Dr Rupy: Should everyone do some form of fasting?
Dr Leo: No.
Dr Rupy: Could too much comfort actually be harming our health?
Dr Leo: Definitely.
Dr Rupy: Is stress the biggest hidden driver of chronic illness today?
Dr Leo: No, because people should define stress.
Dr Rupy: Can temporary stress like cold and heat exposure trigger some anti-aging processes?
Dr Leo: Obvious.
Dr Rupy: Okay. Obviously, yeah. Okay.
Dr Rupy: Can short bouts of intense exercise mimic ancient survival challenges?
Dr Leo: Yes, if you do it in a functional way.
Dr Rupy: Okay. We're going to get to that. And finally, is being in nature medicinal?
Dr Leo: It is a basic necessity.
Dr Rupy: Look, I'm super excited to have this conversation with you. I wanted to start with something that I heard you say, or perhaps it was something you read actually. You can take a human out of being in nature, but you can't take nature out of the human being. Can we expand on that?
Dr Leo: Yeah, that's I think one of the most important human characteristics. Obviously, culture has become our way of living, which is not at all some reaction on nature. It is the natural consequence of nature. And you can imagine that the number of mortal factors in nature were so high that we had to develop our intelligence to get out of it. So we got out of it. And human beings haven't done so industrial revolution, the first, the second and third, they're not bad. They are not bad inventions. The thing is we did not know about the consequences. I love the fact that there are aeroplanes. You're here and I'm here because there are aeroplanes. But we didn't know that all those nanoparticles could be that toxic. I definitely know that that if we would have known what homo digitalis is suffering at the level of fertility, I definitely know we would never ever have invented computers. But we didn't know. So we just did it and it it it it provided an enormous amount of advances, but the consequences at this moment are huge. We really have too much culture. So we got out of nature, but luckily enough, we never can get rid of nature which is inside us.
Dr Rupy: It reminds me of this quote I've been reflecting on quite a bit recently. I can't remember who coined it, but it was something along the lines of there are no solutions, only trade-offs.
Dr Leo: Yeah. Yeah, and and and you shouldn't feel sorry if there's no solution. And if there's a solution, you shouldn't feel sorry, which is which is more or less in the same line. And that means that we are constantly giving and taking. So energy distribution, which is the most important mechanism every every living plant or organism is facing, is always above anything else. So so it means that you cannot you cannot have this brain we have, use it as we use it, and at the same time be very fertile. That's impossible because it's too much energy. And today we we we invert an enormous amount of energy in our cognitive capacities or skills or tools. And that means that that that we are losing fertility, which is which perhaps after menopause is not a problem, because women after menopause, you know what they should do? Learn a new language with a computer. That's the best thing they can do. That increases their life expectancy, but really increases their life expectancy. But if you're young, if you want to have a kid, don't engage the whole day in digital work because it affects fertility because of an energy distribution conflict.
Dr Rupy: Is that because we're utilizing too much energy in engaging with devices, utilizing our brain, using utilizing other elements of our physiology that are directing away from things like metabolism?
Dr Leo: If you look at at at homo digitalis, which is really an anthropology, an existing species already, then you see those people that learn online, they learn online. That's not the same as gathering information. When they learn online, that's that's brain stress. But it's a very healthy brain stress. What you see is an increase of the hippocampus, but you really see in volume and in neuronal number, you see a huge amount of new connections, which is incredible. But at the same time, that brain releases some packages, extracellular vesicles, and they travel to our germ line, which we never thought that was that that was possible. And the germ line, our gametes, the oocytes and the spermatozoa, the wise man barrier, that doesn't exist anymore. This guy won the Nobel prize because he said that oocytes and and spermatozoa are impermeable. It's not true at all, at all. There's a constant communication between the soma, of which the brain is the most important part, and the germ line. And so that that investment in in in brain learning processes, which we have never done that much than the last two generations, is really in is is really informing spermatozoa and oocytes. And if you then look to the way the epigenetic, so the way those cells start to function, you will be very, very surprised. Spermatozoids dying because of neurological activity. But the thing is, which is incredible, but but also already evidenced, that if the spermatozoa become really in in in in danger, which means no spermatozoa that that would be surviving, then spermatozoa, they can travel to the brain, convert themselves in a neuron and affect our brain. So if you if you look at it, it sounds like science fiction, but this is really happening in the human body. If we would have known that, that's what I said, if we would have known that, we would never have invented all those things we have invented because we never knew the consequences once again.
Dr Rupy: I feel like we could have a full conversation all about the decline in fertility and the various mechanisms behind that. I want to talk about the paper that I found absolutely fascinating and it's called intermittent living, the use of ancient challenges as a vaccine against the deleterious effects of modern life. And my from my reading of this, it's around how our modern lives are more comfortable than ever. We have food on demand, we have heating at the touch of a button, you know, we don't need to experience the hardships of our natural environment anymore. Yet we're seeing rising rates of things like chronic fatigue, anxiety, metabolic diseases. I wonder if you can expand a bit more about this term intermittent living and how this relates to this paradoxical picture that we have today.
Dr Leo: Look, two of the of the two main sciences, so disciplines, they are bankrupt, which is psychiatry and psychology. If we look to all all the statistics about depression, the number of the number of people suffering from depression is constantly increasing. If we if we look at the number of suicides, so if people suffer depression and our interventions would be okay, the number of suicides should decrease. Not happening. Number of depressions is increasing, number of suicides is increasing, and at the same time, the amount of money we're spending in all the medicines to treat people with depression, they have increased exponentially. So something is wrong. Something is wrong with the way we look at health and the way we look at at mental and and physical health. Okay? Where does where does this come from, this intermittent living thinking? It it comes from the fact that when when I studied anthropology, cultural anthropology, then then my teacher, who was a white woman who lived with white people in Africa, and she thought that she knew about evolution. I said, how can you how can you say that you know about evolution? You lived with white people in Africa. You you only have seen how white people live there. We have to understand where where longevity and health come from. And if we look at at our ancestors, and if we look at the way they achieved things, it was always based on four characteristics. Okay? And those four characteristics end up with a mindset. And and mindset, now gradually people start to believe, which is lasted a long, long time, how emotions, how the way we think affects our health. Okay? So the last word is mindset. So if we look at our ancestors, if they had were in need, they were hungry or thirsty or they were cold or hot, or they had a wound, then then they they had to do something to to um solve that problem. They had to move, exercise. Okay? And that took time. if you look at at at our ancestors, normally, normally, it took them in between three and six hours to hunt or to gather. Then it took them more or less three to six hours to prepare the food, which is 12 hours. And then they ate. So there was a huge time lock between their hunger and the reward. So it was about an effort, it was about time, and they had to take risks. And that and that was that were huge risks. There were lions, there was everything, and there were co-species who was hunting or gathering the same food. And then they achieved their reward. And that produced something which is the most important mindset to to um to gain, let's say, the to gain or to win or the best way is you have to deserve health. So can you imagine that when I when you then find your food and you have done everything you you've done and you took you took your risks, then the feeling is I deserve this. And health, you have to deserve. That is not for free. And we think in our cultural, comfortable life that people that longevity in the blue zones is based on comfort. Longevity in the blue zones is based on very hard work. Very hard work. They move at least six to eight hours a day and they're always taking care of the family. That's an that's an effort. And they have to take risk. And and they deserve it. And and that feeling of deserve it, that's a mindset which activates the reward system in the brain. And if you want to know, we could discuss it a little bit later, but that that part of the brain is responsible for which immune response you are going to mount in which contextual situation.
Dr Rupy: So just to relay that back, these four characteristics, you mentioned hunger.
Dr Leo: So no, I mentioned effort.
Dr Rupy: Oh, effort, sorry, yeah.
Dr Leo: Time, risk, and mindset.
Dr Rupy: Okay. And these are the outcomes of some of the stresses of the of their lifestyles, i.e. the hunger, the thirst.
Dr Leo: Basic needs.
Dr Rupy: Basic needs, yeah.
Dr Leo: Thirst. I don't know if you if you if you have ever been in in with hunter gatherers, I've been. But the the Yanomami Indian and the Tsimane Indian in South America, although perhaps they live aside a river, they can't drink that water because that water is completely polluted with the faeces of of wild animals. So they have to find water. And it's incredible that they that they know that there are only two two tree types in which you of which you can drink the water because all the other other trees, if you drink their water, you you die. And they know those trees. It's incredible. And and and so they drink that water. So that's if you think of that, wow, that that's philosophy, that that is wisdom. That is not information on a computer, that is knowing about life. Okay? So if you see how they how they what they do, then then it it is not effortless. And that is you know something, we have the weirdest reward system of every single animal. Our reward system is functions really different. We cannot I do a lot of comparative physiology. So I investigate brown bears, elephants, and see why they don't get certain diseases in their natural habitat. They also have a thing which is called species specific stress exposure. You understand? Every species needs its own stress exposure. Okay? So can you imagine brown and black bears in Canada? If they live there, they cannot develop cardiovascular diseases. It's impossible. And you say, how come? Obviously, deterministic genetic thinkers start to find to search for a gene. That's that's that is with all respect, has got nothing to do with it. Although they would find a gene that would never explain why they don't develop cardiovascular disease. But they can't.
Dr Rupy: For for the listener, can you just define deterministic genes for them?
Dr Leo: Yeah, so deterministic genes is people thinking that the blueprint of life are genes, they always search for a genetic answer. That's genetic deterministic thinking. I don't think like that. So so those brown and black bears in Canada, they have to um they have to survive the winter. So there are three months in which they live in a torpor, in in overwintering. So and that's very cold. And they have to down regulate their metabolism. And then in those three, four months, their body temperature is perhaps 31 degrees Celsius.
Dr Rupy: 31 degrees Celsius. Wow.
Dr Leo: Yeah, yeah, yeah. And I don't know if you know, but if you overwinter, if those animals hibernate, they don't sleep. People think that is that they are sleeping. They are not sleeping. They are awake. But with a very low metabolism. And they wake up every day to sleep for eight hours.
Dr Rupy: Really? Oh my gosh, I didn't realize that.
Dr Leo: No, nobody knows that. I literally thought they just go to sleep. No, everybody thinks they are sleeping all the time. They can't. No, that's that's impossible. They would die. They would die. So they are in torpor. They so they decrease their metabolic activity. That's what they that that is almost magical how those animals do that. And when and when you then see what happens with their with the brain of those animals during those three months, it really gets atrophic. But then they come out out of the torpor, out of the sleeping period, and in 24 hours, their brain is completely normal again.
Dr Rupy: After 24 hours.
Dr Leo: Yeah, yeah, and we should and that's what we should investigate. I'll explain you how important this is. Okay? So they come out of it and that's their species specific stress exposure factor. Very cold winter. That's what they need.
Dr Rupy: And that's why they don't get cardiovascular disease.
Dr Leo: And that's why they don't get it. Because you then you take them to a zoo in Los Angeles and they get atherosclerotic changes, although they eat fish, because we know what those animals eat in in in in the wild. But we don't understand that that stress exposure is incredibly important for us.
Dr Rupy: That's a really good point and I want to I want to highlight that for the listener actually because you're taking the same bear that does not experience cardiovascular disease, putting it into a different environment where the cardiovascular disease is expressed phenotypically. So they actually see that in their in their physical in their physicality. So it can't be a genetic thing. They can't have engineered their evolution. They can't have evolved to not have cardiovascular disease because they experience cardiovascular disease in the right environment.
Dr Leo: Exactly. So it's a it's a 100% contextual thing. The context changes and the text is not capable to adapt to that new context.
Dr Rupy: Gotcha.
Dr Leo: And that's very important. So we are living in a new context, in a cultural context. And and it's incredible difficult to adapt. And if we want to wait for some some bottleneck, then we can wait for a long time. You know why? Because modern life is toxic, but it doesn't kill little children and it doesn't kill pregnant women because that's that would produce a bottleneck. That would produce perhaps the death of 7 billion people. But it's not going to happen because all those danger factors we're living in, they make us ill, but because of the fact that we have an incredible advanced acute medical system, acute medical system, we survive. And because of the fact that we survive, there's not going to be a genetic polymorphism or or a thing that's said, oh, you can achieve uh you call that non-fragility in this in this context. Forget it. But that does not mean that there is not a possibility to adapt, which is called turbo adaptive capacity.
Dr Rupy: Turbo adaptive capacity.
Dr Leo: That means that is that's very speedy. So not wait, I don't I don't want my kids to be ill. I want them to adapt to this environment today. Okay? And I'm not going to wait for some gene that would give me some advantage. That advantage we can achieve ourselves.
Dr Rupy: Okay. And I was just thinking back to those characteristics that we were talking about earlier, effort, time, you know, risk, uh I I'm just struggling to think of days where I've done any of those really. I mean, like apart from cooking, but because everything is so convenient these days, even the red lentils that require cooking soaking only need about 15 to 20 minutes because they've already been hulled, they've already been taken from their legume structure. Like so much of that stuff has been done for us. So we live in a very sort of luxurious period where we don't need to invest the time even to do the most basic of things like cooking.
Dr Leo: I'm going to I'm I'm going to answer or tell some say something about what you said, but I I I look, a lot of people think that health, they say, I don't understand why I get cancer. Look, I don't smoke, I don't drink, I eat organic. I shouldn't have I should not have cancer. And then I said, that are three things out of 25 domains.
Dr Rupy: Okay.
Dr Leo: So don't think that eating organic, um not drinking and not smoking, that you there you're going to win the Olympic games. Forget it. Then when you're 50 years old, you can have you can have cancer like anybody else. Because that's what you say. Okay, I don't smoke. You know, then you don't have to buy it either. So perhaps, perhaps you investing a little bit of money would be better for you because that's nice stress. Okay? Then you don't drink. I don't know if that's always the good thing to do, not drinking a glass of wine in a social situation. Okay, yeah, yeah. And eat organic food, definitely. But one moment, how did you get that food? Ah, it was brought or you went with the car. Aha. And and how do you drink? No, I I have the water water bottle next to me. Aha. And and how is your sex life? And how is your sleeping? And do you chant? And are you spiritual? And do you socialize? And so if I'm I would finish, there are 25 domains that which all are basic needs for human beings. Competing, playing. Competing is so healthy for people. It's so so mythological, not true that that that they think that we should not compete. That is so incredible human to to compete. It's normal, but not to kill anybody. No, just to become better. And and that and that is our reward system. So we need that those challenges. And and if you if we afterwards going to talk for instance about about hypoxia and the use of of of breathing exercises, it's an incredible game to do apnoea in a group and see who who who holds the longest. And then but then you come to measure afterwards the cortisol level and the noradrenaline level and the immunological cytokines, and you fall from your chair. You say, wow, the person who won has the lowest cortisol level.
Dr Rupy: Oh, really?
Dr Leo: And then you say, what the hell is this? How can this be? You understand? But the testosterone comes out of his ears or her ears. So so you really can influence everything in your body. And that is so important that people have to understand that hormones and cytokines, they are not in charge. Genes are not in charge. We are in charge. We are an organism and we determine how our organs function, how our systems function, how our organelles function. And the and the organelles are not in charge. We are in charge. So so I always ask people, look, evolution gave us an incredible brain. But why don't we use it in our benefit? You understand? That that is what we should ask everybody. Everybody knows that exercise is necessary. We don't. Everybody knows we shouldn't eat that much. We do. Everybody knows that sitting time is very toxic. And what do we do? We sit on our gluteus maximus for eight hours a day and nobody feels, and that's very important, the need to stand up. I think that and that's something which is very important. We don't feel the need to stand up. We don't feel the need to gather food. We don't feel the need to stop breathing. We don't you understand? We don't feel it. So so we that's why we don't do it. And there is not something like a symptom that would make us do breathing exercises. That would be fantastic. It would be fantastic that people stand up from their chair every half an hour because sitting produces a symptom. It doesn't produce a symptom. That's weird, eh?
Dr Rupy: I love that that that idea that there isn't this innate drive to do something that is very natural for humans. In the same way, you know, I mean, if you were to hold your breath, there is the innate desire to take a breath, to to breathe. You know, we do have these mechanisms in our brain that get us to do certain things, but in terms of going out today and experiencing stress intentionally, we're we're sort of always defaulting to the easiest option. And again, I've always thought about that through the evolutionary lens. Is that an evolutionary advantage for us? The fact that we are seeking comfort?
Dr Leo: Of course. What what we did with that is um diminish acute mortal factors. Look, the brain is robust, but at the same time it's flexible. All our systems are robust systems, but at the same time, very flexible. If that wouldn't be like this, would be very weird. But you can imagine that that the highest achievement whatever animal could achieve is having everything in a hedonic way without any effort. That's completely normal. Obese people who don't engage in exercise and eat 20 times a day, they are the normalest people in the whole world. We are weird people. We are crazy. People look at me, that guy is crazy. He stands up and starts to do push-ups. But why does he do that? We are we are comfortable. We are why should we do that? That's that's it. You should do it, but it's something you have to you have to in our environment, you have to choose for. It will not it will not happen spontaneously with one exception. Afterwards, I'm going to explain you the exception.
Dr Rupy: Okay, all right, fine. Well, I I love that point about us trying to experience hedonism in the most comfortable way possible. And how I I guess like we're all experiencing this incredible point in our evolution where we have so much accessible to us that we have to engineer our lives to be slightly more stressful for our health benefit. And I don't think we've ever experienced that along our timeline. So this is where I I think this idea bringing it back to intermittent living is so, so important. And I was going to start off with some of these ancient triggers with health benefits starting with fasting, but because you've mentioned hypercapnia, I think why don't we start there? So what is hypercapnia? And why would we have experienced that evolutionarily and what potential advantages are there for us?
Dr Leo: You you probably can imagine if if we if we um climb over the Caucasus mountain, we're going to suffer hypoxia, definitely. Because the the the the oxygen pressure um is perhaps 11% and not 21 like
Dr Rupy: 11%?
Dr Leo: 11%. Yeah, yeah, yeah, yeah. And then so you hardly have any oxygen and you're going to produce an enormous amount of CO2. Which is an incredible uh stress factor, both of them, both of them. It's very interesting. We do not have oxygen receptors on every cell, but we have CO2 receptors on every cell. So CO2 fluctuation, down and up, is something which is um sensed by every single organ and cell. And it produces an increase of blood flow if it's CO2 high, hypercapnia, eh? If you look at the immune system, all immune cells have CO2 receptors. And high level of CO2 eases the immune system. But it does even something else. It helps you, if you train this, and you have to repeat the training because because otherwise it doesn't work, then you gradually, you gradually stop being panic sensitive because CO2 is a panicogen. It is the the substance producing panic attacks, producing anxiety. No, anxiety is not true, panic attacks, panic attacks, eh? Because it's in the in the brain stem. And and panic attacks is a consequence of direct danger in time and in distance. We have three types of fear. We have panic, fear, and anxiety. Every every type of fear is localized in another part of the brain. The brain stem is panic, then the limbic system is fear, and the prefrontal cortex is anxiety. But they are all the three of them are based on evolutionary development of of first reptiles and then mammals and then human beings, completely normal. So H CO2, um carbon dioxide makes people incredible panic resistant.
Dr Rupy: Okay.
Dr Leo: And you can imagine how that works for instance in deep deep sea divers or in Olympic swimmers. You cannot imagine Olympic swimmers. I I have trained several Olympic swimmers uh in the last in the last uh Olympic games and uh and they they trained hypercapnia every day, four times a day, 20 minutes.
Dr Rupy: You can imagine with a plastic bag.
Dr Leo: 20 minutes. So no breathing for 20 minutes.
Dr Rupy: No, no, no.
Dr Leo: Breathe one and a half minute in a plastic bag.
Dr Rupy: Oh, into, okay.
Dr Leo: Yeah, which which means they they inspire CO2. Yeah. 30 seconds pause, one and a half minute, 30 seconds, one and a half minute, 30 seconds, 20 minutes in a row, four times a day.
Dr Rupy: Wow.
Dr Leo: And um and they're and and their resistance, their anti-fragility, so increased enormously. But it is dose dependent.
Dr Rupy: Okay.
Dr Leo: So it's not, oh, I'm going to do two minutes of hypercapnia training and I I I will win the Olympic games. Forget it. You have to you have to challenge yourself. And you know, the feelings of the of of the feeling it produces is a feeling of power. Nothing can uh hurt me anymore. That that are really the feelings people uh say, when we don't do those things, that that that produces a feeling of being in charge.
Dr Rupy: Yeah. Yeah, yeah. Have these techniques ever been used outside of like really motivated individuals like Olympic swimmers and used in a a population of of folks who are suffering generalized anxiety disorder or panic attacks to good effect?
Dr Leo: Very much. You know, and and and COVID-19 was very interesting because COVID-19, people didn't know, but nurses and doctors in the beginning of COVID-19, we were all all in panic. So how were people treated? Like they had as if they had tuberculosis. So with a mask, but with a closed mask. So what what were they doing? Hypercapnia. They didn't know that they were doing hypercapnia. And those and those experiences, they they have been um published in nature and science. And people say, it was so weird. We didn't know what happened. But afterwards, we understood we were doing hypercapnia. And what they really were doing is therapeutic hypercapnia. As if it was, so they they became, they became through hypercapnia more or no, more protected against the virus. So so that is something. So you you use a breathing exercise that produces a thing which is called biological amplification and it protects you against pathogens. Fantastic. It's so easy. It's the most easiest way to protect yourself against pathogens, doing breathing exercises.
Dr Rupy: And are they are these all sorts of breathing exercises or I mean, I'm assuming there's like a bit of a smorgasbord of of different types of training that you can do, you know, hyperoxygenation, uh breath holding, uh certain types of methods where you you do box breathing, etc. You know, what which ones do you think if if someone's listening to this and they're like, you know, I I want to become more confident, I want to become less fearful. Um what are some of these training techniques for hypercapnia that people should should perhaps investigate or try?
Dr Leo: The plastic bag breathing is the oldest one. And that was already published in 1932.
Dr Rupy: Okay.
Dr Leo: So there's nothing new.
Dr Rupy: Uh-huh.
Dr Leo: But everybody forgot about it.
Dr Rupy: Why do we forget?
Dr Leo: Because it's not you can't there is not one patent for it. You cannot sell it. It's it's really it is too cheap.
Dr Rupy: Does it come down to that, do you think?
Dr Leo: I definitely know so. I don't I don't but now it's coming back because because um the audience is is much more um informed. It's I don't think it's all knowledge, but they have a lot of a lot more information. People are fed up. I think that you also know, people are fed up that they have to go to 20 specialists because they have 20 different symptoms. And they are searching for not for alternatives because I don't because I don't want to to call this alternative medicine because it is not alternative medicine. It's very conventional medicine. It was only forgotten about. The moment the moment pharma industry became important, we lost all those uh interventions in nature. Because because believe me, our ancestors, they there was they couldn't phone a doctor. They had to solve their problems in in whatever way. And and so nature should has to have the answer to all to all our diseases. It's it's impossible that that that the answer is not there. It has to be there. Perhaps we haven't found it, but it has to it has to be there. In in behavioral things, in breathing exercises. And and and perhaps because of not being susceptible to develop a disease. Because I think that that is the most important thing. So did our ancestors suffer atherosclerotic diseases? Uh no. If you look to the Maasai today, do they have atherosclerosis? You cannot imagine, much worse than you and I. But it is non-symptomatic atherosclerosis. It's not it's not an atherosclerosis um with inflammation. It's a stable atherosclerosis. And and they don't have any problem with it. So nature has to offer all kind of of solutions. And perhaps we only have to search for it or not even search for it anymore. Perhaps it is inside uh inside our um actual environment because you you we can do those breathing exercises. And I think that's one of the most important things people should hear. It are not the challenges that improve our health. It's the reward after it. That's so important.
Dr Rupy: So it's not the challenge.
Dr Leo: It's the reward.
Dr Rupy: It's the reward. Okay. So it's it's the the coming back to normality, I was going to say, but coming back to balance, coming back from the the sort of stressed state to the
Dr Leo: But but can you imagine you haven't eaten for 18 hours. And you worked out. And you worked cognitively and physically. And then you yourself or your partner or the family makes a beautiful meal. And you eat that meal. And that meal is composed of everything we we would need, micronutrients, macronutrients, it looks good, it smells good, it it everything, all the senses are triggered. And we and you haven't eaten for 18 hours. That meal is a medicine.
Dr Rupy: Yeah.
Dr Leo: But that meal is a medicine. But it's not the 18 hours of fasting. If you look at the body when we are fasting, we are in stress. We have high cortisol, noradrenaline. I don't want this. But afterwards, you activate the reward system. And so the expanded acute stress response, that's what we coined, it's not an acute stress response anymore, it's the expanded acute stress response, which involves the whole body from the hair to the to the germ line, to your big toe, the antidote is is the activation of the reward system. So if you can maintain this rhythm, it's very difficult to develop a disease.
Dr Rupy: Yeah. Um let's talk a little bit about fasting actually in that respect because you hear people talk about fasting and I think this is really refreshing for me to hear because most people talk about the stressed state and how that is where the medicinal effects occur. So you you you upregulate autophagy, you improve nutrient sensing, uh the calorie restriction has some benefit to it as well. Not really on the other side when you break your fast. Uh and what I'm hearing from you, it's it's that point where you reach where you satiate yourself, where you actually have food again. That's where the medicine is. And I think there's there's a disconnect in in the way I've certainly thought about fasting and its potential benefits up to this day. And I wonder if we could dive into some of those mechanisms. Is it that dopamine reward that you get at the end? Because the way you describe it to me, it sounds like, wow, I'm I'm going to experience this food and it's going to be a wonderful, wonderful experience, a wonderful feeling to be satiated. And that's, you know, perhaps that's what the benefit is because of.
Dr Leo: I'm I'm going to I'm going to give you an example of very recent research we've done. It's not published yet, but it's going to be published. So and that we we we it was already done in in mice, but not in human being.
Dr Rupy: Okay.
Dr Leo: Okay? So we we have a whole bunch of of ex-terminal cancer patients. But I'm I'm saying ex-terminal because they are not terminal anymore. So they were cancer. A few of them, they suffered an enormous cachexia. So they they um they they did not even have the motivation to continue living. And and although we we we did everything to um motivate them again to engage in some purpose in life and motivate them to to engage in all the things we're talking about, we didn't achieve that. And we thought, what the hell is this? Okay? And then that study in mice, that was published in science, that was very very opening our mind because they they showed that that the tumor itself produces an a neuroinflammation. The neuroinflammation affects two very important sides of the reward system, the pallidum and the nucleus accumbens, not important, eh? And they when they are inflamed, they produce GABA. So they they so they produce a neuroinhibitor and that inhibits the reward system. So that that makes sense. If the the tumor itself makes people surrender. So cancer only has one purpose. It wants to kill the host. And it it uses even psychological mechanisms to make a cancer patient surrender. So what we did then do, that's what we did, is those those um the enzymes that are that are responsible for the cachexia, they are all vitamin B dependent. So then we started give people very high the cancer patients, very high uh amounts of B vitamin supplements. The cachexia disappeared and they started motivation again. So then we measured in in the urine dopaminergic metabolites. Before the intervention, we didn't have any dopaminergic metabolites. After the interventions, they had much more dopamine.
Dr Rupy: So so just to explain to the listener, the dopaminergic metabolites, what was that indicative of? The fact that you found that in the urine?
Dr Leo: Yeah, because because if if there are metabolites of dopamine in the urine, then you produce dopamine. If there are no metabolites of of of of dopamine, that's much more um validated than dopamine in the blood. Doesn't say anything. You have to measure it in in in the urine. So it was incredible interesting. So so it is really about dopamine. But it but it goes one step beyond because it's not dopamine, it is it is when dopamine is produced and the person that is engaging in a search and that search is successful, the dopamine is converted in endogenous morphine, which is not the same as endorphins and enkephalins. It has got nothing to do with it. Morphine is the end. What and what I mean literally is the end, eh? I'm hungry and I want to find food.
Dr Rupy: Okay.
Dr Leo: Okay? People think when you're hungry, you only have to find food. But that's not true. Hunger should be nutrient specific. We have receptors for magnesium, we have receptors for calcium, and we have receptor for zinc. We have to receptor for natrium. We have receptors for every single micronutrient. So hunger should be nutrient specific.
Dr Rupy: Okay.
Dr Leo: So it's not true that hunger is some some universal feeling people have. No, we can really have magnesium, calcium, zinc hunger. The three of them have the same taste. They're bitter. And they are umami. So so what what should attract you is nutrients with umami taste and or green. You understand? We our brain and our body really knows about it. There are two receptors which is called TRPM6 and 7 and they are used by the three micronutrients. So just suppose you have magnesium hunger. You have so not hunger, magnesium hunger, eh? So you're hungry and you find magnesium rich food. What did you do? You had to find it. So it was an effort. It took time. You can imagine, it took time. You had to take a little bit of risk. And you found, you you have found the right nutrient. It's not about nutrient, the right nutrient. This is one step beyond. It's it's not only I deserve this, no, it's the end of the searching process. At the moment that the prefrontal cortex detect, detect the right reward, the dopamine which we have produced by moving is converted by a liver enzyme, you see, a liver enzyme which is vitamin B dependent, converted in morphine. And that moment, your brain and your immune system are at ease. The end. Those two systems responsible for the fact that we prevail, the brain and the immune system, they don't like open endings. You you've written books. If you if you ever write a novel, never write it with an open end because that makes people ill. We don't like open ends at all. We hate open ends. I I I don't know you, but but but um the hobbits, the trilogy, the trilogy, yeah, yeah. The first one, I knew it was a trilogy. The second, I didn't know. So I I went with my kids to the cinema thinking I would only it would only be one one movie. And when five when there were five minutes left, I said to the kids, there has to happen a lot still because I and then it said, and part one.
Dr Rupy: One, yeah. Yeah, yeah.
Dr Leo: One and a half year waiting for the second. So what did I suffer? A low-grade inflammation. I suffered a low-grade inflammation. My immune system was was really disturbed because the brain and my immune system thought the end. No, the end. So that's that's how we people search and that's how the reward system functions. And that is so beautiful to see that if people we search, we are always searching for food and for water and for love and for social interactions, etc. And if you then achieve what you're looking for, that's as I say, then you really have two two very important mindsets functions. I deserve it and I'm I am okay. It's not about happiness. Happiness lasts seven seconds. It's not about it's not even optimism or positivism. No, that's not true. It's about this is what I've I've been looking for and I've achieved it.
