job and then get out of the way and so probably although this is by by uh far from being established for igf-1 but probably you have the same you can have the same uh argument for for igf-1 okay I have a bunch of questions um and I think you're right I think that there are a lot of people in the plant-based community that are aware of differences in amino acid sort of ratios in plant foods and then um finding specific ways to kind of make up for that and I'll tell you I think in the certainly in the sort of muscle hypertrophy strength Community there's a lot of talk of of research that shows sort of optimal protein intake for hypertrophy being at 1.6 grams per kilogram and that's a threshold Volta that everyone is kind of referencing out there um including a lot of professors and and science folks yeah okay don't forget uh acute versus 110 healthy right two different worlds I I can inject you insulin and I can show you lots of benefits and I can publish a thousand papers it doesn't remove the insulin resistance later on and the diabetes that you're gonna get eventually right so our job is to make people live to 110 you know somebody's job is to prepare somebody for the Olympics uh that's a different job right so we we might be talking about two different goals here and that was kind of my question um with regards to let's let's take me for example um I only eat plant protein that's where I get all of my protein comes from plants and I want to come to your paper with Morgan Levine um because I know in there you looked at this the the effect on cancer incidents um you went a level deeper and looked at a protein Source animal versus plant and you saw some interesting things in there but let's let's take me for example um you know I'm wondering can I have my cake and eat it too here so I'm I'm getting all of my protein from Plants but I would be consuming above the the RDA right and so and I also fall into that kind of mid-life bracket that you're talking about where low protein you recommend um do you think for me someone who is metabolically healthy consuming all protein from plant sources that consuming above the kind of RDA is is going to have some sort of long-term deleterious effect on my health the data uh suggests yes right so so um for cancer uh when we went from animal to plant-based those that had more than 20 percent of calories coming from uh um proteins uh if it was animal based there was a 400 percent increase in the risk of developing cancer and if it was more plant-based it was a 300 percent uh now the the effect on overall mortality went away when uh it was a plan it was we were looking at subjects that were on a more plant-based uh source so um yeah so then um they can definitely be differences but I think that um at least the data will suggest that if it doesn't really matter if it's plant-based or animal based once you get so high that the plant-based amino acid profile is equivalent to that of the animal base right so this is probably why the igf-1 in the papers that were published the igf-1 was returned to uh um to normal levels uh from the from eating more you know plant-based proteins yeah that's that's um very interesting do you think that some of the the benefits that we see in the research um where we see people consuming more plant protein is is also driven by the entire package the the differences in saturated fat and and fiber Etc yes so um the the igf-1 and lots of markers are not gonna I tore including Tor are not just going to be affected by uh by plant by proteins and amino acids probably the levels of sugar insulin and lots of older factors um coming for nutrition and maybe not just nutrition are gonna be um uh playing a role saw um yeah so then everything matters but certainly if you look at the studies the uh the proteins and the amino acids um are are playing the key role uh methylene certainly being one of them losing being another one uh so those leucins certainly seems to be associated with levels of tour and methionine and cysteine with the levels of igf-1 so not surprisingly plant-based uh brought in sources have low levels of these and and so um yeah so those are at the center of growth Pathways but everything else probably matters and we also knew this from from very basic studies in yeast where we we had the amino acids and torque signaling goes up but then if you had sugar that also that also drives towards signaling um so I mean this is a very simple system so we can tell exactly what's happening as you go to humans it's very complex uh environment it's a lot harder but but probably that that's the case too that multiple components are contributing to to uh growth signaling from a from a kind of mechanism point of view so you've you've sort of explained this Association that exists Higher igf One um higher risk of of cancer and is that because igf-1 is a growth factor is promoting the growth of pre-cancerous cells or what's happening at a kind of basic physiology level here yeah so we actually did the this experiment with with human blood believe it or not right so the little people of Ecuador have very low igf-1 and they almost never develop cancer we've seen one cancer in 50 years out of hundreds of them right and this is all over the place Europe South America Middle East and so we um and then the mice they have low igf-1 they have about 30 40 reduction in cancer they have delayed cancer a lot more benign too much so it's pretty clear right the the that this happened and and so we took the blood uh of the little people igf-1 deficient or the relative controls and then we took human epithelial cells they typed their give rise to breast cancer and then we damaged the cells with uh oxidative oxidants right so um free radicals right and so we started to induce like a cancer-like state or a pre-cancerous state and and then it was very interesting right when we added the blood there was very igf-1 deficient uh there were two two changes one we expected one we didn't think about one was much lower DNA damage right so the the blood from the little people of Ecuador igf-1 deficient um if if the human cells exposed to it were were hit with a lot of free radical toxins the DNA damage was a lot lower compared to the blood those exposed to the blood from the normal people and the other thing was uh the ability to commit suicide was higher so there's two defense levels so the you protect the DNA and uh which we expected from the work and microorganism but also we didn't expect so much apoptosis or suicide was the threshold for suicide was lower meaning that as soon as they get damaged because the igf-1 is a very very well established anti-apoptotic Factor what does it mean it means that it prevents the human cells from committing suicide right and this is why this those Pathways this apoptotic pathways are very much targeted in cancer therapy because you want the cancer cell to commit suicide so as soon as a cell becomes damaged you want that cell to get out of the way but if you have a high igf-1 the igf-1 and now there is probably 10 000 papers on this right because of cancer therapy that igf-1 blocks that and uh and then they sell as factors like called bcl2 and etc etc that are in the same Pathways as igf-1 that blocked the the the the cellular suicide programs sell that if we thought of two scenarios here let's let's think of okay I use myself as an example before so let's just use me continue using me here um protein in my diet coming from Plants but consuming above the RDA more towards the level that has been shown to kind of optimize hypertrophy which I appreciate is a very different area of science than what you're interested in here so we as you alluded to we could be talking about people with very different goals um so it can be hard to compare these directly sometimes but if we think of of two scenarios here so one is myself doing consuming that diet and not doing any form of resistance training and the other is consuming the same diet but doing resistance training breaking down muscle and I'm wondering if when you pair it with a lifestyle that has that resistance training and you get that muscle breakdown do you do you get the the leucine you know sort of activating these growth Pathways more preferentially in muscle tissue um or do we have any idea of with Tracer studies or anything like that of looking at okay after you do a workout and you have a very high leucine meal what percentage of that leucine goes to sort of increasing igf-1 and activating mtor in muscle tissue as opposed to floating around the body and potentially driving growth in pre-cancerous tissues yeah I I don't think you want to transform your audience into into biochemist um but um I I could tell you that um we we did that right so we in in a cancer clinical trial in Italy so we took a lot of women they weren't on hormone therapy and um uh cancer therapy and um and then uh we put them on a fasting um uh fasting mimicking diet together with the therapy uh but then because we were worried this fasting mimicking that is five days of fasting like let's say nutrition happened every month or so right so we were worried about uh muscle loss of muscle mass and so what we did was to give him a um we give him a video where they could do muscle training and then in between we give them a Mediterranean diet I argue um because of what I was saying earlier I argued that the military there shouldn't be a Mediterranean diet should be the mile longevity diet so that we wouldn't have helped the cancer cells stay alive and grow the doctors at the oncology Hospital argued that um you know they they didn't like it's too much we're gonna give a Mediterranean diet and what happened was very interesting was the the women kept gaining muscle mass right so so of course in that case it was a bad bad idea but the training even with the fasting even with just a Mediterranean diet it was not very high in protein but sufficient produce you know let's say moderate protein intake it was not a law product but with the modern protein take the 20 minutes I think is 20 minutes a day or very very light muscle training um and they kept gaining lean body mass right so so that my point is that you don't need uh you know very much proteins um and uh um to to to get the muscle and at the same time get the the benefits um and so now our leucine is distributed uh between muscle uh and and the potential Target of cancer I mean that's an extremely complicated world that you don't want to think about that you want to think more about you know the um how do I I how do I keep my protein intake and protein profile vegan and low vegan enough right because then everybody's going to be vegan but let's say and this is why I preach pescetarian diet right but so how do I keep it vegan enough and low protein enough but at the same time get as much muscle as I want right these women for example they probably didn't even want and that was my argument with the oncologists like they didn't want to gain muscle mass they wanted to stay the same right so there was no reason to uh to give them one point between 1.2 and 1.5 grams per kilogram a day right and we could have Captain much lower and they I think they will stay steady and in that case will that be much better idea now if you are trying to gain muscle mass then yeah you could have gone to let's say a fairly plant-based uh maybe 1.2 grams I would say that there is I I seriously doubt somebody does the expense and and the experiment has already been done by the way as I mentioned earlier so I I don't think you're ever gonna see any improvements going above 1.2 no matter what right so um so I mean unless you really talking about Olympic Training and maybe there is like a very specific super protein loaded you know period that is going to help you build very quickly but um you know those the studies that I mentioned before suggest that 30 grams per per training uh period we're optimizing muscle mass muscle synthesis within your your sort of overall framework and and Longevity kind of lens how how important do you think muscle tissue is you know not just from a kind of strength and Mobility point of view but even from a metabolic Health Point of View and being such a big sort of sink for glucose um not very important um in in I mean I think it should be important but it's but it's not in the sense that if you look at most centenarians that I visited they look not so good you know with muscle whether they're okinawans or or Italians or or uh in Loma Linda California uh so I I don't think that should be the case I think that would probably be better off because of freyati so if you look at the the southern Italians for example they're very frail compared to the northern Europe they live they have record longevity but they're very frail the frailed is almost twice as high as those of the the Europe Northern Europeans so then um so then the the Frailty does not seem to interfere with longevity but it's certainly not a good thing to have because of course the quality of life is going to be a factor so I think that yeah you you probably want to uh put more emphasis not an increase in protein a lot but increasing protein a little bit and and for sure increasing uh strength uh training like we did for the for the clinical trial so that um and they could have the say the strength of the northern Europeans and the longevity of these little towns in southern Europe yeah I think I think the exercise and kind of resistance training aspect and trying to do some of that in your lifestyle is something that most people um agree on so just to summarize your position it's essentially you know move your body and try and build a good amount of muscle and strength with as as low protein as possible would that be a fair statement at least up to the age of 65 yes yeah and then um and I think that may even help again keeping the igf-1 receptors sensitized so that when you do have the proteins everything is working very well everything is everything is getting built correctly um yeah so they may make in the long run in the short run not maybe two grams or kilograms of protein make things easier but in the long run I think that the sensitization is going to make things a lot easier maybe this is why these women they probably always had the 30 law you know protein intake they were gaining muscle mass very easily just doing 20 minutes a day of exercise right okay I I hear what you're saying so potentially if you're doing a high protein diet to absolutely optimize say muscle protein synthesis and hypertrophy today there there could be a trade-off with regards to what your health span is going to look at um so I I understand what you're saying there can you come back to that paper that you did that found the the kind of low protein midlife and and high protein later in in life um if someone hasn't heard you talk about that can you just quickly summarize that and then I have a question about the sort of over 65 year olds yes that paper um we we basically first look at everybody and say you know what happens to people that have a high protein versus people that have a low protein diet and then uh and and if you look at the entire lifespan you see absolutely nothing it looks like it doesn't matter and then if you break it down 65 and younger 65 and older then you see a big effect right so the 65 and younger are if they have a low protein diet they have a big big reduction in the risk of developing of dying of cancer and also a big reduction in the risk of dying of any cause uh but then as as we were the database went to the 70 80 90 year olds that turned around and this is probably when you look why when you look at everybody you don't see anything meaning that the 80 year old report in a low protein intake wasn't doing so well at all and um so and now that group probably included people that were sick and frail and lots of problems so it doesn't necessarily mean that an 80 year old could not have a relatively low approach anything if this person was exercising and was doing training Etc et cetera but I say overall in the United States the people that were interviewed they were not doing very well if they said I have a very low protein diet if they were 80 years old yeah um yeah so then um the uh then we also did this in mice and so we we took a mouse that was young and we put on a very low protein diet and uh and nothing happened um and this was like a four percent protein diet I mean it was extremely low and after I forgot think at least 10 days but nothing happened um and then we did the same with all Mouse and and that almost did not like this very low protein diet at all and within 10 days I already lost a lot of its uh weight and and yeah so it was probably telling us that and also from the the database we knew igf-1 levels when we looked at the younger people those had the high protein diet had a high igf-1 about 200 and 50 or something like that then the people that had moderate protein intake at the in between igf-1 level and those had the low protein intake had an igf-1 level that was you know around 200 or less than 200. um but when we look at the 66 and above group there was no longer any significant difference between the agf1 level that means that the igf-1 level after a 66 years of age was already law to begin with and probably having a low protein diet and driving it even lower is not going to help you it's probably only going to contribute to Frailty um and yeah so that's probably that's part of the explanation of what we see but um yeah and just quickly you mentioned so low protein moderate protein high protein those are kind of relative terms but low protein was around the RDA 0.8 grams per kilo no in this case it was calories it was less than 10 percent of calories coming from proteins uh moderate was between 10 and 20 and high was above 20. so somebody out as I said 2500 calories a day then people that had more than 500 calories coming from proteins they were in the high protein group I think you may have just answered something that I had some difficulty reconciling from this paper um what I what I think I'm hearing from you is that as you get over the age of 65 protein may have less of an effect on igf-1 and because I I had sort of read your paper and spoken to people and one thing that I was left thinking was if protein increases igf-1 and elevated igf-1 increases the risk of cancer then why would protein all of a sudden be a good thing after the age of 65 given that age is one of the primary risk factors of cancer so I I think you may have answered that but um I'd be interested to to kind of hear you elaborate on that yes so this was shot right so we showed that hf1 is not significantly increase uh even between the high protein and the low protein group so not just between the moderate and over there over the age of 65 it did not the the high protein in the high protein intake group and the low protein group did not have a significantly different level of igf-1 um but of course now I had more nourishment and and of course uh um with the high protein probably also comes uh lots of older um nutrients so so the story is probably a little bit more complicated and I think the argument could be that you can still be fairly low protein but sufficient fairly low but sufficient protein in the uh at older age and and there may be even an advantage then uh but maybe not a big Advantage as it was if as if as it was before so yeah the argument could be that if you kept at the motor and that's what we saw right the moderate we're already doing as well as the high right so there was no difference between moderate and high so it was it was enough to be in the modern approach and intake range between 10 and 20 of your calories coming from protein to get all the benefits so then that's why we concluded low product and up to age 65 and then moderate after if if someone's listening and thinking I'd be interested in going and getting my igf uh one levels tested is there an accurate test that someone can do basic blood tests do we have kind of reference values that would indicate if someone has a healthy igf-1 level if their igf one level is raised and putting them at risk of cancer and is it something that you would measure in the fasted State presumably away from meals yeah so now lots of clinics almost every clinic in the world can run on igf-1 test uh we publish a meta-analysis recently looking at um you know and basically saying we think igf-1 level should be used as predictors of of lots of problems or or um also which could also be you know extreme Frailty so if you see an igf-1 of 45 something is wrong right so um either malnourishment or um or this is a response to some bad problem and um yeah so then it looks like I I think we came up with uh from the meta-analysis about an igf one around 150 or so seemed to be ideal um and um and so if you look at mortality from all causes the people that kept 150 they seem to be there doing the best and um and then as you went much lower you saw problems and you so if you went much higher you saw problems but I think in the 120 to 160 180 range um that seemed to be um that those individuals seem to do very very well long term yeah I wanted to ask you about low igf one um because I had come across a few papers suggesting that low igf-1 was Associated um with greater risk of cognitive decline I saw another paper that suggested that that people with metabolic syndrome often have low igf-1 which I couldn't quite wrap my head around but um what's what's going on here why why is low igf-1 potentially a problem yeah and this is why we say you know the devil is in the details and um and so we already know very very well that um low igf1 doesn't cause the problem lower gf1 is the consequence of the problem right so the little people of Ecuador they are born with extremely low igf-1 they have extremely low idea from their entire life and they do extremely well and they get they don't get diabetes often even when any endocrinologist in the world will say there is no way this person is not going to develop diabetes so they're protected and the mice they have extremely low igf-1 the growth are more receptor and growth hormone the fission mice they they have 40 increased lifespan in fact they I think they still hold the record for lifespan extension right so so yeah so that tells us the igf one does not lower extremely low igf1 if anything is a solution um now keep in mind this is the circulating ngf1 it's not the autocrine so that the brain cells and every other stomach a gf1 when needed right and so that seems like to be the ideal um the ideal uh situation and um yeah so um so I think it's um it's good to keep a very low igf1 but if you see low igf1 in somebody that um you know goes to the doctor and gets the tested that tells you there's a problem out there and this is why the metabolic syndrome the and people there um this Association that you were talking about is that um the body can protect itself and that's probably what it is although I don't know there is enough studies on it but the body might you know because igf-1 contributes to insulin resistance um maybe the body in response to metabolic syndrome reduces igf-1 to try to solve its own problem right so it may be and same thing with cancer um you know igf-1 can contribute to the survival of cancer cells and maybe the body and there were some papers suggesting low igf funny in in cancer models and um and so this could be a a response to try to uh to not help the cancer survive um yeah so the clearly and that's what we argue in the in that paper that lawyer fund must be a consequence and not a cause of these problems can you become resistant to the effect of igf-1 yeah there was a number of papers showing igf-1 resistance um and um in uh I think they were mostly neurobiology papers um but um probably many different issues can become my geophone resistant and uh so that's an understudied you know we always wanted to study that we never quite got around to to doing it but I think it's a very very interesting you know so for example the muscle cells uh become igf one resistant and that's a good question I don't know if anybody's ever carefully looked at that yeah well my my head my kind of brain was immediately you mentioned before you know insulin um another hormone and um you know as as someone progressively becomes more insulin resistant the the pancreas can start to get overworked right and and it can end up producing less and less insulin so I was um you know just thinking that more potentially the the pituitary gland could become overworked if someone is developing igf or resistance to igf-1 um which then could see levels go down but that was just a hypothesis that's possible yeah that's possible usually the endocrine system works like that but it doesn't mean in this case that you're going to have have the same effects as you see in the pancreas sure the other the other sort of interesting um area of science that I think muddies the waters here at least for me is the mendelian randomization studies and I was reading a 2020 paper by Larson which looked at 400 plus genetic mutations which affect igf-1 levels in humans and um I believe they did find an association between Higher igf One levels and colorectal cancer but it was quite inconsistent evidence for for breast and prostate Cancers and um not much evidence for for other cancers what do you kind of make of the genetic evidence that we have looking at different polymorphisms and that affect igf-1 and and rates of cancer yes uh I think that I I teach my students in my longevity classes not to pay attention too much attention to any single study um and uh and also to have limited weight on any one discipline as I mentioned earlier um you have to put it all together right so um as uh as you put it all together nah not every study gonna confirm um you know so somebody there could have could be genetically um uh you know predisposed to have high igf-1 might very well have also the uh develop uh with the years a second mutation um that blocks uh that negative effect I'll give you an example these these people in in southern Italy are condemned to get Alzheimer's and um and so they get Alzheimer's in their 40s and they have a mutation in nicastrin it's called and it just condemns them to get Alzheimer uh then there is some families they have probably developed a psycho mutation that makes the first mutation in not irrelevant but no longer so they can now live to let's say 90 or 100. um yeah so then um you know if it's genetic igf-1 regulation then through the thousands of years or or you know or tens of thousands of years um this sort of if the first igf-1 let's say mutation calls very high cancer rates um it's possible that you develop eventually you select for a second um mutation or allele that blocks the first so that all the families now they will have both right they have a good and very bad one and a very good one to counterbalance each other now it's just speculation but I'm just saying give you an uh a scientific example of why you need the multi-pillar system and if you look at multiplayer system then you know the Aging research the cancer research the epidemiological studies the ones that I just mentioned either password is a little people with no igf-1 or the mice we know igf1 have record longevity and now this has been shown by 20 Labs right including mine and and um yeah so if you put it all together if it was a courtroom um I think the jury will say there is no Reasonable Doubt uh that does not mean that everybody with higher hf1 is going to get cancer um but it just means that you probably don't want to have high agf1 all the time and uh and you want to try to stay in that domain where Frailty is low and prolongevity is very high and that takes some work you know and um and that's why you know we have clinics um implementing the area non-profit clinic by the way I want to talk about your kind of overall framework and how it works in terms of longevity diet and fmd just quickly to tie off so that blood test you recommended 150 I think is that's nanograms per milliliter ml yeah I think it's nanogram per milliliter uh and it would that be a test that you you would do in the fasting State like fasting blood glucose I think yeah I think they're always done in in fasting because there is just a regular blood draw and then they also look at gf1 igf-1 is not as uh as pulsatile as growth hormone so it's usually pretty steady um they all go down eventually as you stop eating but but not in the morning after the I mean not in the night fast okay I want to talk a little bit about your research looking at fasting and cancer as a sort of adjunct therapy to immunotherapy um before we slide into that you've mentioned longevity diet a few times I think people will be well aware um you're quite well known for the fasting mimicking diet just at a kind of high level framework for for the average person out there how how does this look is this the longevity style diet you're eating um on a daily basis and for the for the many reasons that we've already discussed along with resistance training and and a lifestyle that helps you reduce Frailty you're doing that daily and then periodically you're doing a fasting mimicking diet depending on where your health is at yes so um so for for 30 years now since my days we Walford um I'll be looking for the the substitution for the character section which I mentioned earlier right so and then I think it took me 20 years and then about 10 years ago or maybe a little bit or earlier looking at cancer patients but also in general um I we started asking the question what if you just instead of being restricted all the time and be miserable all the time what if you just most of the times eat normally whatever you can do whether it's a longevity diet or whatever you know not not so good diet you may do and then you just intervene for let's say four or five days um you know it could be once every six months so all the way to once a month right for five days and uh so now you know going forward 10 15 years um it seems to be working very well so that uh um that you know for example if you think about I'll just give an example in mice we took mice and we did a sort of a little bit of a crazy experiment so what if you just give them high calorie high fat and you know just the worst diet that you can think of and then uh once a month you give them five days of the fmd and then you give put them back in this terrible diet it's just remarkable the if just five days a month of the fasting mimicking diet is able to reverse all the problematic effects of of this high fat high calorie diet so the cardiovascular disease or conditions the um the weight the um lifespan right so people on the west mice and the west and I lived a lot shorter and very sick cholesterol super high and you know they they look very much like the the human reflected very much their human profile and they justify this amount completely reversed now this is not to say you know keep a bad diet and then do five days a month but um that's how powerful that those five days could be and now it gets tricky right because then some people say well if five days is so powerful but when I do 30 days right why don't I keep going well the body has a way to then eventually switch you to what's called a Thrifty mode right so so you just got to get it right uh and and in-depth study we've shown that the mice and as we've seen for the people in the clinical trial they seem to if anything accelerate or continue fat catabolism so they keep breaking fat even after you return them to the bad diet right and um but what you don't want is the opposite eventually the body enters in this uh saving mode because it detects a very rough environment and so then it goes into hyper metabolic mode and this is actually an old New England Journal medicine paper if you push enough the too much color restriction the body goes into a saving mode and now you're burning less fat and less energy so your energy expenditure is reduced now you got a problem because now the body you're gonna you the system is Gonna Wanna regain the weight and maybe even overshoot the regain of the weight and gain more weight and then you yeah the original right so this is why we we tell people be careful because uh it the there is a lot of mechanisms and um and you need to understand them uh very well otherwise you can have a problem so what exactly is the the fasting mimicking diet it's five days of less calories specific Foods what what does it look like well the the festival Mickey died um is actually looking at um which ingredient as I mentioned earlier affects igf-1 which ingredients affects glucose level insulin levels and which ingredient makes the the person um happier and and so Society is uh um is high and and the hormones that the control are left and ghrelin Etc are in the right place so so it's a essentially it's a high plant-based fats um low protein very low protein very low sugar low calorie diet is and and we have all kinds right for cancer patient is about 600 calories a day for not for normal people it's about 1100 calories a day a day one and then goes down to 800 calories a day two three four five and the idea is to if you measure igf-1 igfbb1 glucose k Edom bodies they should be very similar to those that you will obtain if you were just doing water only fasting usually from lots of work in mice and humans it's about one so four uh five days of the fmd are equivalent to maybe four days of our water only fast but you know the water only fast uh obviously it's uh it's extremely difficult to do but it's also fairly dangerous you know and uh um you know because of hypotension hypoglycemia and lots of other problems so people could do it but I would not do it outside of a specialized Clinic is someone's wanting to do fmd where's the best place for them to go to to learn more about that I cannot say it because uh I'm the founder of a company that this that does that and um I could donate everything to charity or to research uh but uh yeah so I think that uh unfortunately I cannot talk about I cannot talk about companies uh yeah right um but you can you can get a copy of your book and you can Google it and and probably find it pretty easy um in terms of of like how often someone would do uh fmd I've heard you speak before is that going to depend on where someone's health is at say for example someone who has really good metabolic health is healthy body weight very active versus someone who has Type 2 diabetes uncontrolled blood glucose for example yes so now we're very happy that we we um in the sense that our collaborators let's say have done lots of studies now on Diabetes pre-diabetes and um and so uh it works very well for pre-diabetes and diabetes and our new study came out of University of Heidelberg where they did once a month both Universal weidelberg Universal Laden uh in Germany and Holland did the studies and diabetes diabetic patients both worked extremely well and these were monthly cycles of the fmd right so um but at the end even in the 12 month long study um not most people or a lot of people did not do it every month so they skipped some Cycles but it still was very effective let's say if they did between six and 12 times and year one so yeah so if you're a diabetic probably starting once every month or once every two months is gonna be the way to go with the hope that so for example we just at the clinic in Milan we treated a doctor and he had diabetes and um and so on year one I mean we did a combination of the longevity diet and the fasting making diet he did it maybe five times in the first year and a half and then you know two years later it was diabetes free right so now maybe there's a couple times a year once is um back in the normal state so yeah so then I think that's uh that's how you want to think of it you do it when you need to do it a diabetic person maybe once every month every two months somebody's pre-diabetic maybe every three months um and uh and then somebody's an athlete and extremely healthy and very insulin sensitive etc etc uh maybe you know a couple times a year now keep in mind that um we um in mice we clearly shown this regenerative stem cell based regenerative power of the fasting making diet what does it mean that now whether it was the pancreas the gut the the nervous system uh you know lots of different systems weak the blood system the hematobated stem cells the faster you're making diet cause the turning on of uh stem cells and then during the refeeding period these stem cells went to work and contributed to the Regeneration of various systems now in people it's harder to prove it so we're starting to to to have evidence for that but uh but it's going to take a while so yeah so then I'm just trying to go away from the diabetes and into you know processes that everybody will want um yeah if this is also true in people now this fasting making diet refeeding Cycles can gen can introduce a multi-system regenerative uh effects that um that could could make a big difference in in lots of organs how much do you uh feel or do you have a sense of of how much of this kind of regenerate regeneration and Improvement in certain metabolic um or biomarkers of metabolic health when doing fmd are driven by calorie restriction and weight loss versus the kind of specific foods and nutrients that are within that diet um I mean obviously you can get lots of the effects of um of the fmd with water only fasting um we do have papers where we show that for example the Prebiotic content of the fasting making diet was very important in the in the effects in the inflammatory bowel disease in the mouse model so so I think it's it's bought but um the um the weight loss in our latest human paper we're actually showing no correlation with the weight loss um meaning the weight loss happens is probably beneficial but it wasn't that people that lost most weight were benefiting the more uh on lots of markers and um and risk factors so yeah so there was no correlation with the weight loss um suggesting that that's not the weight loss is not key in this but it's more the um push in the system um to a state a metabolic switch right so if you just think about diabetes right and and the origin so we look at diabetes as a disease and and then you give people lots of drugs and um but uh if you think about 10 000 years ago um people in the summer had to become probably overweight or obese and I always talk about the emperor penguin right the emperor penguin um they become fat um because they're gonna go about two to three months with no food at all right so every year they become fat and they become insulin resistant um and so they put away the fat that allows them to survive for those two or two or three months where they have no food at all and so this is clearly our history too right so we used to have moments of lots of fruits and lots of nuts and lots of Honey um so yeah you had to become fat During the period and then well unlike that state it was probably fasting the first five days of fasting now probably if as I was saying earlier if you continue now you go from a fat accumulating more to a energy expand low energy expenditure mode right so yeah so then that's why the fasting mimicking diet and not the water only fasting you want to switch person to the insulin sensitive mode but not to the low energy expenditure mode right the the true starvation response and that's tricky and this is what we specialize in and uh yeah so so I know people like to improvise and like it but uh you know usually when you do that you get hurt and in the long run you might understand it and see it in the long run you're going to get hurt and I mean we work very hard to make sure that we try to get it all in the right place and you know we're slowly getting there yeah you see all sorts of you know um very long term 30-day 40-day water fast people doing them on online so um something to to kind of think about there but that that that last point that you made um so a protective so insulin resistance can be protective um in an environment where there is a shortage of calories and you're coming into a famine and then you're going to need to draw down on some of that fat um but then as you say if you're in a really big calorie deficit if I'm hearing you correctly your body then goes well hang on there's low food availability where um we're not getting many calories in here and storage is running out let's let's reduce the amount of energy that we're we're burning or utilizing as an organism to to kind of help preserve some of this energy as a survival kind of tactic is that right yeah and this is you know shown by the New England Journal of Medicine right so people forget these papers like that I'm not it's entertaining like somebody was saying every 30 or 40 years people like to repeat the same science but uh yeah these papers are out there and um and uh it's very clear that um that's a mistake right to to to not do it it's a mistake as 99 people don't do it so everybody in the world should do at least one or two cycles a year just to unlock that insulin resistance state of the fasting making diet and of course you don't want to do water only fasting because you know most doctors will say in most experts would say this is not something that people should do at home stop eating and also because of what I was just saying the water only fasting may drive you into the because it's not clinically tested and it may drive you in this Thrifty mode even you know in in a few days uh not clear but some of these studies are not allowed anymore right so pencil keys back in the 50s and 60s had done this semi-sterivation studies in humans and that was probably the last time in human history those will be allowed but this if you read them they're just remarkable remarkable uh studies of human volunteers they you know undergo this four weeks or more of starvation time but the the biology the physiology out of that is just incredible yeah I'm not sure that'll get ethics approval not sure putting their hand up to do that you'd have to pay them a lot of money you'd be surprised you know you'd be surprised if it was like a study done by University there'd be some uh some volunteers for anything but yeah I don't think it'll get a ethical approval I want to finish here on uh fmd as a potential adjunct therapy for someone who has cancer and I know that you you had a study that you shared with me looking at mice with with breast cancer um where you investigated the effects of of fmd so talk talk to me I guess firstly about the the interest in in fmd and cancer in the first place and what your hypothesis was or is yes um my point uh um is that we have the nobody that we've ignored in the oncology field is differential property or normal and cancer cells so I always talk about the analogy of the desert you take a billion people um you put them in the desert you give them um no water no shade and you make them run and you come back after two weeks and 100 of them will be dead and if you put them in the same desert and you uh give them water and you give them shade and they can let them sit I would say after a couple weeks they're all alive right so so yeah a billion people is a password that you could change such a few things and a billion people be either all alive or all that yeah so the same is true for for cancer or let's say in this this principle can be applied to cancer why because the cancer cells cannot stop running and so um so if you take away the food um they uh they're in trouble because they now they have less food but they're running uh but this is why now the combination with standard of care comes in right and that's uh and that's why we always say you know you have this Camp of the alternative people and the the the ones that are obeying so the FDA and the medical rules and the ones that refuse them right but in fact it's a combination about that seems to be very effective why because now if you are a Cancer cell and you're just giving fasting or fasting making diet you can still manage because you steal from from the system right you steal from all the cells so you can get the amino acids you get the sugar you just deprive the other cells from it uh this is why the the chemotherapy the immunotherapy kinase Inhibitors hormone therapy Etc they're so effective together with the fasting making that so you generate a differential uh environment right so the normal cells they know exactly what to do they've been starving for billions of years if you start from the bacterial ancestors so they know exactly what to do the um the cancer cells just do all the wrong moves right they keep on going and now they can still keep on going as long as the immunotherapy or the chemotherapy or the radiation comes around and then and then it's clear that this is why in Mouse model we see you know cancer-free survival over and over and over um if you combine the the fasting making diet with the the whatever most effective cancer treatment you have for that cancer now in people well uh the now there's lots of studies uh for the fasting making diet in in clinical trials and they look very very good so for example the 125 patient randomized trial breast cancer done in University of Laden published a couple years ago showed a um a both clinical and pathological effects so the patients that did the fasting making diet together with chemotherapy responded much better and I think there was a five-fold reduction from 27 to 5 of the non-responders so the patient the portion of patients did not respond to the chemo and another fantastic thing about the trial is that those respond if you look at pathology so the the surgeon takes the cancer from the breast and then it looks at how many cancer cells are active uh in that cancer and then they they score it and it's called Miller pain scoring and um and there's a dose response the patient that did the all the cycles of chemo with the fasting making diet were the one that by far had the the lowest um um you know score meaning that the at least active cancer cells within the uh the the two more mass right so it's very nice when you see that um that you know those response um yeah then another were studied by Claudio vernieri at the Italian Cancer Institute the National Cancer Institute actually they did two papers 100 patients and one of five patients but I really like the one on five patients because it showed I think in the time had extraordinary survival or extraordinary effects of standard of care together with the fasting machine died in five patient one had pancreatic cancer so I really like that because I liked the sort of Hope factor and saying hey you know maybe um if you run out of options uh you know the fmd in this case could make a difference it may not we don't know yet but but it could right so so talk to your oncologist and and um and ask him or her to consider the the fasting mimicking diet together with the standard of the care because in some cases in many cases of course we follow thousands of patients but I I don't like to talk about that because people then say oh yeah he's talking about a case he's trying to make a clinical trial out of case but we've seen it with many patients but the clinical trials are now are starting to to show the the effects that we've seen with with lots of stories and um and lots of hospitals are now starting to do it and I've heard from U.S Hospitals now they're saying now we do it with every patient we give them the fasting making diet so so yeah so we'll see but uh looks very promising and also very inexpensive right you know people can even somebody's poor um and can only afford to get the all chemotherapy that certainly water only fasting if that's all they got is something that could make a big difference in their treatment in these studies where they're using it alongside traditional treatment for whatever cancers the the subjects have in the study is it being done in the same manner as say for example what you've used in studies for people with type 2 diabetes is it still a five-day thing or are they doing it every day throughout their treatment or 10 days I'm presuming it's not every day because that they're being too much of a calorie deficit what's the the protocol look like no the you know it's not every day it's actually shorter it's four days it's about 600 calories for four days uh the normal people is five days higher calorie this is four days lower calorie and um yeah so this was now it's been 15 years of arguing with oncologists and and Physicians and and trying to come up with something that we're all happy with and I think you know we're close to there there meaning that as I mentioned earlier we don't see loss of lean body mass if it's done correctly there is a exclusion criteria for you know somebody comes in with too much uh Frailty or cachexia or um other um or you know muscle type degeneration um yeah so then some some people are excluded um but I'll say that the majority of maybe the great majority can be included or can be brought to a level where they can be included maybe with some muscle training Etc and and or improve nutrition and then they start the fasting mini diet so yeah so then yeah four days um combined that time with now with the immunotherapy with the chemotherapy with the radiation uh so in every case uh there is a different design um in the clinical trials we spent some time with the oncologists uh to to make sure we time everything correctly so that um you know for example in the case of immunotherapy we wanna um we want to make sure that we don't interfere with the efficacy of the immunotherapy um but at the same time get the maximum effects what's it going to take to to kind of um build on your confidence as to how effective fmd is um during cancer treatment and potentially to be say included in cancer guidelines and to have more oncologists I know you mentioned that there are plenty that are using it but to to kind of get the word out there to to more and more oncologists you know what what further research is is required yeah first of all I think the patient is number one meaning that the patient choose if the oncology said the treatment is not working I don't see it you know I don't see I don't have much uh hope I think it's good to go to oncologist say can we can we try the fasting making diet together with whatever it is that that you recommend and then of course uh like for everything you know uh it takes a long time and I'm for that's unfortunate because uh um I think I always say the science goes very fast and the FDA goes very slow and there are good reasons for the FDA to go very slow because you know they have to make sure they filter out a lot of ideas that are not uh true right so you know we covered we heard lots of stories right at the beginning of what was making patients uh healthier and then the great majority of it was not true right so yeah so then the oncologists know this and and they basically say most of the stories we heard were just stories and eventually did not make the cancer patient live longer um so yeah so I think that you know it's going to take a long time and um but you know there's a lot of Trials and uh and I think that as the success stories uh uh like the one I just mentioned come out and the papers him animals increase then I think there's going to be many many hundreds like I don't know if it's going to have the potential of immunotherapy but let's say that it did um then um you know eventually there's going to be hundreds of hospitals that are going to start doing clinical trials on immunotherapy and this is what happens so immunotherapy was first discovered in the mid 90s right it took a long time for that for the explosion probably around 10 years ago you started seeing the explosion on the clinical trials and immunotherapy and then the success stories um in various cancers right so so then from the 95 discovery of immunotherapy to the now it's what 27 years uh so 27 years to get to where immunotherapy is a central part of of cancer treatment and that's uh that's the way it is and uh you know and and part of it is because you have so many cancer and so many therapies I you have to eventually check everything with everything right so immunotherapy in in together with some other drug for the treatment of this stage of this cancer right so there really hundreds of combinations and and that's why you need hundreds and or if not thousands of studies you know what do you think about the ketogenic diet because that's another kind of diet that gets thrown out there as a possible um or possibly being beneficial for folks with cancer moving to a kind of low glucose um diet you hear people saying that glucose feeds cancer cells and I know that there's the fmd is low in kind of high glycemic carbohydrates or refined sugars so is there some overlap in the science the sort of thinking Behind These two different ways of eating yes and no um I obviously I mean the the fasting mimicking diet and cancer it's a very theoretical I mean it started with yeast and and very fundamental ideas right so so um and that's why the starvation part is the most important part of all right so you want to create a differential property in the ketogenic diet you start with the wrong food right because you're giving High calories right you give you normal calories and you know and Cancers usually many Cancers and we know this love you know the ketogenic diet and uh many cancers hate the ketogenic diet and many cancer could hate the ketogenic diet first and then start loving it because one cell is mutated and that takes over right so so I think that I'm very supportive of lots of studies and the ketogenic diet and and we're you we're now combining with the fmd and see you know for certain cancer okay we get even a better effect but but I think that in general um the uh the fmd I think it's gonna stand because of the the Extreme color restriction uh you know enough days or four or five days enough days to try to kill as many cancer cells as possible but not enough time to disrupt the normal feeding of the patient um so so yeah so there is a lot of classes um but but the ketogenic diet does allow you to eat all the time so so um so it's interesting and that's what we're testing now and I think other people are testing and I know that some of the clinical trials with the ketogenic diet also had the fasting or a fasting meaning that with it even though they they were described as ketogenic diet trials so yeah so I think that you know we need to look at it and we need to certainly find out which Cancer's love high fat and high protein um then distinguish between high protein ketogenic in low product then I would say high protein ketogenic should be out and there should be only the low protein ketogenic and and you get bought right out there in the clinical setting you get the high protein ketogenic and the low protein ketogenic so there's no reason to go high protein um I've seen no evidence whatsoever but the low protein ketogenic could be promising for certain Cancers and and that you know so one thing we're testing now is like normal diet ketogenic diet the fasting making diet you know in Cycles um and and sometimes uh yeah so then sometimes you exit the the fasting making that then you go into La low protein ketogenic diet and uh and we're getting a surprisingly mixed results right some cases is working very well in some cases not working at all and maybe even making things worse you know so so and the good thing about the fasting making that are now maybe 20 Laboratories so far we haven't seen a single negative I mean it's it's coming right it's coming I know it's coming but it's interesting right after 15 years uh we haven't seen a single negative study on the fasting uh and fasting diet in cancer uh so that's very good news right that it's going to be out there we're going to see something growing more some cancer doing worse uh for doing fasting but thus far nobody is published that so so very very um very promising at least that you know if it does make something worse it's it's fairly rare definitely Walter this has been uh extremely interesting I really appreciate you taking the time to to come back and speak with us again was there anything related to the topics that we spoke about today that you wanted to kind of add before we wrap this up that you perhaps didn't get a chance to touch on or do you think we covered it all one thing the paper we just published so we published a paper on immunotherapy and cancer last week but we also published a paper an Alzheimer's which included 30 the first 30 patients University of Perugia University of Genova and I I just wanted to say uh you know it was a mouse paper so very powerful effects of the fasting making that demise but also interesting that we did not we could get the patience the Alzheimer patient to do it for for a year and there was a Dropout but it was a very similar Dropout between the control diet and the and the fasting making diet so yeah so that's an interesting uh it's just a promise there because in humans we have no no data and cognition yet but I I thought it was very important to start thinking about in addition so so many drugs have been tested for Alzheimer's and they all failed and so now I think it's interesting to think about combining with the fasting indicted we're doing for cancer so we're just encouraging anybody that wants to do trials in the division or or anybody that wants to talk to their neurologist about uh um you know also introducing a nutritional treatment or potential treatment for Alzheimer's uh yeah I just wanted to mention that absolutely fascinating well um thanks again and and as always always uh welcome to come back on and speak with us whenever you want perhaps if you have any new studies coming out that you'd like to share with us that would be great sounds good thanks a lot thanks falter thank you for joining me for this episode and your interest in science-based conversation I hope you enjoyed it and found the information covered interesting and instructive if you did and you'd like to show your support for the show please subscribe to our YouTube channel where you can stay up to date with new 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Channel: The Proof with Simon Hill

Views: 109,332

Keywords: simon hill, science, nutrition, evidence, facts, diet, how to, vegan, plant based, healthy living, wellness, podcast, conversation, the proof, the proof podcast, plant proof, health, the proof with simon hill, fitness

Id: z4GD5cKG1sE

Length: 95min 23sec (5723 seconds)

Published: Tue Dec 06 2022

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Dr Valter Longo is the Edna M. Jones Professor of Gerontology and Biological Sciences and Director of the Longevity Institute at the USC Leonard David School of Gerontology, one of the leading centres for research on aging and age-related disease. Dr Longo is also the Director of the Longevity and Cancer Program at the IFOM Institute of Molecular Oncology in Milan, Italy. His studies focus on the fundamental mechanisms of aging in simple organisms and mice, and on how these mechanisms can be translated to humans. With extensive education and a prominent career, Dr Longo brings an incredibly interesting perspective to today’s conversation.

0:00 intro

2:58 Ideal diets for longevity

9:15 Important Pathways for aging

16:24 IGF1 Elevation

19:46 Actue vs Chronic elevation of IGF1

25:11 Danger of Protein Over Consumption

32:52 Impact of exercise on IGF1

38:35 Muscle Mass and Longevity

41:59 Study on High Protein Later in Life

48:03 How to get IGF1 tested

49:54 Low IGF1 & Cognitive Decline

53:00 Resistance to IGF1

54:38 Mendelian Randomization Studies

59:21 Fasting Mimicking Diet

1:16:03 Fasting and Cancer

1:27:51 Ketogenic Diet & Cancer

1:32:15 Outro