Dr. Valter Longo Episode #6 Dr. Victoria Maizes: Hi, Andy. Dr. Andrew Weil: Hi Victoria. Dr. Victoria Maizes: So it's good to see you on Zoom. We are, at home, sheltered at home, like much of the rest the country. Dr. Andrew Weil: I believe the subject today is going to be fasting and fasting mimicking diets. We're going to be talking to Dr. Valter Longo. Dr. Victoria Maizes: Yes. And I know that, you have been interested in fasting, but also have sometimes been a little doubtful about fasting. I'm wondering if you could tell our audience your thoughts. Dr. Andrew Weil: Well, I have been fascinated by the growing attention in the scientific community and lay community. Intermittent fasting and the value for resetting metabolism and the challenge, I think is to find a practical way of doing that. Victoria: So it'll be fantastic to have our guest, Dr. Valter Longo, who is really one of the leading researchers, and he is going to take us through the various kinds of fasting and some of the research he's done on something called fasting mimicking diet. Dr. Andrew Weil: Yeah. Which looks to me like the most practical, taking advantage of the benefits of fasting. Dr. Victoria Maizes: All right, let's go to Walter Intro Music Dr. Victoria Maizes: It is my great pleasure to introduce Dr. Valter Longo. He is the director of the Longevity Institute at the University of Southern California, and he also directs the Longevity Center and Cancer program, in Milan, Italy. He's written a bestseller, the Longevity Diet, and really he's perhaps one of the best known researchers around the world looking at fasting. Dr. Victoria Maizes: Hi Valter. We are so delighted to have you on our show. Many of our listeners will be familiar with fasting from a religious perspective, in the Jewish religion, people fast for up to 25 hours on Yom Kippor, Ramadan has a fast that goes from Dawn until sunset so it varies depending on what month it comes out, but usually 11 to 16 hours. People fast on Lent, and that's a very different fast that's giving up meat whereas the, the Jewish fast is nothing, no food, no water. So when you think about fasting, what does it mean? Dr. Valter Longo: Well, I always say that fasting, it's, it's kind of like saying, eating doesn't really mean anything. Yeah. And unfortunately, it's be used very loosely like that, but let's say that the, the main, matters, fasting associated matters are what's called a time restricted eating. Which refers to anywhere from 12 hours of water only fasting, to about 16-20 hours, right? The most, you see, usually it's about 20 hours. And so the answer is called a alternating day, fasting out the day, fasting it's just that one day don't eat than the other day, or have a low calorie or very low calorie diet on the alternate day. And then, there's something called five -two that are different, different versions of that. And the five-two refers to either one day a week or two days a week, I mean, two days a week, or either consecutive or non-consecutive fasting days. And it could be, again, fasting, or it could be, let's say 500 calories of different composition. And then what we've been focused on is what we call periodic fasting, and or fasting mimicking diet, which is something that you don't necessarily have to do in an intermittent fashion, but it's a more on a need to do a basis. Ah, so you do it, when you need to do it. And then refers to longer periods of fasting can be a two, three, four days all the way to a one week at least in a way, we've been testing it clinically. We started with a cancer patient. With water only fascinating. They moved to a, a fasting mimicking composition, which I'm assuming we're going to talk about. Dr. Victoria Maizes: Yes, we will talk about it. Andy, I know you've experimented a bit with fasting. can you tell our listeners about your experience? Dr. Andrew Weil: Yeah, it goes back a long way. In the 1970’s, I experimented with water fasting for several days to especially to see what the effect of consciousness was. So I would do a three day water only fast. And my, my initial experience was that one the second day I really felt awful both mentally and physically. And on the third day I felt great, just really high and my mind worked at peak efficiency, you know, very interesting. But then I found it very difficult to come off of that in a sensible fashion, and I would find myself overeating tremendously at the end of it. Then, I'd appeared somewhere in the, I think early or late 1970’s I was in a pattern of fasting one day a week. So on Mondays I would have water. And that just seemed like a, to me, a good discipline. I think I did it mostly as a spiritual discipline more than for any physical effects. As the information began to come out about the benefits of intermittent fasting, I was very fascinated by that and I had a number of friends who were doing it and reporting great effects with it. I tried various schedules of doing it, you know, first compressing my period of eating to six hours or eight hours. A problem, I would find myself ravenously hungry when I did eat, and I would probably eat more than I would normally would if I weren't doing that. So that just didn’t work. I tried other schedules, also had the same problem, but I've been very interested in the possibility of fasting mimicking diet. So, that really drew me to a to Valter Long’s work. Dr. Victoria Maizes: So from an evolutionary biology perspective, what's the role that fasting plays? Dr. Valter Longo: Yes. Fasting has been around forever. Right? So from the very beginning, you know, we, most organisms on earth are starving all the time. And once in a while they, they, they get lucky and they get some food and they go back to starving. This is true for most bacteria, for most microorganisms. And this was also true for us, you know, most likely, we got food once in a while. I mean, they may probably periods during the summer where we had food all the time, but then we certainly, almost undoubtedly most of our ancestors had long periods of starvation very frequently, and they could be fairly long periods. Yeah. So. For example, we, we, I believe that the summer was the moment where, you know, the, insulin resistance was generated, and fat will be stored so that then, you could get through the winter using the fat store during the summer. And now we're forgetting this, this evolutionary issues. We come from, from a starving world, every organism. This is how I got started with fasting because I was starving bacteria and they were living a lot longer. I was starving yeast, baker's yeast, and they were living a lot longer and they also became very strong. You could hit it, hit it with, toxins and they will not die. And that's when I thought, if bacteria precarious have this, this in common. This must be really about all organisms and, and sure enough, I think, I think it was. Dr. Victoria Maizes: So, I think a lot of people have that challenge that they don't feel great when they fast. I mean, I know people who. They loved to fast, and they say things sometimes like, Oh, I forgot to eat. I never forget to eat a meal. I'm hungry at breakfast, lunch, and dinner. And so fasting is not easy for me. and I often feel weak when I fast and yet I certainly know people and I sometimes think they’re the Vata type from the, tradition of the Aryuveda. They're tall and thin and airy, and they just seem to have a really easy time with fasting. So I'm curious, Valter what your experience has been with people's ease or difficulty, and I know it's the difficulty side that had you develop the fasting mimicking diet. So maybe you could address both those. Dr. Valter Longo: Yes, its a difficulty, a side, but also the safety side and compliance. So when we first started, or, you know, 10, 12 years ago with the clinical trials on, on cancer here at USC on a fast, water only fascinated and cancer, we realized, we thought, of course everybody's going to do it. Even if they have a possibility of doing better, having less side effects. And we were wrong. Nobody wanted to do it. And the oncologist struggled to get people to, to be on it. And, so yeah, we went back then to the NCI, the National Cancer Institute, and basically ask for funds, to develop a fasting mimicking diet. There was a very good idea, again, both for compliance and safety. Now, we published a number of trials on this and this year we're going to publish a three or four more. And, the compliance if done with a registered dietician. in the cancer, setting is, let's say the minimum we see is 70 - 80%, all the way to 90-95% compliance, even going many cycles. And the other thing is safety. And, and the, you know, let's say lean body mass loss, the loss of muscle. This is been, at the beginning was a true war with the oncologist. But, then I think they realize that, I know there was a lot of science there and we were trying to address exactly that. We didn't want anybody to do, did and become cachectic and lose muscle mass and, and become frail, and sure enough now we are about to publish that that's not the case meaning that, patients, even if they're doing all kinds of cancer therapies going from chemotherapy to immunotherapy to a hormone therapy, they can maintain a normal weight now. Sometimes we do exclude the patients from the trials because they do lose weight and they cannot regain it but I would say it's a very small percentage of patients where in fact, we were surprised how small it has been. So, yeah. So for those reason, I, I think it's, It's good to start thinking about standardizing fasting in a way that the medical community, I mean, fascinating, as Dr. Weil knows is been around for a long time and, and, and even in the medical community every 50 years or so, arises and then it disappears. And it disappears because you see as many benefits as, as, problems. So I think, yeah. you know, it's, it's really important, to standardize it and, and to test, you know, specific a fasting mimicking diets in for specific purposes. Dr. Andrew Weil: You know, I've been fascinated by the literature on a very successful treatment of autoimmune conditions with long-term water fasting. You know, really interesting reports of total emission, of rheumatoid arthritis. Ulcerative colitis, some forms of asthma on long-term water fasting obviously has to be known under supervision and the problem is that the conditions tend to come back. You know, once eating is resumed. The question is whether you could find some way of transitioning from that, that would maintain the remission. Dr. Valter Longo: Yes. So that absolutely. So unfortunately, those trials always show. If at first of all, let's say you do two or three weeks of what only fasting, that's extremely tough. And most, most doctors, will tell you, that should only be done in a clinic, which then makes it very expensive. And now, so the recommendation would be go to a clinic, do two or three weeks of this, and then it’s going to come back anyway? And so, you know, and this is, as you know, old studies, this was published in, you know, 30 years ago or, or whatever. And then it never made it into mainstream medicine. It was because A. there was no, no idea and in fact, I think it was mentioned in the paper this is likely to come back after you finish the diet. So yeah, we try to turn that now we've, we've finished a trial and multiple sclerosis with the FMT fasting mimicking diet. Now we're doing a three or four more trials. Stanford, has just started with IBD the fasting mimicking diet and, and, you know, we have multiple sclerosis and other, conditions so awfully rheumatoid arthritis also be in our, one of our targets. And, so we'll see what happens. But yeah, the idea would be, let's say, in our trial, we do seven days of a fasting mimicking diet, that comes in a package, and the patient will do it every two months so it's seven days every two months. If their work and it kept it, the autoimmunity in check now it becomes, I think, reasonable and feasible, for lots of patients. Maybe not everybody, but certainly, lots of the patients that have these conditions. Dr. Victoria Maizes: Can you help us understand how you formulated the fasting mimicking diet? I will tell our listeners that I did it and I found it much, much easier than a water fasting. Of course, it's structured so you know exactly what you're going to eat, but is it that it's low calorie? Is it that it's feeding a certain part of the microbiome? How do you, explain one, how you put it together so it actually mimics not eating, at all a water fast, and two, what you think the mechanism is by which it's having this effect on the immune system. Dr. Valter Longo: Yeah. Well, yeah. So first of all, believe it or not, the foundation of this is, it goes back almost 30 years to the days where I was with Walford and Steve Clark at UCLA, and, and looking at starving bacteria, starving people, starving yeast. And, and so we realized a long, long time ago a connection between certain nutrients and certain genes, right? So for example, certain amino acids and tore kinase, certain amino acids and, and growth factors like IGF, one growth hormone, a certain, carbohydrates, specifically sugars and PK. So I'm just throwing out names, but that names, so what we call, what we are now viewing, not just me, but many of us are master or central regulators of aging. So what does that mean? For example. These protein response pathways, these genes, the response. So if eat lots of products, IGF one levels will go up. And now this IGF and is recognized by many of us as a central regulator on the aging process to the point that if you knock out the growth hormone, IGF, one axes in mice, they will live for 50% longer. But, more importantly, they will have much, much lower level of diseases, right? So they live longer and they have less diseases. And then in our studies of people in Ecuador, they have the same type of mutation. So they, they are, it's almost like if they never ate proteins, but they of course, eat proteins, but they don't have the genes that respond to them. And they're very much protected, from cancer, diabetes. So far, we and others in Europe have shown these are facts. So this is seems like it regulate aging is simple organisms also regulate aging in humans. So anyways, the diet, the formulation is based on the understanding of this. So how do I regulate. Growth hormone, IGF one, Tor, PKA, you know, what's the kind of, what's it formulation that's going to do that? And how do I do it in a way that is feasible, and in a way that promotes also all other changes. For example. A microbiota, you know, the, the growth of lactobacillus. We feed the bacteria in the gut. So, how do we, how do I also make sure that the patient doesn’t become hypotensive, hypoglycemic? So we've been thinking for, for decades about a lot of issues that we try to solve. And so the, the end result should be you get a package you know, we do with other physician, maybe a registered dietician follows you. And, in the great, great majority, the people will not have side effects and will benefit from it. And also, while minimizing the burden of, having to do a water only fasting I've done water only fasting once. And, I think last time I really struggled. And, so I, I remember there was maybe, you know, 10 years ago. I say that I'm never going to do this again. And I, it, it really, I remember every part of it. Yeah. And of course, people, some people do it with no problems, you know, so I'm not saying that everybody's going to have the reaction, but, but yeah, I will say lots of people, would struggle with water only fasting. Dr. Victoria Maizes: The mimicking diet has. lots of regular things in it. I mean, there's soups that are made from vegetables and there's nuts in a bar. So it's, you know, it feels like things you'd see in an irregular, maybe healthy diet. Obviously lower, total volume and lower calorie than one might normally consume. But somehow, you're saying this particular mixture helps the microbiome and is a low enough load that it alters the immune regulations. Dr. Valter Longo: Yeah. So for example, if you look at our recent mouse study, and also include the clinical component, but we compare, we had an IBD, inflammatory bowel disease, a models so we give severe inflammation to the mice, intestinal inflammation to the mice. And then if you look at water only fasting together with the toxin the, gut of the mice becomes even more leaky during fasting and it makes sense, right? The fasting, basically the, the signal to the intestine is there is no food, so you don't need to be as a densely populated with cells. And, but with the fasting mimicking diet, we didn't see that. We saw a higher degree of protection and we saw also STEM cells being increased in the, in the gap and inflammation being decreased. So it seems like the FMD is given fuel prebiotic ingredients to the lactobacillus bifidobacteria and is allowing, is also giving us signal to the gut. Don't over. Don't overdo the breakdown process because there's still food here. So yeah, so that was an important, and where do the ingredients come from? You know, the ingredients also come from, Andrew Weil’s book and certainly. Yeah, we, I made it a point in, having a common denominator. So, you know, if you look at epidemiology, if you look at the centenarian studies, if you look at the basic research on longevity. What are some of the ingredients that we keep coming up as positive, you know? And so then the effort was made let’s pick only ingredients that are clearly beneficial to longevity and health span. There was a good idea was some of it we didn't learn until later as I, for example, the FMD was formulated before showing that in fact, the lactobacillus and some of the, the protective microbes, microbes, would benefit from those ingredients. Dr. Victoria Maizes: Andy, you've talked about the possible downsides of having a really robust immune system and we're certainly seeing that with Coronavirus when people have cytokine storm. Do you think people should be fasting now? Dr. Valter Longo: [Laughing] I’m glad you asked him that question. Dr. Andrew Weil: I don't. Valter, what do you, well, let me, let me make a comment first. You know, clearly the 19, 18 flu was even more, provocative at causing a cytokine storm. And most people died of that, and that selectively killed the young, healthy people that have had the most robust immune system. So we're not seeing that with COVID-19. But I think in that kind of situation, you would want to downward regulate the immune system. And this, it makes me nervous when I hear people casually talking about boosting immunity and enhancing immunity, there’s a downside to that. But I'd like to hear Valter’s opinion. Maybe no fasting and fasting mimicking diet modulates immunity in a desirable way to protect you. Dr. Valter Longo: [Yeah, so in mice it definitely does. So we also receive grants, both from the NIH in the NIA and from a foundation in Italy to do the clinical trial for, for the flu. I saw a response to the flu vaccine, but we, we haven't started trials either one of them. Yeah. So, so we don't know. And I think that's the answer. We don't know because as, as Andrew pointed out, if you have an inflammatory response that is too high. You could have a problem. Now with coronavirus, you know, the problem seems to be this pneumonia and what are the reason for that? And then what do patient actually die from the die, from sepsis, do the die from, from the inflammatory response. So I think it, it just, we need a lot more, you know, people looking at the clinically and pre-clinically at, the specific virus. And, I hope we come up with a system that's much more rapid so that, you know, by the time everybody's infected, we already have a solution rather than talking about the next two or three years. Dr. Andrew Weil: Practical problem at the moment is that with all of us in lockdown, overeating seems to be the major problem. And I know several people who had been doing intermittent fasting have given it up in the past few weeks because they find it very hard to relate their food intake. Dr. Valter Longo: Yeah. So the recommendation is being, if you're at home, you're isolated, you, you have really low exposure low chances of being exposed and say you can stay on for next week. Yeah. I think the fasting mimicking diet is a very good, or other types of, of, let's say, shorter fasting. It's a very good time to do it. and while also counteracted the counterbalance, any overfeeding that most people are doing at home. So, but I, but I would say medical personnel or anybody that has somebody infected around, I would tell him no, don't fast and not, not a good time to, I mean, there is a, there is a slight decline in white blood cells. When you fast, there is a, some type of reduced redistribution. There was recently several papers in, in the journals, looking at the tremendous effect of, of fasting, following our own papers, a number of our own papers, but, they confirmed these tremendous effect of fascinating redistributing, all kinds of immune cells. So some cells go from the periphery to the bone marrow. Some cells do the opposite, some cells die, and some STEM cells are, are setting up. The STEM cells are setting up to generate new white blood cells. So it's a very complex, set of changes and I think, luckily we are funded to test this clinically. So let's see what happens in this, in this, flu trial and hopefully as soon as there is a COVID-19 vaccine, then we're going to do the same with COVID-19. So we do the two cycles. These are in the summer, two cycles of the fasting mimicking diet, followed by the vaccine. And then we look at the antibody formation. Yeah. And then we look at the antibody tire it’s called. And then we followed the actual, infection rate, you know, do they get the flue and, and, and so, if so, how bad is it then, what are the consequences? Dr. Andrew Weil: I have a question, I'd really be interested to hear your opinion on is little bit off the you mentioned that you had studied with Walford, you know, Roy Walford. I knew him well when he was sealed up into the biosphere here, and he was a major proponent of caloric restriction. Practiced himself and predicted that he was going to live to some great age and he died far short of that of generative diseases. Around the same time I had seen a number of patients that caught my attention of fairly young, ultra-athletes that ALS. So early onset ALS and relatively young people who were extreme exercisers had no body fat. And it made me wonder whether, you know, with caloric restriction, I'm sure you get great improvement in cardiovascular health, and maybe that's the major gain that extends longevity and that's at the possible expense of neurological. Dr. Valter Longo: Yeah. Yeah. So I think that the big disadvantage that Roy had was that, it was too early for the molecular biology was too early for the genetics, et cetera, et cetera. We had a huge advantage because, you know, having the genes, and having for example, know that we did the spot in mice and humans, there's genes that I would show is talking about mutation in the growth hormone. That way they improve cognitive function in both humans and mice. So we looked at the Ecuadorians, we've got our more receptive deficiency, and they were cognitively younger. They were about maybe 10, 15 years younger, really impressive. And the mice, very, very much, cognitively improved. Now, if you look at the fascinating that our first publication was actually showing that improvement in cognitive delay in cognitive decline in the mice doing the FMB. Pretty soon we are going to publish on humans on the FMD with FMRIs. Yeah. So if anything, that is one of the things that we hear from people. My, cognition, I was so much clearer. I could remember things better. I was much sharper, so, yeah, we, we have seen that. Now, this is very different from calorie restriction. You know, this is why I never, I never, I mean, I learned a lot from, from being in Walford's lab for, for two years, but I never, I never worked on calorie restriction because I was there in Arizona when they came out of Biosphere 2. And they look terrible. Yeah, yeah. And there was, you know, I would just, I just got started in the lab a year earlier, I think, and I thought the does not look promising. It just looks like, you know, we have to find a way. How do we get all the benefits without causing all the problems? And like you say, the fats, and we see these also in mice. I mean most people don't know that about a third of the mice genetic background. If you take all kinds of genetic background, about a third of them would benefit from chronic calorie restriction. So let's say eating 25, 30, 40% less all the time. So after the mice would benefit greatly a third, we get no, neutral effects. And now the third will die earlier. Right. And the ones that die earlier seems to be, there seemed to be the one that have a less fat storing capacity. And so this is also consistent with the idea that people that have a little bit of extra weight in their seventies and eighties they tend to do better Right? They're not, not morbidly obese, but those, they seem to have, let's say a BMI of 26. It's not so bad, you know, for older people. Yeah. So absolutely. A calorie restriction, was a pioneer in intervention. Very interesting. But we're in a completely different world when we do FMD, and in fact, we recommend that the Prolon FMD maybe three times a year for five days. So this would be, you know, 15 days in the entire year. And I say, you know, people, if they don't need to, they shouldn't do it more than that. This is not about, “I do it as much as possible, so I get more benefit.” You do it three times and that's it. Unless, you know, you have diabetes, et cetera, et cetera. Now we have four clinical trials on diabetes right now. We'll, we'll see soon enough what the results are. But you know, we already have data, on prediabetes and I worked very well with the prediabetes and our patients. So, yeah. So I think that, that, that is a, the way to do it is a, don't, don't overdo it. Don't do what Walford did, you know, push yourself to the limit. And also the monkeys. If you look at the calorie restriction studies in monkeys, both in Wisconsin and at the National Institute on Aging, the overall, the benefits on overall mortality. You know, how long did they live were not that good, you know? Now they had in Wisconsin, the monkey, the wear calorie restricted all the time, and they had a tremendous effect on diabetes, tremendous effect on, on cancer and cardiovascular disease. But overall, a lifespan was not was not that much longer. And in the NIA, the National Institute on Aging there were no different, there was no difference in longevity right? So, yeah. So, I think we need to move from that to where we're going. And by the way, I don't make a penny out of all of this. I donate a hundred percent of everything to charity and the research. So I want to make sure people know that are not advertising. In fact, I don't even take consults from, from any company related to this. so yeah. Dr. Andrew Weil: Oh, that's great to hear. Vault. I think that's very sensible advice and it feels very doable unlike the other systems that I've seen out there. Dr. Victoria Maizes: I do think it's doable to do something, you know, two or three times a year where you are, you know, changing your habits significantly. Any gender differences, men versus women. Dr. Valter Longo: Very little as some. Yeah. Some, I think we're going to start, we are, we are going to publish later this year, another trial on the hypertension and prediabetes and diabetes. And I have to say there are some differences, but they're not, nothing significant or just in a few cases. But overall, I'd say we measured like a hundred different things and most of them seem to be fairly similar between male and female. But as we get more and more data, I think we're probably going to see, we're going to see differences, sex specific. Dr. Victoria Maizes: Do you find that following a fasting mimicking diet ends up changing people's relationships to food. Dr. Valter Longo: Yeah. So this is one of the most impressive things that we see with lots of people. And they may be in part because it's only five days. And even in the clinical trials we give them this box, they do it for five days, and we gave them no rules about the rest of the time. And, we see the most people, especially if they do, after they did with two, three, four times. then they begin to say, I am completely voluntary, in a completely voluntary manner, starting to change my habit. For example, if I never ate vegetables, now that I've been exposed to let's say, 15, 20 days of this vegan diet, I am more, much more prone to, to appreciate that, eating more vegetables or eating less meat the ect. So I would say the great majority of the people eventually undergo this process of, of changing, you know, in, in, in, in science that is on the call food aversion. So when, when the patient may become, may reject a certain type of food cause they associate that food with, some pain, and, for example, chemotherapy, right? So if you come combine chemotherapy with a certain food ingredient, eventually you may become, you may reject that ingredient. What we're starting to think there might be the opposite that you now have, certain vegan ingredients that make you feel a lot better. And if you never had those and you started eating more, during the, the, the ProLon FMD now are you eventually your brain is telling you, I need more of those because I felt so much better when I was under those. Dr. Victoria Maizes: So a closing question. You are both really passionate about healthy aging and besides fasting, or a fasting mimicking diet, I'd love to hear from each of you, some practical recommendations that you could give to our listeners about, how they can live a long, healthy life. Andy, let's start with you. Dr. Andrew Weil: Well, you know, I, I've always cite the MacArthur Foundation's report on successful aging and the two factors, common factors that they found in the population that they studied were maintenance of physical activity throughout life and maintenance of social and intellectual connectedness. So I think in addition to sensible nutrition, I would say those, those two are really important. Dr. Victoria Maizes: And it seems like during this time of the Coronavirus, certainly social interactions being challenged. Dr. Valter Longo: Yeah. Yeah. So, I usually have, you know, the, my, my recipe and, and, again, I like to use the five pillars of longevity, you know, epidemiological study, clinical, basic research, centenarian studying, and studies are complex systems. And so that leads to a, I think, a pescatarian diet fish maybe a couple of times a week plus vegan. I don't like the vegan. And, and, you know, in talking to lots of people that have been, studying the vegans, they, they tend to do worse than the vegetarians, and were the worse than the pescatarians and then I may have to do with the immune system, may have to do with malnourishment, et cetera, et cetera. It doesn't mean that you cannot be vegan and very healthy. It just means that most people that are vegan are probably, you know, kind of like the calorie restriction. They may have lots of benefits and lots of, lots of problems. Dr. Victoria Maizes: Valter one thing I like to ask our guests is, we're talking about health and health promotion and long life. I always like to ask people what their one guilty pleasure is. Dr. Valter Longo: I have many. Dr. Victoria Maizes: You can share more than one if you want Dr. Valter Longo: Well if it was up to me, I will eat sweets all day long, but I'm very good and so I narrow it down to now 85% cocoa, chocolate every night, you know? So I, I, yeah, I'm happy with that. That's the thing, right? If you do it long enough, the good food and you eat good food then you start, I appreciate any less lasts this or the junk, a type of food. So I now I'm very happy with that and I don't, I don't feel as I used to. There is something in Italy called panettone right. It is a lot of saturated fats, but it's great. And so I used to dream of panettone and I was a little bit last year. Dr. Victoria Maizes: Valter thank you so very much for being on with us. And, I think that, you've shared a lot of really valuable information that people are going to find very, very interesting. So thank you. Dr. Andrew Weil: Good to meet you. Virtually Dr. Valter Longo: My pleasure. My pleasure.