Fasting is often presented as a contest of discipline. Valter Longo’s work asks a quieter question: what happens when the body receives the benefits of nutrient scarcity without being pushed into chronic depletion?
This transcript is provided for reference alongside the edited article and key takeaways.
welcome to the metabolic link a podcast that explores the common thread of metabolism in health and disease this is where science meets Society welcome to the metabolic link I'm your host Dom D'Agostino today we're talking with Dr Walter Longo Dr Longo is an Edna M Jones professor of geratology and biological sciences and director of the Longevity Institute at the University of Southern California he has an extensive resume and I'm just going to mention that it talks about his experience in training in neuroscience and Longevity and Immunology and endocrinology microbiology genetics and pathology so he did some of the seminal work in calorie restriction and later did work on developing and really branding what's known as the fasting mimicking diet or fmd so he's shown that these diets can increase stem cell production and enhance longevity and uh in 2018 one uh interesting aspect is that he was time magazines one of the most 50 influential people in healthcare for his research on fasting mimicking diets and as a means to improve Health and Longevity we cover a lot of topics and a lot of ground in this area and we talk about various aspects of fasting and protein metabolism as a means to increase longevity and and aspects of performance so I'm excited to share this content with you and I hope you share it with others thank you so thank you again for agreeing to do this interview Dr Longo and we were super excited and honored to have you as one of our first keynote speakers at the metabolic Health Summit when it was hosted at University of South Florida College of Medicine years ago I think that was 2016 or 17. yeah it was a great conference yeah
yeah it was a great conference yeah thank you yeah I mean we were super excited to have you I've been following your research for for a long time and keeping up on everything and it's to tell you the truth it's hard to keep up on everything that you're doing now we know you're super busy I looked on PubMed and I also looked on clinicaltrials. gov and I think I mean you have really you are the epitome of moving the science into human application with and you are studying I mean just a brief overview and I encourage people to go to PubMed and pull your articles and also go to clinicaltrials. gov and see the amazing work that you are you've collaborated with so many people across the globe you're studying aging diabetes cancer cardiovascular disease uh immune function Ms uh irritable bowel syndrome depression PCOS uh skeletal muscle function uh looking at randomized clinical trials on all these things so maybe if you could give our audience an overview of you know some of the recent studies that came out that you're excited it out yes so I mean one day we're very excited about is the the work that came out of Heidelberg um and and this was an interesting one it was a diabetes and diabetic nephropathy and I had almost forgotten about that until I got a uh email some time ago and they told me well we're done and it looks great you know and so these were a randomized clinical trial and uh on diabetic patients receiving a fasting mimicking diet cycles and they received six Cycles once a month of the fascinating diet and so it was great to see um first of all the reduction of drugs in in a major portion of the patients and and this was an interesting one because it was done against the Mediterranean diet right so it was five days a month of the fast mimicking diet against five days a month of of a Mediterranean diet so it was nicely
Mediterranean diet so it was nicely controlled uh uh study and um and so the Mediterranean that I didn't do anything uh but the fmd did a lot in in the reduction of A1C and so the insulin resistance and the reversal of the diabetes in in a portion of patients but in the majority of them reduction of both uh what in under of diabetes drugs but also in some reduction of hypertension drugs right so um so I I was very happy about that and now there's three or four more that are close to being published so um I was uh particularly happy about that because I you know knowing that the other ones we have published on pre-diabetes before and 100 patient randomized trial but this was the first one addressed in diabetes and now having these are a couple of uh trials that have looked at diabetes uh or pre-diabetes I was uh uh very happy to see such a strong results so that's one and then um last a couple weeks we we published uh one paper an Alzheimer's um two different Mouse model of Alzheimer and then the the preliminary data pilot data on the clinical trial that is now going on in Italy um and this was only the first 30 patients enrolled in the trial but since it's such old population we were actually a very um very happy to see that you know 80 year olds could complete uh one cycle a month of the FME for a year which we didn't actually think that we would get uh you know pretty good compliance I mean some people dropped out but uh but still the majority of people seem to be underway to be able to finish it and in the mice of course the none of course but in the mice the the cycles of the fasting making diet are worked very very well in two different Mouse models for
well in two different Mouse models for Alzheimer and uh showing reduction in the pathology but also reduction in the cognitive decline um and so um yeah there was uh there's there was a long study that took us maybe seven or eight years uh about financial finally we get it out and then um finally the the paper that we just published on immunotherapy the combination of fasting diet and immunotherapy uh we have been also been working on that for a long long time and um and so this is just mice but in mice is working very well in making non-immunogenic uh cancer uh cancers immunogenic or at least some of the non-immunogenic cancers immunogenic so um that's uh of course very promising in in at least initiating clinical trials so that we can see if uh if we get similar facts in people yeah I'm super interested in that in the cancer work and have a lot of questions about that so maybe just one question before we go on the kind of like another topic so with the fasting mimicking diet then are you seeing that implementation of the fasting mimicking diet augments the immune system in a way that makes the immune system more uh Vigilant I guess would be a term to identify cancer cells or uh to sort of augment cancer-based immune system or does it augment different therapies that are immune-based therapies that are used for cancer or both Maybe if that makes sense the uh I mean we had published on on the enhanced function of the immune system this was close to 10 years ago but here I think what we're seeing is the um is the cancer being heavily damaged by the uh by the combination of the uh well but
by the combination of the uh well but the fasting making diet um and now the immune system being made more aggressive in the case of immunotherapy um and so we're suspecting and we have a lot of data to to suspect let's say that it is the super the high level superoxide high level of free radical generation specifically in the cancer cells that is making them much more immunogenic so much more visible uh as antigens to the immune system and then the immunotherapy sort of closes the deal by now removing that self recognition um mechanism with the pd-1 pdr1 and so yeah so so we're in fact we just got some funds to do a clinical trial and colorectal cancer uh with the Dr Joseph lands at USC and and the the idea would be to do um uh immunotherapy plus fasting making diet plus vitamin C um so in in KRS mutated cancers right so we're starting to move to is there a way to get a very non-toxic or or very low toxicity treatment that is more effective than the traditional treatments yeah so that that's an interesting approach so the fasting mimicking diet would probably lower glucose and glucose availability and Insulin suppress the hormone insulin and that may create like an energetic crisis where you said you get more superoxide production more oxidative stress and then that would decrease the pentose phosphate pathway maybe that glycolysis us but with the vitamin C if you're giving an intravenous that could actually function maybe as a pro-oxidant and then you're driving like the fentanyl reaction and other things so you're is that what you're thinking like with vitamin C I know you know it's an
with vitamin C I know you know it's an antioxidant but when it's given at a high dose it could also has a pro-oxidant effect at a high dose and maybe it could be augmenting that that redox state to sort of sensitize the cells to have a cancer killing effect through a redox state is that sort of the the idea behind it yes actually we published on that a few years ago and so we with lots of caress mutated cancers which is uh a big portion of all cancers uh we saw that vitamin C this was described by Lou Cantley and others and starting back in the days from Linus polling um so like vitamin C can have a pro-oxy into the fact on cancer cells but it's uh it turns out that proximate effect is very limited and then we showed in the paper it is very limited because vitamin C causes deactivation of something called ho1 in the cancer cells in different type of cancer cells but certainly yes right hem oxygen is well yeah so he maxogenase one is actually controlling we shot in the paper ferriting so so the cancer basically protects itself against vitamin C by making more iron Scavenging uh proteins available right so now the iron that will be available as you just mentioned for Phantom chemistry is no longer available the sponges that out and that is able to have a very strong protection actually against the vitamin C with the fasting mimicking diet you take the h01 down you take the ferritin down now the free Iron becomes available again and uh and they can do tremendous damage and um so this is very interesting not so much because that happens in the not only because it happens in the cancer cells but because it doesn't happen at all in the normal cell right so the normal cells have a dual protective effect right vitamin C
dual protective effect right vitamin C anti-aging let's say but fmd anti-aging so now you have two protective effects on all normal cells by definition right because you know we've shown that fmd Cycles extend the lifespan of a mouse and uh and make people uh healthier let's say and vitamin C You could argue it could be between neutral and positive effects right so now lifelong right so people take it every day for the entire I mean Linus falling to seven grams a day and that died in the 90s right so yeah so I think that that that's a very interesting possibility to use such a simple I mean and this is I think KRS B ref the category that is sensitive it could represent maybe about a third of all cancers right so that's that's remarkable if just to think about the possibility there's such a simple uh intervention could replace chemo or even more effective uh therapies you know that that's really interesting I did not know the heme oxygenase a story I actually did my PhD on heme oxyase too the constitutive form whereas hemogenes one is the inducible form uh but I'm also aware of you know vitamin C also uses the same transporter as glucose so from my knowledge and that giving a high dose of vitamin C could function as a glucose antagonist to the transporter and that could impair glucose uh uh consumption by the cancer cells and and actually further augmenting or inducing that energetic crisis uh you know within within the cancer cells I I've always been interested in but I haven't really seen a whole lot of experimental data that really you know showed the glucose antagonist effect I have a file of papers but it's not super well uh you know I was wondering if
well uh you know I was wondering if mechanistically if you're looking at that too we haven't looked specifically uh uh but you know that would make sense if it also I mean of course during fasting and fasting making diets you're already struggling and what we see very clearly is this anti what we call anti what we name anti-warburg effect right so the the by lowering glucose the cells now and this new paper we see exactly the same thing two two triple negative breast cancers the cells now go back to the mitochondria either a bit oxidation or you know utilizing more of the mitochondrial respiration for energy and of course that's that's the problem for them right because they the mitochondria probably is impaired somehow and so trying to re-establish that you know mitochondrial function is devastating and um yeah because they've already genetically rewired to be glycolytic so now they have to it's impossible to go back you can go you can have game mutations to or maybe even epigenetic changes but it's a it certainly seems that they're not able to switch back to the previous States and therefore lots of superoxide lots of hydroxyl radical lots of DNA damage and that's why when you compare you see you know the the treatment alone very low DNA damage let's say when we do it with fmd alone not so much DNA damage then the chemotherapy alone and then you see the combination and then the uh the DNA damage goes Sky High so yeah so it it and it does so only in the cancer cells so that's uh yeah that's I think the most important part is differential stress sensitization yeah well I know you've done a lot of the work uh seminal work even on caloric restriction on the effects of caloric restriction kind of mechanistically looking at
mechanistically looking at different pathways you know uh there's there's discussion I hear people talk about you know it's all about calorie restriction so is would is a fasting mimicking diet are the benefits to fasting mimicking diet the outcomes that you're looking at uh completely dependent upon producing a calorie deficit and could you know the fasting mimicking diet could be more of an optimal way to produce that caloric deficit or are there advantages above and beyond the intermittent calorie restriction that you're given so I mean I guess it stated another way if you create I mean I understood restriction yeah so uh and I mean you work on the ketogenic diet right so that's your answer right there right so so no it doesn't have to be it does not have to be characteristic uh but calorie restriction certainly is a big component right so so I think that in the ketogenic diet I think what we see and you know I've been reviewing lots of papers in the field of cancer especially today you see it go both ways right sometimes the cancer loves the fat and the Ketone bodies and sometimes the cancer is killed by the keto bodies and um so I think that the calorie restriction or very low calorie is now making a much more difficult for the cancer to adapt because there is nothing to adapt there's just not enough amino acids not enough sugar Etc not enough growth factors to carry out that growth right so yeah so it's part um it's part color restriction but it's part also the the you know low amino acids certain amino acids and the low sugar um and uh so yeah then theoretically and we've done that right you could keep they say
you could keep they say um the calories normal you just decrease the protein level and that's enough already to slow down different type of cancer some cancers don't care at all right the same as the ketogenic diet if you lower protein some cancers grow just as fast but some cancers you completely change their growth rate uh so yeah then then we know very well that it's not just about calorie it's bought about calorie and content and that's where the fasting mimicking properties come in um so you want to have uh you know even though the fats are relatively High they're still making um making place in the cancer cells in a situation where there's just not enough to grow or if they attempt to grow they get in a worse and worse situation just because um you know eventually they're gonna run out of all the the building blocks to move forward yeah I do want to touch on the uh the protein aspect too because I mean that has been a kind of a big issue in the ketogenic diet world that the protein was too low with kids and it would stunt their growth but uh before I get into that so one of the any you you published a paper fasting mimicking diet and markers or risk factors for aging diabetes cancer and cardiovascular disease and uh so I would like to know like what are the top when it in regards to biomarkers that you track in the clinical trials uh I have kind of two questions about the the clinical trials are you controlling for calories in that when you compare between different diets you describe the fasting mimicking diet versus the Mediterranean diet and I was wondering if calories are controlled for uh on the two or a factor and looking at the outcomes and then like in your opinion what are the top five biomarkers
opinion what are the top five biomarkers to be tracking uh for those things I mean we're very much interested in uh blood pressure insulin glucose triglycerides HS hscrp those things in the trial that we're running now but uh and I know there's more than five but I just in the you know the interest of time to keep it uh kind of short so it's kind of two questions there yeah uh with the clinical trials are you kind of looking at uh calories uh you know and controlling and counting calories and the biomarkers that are most impacted by the fasting mimicin diet that are most important yeah I mean uh we're not I mean we didn't do the trial in Heidelberg so they decided to go with a normal calorie um control uh Mediterranean diet uh and there and I think that was a good idea because basically if we're already saying that severe calorification is already part of the at the effect we were not claiming that this is why the fasting making diet is very low calorie uh so so the point is that you need very low calorie but you also are enhancing that effect uh with the uh you know low protein low sugar high fat uh so that's the idea right to to have it all and the idea is also long term if you're thinking about somebody maybe doing this for 40 years or 50 years we don't want to generate an intake that is not consistent with the actual fasting response right so so you know during fasting yes you're not taking in fats but you already have the fats in and they're being released so to the body having you know fats in circulation fatty acids in circulation is perfectly normal it is a fasting response that's what it's always had during long-term
what it's always had during long-term fasting so we also been trying to think about being respectful of sort of the what people have been exposed to very regularly for tens of thousands of years right so whereas let's say that you could do uh let's high protein um fasting making diet which may and let's say it may work it may not work because now igf-1 can still be increased but let's say that it worked we will still be concerned that in the long run um now you have high protein and a lot very low calorie what happens if you do this for 100 Cycles right so yeah and there are some issues I think with with some old studies with this uh high protein fast diets that cause some some damage to patients um and so yeah so that's the type of things that that I'll be worried about and then um as far as markers um I think we were really focusing on uh how do you make somebody live longer healthy and uh so to us it's it's not about one market or the other but is you know in fact soon enough we're going to publish about biological age and um and I I hope we follow it up we have we use the the bioage model by Morgan Levine but I think we we hope to follow up now we're doing something with Steve orbert with mice and then soon enough I think we hope to move it to to the human trial we're starting a huge uh 500 patient trial in southern Italy where we're gonna do the the epigenetic clock um so yeah we're looking at everything and of course cholesterol and and you know blood pressure and fasting in A1C and all of that is in there but then again sometimes I I remember when we first published the 2017 paper people say well it didn't really reduce this or that and
it didn't really reduce this or that and and we said we shouldn't reduce this or that because most of these markers were normal right so we have shown that it didn't reduce glycemia in people that had normal glycemia it didn't reduce blood pressure and people had normal pressure and we thought it shouldn't right so so we were interested in the it was interesting the the criticism uh because um that's probably an underestimated issue which is if somebody has the normal range fasting glucose you don't necessarily want to drive it down too much because now you enter in maybe another danger zone uh that may be as bad as the hypertension yeah or even insulin and igf-1 right I mean because you push igf-1 down really low and then that can kind of cause some some problems too if people become more frail uh even blood pressure I think there was a study in 2014 right it's like if you get if you make it to over 90 you know those people the people that were better off that had better you know less mortality actually had a little bit higher trended to be higher blood pressure so if you're over 90 you know low blood pressure is a bad thing you know it's and look at it and look at us so wait now it turns out that issue maybe a little bit uh overweight uh if you're 90 you might be doing better um yeah so I think it's uh I think very important to start thinking about you know healthy longevity and how do you get there but also I uh of course what about the the short-term effects you know somebody may want to have certain performance related uh effects and I understand that so then then there's gonna be some compromise between the you know so somebody wants to have a lot of muscle and uh and it's not so worried about getting into 110 yeah then I think it's okay probably to do some changes that you might not want
do some changes that you might not want to do when somebody says no first of all I'm worried about living very long yeah yeah you know you talk to different people you hear people talk about the more muscle you have the greater strength and functionality you'll have and Longevity being associated with a higher muscle mass and strength but and that'll reduce Falls and and other than muscle is also an endocrine organ that release like myokines and other things that could be beneficial but I guess from your perspective what do you have to do and eat to maintain that muscle is also impacting organ function and things like that and uh you know the the discussion about protein always comes up in different groups especially that I'm associated with and there's like a big following with a carnivore diet uh I don't know of any centenarian carnivores I don't know maybe you do but I I think I heard you on one podcast that so many of the blue zones that except maybe like Okinawa they do eat red meat but it's like you know once once a week or something like that so yeah and yeah so I was actually I wanted to know uh you know in regards to protein I I heard your recommendations are pretty low uh in regards to you know a little bit lower than the standard I guess also what would you say to the person who's on a high protein diet not not necessarily a protein sparing modified fast that you had mentioned before because there's some problems with that but what would you say to someone who's on a higher protein carnivore like diet that is getting two grams of protein per kilogram and all their biomarkers are kind of going in the right direction I mean just for the record I'm not a fan of the carnivore diet but I get a lot of emails from people who are just eating meat and eggs and maybe some fish with that and they're just like no fiber no plants or
they're just like no fiber no plants or anything and they share their blood work and all their biomarkers but you know I look at it and say this is a calorie restriction effect you know what I mean they're eating this way and they're producing a calorie deficit and but I I don't think we know the long-term effects of that well no we do right we do and uh and they're not good you know uh meaning that at least from epidemiological studies right so um and in my book I talk about you know the need to move away from one pillar type of science so I use the clinical trials the randomized clinical trials which you could say you know the people that write to you they're doing sort of like end of one clinical trial not randomized but um yeah so that's one pillar now you got four missing right so then then you want to say well what about the centenaries you want to say what about the mice and the Flies and you know do they live longer when they eat a lot of protein and then um you want to look at epidemiological there right so what about um you know millions and millions of people that meet in a lot of protein versus low protein and and all of that and and you know in our case we also look at genetics of protein signaling right so for example the longest lived mice um in history are the ones lacking the growth hormone receptor uh and they'll and the people that we study for many years the larons uh lack the growth or more receptor they they rarely get cancer they rarely get diabetes they cognitively younger than than their chronological age yeah so I think that when you look at all the pillars um it the people that have high protein and we publish that years ago the Americans had eyebrow then had a 400 increased risk of developing cancer 75 percent increased risk of um dying early um but that was only until age 65 7 right then it turned around then the 80
right then it turned around then the 80 year old that was eating low protein reporting in Europe it wasn't doing so good at all and now when you go to the going back to your questions when you go to the zones like Sardinia lomali index Etc if you think about it what you said earlier is true for the past but it's not true for the last 30 years so the centenarians had a very poor protein diet maybe meat once a month right on average or once a week to once a month but then eventually in the last 30 years when they got to 70s and 80s they moved in with their children many times right or they moved in in nursing home let's say Loma Linda nursing home now all of a sudden they have a ton of products and maybe every day every year or a day right so so and that makes it matches very well what we saw with the epidemiological data right you do 60 70 75 years of a very poor restricted diet but sufficient yeah and uh and then you move to a much richer more variety of food more proteins yeah so that we believe that that's probably uh you know with it was talking about generalization now and everybody's different so obviously there's going to be a lot of personalization but in general there seems to be like uh it seems to be what works you know to to um block the the growth Pathways uh without interfering with the growth of muscle etc etc why because having high igf-1 doesn't necessarily help you um having more of an igf one effect right like having lots of insulin all the time and Insulin igf-1 are very similar um at least the receptor is very similar so having a lot of insulin doesn't help you at all right in the long run it helps in the short run right so yeah so then goes back to the people that make
then goes back to the people that make those comments well don't confuse acute effects like you can't confuse the acute effect of insulin with the long-term effective insulin so short term if you inject yourself with insulin you will say I feel great my glue cause dropped my A1C dropped I'm you know let's say a normal person 40 years ago eventually what's going to happen to you you're going to develop insulin resistance and and you're gonna die early and uh and so all the epidemiological data and and low of carb diets uh seem to confirm that with the exception of the vegans right the law the relatively low carb vegans in fact they have around 40 35 40 carbs and they're mostly plant-based those seem to be doing the best of all right so so yeah after that is the high carb groups and and as you probably know the landsat and this meta-analysis out there are showing that that um you know it's best to be better to have a 80 carbohydrate diet than to have a low carb diet for overall mortality and Longevity so yeah so the carnivores uh couldn't work yes it could you know we could be surprised and even though it's not something that makes any sense uh it surprises everybody because they're doing a very special you know High animal protein because so nobody does that right so nobody eats like uh in the Palio years so so it is possible right that that if you did that yeah I think I'm sorry to interrupt but but I think like a common theme that you have mentioned many times is really the energy balance I think I mean the biggest problem there's the macronutrient debates but I I think like you know we are just eating too much food and if all you eat is meat you inadvertently create a calorie deficit and you know I've seen the insulin levels of these people just eating in a meat only diet and their insulin was
meat only diet and their insulin was like two or three and their igf one's low uh even though they're eating uh two grams plus of you know of protein per kilogram and it's because they've created a calorie deficit and and I think because they're not overeating so I think that's right most of the times when you do that you can't eat meat all the time so you start eating yeah so absolutely but my point was you know we don't know right we could begin yeah right then they yeah so it's like really a gamble it's like going to Vegas on your with your life right then any good work but most likely you're going to come out of Vegas losing right so so yeah so that's the the likely scenario that they're gonna lose out of this but they could surprise us all and sometimes people go to Vegas and come out with a lot of money so so yeah everything is possible a subset of them but I think like I think what we can agree on is that creating a calorie deficit even periodically is the way to go and and the optimal way to do that is probably with a fasting mimicking diet because you don't necessarily tell people what to eat you just give them a prescription within a predetermined time frame and it's like it's pretty easy to implement so uh because I think you know I think that if we want to move this because fasting ideas have been around for 2000 years right and they have basically up to maybe 20 years ago that little role in medicine now all of a sudden you know the New England and they're starting to write out articles about this and lots of papers out there and it's starting but I think until we have more of a FDA like very careful lots of Trials lots of you know composition that are exactly so recently we approached the FDA for the cancer using the fasting making diet for hormone therapy in combination with hormone therapy for cancer treatment and the FDA in the initial discussions was basically saying you're gonna have to
basically saying you're gonna have to make this much simpler much more um repeatable let's say right so we we will have to be able to reproduce the same exact uh fmd every time right so then that and only that could be tested on an FDA trial so yeah so so I think that for this to stick around and being the toolkit of doctors and nutritionists and all over the world I think we're gonna have to standardize it right then and maybe the FDA will say you don't need to have a approval for everything because this is food but I think then again we cannot say oh go home and improvise uh because even though some people could benefit I would say that probably as we've seen before when people did that and we we looked into it there's more damage than good you know so people go home and say oh I'm gonna do 16 hours I'm gonna do 18 hours I'm gonna do uh you know every day I'm gonna do two days a week and I I think that the result of that is probably more damage than good now three papers just came out and and I actually wrote a little preview for two of them in the um in in cell metabolism and sure enough what we have been saying for years people that skip breakfast they took people they moved the breakfast forward by four hours and that was enough to reduce energy expenditure and and increase hunger right and so now think of all the people that do 16 hours and Skip breakfast now you know there could be still beneficial but you know and now compared to maybe doing 16 hours where you skip dinner uh that could make a big difference right so I'm saying that standardization and also lots of Trials and you know making sure that people follow what's been very well tested um yeah it's going to be the way in the
um yeah it's going to be the way in the future that this could make a big difference on people yeah it's in lunch and then eat you know at the end of the day and fast throughout the day but I end up eating too much food at night time and trying to get in all my calories and that can disrupt sleep so I found that you know this morning I had steak and eggs which you know I but I limit it to a a certain amount and then I fast all day and it's been about you know 10 hours and then I eat I fast basically do like too fast per day like I will Fast overnight and then I'll eat a breakfast at eight o'clock or no seven o'clock and then I eat my dinner around six or seven so yeah I do the same yeah I've been doing the same thing for 20 years ago yeah and I think and that that's what I wrote Us in my book I think that's the best way to do it right because now you um you don't push the fasting the daily fasting to more than 12 hours and so you get lots of benefits as such in Panda and others have shown and you get lots of benefits from the time versus the eating but you don't push yourself to that range that seems to be associated with your shorter lifespan so most people just keep breakfast or most studies showing people skipping breakfast show that they live shorter and uh so why is that well maybe because one possibility is and Sachin will say absolutely not so I don't know maybe it's right but it may be that 16 hours if you do it for 30 years or 40 years is causing problems right in cardiovascular problem could be one of the ones that it's causing whereas the 12 hours that we see everywhere and I always say I've never seen a negative studies on the 12 hour timer still eating and that's what is showing about 11 hours is showing to be very very beneficial in in helping people metabolically right so yeah so I think this keeping the lunch having breakfast and dinner and keeping the fast the daily fast to say oh the night really
daily fast to say oh the night really fast to about 12 hours that to me seems it's very safe and seems to be very effective yeah okay good to know so I can't maybe I'm on the right track I've gravitated to that you know after many different you know uh dietary protocols so that morning breakfast I just feel better later in the day sometimes I feel better in mid-morning if I didn't eat breakfast but then I just end up overeating you know later in the day so you know I'd like to get your opinion on what is the future of this approach like I talked to a patient yesterday actually one that's using fasting mimicking diets I think maybe they're Consulting with one of your dietitians Kim is one of them maybe that is and you know getting great success from it they're happy they feel like this is the approach to to go but I'm wondering like what what you envision the future approach would be the people that I talk to that want to implement this they want the food to go on their doorsteps they want like you know uh all the food they want the option for the food to be delivered to them sort of like a prescription right and they want uh in addition to that I think it would be really helpful to have a bio wearable that the data would go to the uh the clinician or The dietitian where they can see the compliance that they're actually following the food that's that that's being given to them and then the patient too would have like 24 7 access through an app if they had any questions so that's that's really like the three things that I think would be real important it's come out of many discussions that I've had that patients need to have you know their food right there for this to be pre-prepared probably tailored to them in a way or personalized because not everybody likes to eat the same kinds of foods but the same basic macronutrient ratios with the low protein uh or the and they need to have that biow wearable device that can show
biow wearable device that can show compliance and I think that's going to be really key and they're always going to have questions but to have some kind of system where they can ask questions through an app and yeah you know that that's what I think of when I think of like the future of metabolic-based dietary therapies yeah and that's already pretty much right so so it's all been done um I think that with the fasting mimicking diet um I think it's not being it's not about being uh you know personalized but it's about not having anything in it that somebody dislikes so much that they have a food aversion right so let's say you have onions and somebody says I can never eat onions of course then you have a version without onions but other than that I think it's a medicine like you say right so it has to be treated as such and and it's not a medicine that is going to replace people's food people can still eat whatever it is that they eat you know say 350 out of 365 days a year right so then for those 15 days break broken down to once every four months and this is exactly the trial that we started in Italy right so that's what people are gonna do and uh yeah so for those five days you want to have the medicine I mean imagine if somebody say I want Lipitor but I won't leave it or made for me no uh so yeah you can't do that right so you have to have FDA trials and sometimes Lipitor or or some some cholesterol inhibiting drug may not work for you then you can change you can have two or three versions right but so that's I think almost uh there and then the um the devices uh for example in the trial we're collaborating um with uh um with an expert in uh um in sleep uh Matthew Walker uh at Berkeley and um
uh Matthew Walker uh at Berkeley and um and in the trial we're gonna have for example the ring uh the wearable ring and so we do to follow the um the sleep and and in the trial in southern either we're doing the longevity every day longevity diet which is uh of course um you know it mostly pescatarian diet low protein um and then um you know the 12 hours the skipping lunch is in there and etc etc or that plus the FM no sorry the fmd alone every every four months or that plus the longevity diet right so we want to see um what happens and and uh you know we're also starting to use continuous glucose monitors and lots of patients so for example we have some doctors that we use that on um and but I think at some point soon we'll probably do clinical trials where um that is tested and then an application those are being developed and soon enough I think we should have the application so like you say people can can monitor their own uh uh status and um and you know be able to react and see how um you know the fmd is working for them yeah and maybe the future is the data from the fmd you know through the biowareables the glucose monitoring and the sleep too I can imagine sleep would probably improve I would go to an AI platform and then that that data can come out and give actionable advice to the uh to the participant or the patient or the participant and I think really that could be the future you know just uh and that would further validate uh the science and the application of fmds or any diets really I mean that's what we're kind of trying to do with the ketogenic diet and epilepsy you know if they if patients were a CGM or a continuous Ketone monitor or a continuous lactate monitor which is being developed now and being used in some studies
some studies so uh so yeah yeah I have a maybe one other personal question like every day I have there's certain foods I wanted to ask you uh if if people should avoid and I know protein should be you know lower in moderation that was a big part of the protocol that you're working on but like I have dark chocolate I have blueberries I have wine pretty much every day a lot of people ask questions about you know these things and um you know everything's sort of in moderation is there any particular foods that would be excluded from uh you know the the protocol the longevity protocol that you are putting together uh should people avoid alcohol so I'm seeing a lot of data coming out there's mixed reviews on alcohol but some of the data indicates you know uh a glass a day I mean I'm sure coming from Italy you know my family was big into wine and even in the pasta and everything too uh as should we be avoiding processed food or alcohol uh or should it just be considered you know moderation approach yeah first of all I encourage people uh so I started two clinics for the foundation non-profit clinics one in Milan and one in Los Angeles and the Los Angeles is Cree cures uh um dot org is the clinic and so um you know for example low protein we're I'm a little worried when I say that because some people when I say low product and they think well I'm just gonna avoid products and then they become manures right so so that's why I think it's so important even if you do it by telemedicine to talk to somebody if it's not our dietitian talk to somebody else they know what they're doing because for example if somebody is vegan they may need to be more around one gram or maybe even 1. 2 grams of proteins per kilogram per day but it's only the vegans that are eating mostly legumes if you're eating legumes seeds and nuts you may
eating legumes seeds and nuts you may not need to go as high right so it gets pretty tricky particularly if you are one of those groups that are doing something in particular like you know being vegan or even being vegetarian Etc so yeah so I think it's uh um it's worth uh the investment um so food to avoid um I think that um I always say if you think you always must avoid something it's time to have it uh so so and I'm excluding of course people the the ideology based on somebody is against animal being killed and all that that's a different story but but I'm saying other than that um then I think that these um you know sort of obsessions are just that but uh but then again as you see in the latest um paper representing millions of people three continents by by the group in Norway uh sure enough people that had consistently Lagoon rooms were number one uh whole grains were number two and nuts uh were number three as the super healthy life expectancy Foods red meat was to be avoided or removed processed meat to be avoided or removed and um and uh yeah so those alone uh you know these changes in a few more compared to a western diet were associated with 13 years of increased life expectancy it started at 20 11 to 13 years and I think eight to nine years it started at 60. it's pretty remarkable right if you just think that this is just a part of what we and others have been been proposing with the longevity diet so yeah so I think that um you know even white meat to me should be minimized uh in the 20 to 65 70 range
be minimized uh in the 20 to 65 70 range and animal based products should should be minimize but it should not be excluded because again it's very difficult to get certain amino acids and to get all that you need from a truly vegan diet and it takes work and most people I think eventually might become maloush not surprisingly one paper aside now is the fracture recent paper they came out on fractures showing the vegans had two and a half fold increase in certain type of fractures and overall they had an increase in infractions compared to the carnivores right so with the pescatarian didn't and the vegetarian didn't but the vegans did right so yeah so those are some of the the examples that we're gonna see more and more coming up in both sides right so the ones that eat the Western diet you know we give the Western diet to the mice and and not surprisingly they started developing high cholesterol cardiac problem they become uh you know fat and they die much earlier than the the control minds right so so that's pretty obvious that um yeah so it's as far away as you can stay from that Western diet I mean you know your your protocol does incorporate fish a couple times a week at least and the data on fish is very good right very good yeah absolutely yeah yeah maybe even three times a week you know especially if you change it right then avoid the low mercury change around so don't have to I guess it's starting to be allow toxicity associated with a lot of fish right so probably good to change it around and now I always have the same one just to avoid that that is let's say some of the steady fish contain some toxins and you keep eating that three times a week that could be a problem so unfortunately now we're also faced with with a polluted
we're also faced with with a polluted world and um and so yeah so then maybe thinking about that is also helpful but yeah probably three times a week now I think it's uh it's good to have three fish meals um and especially if omega-3 uh containing fish you know High Omega-3 salmon Etc Etc a tremendous amount of fish and I recently got my heavy metals tested I did the hair test and the blood tests and my metals were very low but I tend to eat a lot of uh sardines a lot of sardines and mackerel and maybe some other salmon here and there but okay the last food I want to ask you about is uh eggs so I know there's a bit of a controversy on eggs and they can be incorporated into a vegetarian diet and uh you didn't mention eggs in the diet they're to be avoided or to be incorporated I know fish and eggs are some of the most nutrient dense foods that we have high in protein but nutrient dense foods so what's your thought on egg is an economical source of protein that you can have as a vegetarian is that incorporated into your program but I think there's a New England Journal medicine meta-analysis and eggs right and I believe I remember correctly starting with three a week or more you're starting to see the problems right so that's what we've been I've been preaching stick with two or three eggs a week uh and probably uh the nourishment is gonna uh is gonna be more important than than problems because even the New England cannot see anything wrong with uh in those eight two or three a week as you get higher uh just like with alcohol as you were mentioning before so the meta-analysis are showing about up to five drinks a week uh no problem you know very little effect now what I've been saying is that whether it's eggs or with cholesterol let's say if you're genetically predisposed to
if you're genetically predisposed to have Sky High you know cholesterol and responsive eggs or if you're if you have some one of the cancers that is um there has high risk factors that are also affected uh so if you're already predisposed to for example the gesophageal cancer is one of them then if alcohol is also a risk factor for that I wouldn't combine two risk factors right so I will find out is there I mean there is not very many but there's like four or five cancers that are clearly uh associated with um so high alcohol consumption increases the risk for those cancers so if you have another risk factor that adds to that probably not a good idea to even have a low uh drinking pattern but other than that I just don't see any reason to take out the pleasure of having these five glasses a week from the great majority of people especially because the data and Longevity is neutral to positive right so if you have to say three or four or five drinks a week those people tend to live the same if not a little bit longer than everybody else yeah yeah and uh so your pro coffee too I mean I see a lot of the data seems to be pretty overwhelming on coffee and it just seems like one of those things if I had to give it up that would be hard for me to do I'd probably get about three to five cups a day you know and uh so that's something that's incorporated into uh the protocol too I think you had mentioned having coffee like for lunch instead of uh you know for yeah and that's what I do you know I have coffee for lunch and uh yeah coffee actually very little negative data when you're in the one to two cups actually positive data's in the three four cups a day for a Parkinson some data for I mean reducing Parkinson and reducing Alzheimer's uh in those that have heavy
Alzheimer's uh in those that have heavy coffee drinkers but of course you cannot recommend it because when you get to that three four five cups a day a lot of people have problems so so yeah so I would say though and I think I said this in the book is somebody that has a lot of Alzheimer's in the family um or a lot of Parkinson in the family maybe genetic familial Parkinson or you know Apple E4 let's say uh in the fan in in the jeans um Leo may not be such a bad idea to talk to a nutritionist that they teach and talk to the doctor and say hey let me try three or three cups a day of coffee um and see how I respond and if I if I'm okay um maybe it's a good uh you know that and lots of olive oil it seems to be also a good um you know a good uh potential reducer of the risk of developing Alzheimer's certainly progressing with the cognitive diseases well that that's great to hear because uh it's going to be a while before I give up coffee well Dr Longo thank you so much for sharing this uh all your knowledge and your wisdom on this topic of longevity I encourage people to check out your website the create cures Foundation website it's uh it's an awesome website it's got a lot of information on what you're doing uh also you've written a number of books so encourage everybody don't mention them all but I I like that you had a book on longevity begins uh with kids with the Bambinos so and I think that's like almost a low-hanging fruit we really have to educate uh our youth and our kids to to get off sugary drinks and to really uh create these uh habits early on to prevent you know all these age-related chronic diseases from creeping up when you get older so it's not just sugary drinks because in that book we showed that the Italian is so
book we showed that the Italian is so far is only in Italian and We're translating now into English but we show that Italian children ate about a pound a day of high starch food you know refined starch food so pasta bread potatoes fruit juices so they all upon the day and there was much at least in the Italian children we thought it was much more of a problem than the sugary drinks of which they only drink one a week you know so they had the sugary drink a week but they had a pound a day of bread and pasta and fruit juices so yeah so sometimes the the you know the the sources of the problem and and it's surprising how many parents we talked to and uh they had no idea they just thought well well pasta I mean of course what's wrong with that and we say there's nothing wrong with that it's just wrong when there's an 100 extra calories coming from starches per day and eventually that 100 calories you know of course in a month is 3 000 calories right and uh and So eventually it goes very quickly and now you have an obese child in in Italy for overweight children and surpassed the United States right so not obesity but overweight especially in the South so very interesting right so sometimes uh that you know the source of the problem is not what we think it is well thank you for all the work that you're doing on longevity and also keeping our our kids healthy too I think that's a great area to start putting your time and energy into in addition to all the different diseases that you're treating diabetes and cancer I wanted to get more into the cancer but maybe we can follow up you know at another time or maybe you can give you know Phyllis in at uh you know giving a presentation at metabolic Health Summit perhaps in the future so we would really love that we had Dr Sachin Panda was one of our speakers uh last time he gave a great talk uh well thank you again uh Dr Longo
talk uh well thank you again uh Dr Longo for for doing this interview for giving up your time and for all the educational Outreach that you do in addition to all the podcasts but all the books and and through cures uh create cures foundation too that's an amazing and I know a lot of your book proceeds uh go and support all of it oh all of them that is fantastic yeah well thank you I mean that's just sort of solidifies your your passion and your commitment to really making a difference and making an impact on metabolic health I can't think of anybody else that's actually like moving the science into human application I mean you are really at the Pinnacle of doing this okay thanks I appreciate it thank you very much and great uh great podcast thanks a lot Walter thanks for tuning in to this episode of the metabolic link if you've enjoyed this podcast please share it with others leave a comment leave a review and also follow us on social media at metabolic Health Summit we look forward to seeing you next time thank you
Transcript auto-generated by YouTube. Verbatim — duplicates intentionally preserved.
Longo’s fasting-mimicking diet is built around a specific biological signal: lower calories, lower certain amino acids, lower sugar, and a temporary reduction in growth cues. The point is not suffering. The point is to give cells a short, structured period where repair and protection pathways become more active.
The conversation returns often to evidence quality. Clinical trials matter, but so do epidemiology, genetics, animal models, and long-lived populations. No single pillar is enough. In practice, this creates a more grounded approach: use fasting as one tool, then measure whether glucose, blood pressure, lipids, energy, and function actually improve.
Longo distinguishes between periods of life where lower protein may support longevity pathways and later decades where frailty and muscle loss become more urgent risks. That nuance matters. A longevity protocol should protect the future without weakening the present.
The interview favors a modest daily eating rhythm over extreme long-term fasting windows for most people. A roughly 12-hour overnight fast, consistent meals, plant-forward nutrition, legumes, whole grains, nuts, and fish form the base. The sophisticated part is not novelty. It is consistency matched to biology.
Longevity is not built by one rule. It is built by choosing the right signal at the right time.
Use fasting as a structured intervention, not a permanent identity.
Anchor the everyday pattern first: whole foods, metabolic stability, and a rhythm you can maintain.
Be especially careful with aggressive fasting if you are older, underweight, ill, pregnant, or trying to preserve muscle.
