The Dr. Hyman Show

The Future of Medicine Is Energy: Dr. Martin Picard Explains

109 min
Nov 19, 20255 months ago
Listen to Episode
Summary

Dr. Martin Picard, a behavioral medicine professor at Columbia University, explains how mitochondrial function and energy flow are fundamental to human health and disease. The episode explores the Energy Resistance Principle—a framework suggesting that optimal health requires balanced energy resistance, not constant high or low states—and discusses how stress, diet, exercise, and lifestyle affect mitochondrial function across mental health, metabolic, and neurodegenerative conditions.

Insights
  • Energy resistance (how easily energy flows through the body) is a unifying principle underlying all chronic diseases and aging; too much or too little resistance is harmful, but oscillating between high and low states builds resilience
  • Mitochondria function as an intracellular communication hub receiving signals from stress, toxins, microbiome, and immune system—not merely ATP-producing powerhouses—making them sensitive indicators of overall health
  • Psychological states directly alter mitochondrial structure and function; optimistic individuals show more mitochondria in the prefrontal cortex, demonstrating the mind-body connection at a cellular level
  • GDF15 (Growth Differentiation Factor 15) is a pan-disease biomarker that signals energy resistance and appears elevated across depression, diabetes, dementia, bipolar disorder, and cancer—offering potential for unified disease monitoring
  • Functional medicine's approach of removing harmful inputs and adding supportive ones activates the body's innate healing mechanisms by optimizing energy flow, rather than treating individual disease labels
Trends
Shift from disease-centric to energy-centric medicine: treating root causes of energy dysfunction rather than symptom management across disparate diagnosesMetabolic psychiatry emerging as a clinical field: ketogenic diets and mitochondrial support showing efficacy for bipolar disorder, schizophrenia, and depression by improving brain energy metabolismContinuous biomarker monitoring replacing single-point testing: future of personalized health will use real-time energy resistance tracking (like CGM for glucose) to optimize lifestyle interventionsMitochondrial supplements and metabolic therapies entering mainstream clinical practice: CoQ10, NAD, NMN, and ketogenic protocols gaining evidence-based support for neurodegenerative and metabolic diseasesEnergy resistance as a unifying framework for aging and disease: consolidating hallmarks of aging (inflammation, DNA damage, telomere shortening) under a single energetic principle applicable across conditionsPsychobiology and mind-body medicine gaining neuroscientific validation: stress transduction through mitochondria explains how psychological states directly cause physical disease and agingHormesis and stress-adaptation becoming central to longevity strategy: controlled energy resistance spikes (exercise, fasting, cold exposure) followed by recovery periods activate longevity pathwaysFunctional medicine gaining academic legitimacy: major research centers (Columbia, Stanford, Mayo Clinic) now funding mitochondrial and metabolic health research previously dismissed as alternative medicine
Topics
Energy Resistance Principle and mitochondrial bioenergeticsMitochondrial dysfunction in mental health (depression, bipolar disorder, schizophrenia, autism, ADHD)Ketogenic diet and metabolic therapy for psychiatric illnessGDF15 as a pan-disease biomarker for energy resistancePsychobiology: stress transduction to mitochondriaMitochondrial supplements (CoQ10, NAD, NMN, carnitine, urolithin A)Exercise physiology and metabolic compensationSleep and circadian rhythm as energy resistance cyclesMicrobiome and immune system effects on mitochondrial functionFunctional medicine framework for health optimizationHallmarks of aging and mitochondrial dysfunctionVO2 max testing and energy capacity assessmentIntermittent fasting and metabolic resilienceMitochondrial DNA inheritance and genetic mitochondrial diseaseInflammation as downstream effect of energy resistance
Companies
Columbia University
Dr. Picard is a professor of behavioral medicine and directs the mitochondrial psychobiology group and chairs the ene...
Mayo Clinic
Offers clinical GDF15 testing for mitochondrial disease diagnosis; conducting research on mitochondrial function in v...
Timeline (MitoPure)
Supplement brand containing urolithin A for mitochondrial renewal; Dr. Hyman endorses and uses the product daily
Metabolic Minds
Organization funding mitochondrial and mental health research at Columbia and other institutions; founded by Jen Bazu...
Stanford University
Sabani Setti conducting metabolic psychiatry research on mitochondria and mental health
UK Biobank
Large-scale study of 50,000+ people analyzing protein biomarkers including GDF15 across 900 clinical phenotypes
People
Dr. Martin Picard
Primary guest; researcher developing Energy Resistance Principle and studying mitochondrial psychobiology and stress ...
Dr. Mark Hyman
Host conducting interview; shares personal experience with chronic fatigue syndrome and recent recovery from catastro...
Chris Palmer
Mentioned as pioneer in brain energy approach to treating psychiatric illness using metabolic therapies
Sabani Setti
Conducting metabolic psychiatry research on mitochondria's role in mental health conditions
Suzanne Goh
Using mitochondrial supplements and functional MRI to treat autism spectrum disorder by improving mitochondrial function
Jen Bazuki
Founded organization after son's recovery from bipolar disorder via ketogenic diet; provided over $1 million grant to...
Herman Poncer
Conducted energy expenditure studies with Hadza hunter-gatherers in Africa, discovering fixed energy budget across ac...
Quotes
"Energy has been the missing dimension of medicine. If your mitochondria stop working, you're dead in seconds."
Dr. Martin PicardOpening segment
"You are energy. You're not a machine that is powered by energy. You literally are energy."
Dr. Martin PicardMid-episode discussion
"The reason stress is bad for us, the reason stress makes us tired and ends up damaging our organs and ends up aging us faster is because it steals energy from the things that keep us healthy."
Dr. Mark HymanEarly discussion
"Health is a field-like state that emerges from the flow of energy through a structure. It's a dynamic process, it's a dynamic state that is energetically sustained."
Dr. Martin PicardDefining health
"GDF15 is by far the best marker for most diseases. It's a pan disease biomarker because all of these diseases have an energetic etiology."
Dr. Martin PicardBiomarker discussion
Full Transcript
Energy has been the missing dimension of medicine. If your mitochondria stop working, you're dead in seconds. Dr. Martin Picard is a professor of behavioral medicine at Columbia University and directs the mitochondrial psychobiology group, Howe psychology affects your biology, where he explores how our minds and our mitochondria connect. As the chair of energy and health at Columbia Aging Center, he leads NIH-funded studies making stress, energy, and healing and work with scientists around the world to transform our understanding of health. What are the mitochondria and how we should be thinking about them from the perspective of how they're integral to our entire communication network and our energy network that runs our body? The potential energy inside your body, it's equivalent to a lightning bolt. And somehow we don't combust and we don't burst into flames. If you mess up with the energy, like just a little bit, you can actually alter the human experience. You can alter your state of mind. You're saying we shouldn't be focusing so much disease, we should be focusing on creating health. You look at which diseases are there evidence for that mitochondria are impaired in some way. And it turns out every disease, the reason stress is bad for us, the reason stress makes us tired and ends up damaging our organs and ends up aging us faster is because it steals energy from the things that keep us healthy. So people listening, they're all, okay, I have some of these conditions. Where do I start? I'd start by saying you're not broken and there are no parts I think to be fixed or surgically removed or transplanted. There are things that we know can unleash the healing potential of the body. Wow, what a conversation. At 65, I'm still pushing my limits, cycling long distances, trekking through Patagonia and living life to the fullest. But staying active as I age isn't just about willpower. It's about giving my body the vital support it deserves. See, as we get older, our mitochondria, the powerhouse of our cells, naturally begin to slow down, stealing our energy and strength. That's where timeline powered by MitoPure has truly been a life changer for me. It contains urolithin A, which helps renew and recharge my mitochondria, keeping my muscles performing like they did when I was younger. MitoPure is backed by solid research, showing it can boost cellular energy, increase muscle strength, and support overall healthy aging. Personally, I take MitoPure every day. It's helped me keep up with my active lifestyle, whether it's a high intensity workout or an adventure in the mountains. So if you're looking to support your muscles and want to feel younger from the inside out, my friends at Timeline are offering 20% off your first order. Check it out at timeline.com slash drhymon. That's timeline.com slash drhymon. Your future self will thank you. Well, Martin, welcome to the Dr. Hyman Show. I can't tell you how excited I am to have you here. Thank you. I'm excited to be here. You are a really deep thinking scientist. You're going into the weeds on how to understand the human body in a new way. You're at Columbia University. You've published many papers that are revolutionizing or thinking about how the body works. And you're not a practicing doctor, but you're a scientist. And what's striking to me as I've read your work is that you come to the same conclusions about the nature of nature, the nature of biology, the nature of how our bodies work, as I have as a practicing physician for over 40 years. And I've observed things clinically that I knew were true, but the science hadn't fully caught up with. And before the podcast, we were talking about my book, The Ultramind Solution, which I wrote in 2008, which was based on what I was seeing in my practice, which we call anecdotes, but I think it's more like anecdata. And I was observing how, particularly in terms of mental health and the ultramind solution, how energy metabolism was such a key part of so many conditions of the brain, from depression to bipolar disease to schizophrenia, to Alzheimer's, to autism, to ADHD, and on and on and on. And I'm like, I know this is true in my cells, in my bones, I know it's true. And I can't wait till science catches up with it. And guess what? It has. And it's so exciting. I mean, I got to meet you through a friend of mine, Jen Bazuki, basically had a son with bipolar disease. And she had read my book, they watched a broken brain series that I had as a documentary. And they got this aha moment and they put him on a ketogenic diet, which really shifted his metabolic function in his brain, and that led him to fully recover from bipolar disease. And if people want to learn about it, then go to metabolicminds.com. And she's recently given you over a million dollar grant to do work at Columbia to dig deep into the role of mitochondria in mental health. But mitochondria we're going to talk about, because that's your gig, is mitochondria. And probably people don't know what those are, but I want to have you explain it a little bit. But, you know, this is a high level, you know, in functional medicine, which is what I do. The framework is really about the science of creating health. So people say, what is functional medicine? I says, it's not about diseases. In fact, I don't really care that much about diseases. I care about the science of creating health. And when you create health and you engage the body's repair, renewal, regenerative mechanisms, the body can heal. When you change the circumstances, you talk about subtracting versus adding. In medicine, we add drugs and all kinds of stuff, as opposed to subtracting, like taking away bad food, taking away too much stress and so forth. That there's a way to take out the bad stuff and put in the good stuff that allows the body's own system to repair and heal. And that's the fundamental premise of the future of medicine. What I would say we're in this incredible moment in science where we're understanding the nature of nature. We're understanding the laws of biology. And if I said to you, what are the laws of biology? The average person, I don't know, evolution, maybe. If I said, what are the laws of physics? You know, there's thermodynamics, there's gravity, there's quantum physics, there's all these, they're not equations, but there are equations and it's a knowable thing. But for laws of biology, we're just beginning to understand what those are. You know, Einstein said, I don't wanna know the spectrum of this or that element. I wanna know the thoughts of God and the rest of your details. So in a sense, we're actually being able to see the mind of God. And if you don't believe in God, whatever the thing you believe in, the way we're created, nature of nature, is just so exciting to me. And so reading your work, I'm just jumping out of my chair because I'm like, wait, wait, wait, this is what I've been saying for 30 years. And this is so cool. And I wanna explain how, in your particular field, which is really understanding how our bodies take energy from food and oxygen, and turn it into the energy that runs our body. How we turn the energy, the sun, that's transmuted through plants and animals, and the plants that the animals eat, into the storage form of energy that then we burn, just like the sun creates a tree, and then we can burn the wood and create the fire, that's what's happening in our bodies. And that process is so important to so many diseases, not just mental health, but to diabetes and metabolic health, really important. Everything is connected. And so mitochondria are one of those fundamental physiological systems that we talk about in functional medicine that we have to understand and treat. And what's so ironic is that in traditional medicine, we learn about it, the Krebs cycle, which is first year biochemistry class, which essentially is how we make energy from food and oxygen and turn it into ATB. And that's it. And then we're like, oh, biochemistry is not important, let's talk about real disease, and we forget about it all. We don't know how to diagnose it. If there's a problem, we don't know how to treat it if there's a problem, and we don't really understand how they work. And I personally had chronic fatigue syndrome when I was 36, which is how I learned about all this. And I felt my mitochondria not working. I want you to sort of help us understand, now that we sort of laid the groundwork of, we're gonna talk about the science of health, and we're gonna talk about the fundamental role of mitochondria in our health, and how to understand it, how to diagnose problems with it, and how to treat it. I want you to sort of explain for the layperson, what are the mitochondria, what the flaws are in our current thinking, the limitations, and how we should be thinking about them from the perspective of how they're integral to our entire communication network and our energy network that runs our body. Before talking about mitochondria, I want to say a few words about it. Yes, here you go. I'm so happy to be here chatting with you about this and to find someone who has come to, a conclusion that energy is really what drives everything in the body. It's also what drives our minds, right? And our ability to interact with another human being and with the world, and our ability to do and feel, and to our conscious self, is really emerges from the flow of energy. And if you think about it, the main difference between a dead body, right, it's just a cadaver, and a thinking, feeling conscious person that actually has experiences, it's not the cells, it's not the molecules, it's not the genes or the organs, everything is still the same, but when the body is alive, the main difference is energy is flowing through it, right? It's the flow of energy that actually brings everything into life. So without energy flowing, the genes, right, like the beloved genome, and there's been so much written about, like the genes control our lives, the blueprint of life, and genes is your destiny. Without energy flowing, genes are just like this, and the genome is just an inert repository of information. There's potential there, but the potential is only manifested once you flow energy through it. So energy is so fundamental to what we are, and you talked about the laws of physics. There are good laws of physics, there are formal descriptions of how the world works, there are equations, and you can use them for predicting stuff, and we don't have similar, equivalently useful laws in biology, especially not around how energy behaves in the body. And I think energy has been the missing dimension of medicine, right? Medicine has been focused, maybe obsessed with molecules, the three dimensions, right? Of space, XYZ, and then little molecules, and genes, and organs, and if something doesn't exist in that dimension, if you can't see something on a scan, if you can't see something on blood work, then it's probably not real, it's probably in your head, or probably not worth taking, paying attention to it. So I think energy has been the missing dimension, right? Which really, I think it's a fourth dimension. I mean, because we can't measure it fully, and there are ways we do in functional medicine, but like this one, we can't really fully measure it, doesn't mean it doesn't exist. Correct. And this, because then we ignore it, and it's ridiculous in medicine. It's a major challenge. Like once you can't see something, and you can't measure something, then either you're forced to kind of believe, right? And think that it's there, or you see the effect of that thing on something else, that's what the physics of fields, field physics works like this a little bit, where you can't see a field, like an electromagnetic field, you can't see it. To know if it's there, you need to kind of put something in the field, you put a piece of metal, and then if you see the piece of metal being attracted, you know, oh, there's a field, right? So you know the effect, and you know the existence, and the properties of a field, by measuring its effect on something else. I suspect that's what health is. Health is a field-like state, where you might not be, health is not a thing, right? It's not a thing you can- It's a dynamic process. It's a dynamic process, it's a dynamic state that is energetically sustained, right? Yeah. And we've come to a definition of, or an operationalization in scientific terms, a way of describing something, so that you can measure it, and you can eventually do experiments around it, and then develop technologies to quantify it, and to track it. So the definition we have of health is, it's a field-like state, right? That emerges from the flow of energy, through a structure, this thing. Human body. The body is the structure. As energy flows through this, a field emerges, just like electricity flowing through a coil, generates an electromagnetic field, right? You can have a coil, if you have like a copper wire wrapped around a cylinder, that's a coil, by itself it does nothing, right? But if you flow electrons through it, you put electricity, now, boom, you have a field. And then with that field, you can power an electric car, right? You can like propel a car, you can do all sorts of things. One of the things that was shocking reading your work was that you said that the amount of, like energy, the potential released in the process of making energy in the cells is like a lightning bolt. It's like the equivalent of like a lightning bolt in our bodies happening all the time. That's how much energy is stored, right? The potential energy of inside your body is equivalent to, if you kind of take all of it that exists there inside your mitochondria, it's equivalent to a lightning bolt. It's amazing. And somehow we don't combust, and we don't burst into flames for good reason. Well, what's interesting when you do the math, and this is kind of what's interesting to me, is that basically just at a high level, these mitochondria are these little tiny bacteria looking like things. I don't know how it's gonna get over a second, because I can, you showed me, you gave me this as a present, and this is like, this is so cool. This is basically everybody, this is a mitochondria, is what it looks like, it looks like a bacteria. And basically it's an ancient symbiotic relationship between bacteria that entered into these cells that then used that bacteria to make energy. And the DNA from the bacteria is different than your DNA, it's your mother's DNA, it's mitochondrial DNA from your mother. And it's a very fragile organelle, and there's anywhere from hundreds to thousands, and even tens of thousands in the brain, which has the most. In each cell. In each cell, right? So, and you've got 40 trillion cells, and you've got, I don't know how many tens of thousands, the math, I don't even know the number. But the idea is that you've gotta run your body, and every second you have 37 billion trillion chemical reactions in your body, all of which require energy. And so, when you think about the fundamental sort of source of life, it's really energy. When you take a cyanide pill, and I'll get in the movies when the CIA guys have to kill themselves, they die in seconds. Why? Because it poisons the mitochondria, blocks the mitochondria. And so that's how important it is. If your mitochondria stop working, you're dead in seconds, right? Another thing from the CIA, the, you know, the trute serum, which was discovered in the mid 1900s, trute serum, the key ingredient that would like, you know, mess your mind so much that you'd be too weak to lie, right? Or to make stuff up, that was the idea. That special ingredient was a poisoned mitochondria as well. Was it phenobarbital, what was it? It was a barbital, it was amethyl. Amethyl, it was like a, it was a barbiturate, right? So it poisons complex one, which is where the energy and electrons enter into the electron transport chain. I use that in my PhD as a poison, you know, for mitochondria to do experiments. And then I learned, oh, shit, this is what people were using to, to mess up with the human mind, right? So if you mess up with the energy with cyanide, then you can kill the whole body. If you mess up with the energy, like just a little bit, you can actually alter the human experience. You can alter your state of mind. And I suspect that's what's happening as well with food and, you know, why the ketogenic diet is beneficial because it changes your energy and just changing your energy just a few percent could be enough to actually change how you feel, right? And how you interact with the world around you. And what's so exciting is that scientists and academic centers are now getting this. Like you've got, I've had a number of people on my podcast like Sabani Sitti from Stanford, who's doing metabolic research on psychiatry and mitochondria. You know, we have Chris Palmer, who's been on the podcast talking about brain energy as a way of treating psychiatric illness. Whatever you're talking about a medicine, whether it's diabetes or autism or Parkinson's or depression or bipolar disease or cancer, or my list goes on, it's all connected to energy. And it is in the functional medicine framework, one of the key physiological systems as part of this network of web of systems that underlies all disease. At 65, I'm still pushing my limits, cycling long distances, trekking through Patagonia and living life to the fullest. But staying active as I age isn't just about willpower. It's about giving my body the vital support it deserves. See, as we get older, our mitochondria, the powerhouse of our cells, naturally begin to slow down, stealing our energy and strength. That's where timeline powered by mitochondria has truly been a life changer for me. It contains urolithin A, which helps renew and recharge my mitochondria, keeping my muscles performing like they did when I was younger. Mito-pure is backed by solid research, showing it can boost cellular energy, increase muscle strength, and support overall healthy aging. Personally, I take mitochondria every day. It's helped me keep up with my active lifestyle, whether it's a high intensity workout or an adventure in the mountains. So if you're looking to support your muscles and want to feel younger from the inside out, my friends at Timeline are offering 20% off your first order. Check it out at timeline.com slash drhymon. That's timeline.com slash drhymon. Your future self will thank you. 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They're perfect for when hunger strikes and you need a snack that fuels your body, not spikes it. Head to paleovali.com slash hymon for 15% off your first purchase and try them today. And you're saying we shouldn't be focusing so much disease, we should be focusing on creating health. And that's one of your key papers that I read and will link to it, was really about this whole idea. And I read it, I was like, oh my God, this is crazy. This is what I've been saying for 30 years, like what's going on here? How is this happening? The paper is really important because it sort of lays out a framework for why do we care more about disease and health and how do we begin to think about the body as a system that we can actually optimize through removing things that are harming it and adding things that help it. Your work is just so critical in that way. And I think one of the problems I think people have, and I honestly admit, I also had this belief until I started really diving into your work was that mitochondria basically take food and oxygen and they combust them like an engine and they produce energy that runs everything in your body like it would be. And yet you're saying you're discovering it's way more than that. It's like a core hub of communication and communication and regulation. And so maybe, before we get down into the weeds a little bit, tell us the expanded view of mitochondria. Cause it's not just like a car engine that consumes gas and oxygen and puts energy through your tires to go run your car. It's more than that. Yes, it's not a machine. It's not a machine. It's not a machine. Before we talk about mitochondria, we talked so much so far about energy. What the hell is energy? And I mean, it's a tough one because even physicists don't agree on what energy is. You know, the great communicator, Richard Feynman, physicist who did so much for humanity was an amazing communicator. He said, you know, we actually don't know what energy is. Right? We have equations. We have, you know, things that describe how it works, how it behaves. Equals MC squared, right? Yeah. Equals MC squared is an important one, but we don't actually know what energy is. So I think currently in science, the most agreed upon and maybe the most widely useful definition is the energy is the potential for change. Ah. Right? So energy is not a thing. And I suspect that's why among other reasons. It's a state. It's a- Dynamic state. It's the potential for change that can feed different states, right? Like when you flow electricity and a little coiled, you know, piece of wire and you have a field that emerges from there, energy is the electricity, right? Electricity is one form of energy. So energy is not a thing, but it takes many forms. It's a potential for change that can materialize or take different forms. Electricity is one form. And then as the electricity, one form of energy flows through the copper wire, now it transforms. And then it transforms into a different kind of energy, which in this case is the electromagnetic field, right? And then you can use that, for example, in the motor of an electric car to then propel the car forward. Now as the car gains speed, it acquires kinetic energy, right? Different form of energy. Yeah, it's physics 101, potential and kinetic energy, right? Potential, kinetic, electrical energy, thermal energy, the heat of your body, right? Is a form of energy. Light is a form of energy, you know, it beams down from this nuclear reactor in outer space. Red light therapy, I'll show you my little, you know, wellness clinic downstairs, but I have a red light therapy, which then works for- Form of energy? In form of energy that helps your mitochondria work better and require a heal. Energy is the potential for change that manifests in under as different forms, right? And what mitochondria do is they don't produce energy, right? They produce ATP, they produce hormones, they, and we can talk about this. Mito-kinds, I never learned about mitokinds. Mito-kinds, yes. Like cytokines are those inflammatory molecules in your immune system, you heard about during COVID, the cytokine storm, but kinds are basically communication molecules. Like they're messenger molecules that the body uses to regulate everything. And so mitokinds are something new I never heard about, which are these communication signaling molecules that are in your mitochondria that regulate all kinds of functions, which I want you to tell me about. The function of the mitokinds, a function of the expanded view of mitochondria now that's emerging is one of connection, like you were saying. Connection, tell me more. Right? Like earlier you talked about how everything in the body is interconnected, right? What interconnects everything? What is the glue? There's this famous experiment where you take metronomes, right? That goes, like when you're playing your piano, yeah, yeah. Yeah, exactly. So if you take a bunch of them, let's say you put four on a piece of wood, and then you have them desynchronized, right? And then you put that piece of one on two cans of coke, two aluminum cans. What happens if you wait just a few minutes is that the metronomes will all come into sync with one another. So somehow there's information about the phase of one metronome that is shared through this conductive medium, right, which is like they all sit on the same piece of wood and then they sit on two cans on a table, and then you can see it moves ever so slightly. And so there's energy, right? The potential for change in one metronome, the movement of one metronome that is exchanged with the other one and the other one and the other one, they're all interconnected. And at the beginning, you look at this, it's a whole mess. They're all asynchronous, desynchronized. And then within a few minutes, they start to be synchronous. And then you can ask, how did this happen? And from a physics perspective, it's very simple. There's energy from one that was transferred to all of the other ones, and then energy is transferred through all of them through this conductive medium that is this little movement. If you were to put the four metronomes on a table that is fixed, they would stay out of sync. But if you put them on the same malleable surface, right? The energy is transmitted through the surface. Exactly. So how do that apply to human health and biology? Cause I think maybe people are a little lost to what you're saying. The point is, I'm a smart guy, I'm getting a little lost. Tell me out here. The conductive medium that allows the metronomes to come into sync and in the end, all behave like a unified whole is the transfer of energy. So then you can ask, well, what's the conductive medium in the human body? And that's energy. Energy and metabolism specifically, right? Metabolism is the conductive medium that connects every cell in your body. So when we talk about mitochondria and their ability to transform energy, food and oxygen, they transform this into first an electrical charge. Inside the mitochondria become charged like little batteries. This is where the lightning bolt calculations come from. And then they start to talk to one another. And mitochondria are these, like an intracellular brain pretty much. Mitochondria can receive information from hormones, from metabolites and from- The immune system, the microbiome, right? Yes, toxins. Thousands, thousands of little inputs, right? Mitochondria behave like a little intracellular brain. So every cell- Kind of looks like a brain-ish thing. Yeah. This is one form, they're married many different forms. And this comes from the tree, which is really crystallized energy from the sun, right? And then mitochondria are in the business of taking that form of energy, right? Biochemistry, the food you eat, and then dematerialize this, literally. Deconstruct it. Deconstruct it, but you take it from material biochemistry into an immaterial electrochemical gradient. So basically what you're saying is like, you eat a food, piece of food, it's like stored energy from the sun in some version, right? Because that's something what it is. They're growing the plants and eating the plants themselves or eating the animals that ate the plants. And then that energy is transmuted, broken down, and turned into electrical energy and other forms of energy that actually drive every thing in the body. Exactly. If you think about the range, like the human body and just life in general is so beautifully complex. The degrees of freedom, they use technical language, right? You have one thing and then how many branches, how many different ways can it go? Yeah. Is, you know- Yeah, yeah. With the number of cells, we have the number of genes, we have the number of proteins. It's instantly complex. Yes, you know, the number of metabolic reactions that happen, every enzyme is basically a little degrees of freedom, a little opportunity for, you know, do I do this, do I do that? Well, I just want to stop you there because what you said, I don't want to lose it, it's so important. Disease is the loss of resilience and metabolic resilience and freedom. And so what you're talking about is, how do you create a resilient system in the body at every level, mitochondria and everything else, so that the body can actually function better and that those degrees of freedom and resilience are what create health. I personally really unfortunately understand mitochondria on a cellular level myself because my mitochondria been so screwed up so many times that I've had to really understand how to recreate a healthy energy system in my body. And I do that with my patients and it's kind of miraculous. The miraculous thing about it is what we see in nature every day, right? Like our ability to heal and to build and sustain health is what we see in nature. Like you take a plant, you cut something and then it grows back and the ability to heal and to transform is just part of what life does. On a personal level, some of you may know this who are listening, I personally had a kind of a catastrophic illness nine months ago from the recording of this podcast. I was completely capacity. I was in bed, I couldn't move, I lost 20 pounds, I was weak, I couldn't walk and I was in a totally low energy state, let's call it. And I had to claw my way back over the last nine months and was able to use the science that you're talking about at 65 and I did not know this was possible because I was kind of scared to be honest with you. I was scared that, oh shit, I'm 65. Am I going to be able to recover? I'm not 35, can I recover and get back to function? Can I get my mitochondria, my health recover? And I wasn't treating a disease per se, I was just in this totally broken down state that happened after surgery and inflammation, infections, whatever happened to me. And this weekend I was in Aspen and I hadn't really been doing a lot of cardio, but doing strength training in the gym and I was able to get on a bike, not an electric bike, and ride up a mountain 11 miles. Your mitochondria working? I was about 9,600 feet of elevation and I did it a couple of days in a row and I could do it again today. And I'm like, holy cow, the body has the capacity to repair. I wasn't treating a disease, I was helping restore my health and engaging what I know as a functional medicine doctor about the science of creating health. This is really the laws of biology. And one of the things that you talk about, which I think was a new idea to me, one of these fundamental laws of biology that you've uncovered, called the energy resistance principle. And most people probably have never heard of it, most doctors haven't heard of it. I've steeped in this stuff and I never heard of it. I read your stuff. I think it's something that you kind of discovered. Hopefully you get the Nobel Prize. I'm counting on it. I wanna go to the ceremony if you do. Promise me you'll send me an invite. And it explains a lot about what happens when we get sick, when we're under stress and how those things affect our ability to produce energy, and what the body does in response to those insults. And the insults can come from everywhere. So when I think about my conardia, I think they're like the canaries in the coal mine. You know, the canarian coal mine was a canary, they put a coal mine and if it died, this coal miner knew the air was bad, get the hell out of there. So the mitochondria are the first kind of sensitive little organelles inside ourselves that are responding to these inputs from psychological stress, you call it psychobiology, which I love, right? They respond to toxins, which we're all exposed to. They respond to things that are happening in our microbiome. They respond to inflammation from any source. When you get the flu, why do you feel achy and tired and weak? Cause the virus is messing up your mitochondria, you know? Right? And so you have all these insults that can happen from various different sources, from mental stress, from physical stresses, from infections, from toxins, from your microbiome. From hormonal dysregulation. And so all those things modify the function of the mitochondria in such a way that reduces energy, which is why we're all walking around tired, why we have brain fog, why we feel like crap. It's not in our head. Well, it is in our mitochondria. So, well, I mean, yes, of course, it can be stress and so forth, but I want you to kind of understand, help us understand how these mitochondria receive all these signals, what happens to them, why they stop working and why it's sort of this universal phenomena underneath so many illnesses. You know, in functional medicine, I think 30, 40 years ago, Jeffrey Blamp came up with this idea of mitochondrial resuscitation. How do we resuscitate our mitochondria? And it's really profound and it's what I've been doing myself, can you kind of help us understand how we think about these mitochondria, how they're impacted by the environment, how we can then start to begin to care for our mitochondria better and use the science that you're talking about and this energy resistance principles, understand what's happening and then what to do about it. I think the reason why energy is, and mitochondria are implicated in so many diseases, we did an analysis a few years ago and it was called the rise of mitochondria in medicine, right, and you look at which diseases are there evidence for that mitochondria are impaired in some way and turns out every disease. Pretty much, pretty much. So, why is that? These are questions. I think fundamentally the answer to that question is because you are energy. You're not a machine that is powered by energy. You literally, you mark me Martin, the experience of you, the experience of me is energy. And I don't mean that in some like woo woo way. Yeah, I'm an energy healer. You know like, yeah, right, right. There might be something to that, but the- Well, there is. You fundamentally, right, if you stop breathing and the energy stops flowing through your body, then your body just will remain what your body is, right? That is not who you are. You are the energy that is flowing through it. And somehow it feels like something, when energy flows through the body, when it transforms, it feels like something. And that's, so the basis of what we are is really energy. And that's why mitochondria are so important because mitochondria are the portal, they're, you know, the conduit through which energy flows and then through which it's like the first step of transformation that brings you to life, right? And that moves your body into life. So it's that structure, that piece of structure, it's like for the analogy of the solenoid, right? The copper wire, that's a mitochondria. Without mitochondria, you could flow electricity, you would never get a field out of it. So mitochondria are so important and perhaps they're like the cannery in the coal mine because they are the first site of energy transformation. So if energy isn't flowing right, then you feel that very acutely because that's affecting what you are. Like the virus, the example you gave, like if you have a bad case of flu, you feel terrible. And then you said it's because, you know, the virus is affecting your mitochondria. I don't know if that's true, but what we know for sure is that when you're fighting a virus like this, what happens is your immune system is gonna start burning a ton of energy. And there's this fundamental energy principle which is energy constraints, right? Or energy trade-offs. What happens is for reasons that nobody understands, no scientist has kind of come up with this satisfactory answer, there's a fixed energy budget that we have access to. So this thing, this organism, needs to manage an economy of energy, right? Then if you measure someone's energy expenditure over 24 hours, right? On day one and then on day two and day three, and you do this over long periods of time, it's pretty fixed. I mean, you mean like they're resting metabolic rate or you mean? Resting is when you're not doing anything, right? How long should you burn walking around and doing your life? If you measure energy expenditure, not just resting, but including everything you do, right? And then that would include, for example, your bike ride up the mountain. I'm sure you've burnt more energy. Definitely, I was so hungry that night. So there are days when you spend more energy, but then there are days when you spend less energy, right? And overall, if you integrate over long periods of time, it kind of averages out. And there's this remarkable discovery a few years ago by Herman Poncer, he went to work with Hadzaz in Africa. Yeah, I've been there. He measured how much energy do these people burn? Like they walk all day. Like some people, some of them up to like 20,000 steps, right? Looking for food and so very active lifestyle. So they're very lean, they don't tend to have metabolic disorders. And so he thought maybe, you know, it's because they expend so much energy, right? Turns out the energy expenditure of a hunter-gatherer, or someone who's like foraging all day, is the same as a sedentary couch potato whose job is to tighten and wiggle. Really, how is that? How is that? Exactly, that's a mystery. It's a bit of a mystery. There are many evolutionary reasons why that could be the case. Imagine you're a caveman back, tens of thousands, hundreds of thousands of years ago. And then if the energy budget was not fixed, right? And then you could have, you know, one guy, he's like, I'm not gonna sleep and I'm gonna just be very active. And then I'm just gonna eat more food, right? Cause if your energy budget was not fixed, the solution to getting more energy would just to eat more food. We know it's not, that's not how it works. If you eat more, then you end up hurting yourself. And then you end up wasting energy, digesting food that you don't need, and then storing excess fat and so on. So an expression of the fact that we have a fixed energy budget is the fact that you can't just eat more to have more energy. So somehow your energy budget is constrained. But you can change it, can't you? If you exercise, if you build more muscle, if you actually increase your VO2 max, which is the amount of oxygen you can burn per minute, and that's related to how much calories you can burn per minute, that can change. What happens if you start exercising to increase your VO2 max, your energy expenditure, let's say it's 1500 calories per day, right? And then you start working out. So then you expand, you go on the treadmill or your cycle or gometer, you see 300 calories. So you burn 300 calories. So then on that day, you'll be 1500 plus 300. So you'll be at 1800. So say, see, I can go over my budget. But then if you do this a few times a week for multiple weeks, what ends up happening is that 300, your body is gonna save it somewhere else. So the 1500 is gonna end up shrinking. It's called metabolic compensation. So the organism is gonna find ways to be more efficient. So that that 300 doesn't come on top of your 1500, it's absorbed into it. And that's why exercise is not a good way to lose weight for most people. No, I would say you can't exercise your way out of a bad diet. Yeah. And that's in part because as you exercise, the body is like, ooh, I can't afford this. Like I have a fixed budget. What can I do to accommodate this? And I think I suspect a significant proportion of the health benefits of exercise is that energy saving, that metabolic compensation, the body basically becomes more efficient. And to become more efficient, it needs to do less of the things that are not useful. It needs to be more less frivolous with its energy budget. So if you have bad mitochondria that are not working really well, you get rid of them through mitophagy. I'm confused because, you know, when I looked at the literature, for example, with metabolic health and diabetes, the mitochondria of diabetics or even first degree relatives of diabetics don't work as well. There's something called PCG1-alpha. And that is sort of a molecule within the mitochondria that regulates energy. And so it's less in people who have type two diabetes and in their first degree relatives, even if they don't have diabetes. Correct. So it seems to me, you know, there's a variation in the quality of our mitochondria across humans. And there's also a variation in what you can do to actually improve their ability to produce energy. Am I wrong? Transform energy. So PCG1-alpha regulates the amount of mitochondria. So if PCG1-alpha goes down, then that happens if you stop exercising, right? Or if you're bedridden for some reason, or if you break a leg and it's in a cast, right? The muscle is gonna atrophy, is also gonna lose mitochondria. And PGC1-alpha goes down. Now if you start to exercise again, and the muscle contracts and it needs more energy, then the muscle says, I'm gonna say, shit, this is costing me a lot of energy. I need to build the machinery to support that energy flow. And then it makes more mitochondria by turning out PGC1-alpha. So PGC1-alpha regulates the amount of mitochondria. And there's a few reasons why. I'm telling you more, you can get more efficient mitochondria. Yes, there's much more wiggle room in the amount of mitochondria you have. Like if you go from being sedentary to training for a marathon, for example, you can double the amount of mitochondria in your muscle. Double. So then does that mean you're burning more energy? It doesn't. It means you can, your max, your ceiling, right? Is higher, but your budget at rest doesn't change. I thought when you train, and you increase your VO2 max, which essentially is the amount of oxygen and calories you can burn per minute, that your resting metabolic rate will increase. That doing nothing, you go burn more calories doing nothing. It doesn't. Really? Or if it does, it's minimal. And there's actually evidence that shows it actually decreases. So if you increase your VO2 max, you make more mitochondria in your muscle, then it means you can push harder, right? You can go more intense. Your upper limit is higher. Yes, your upper limit is higher, but your resting either stays the same, or in some cases, for some physiological systems, it's more efficient. Actually, yes, exactly. So if in your trained state, right? If you're the mark from a few months ago, your heart rate was probably pretty high at baseline. And then if you're picking up steam, making more mitochondria, increasing your VO2 max, going out on the bike, your resting heart rate actually decreased. That's what happened. It was like when I was sick, it was my 70s, and now it's in the 50s. So 20 beats, think about how much energy, nothing is free in biology, right? Think about how much energy the heart burns every beat. It's like this whole contraction, and then this whole relaxation, everything costs energy. Now you're saving 20 beats per minute, and then compound this, or number of minutes in a day, number of minutes in a month. Like you're saving so much energy by having a lower resting heart rate. That's in part what people think is the basis for metabolic compensation. So you start working out, and the body actually becomes more efficient. So let's take this back to kind of practical. We didn't quite explain the energy resistance principle. I wanna explain that. I mean, I wanna tie it back to how this matters to real people with struggling with real issues, whether it's something like brain fog, or fatigue, or depression, or... Diabetes. Diabetes. How do we then be able to apply this in new science? And even, how do we understand the role of, I call it the mind-body effect, but also the body-mind effect? So the core idea of the energy resistance principle, and the ERP for short, the energy resistance principle is meant to be a formal description of how energy behaves in biology. And it's a bridge between physics and biology in a way. And we think there's a little formula that's very simple and over simplistic, but I think it's the first formal equation that bridges physics and biology and describes how energy flows and how energy transforms inside our bodies. And the first kind of assumption for the ERP is that you are energy. Fundamentally, like we said earlier, what you are is this energy that's flowing, and you can lose a piece of your body, energy is still flowing, you still feel like yourself. But if you've changed the way energy flows, you haven't changed the physical structure of your body, but you've changed. So at the end of the day, when your energy is not flowing great, and it's really time for bed, or you're past your bedtime, you're not the best version of yourself. You're literally a different kind of person. Or if you take Amethol or some other... So is your energy like, that's why you're tired at the end of the day, because your ability to produce energy goes down? There's something energetically that changes, and we feel this as fatigue, but what seems to happen, there's a new paper that came out a few months ago in Nature, showing that the pressure to sleep, which is basically a fancy word for saying... Untired. Untired. That study was done in flies, it was a lab experiment. But what they showed is that, what drives a fly to want to sleep, so the pressure to sleep, which is probably equivalent to the fatigue you feel at the end of the day, arises in your mitochondria. And the way it arises is because energy is basically facing more resistance. It's like you're flowing water through a pipe, or through a hose. If you squeeze a hose, you increase the pressure, you increase the resistance. Energy flowing in the body just works just like that. And it works just like in a simple electrical system. To come back to our electrical analogy, you have electrons flowing, and if you have a battery, negative pole, electrons flow, and then they reach the positive pole. So that's a simple energetic circuit, and we have great formulas in physics to describe how this works. Ohm's law or the power law, and then you know from those laws, if you want to transform the flow of electrons, electricity, into light, into movement of a car, an electric car, into powering your, or not, your laptop, what you need is resistance in the circuit. Energy that flows without resistance doesn't do anything. But the equations in physics tell us, you need some resistance, so that the flow of electrons can actually be transformed to power. They're not too much. Into work. Exactly. So the energy resistance principle says, you, your existence as an energetic process, requires resistance, but you need to live at a sweet spot of resistance. Not enough resistance, like if you're a photon beaming in outer space that never hits anything, no transformation. At some point, the photon hits a green leaf, and then the green leaf offers resistance to the flow of energy, right? That electromagnetic energy hits a green leaf, and then it's transformed into something else, a different form. Photosynthesis. Yes, photosynthesis. And then at some point, the electromagnetic energy of the photon gets converted into biochemistry. Okay, what you're saying is mind-blowing, and I thought about this so long, basically what's happening, everybody listening is sunlight, sun, energy, you can feel the energy, if you go on the sun, you can feel it. That is transformed by plants into energy and food. And it's kind of a miracle. And the body is kind of the reverse. So mitochondria are the human kind of... The opposite. Like they're the kind of complement of the photosynthesis. Yeah, they close the life cycle. But the way photosynthesis works, right? The way you transform light into food is through resistance. You need to slow down the photon, right? You bring it down to zero, it goes... So how do you get the right resistance? Because too much resistance kind of shuts things down, and not enough resistance doesn't allow you to actually produce enough energy to thrive, right? So can you kind of walk us through, what are those things that cause too much resistance? And then how do we fix that? So the resistance... So that happens, and I think is tuned in your mitochondria. And that's precisely why you make more mitochondria with PGC1 alpha, or why you make fewer mitochondria by decreasing PGC1 alpha, among other things. So the body, we can think as this electrical circuit that goes from the electrons flow from negative to positive, right? Through maybe a motor or through something that does work. What your body is, is basically like an energetic circuit, like an electrical circuit. And the electrons, the negative pole on the battery is food. And then the positive pole that accepts the electrons is oxygen. So the food and the oxygen, or like the two poles in this electrical energetic circuit. So this is an energetic circuit as well. And the circuitry, the copper wire is your metabolism. It's kind of cool, because plants take in sunlight and carbon dioxide, and they turn it into energy, they store it, we eat it, we reorganize it, breathe oxygen, and then we burn the calories in our mitochondria to produce energy that runs everything. And that fundamental system, what you're saying if I get it right, is essential for the functioning of the human body. And if it's not going well, can explain most chronic diseases at some level or another, correct? When we think about healthy aging, we often think about our external appearance. But beneath the surface, proteins like collagen, elastin, and keratin play a big role in keeping tissue strong and resilient. All of these proteins are built from amino acids, especially the essential ones our bodies can't make on their own. Getting enough of these building blocks helps support not just muscle, but also the structural proteins that support skin elasticity, thicker hair, and stronger nails. 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The immune essentials most people don't get enough of. And the best part, they taste great with real cocoa and are easy to take on the go. This season, don't just react, strengthen your foundation. Try HTB immune energy chews today. You can visit BigBoldHealth.com and use code DRMARK20 for 20% off your first order. ["Miracle of the Moon"] Because if the energy is flowing with not enough resistance, then transformation is not possible, right? If the green leaf couldn't stop the photon, there would not be photosynthesis. So in the same way, if your metabolism couldn't slow down the flow of electrons from food, this little nut that you eat, the fat that you eat. The almonds that I had for breakfast. So if they don't face enough resistance, then basically you burst into a flame. That's what fire is. Fire is you have electrons that are stuck on a piece of paper, a piece of wood, a piece of whatever, and then it jumps on oxygen. So if you warm up something carbon-based, hot enough, then the electrons will just find oxygen. Boom, they jump on it and you get a spark, you get a flame. So fire is the uncontained, unrestricted acceleration of electrons, boom, onto oxygen. So how does that understand like this energy resistance principle from a practical human perspective? Because I think we're getting a lot into the physics, which is cool, but I want to make sure people understand how this relates to them. Because people are saying, well, that's interesting, but I didn't really tune in to listen to physics lesson. I want to know. You know, my joke is everybody's favorite radio station is WIFM, what's in it for me? So I want to get into the what's in it for me now, which is how and things go wrong, does it cause human disease? And then how do we fix the mitochondria? Because, you know, I was saying earlier, in medicine it's pretty much ignored after first year of biochemistry. And yet in functional medicine, we have, I think, somewhat crude tools to assess the functioning of mitochondria through looking at CREB cycle metabolites, energy production, metabolites in the urine, or doing VO2 max testing, or there's newer things that actually allow you to look at various of the steps in the pathways and how they're functioning, you know, cytochrome C and then all the complex one into four, all the stages. I think the way I think about it, just to explain to you guys, mitochondria is like you kind of put energy in, and this is not actually happening, but you put energy in from oxygen and energy in from food, and it kind of goes through like an assembly line. And there's steps on the assembly line that all have to be working. At the other end come out with something called ATP, which is energy. And then the waste product is carbon dioxide, which we breathe out and the plants consume. It's like we're just like one organism, whether we like it or not. And it also produces water, which we pee out, and also produces some free radicals, which can get out of control, but the mitochondria have their own built in antioxidant systems to protect against this rusting or free radical injury. But when those go awry, you end up with more mitochondrial damage and more trouble with your mitochondria and less stability of energy. And that leads to all the diseases, like the mental health issues, the metabolic diseases like diabetes, the cardiac vascular issues, and psychiatric even neurodegenerative issues like Parkinson's, Alzheimer's, autism. So kind of walk us through how we start to think about one, measuring what's going on, like are there clinical tools? And there's one that you talk about like this GD. GDF 15. 15, yeah. Which is a new blood test and biomarker that can help you understand how this energy resistance principle is working. Are you good or bad? And what other tools can we use to measure it? And then how do we start treating people differently by going upstream to treat the mitochondria? And just sort of those listening, everybody knows I wrote a book on longevity called Young Forever. And in that book, I talk about what science is uncovering around what we call the hallmarks of aging, these fundamental things that explain the pace and the rate of aging and chronic disease. And they're upstream to diseases. In other words, they are things that go wrong that are fundamental to all age-related diseases. And yet we're treating all the diseases that we're treating Alzheimer's, we're treating diabetes, we're treating cancer, we're treating diabetes, which is kind of the wrong approach. Yeah, cause y'all converge on the hallmarks of aging. Right, and so the hallmarks of aging I wrote about, and one of the key hallmarks is mitochondrial dysfunction. And a lot of the longevity therapies work on what I call the longevity switches. These are the things that regulate and part mitochondrial function, the creation of the mitochondria, the effectiveness of their producing energy. And so whether it's the mTOR and things like rapamycin or insulin signaling or AMPK, which is basically regulating blood sugar or Sertuans, which regulate mitochondrial biogenesis, DNA repair, they're all kind of connected to mitochondrial function. And so we're learning different ways to intervene, but earlier in the process. And in my book, I talked about how the hallmarks of aging are good and they're a useful framework, but they don't go far enough because they don't ask the question, why? Functional medicine is the medicine of why. Why are the mitochondria not functioning? Yes, and what connects those hallmarks of aging? They're so central to not only how we age, like you're saying, but to do so many diseases. And the reason is because beneath, underneath all of the hallmarks of aging is energy. And anytime I hear the term mitochondrial dysfunction, I get an emotional response. Why? My hair rises because it's so misleading. And it kind of locks us into this old idea, mitochondria or powerhouses. You gave a nice story of how mitochondria kind of are this little ATP producing, you know, engine. I would give a different picture that says mitochondria is kind of the meeting point where you have food, electrons from food, and then oxygen. And what mitochondria do is they basically allow their reunification, right? They were separated. The plants and photosynthesis broke water apart. Electrons stuck onto CO2 and then they made carbohydrates. And then the oxygen, you know, liberated. And then those two are kind of longing for each other, for forever. And then until they meet back inside your mitochondria, and when they meet in your mitochondria, boom, you get water back again. Isn't that a miracle? It is amazing. And that's what energizes your mitochondria. Yes, to make ATP. ATP synthesis is one of like at least three dozen functions. So anytime I hear mitochondria function, I... Wow, because it's reduced to just ATP for most people. Yes, it's like... Yes, and if you say mitochondria dysfunction, it means there's one way in which mitochondria can be dysfunctional, and that assumes that kind of there's one function, which is not the case. So mitochondria, these little living creatures, and they're a portal, they're an energetic portal, where biochemical type of energy gets dematerialized and then it makes all of your other life possible. Heat is generated, reactive oxygen species, other form of energy, probably light, bio photons released from mitochondria, and other kind of signals that then inform the whole of the organism. Yeah, by the way, everybody, you know those sparklers you get in 4th of July with the like bright sparklers? That's phosphorus. That is what ATP is, adenosine triphosphate. So it's three phosphate molecules, and that's kind of what's happening with sparklers inside yourselves and your light beings. Yeah, I never thought about that. So with the energy resistance principle, you wanted to kind of go into the practical applications for this. What's in it for me? What this is referring to is how, with how much ease can energy be flowing, right? The food and the oxygen coming into mitochondria to make water again and then energizing the whole system, how easily is that flowing, or is this flowing with great resistance? So that's what the ERP is about fundamentally. We feel that. And the energy resistance principle paper and the other piece we're writing, and that's in the book, Energy that I'm working on, talks about what it feels like when energy resistance isn't flowing well. And it turns out that all of the hallmarks of aging and all of the classic hallmarks of diseases, including inflammation, damage, molecular damage, to DNA, telomere shortening, epigenetic aging, all of those are downstream of energy resistance. So when energy can't flow easily and it flows with great resistance, like you have too much pressure, right? And a hose at some point, something's gonna blow up. Or if resistance is too high in an electrical circuit, like your computer, it starts to overheat, right? And as things heat up, there's what's called dissipative loss. So then the structure of your body starts to dissipate, it starts to break down, and then that's disease, right? So all of those hallmarks of disease can be traced down to energy not flowing easily. And you mentioned NAD earlier, what NAD does is basically it's an electron transducer, right? So the more NAD, the less resistance there is. But we call the producing of energy in the body the electron transport chain. So basically you're transporting electrons down this chain through all these chemical steps that require nutrients and cofactors, everything from Coke U10 to B vitamins and so forth. NAD, all these different steps. And that creates an enormous opportunity for intervention, for helping people recover from an impaired energy production process. If there's a deficiency in some of those cofactors, NAD is upstream of the electron transport chain. It's what gives the electrons from the Krebs cycle that you mentioned into the electron transport chain. And then from there they're channeled onto oxygen. And some people seem to be deficient in NAD. And I'm not- Well, it goes down as you get older. It goes down as you get older. I see patients in a clinic with mitochondrial disease, I'm an ND, but I'm in the clinic half a day a week. And I see people with genetic defects in their mitochondria, right? So the mitochondrial DNA that we get from her mom, they have a mutation and they feel tired all the time. Many of them have multi-system disease. So many of their organs are not working as we know mitochondria everywhere. And some of them have tried NAD infusions and feel like it's helping them. And I've seen some of them being like pretty angry that this is not true inverse, right? And yeah, it's not traditional medicine. It's functional medicine. Right, exactly. What are the practical implications for the energy resistance principle is we should be treating energy, right? You're not a machine, you are energy. And then the way energy flows through your physical body is what determines whether you can heal, whether you feel vitality. You need energy to heal. Yeah, you need energy to heal, but you need energy to flow in a certain way. If it flows with too little resistance, you'll combust and maybe you feel manic or you feel like you're not quite grounded. And then if energy flows with too much resistance, then it probably feels like a drag. And that's what we experience as fatigue and as chronic fatigue syndrome. And what we experience negative symptoms of depression, for example, right? The apathy and anodonia and so on. And it turns out there's a marker, like a blood marker of excess energy resistance in the body. And that's this protein you mentioned, GDF15. GDF15, what does it say for? Growth differentiation factor of 15. And you can measure in a blood test. You can measure in a blood test. We discovered a couple of years ago, you can measure it in saliva. Is this commercially available? It's not commercially available. So you have to research scientist. You do, the Mayo Clinic has a clinical test for GDF15 that they use to diagnose mitochondrial disease. GDF15 interestingly was discovered and completely separately in different fields of medicine. So it was discovered in mitochondrial disease. Like if you wanna know, does this person have mitochondrial disease or not? They're always tired. They have this symptom, neurological issues, a cardiac issues. And these are rare genetic mutations that are very rare and that are well-recognized in medicine. They usually diagnosed by muscle biopsy. And they cause people to have a lot of these symptoms of system failure and fatigue. But there's a spectrum of problems with the mitochondria that occur in otherwise healthy people that are influenced by these different insults that we get from living in this modern world, the stress, the psychological stress that's transduced through the mitochondria, the toxins, the chains in our microbiome, our nutrition, plays a huge role in the function of our mitochondria. I mean, that's why ultraproses food is so bad because there's no nutrients in there. And it creates a lot of inflammation. And why? Why does it create inflammation? Good question. I mean, I have a theory, but I would hear yours. We think it comes down to energy. The source of inflammation, if you go down the chain, inflammation, the way we talk about inflammation nowadays, which I think is a misnomer is cytokines. If you're cytokines and we say, ah, there's inflammation. Inflammation traditionally was redness, heat and swelling. And pain. And pain, hallmarks of inflammation. And as part of this inflammatory process, cytokines can be used by the cells that are injured, like if you break the skin epithelium, for example, they'll start to secrete cytokines. The immune cells will start to secrete cytokines. So it's part of the process, but the inflammation itself is not the cytokines. The cytokines are this universal language of cell-cell communication. It's how cells talk to each other. It's like the words that we use to talk to each other, this is like the repertoire of cytokines. Yeah, that's the key. The body's a network and it communicates through these messenger molecules that range from hormones to neurotransmitters to peptides to cytokines to mitochondria, to myokines, and any kind of communication systems. It's so fascinating and it's happening at fantastical speeds, constantly in the body. And when those communication systems are arrived, that's when disease arises. If everything is going well in your body and your cells are, you're working coherently, coherence I think is a key concept that isn't part of medicine, but needs to be part of the future of medicine. If we think about health energetically, you get to coherence and to resonance pretty quickly. But if everything goes well in the body, every cell lives harmoniously as part of the social contract that every cell works with every other cell and no one cell is gonna go on their own to in a selfish way that cancer is. But if every cell is okay and is functioning harmoniously, the whole organism, you don't need to secrete cytokines, right? Because the cells are working the way they should. When something's wrong, then if you're a cell and you're experiencing excess energy resistance because your mitochondria are not working properly, maybe there's a toxin that came in, you need to let other cells know, right? Because if you die and then the whole organism is gonna suffer from this. So the right thing to do if for this social collective that's the body, if one cell is struggling energetically, it lets other cells know and then other cells can help support it. That's the basis of physiology and if one organ is in need of more energy. Compensation. Right. So that's what cytokines are there for. And many cytokines seem to be secreted in response to an energetic issue, an energetic deficit. Like even after exercise, exercise is not bad for you. We know exercise is good. You contract your muscles very vigorously. If you climb 9,000 feet of vertical. No, no, it was about 3,000 vertical feet, but it was 9,600 feet of elevation. Okay. And it was 11 miles straight up. So my mitochondria were working overtime. And then during the exercise, I felt so great after. I actually got more energy, which is so weird. Yeah. What did it feel afterwards? I felt great. I wasn't tired. Where in your body did you feel? I didn't feel sore or tired or anything. I just felt energized and alive. And my brain was on fire and I had, I just felt good. So the energy resistance principle says what you were experiencing like this after exercise leaves you feeling, you know, good and energized and you're on fire. This is a decrease in energy resistance. That's what it feels like when energy is flowing in your body and it's effortless, right? That might really actually to the psychological state of flow, right? When you're in a state of flow and things are easy and things are just flowing, there might be a literal energetic parallel in your mitochondria that energy is just flowing. And if you don't overdo it after exercise, that's what you feel, right? And your heart rate is a little higher and your blood vessels are dilated and things are flowing, you know, and that's very comfortable. And that's, again, I suspect that's what happens in the state of mania in bipolar, right? Cause people that are, when they're in the manic phase, they don't feel tired, right? You feel like so much energy. They just step all day for like 10 days in a row in there. Yeah, you don't feel like sleeping. I think they're Jesus. You don't feel this. Yeah, there's other kind of psychological and kind of delusions that come with this, which I think says something about the need to slow down the energy flow in your mitochondria. But when energy is too high, right? That there's something maladaptive to that. So that's why energy resistance principle says there needs to be a sweet spot. You got a Goldilocks principle. Correct, exactly. And when energy is too high, then, you know, it feels uncomfortable. And I suspect that we might have the direct ability to feel when energy resistance creeps up. So if you contract your muscles, right? Like you lift the weight that's too heavy for you and then it starts to burn, right? What is that burning? It's lactate. It's not. That was debunked. That was a theory. When I was a student. What is it then? We don't know. We don't know. You run out of energy though. What's that? You run out of energy. There's still energy that you can still contract, but you know, you feel the burning. Well, I'm doing pull-ups. Like there's one point I just can't get another pull-up in. Yeah. What is that? Well, I think that's a mixture of, you know, there's acidity and there's, you know, buildup of products. And so muscle fatigue is one thing. What I'm talking about is the burning sensation, right? The burning sensation you can get if you're deconditioned and you know, you're going up the stairs or something like that. We used to think it was lactate or lactic acid. Then there was a theory about acidity and like the pH changing. It seems like it's probably neither of those. What I suspect it is, is you're actually feeling the energy flowing through your mitochondria. And when energy resistance increases, yes, you make lactate and yes, you make other things, but maybe we can actually experience the change in energy resistance. Same thing with an infarction. Like a heart attack. Heart attack, yeah. Right? When blood can't flow to the heart anymore, like the pain of this, my dad went through this a few years ago. I'm sorry. He said it was horrible. He recovered really well. But the pain, and he described this as like a pressure, like 200 pounds on his chest, right? Yeah, the alpha and senior in your chest, that's right. Yeah. And then there's referred pain and the heart has no pain fibers. There's no, you know, if you open someone's chest and you poke the heart, like the brain, if you take the scalp off, there's no pain receptors on the brain or on the heart. But somehow we can feel, and it's, I've never experienced this, but you know, the pain of angina or of a heart attack, that could just be energy just can't, that's not able to flow. Right? Energy resistance is too high. So people listening, they're all, okay, I have some of these conditions. I have depression or I have, maybe I have Parkinson's or maybe I have someone in my family with autism, which is not so common, or maybe, you know, I have diabetes or maybe, you know, I have any one of these conditions that maybe related to the mitochondria. Where do I start? Like what tests should I do? What therapies are available? How are we thinking about this wrong? And I know you're not a doctor or clinician, but as best you can, describe what we're learning about how to assess and treat mitochondrial problems. I'd start by saying, like I said earlier, you're not a molecular machine. You're not broken. And there are no parts, I think, to be fixed or surgically removed or transplanted. There are things that we know can unleash the healing potential of the body, right? Like resting is really important. And when you exercise and then you make more mitochondria, you don't make more mitochondria during exercise. You make your new mitochondria when you're resting, right? So, and that's a key element of energy-resistant principle. You need to increase your resistance when you're biking or you're out of breath. Anything that's out of, anything that makes you out of breath, it means you're increasing energy resistance in your body. And then when you relax, right? That's when adaptation happens. So it's the, you increase resistance, then you decrease resistance. And that's, the great thinkers, the creative writers will tell you, like you need to obsess with something, but then you need to let go. You go for a nap or you shower and then the idea comes, right? It's when you relax, it's when you relax that you get the benefit from having the increased resistance. So the chronic exhaustion, maybe the burnout of chronic stress, I suspect come from having chronically high energy resistance. And then if you think about this as the basis of health, energy flowing through your system, right? Is what you are, how do you care for this? How do you support this so that the organism can heal itself? That is, I think should be the basis for medicine. As I think part of the core philosophy for functional medicine, right? How do you restore function? Yes, how do you restore function? How do you allow the organism to heal itself? To do what nature just naturally does, what life naturally do. And I think that's, I think key pieces that we know are generally true across people, but I just wanna preface this by saying, every person is different. And know the kind of science that we do and the science that's out there that's driving culture is very much a science of averages. The things that we end up believing and kind of taking as evidence-based, this is all like group averages. So if you wanna know if something works, the gold standard in science, as you gather a couple hundred people, you expose some of them to the treatment, you expose some of them to a sham or placebo, and then you see on average that I move the average, right? Did I move the needle? So you measure something in your group of a hundred people, and then after eight weeks of this treatment, if the average is up by, you do your power analysis, if it's up by more than X percent, then it's significant, P value less than 0.05, then it's say, ah, evidence-based, this works for people. And then that goes to the FDA, the FDA says, okay, approved, this thing is evidence-based. But when you actually peel off the surface of a trial like this, of a research study, you find that there's some people in this study, they responded, they're cured. Whatever they came in with that was a problem is gone, right? And they're amazing, their life is transformed. These are the people who should be receiving that intervention. But in the same trial as you peel the surface, there are people who didn't respond. These are non-responders, you know, typically, that are called in research studies. And then there are always people who actually are worse. People who were injured or who were hurt by this treatment that now is, you know, approved as evidence-based and as, you know, beneficial or salivary. So everything we tend to talk about is like average, and there are things that are generally true across averages, but there are things that I think we underestimate the value or the power of individuality. And that's where, you know, a really good physician and a person-centered approach is really critical. Yeah, I think you're right. It's all about like looking at the individual because everybody's a little different. And I think that looking through the lens of mitochondria is an important lens. And we talked about this in functional medicine. One of the new lenses we look through, how do we see the same things through new lenses? It's like putting on glasses, and all of a sudden you can see everything differently. And so when I see a patient, I'm thinking mitochondria. I'm thinking, are they working? How well are they working? What's impairing them? How do I help their mitochondria work better? How is that gonna help them feel better? And so I know you're not a doctor or clinician, I mean, you're a doctor, PhD doctor, but you're not a clinician. Where should people start in terms of thinking about assessing mitochondrial function? Because I use various tests, another bit crude. Maybe this new GD, you know, GDF 15 is actually a test we might use to look at this energy resistance in the body and find out if we're in the Goldilocks range. What can we do to assess the function of mitochondria or do we just sort of infer it because based on the diseases? And then what are the therapeutic interventions? Because people like Chris Palmer are using ketogenic diets to improve mitochondrial function and mental health. People like Suzanne Goh are using mitochondrial supplements like CoQ10 or sulfate or carnitine to help autistic kids with mitochondrial dysfunction that measures on a functional MRI machine. Like where is this all going? How do we get this in the clinic? Because the bench to the bedside is just takes decades. And I'm like impatient because I see people suffering and I'm like, you know, like, how do we take this and practicalize it if that's a word? Yes, how do we touch human lives with this wonderful scientific knowledge? Yeah, yeah, I want to spend the rest of the time talking about that. Did a lot of science stuff and I want to get, if you can and if you can just tell me how. Like I'll kind of help you. But I think this is something that I'm so passionate about because like I said, I've suffered from it. I've seen so many patients suffer and I see these therapies work. So in many cases where I think that would be classified as mitochondrial dysfunction, I would not use the term mitochondrial dysfunction. There's an impairment maybe in the way mitochondria work but someone could have mitochondrial impairment because the mitochondria are not making the hormones they should be making or mitochondria are not making the ATP they should be making. Which I think is what the function, dysfunction typically refers to. Or mitochondria are not able to receive the signals they should be receiving or producing the signals they should be producing to turn on this gene or that gene. So what can we do with this? And I think it brings us down to energy flow. Is your organism able to flow energy through the mitochondria the way it should? And I think that's why perturbing the system like doing stress test. I think you've used VO2max as a way of like testing the system and seeing how the mitochondria are they capable? VO2max is basically a test of how much energy can you flow? How quickly can you flow energy? So that's I think one way when you can, that allows you to get an overall read on the organism's ability to support energy flow. GDF15 I suspect I've never been a fan of like a single protein or a single marker because the system is so much more complex than a single thing driving everything. But it seems like it's a convergence point. It's a signal of energy resistance. And energy resistance is that point of conciliance, right? If energy can't flow properly, then you create inflammation. You create reactive oxygen species and you create excess heat and then you create disorder that leads to disease and aging. So energy resistance I'm starting to believe is really the crux or kind of the... It's measuring that's important. The rosetta stone, yes. So we should try to get this test commercially available. That's one key way to look at it and then see whether what you're doing from a lifestyle or supplement or other intervention perspective is actually working. Yes, if you can, yes. Having a way to quantify, to measure energy resistance in the body would be game changing. But we haven't Mayo Clinic doesn't. Like if I'm a doctor, can I send my blood of my patients to Mayo Clinic now? I think so. Yeah, I think so. Yeah, they've used it only, I think... With the severe diseases. For mitochondrial diseases, yes. These like rare genetic disorders. Yeah, they don't think too much about the continuum of disease from asymptomatic to full blown pathology or yeah. Correct, but there's this new study in the UK, the UK Biobank, over 50,000 people where the proteins in the blood were measured and then they were looking, what's the best marker for diabetes? What's the best marker for dementia? What's the best marker for bipolar? What's the best marker for cancer? And you can go down the list. They have 900 clinical phenotypes. And then there's 3000 proteins. And then they're asking, okay, which of these proteins is the best marker for disease one and disease two and disease three, right? And then you go down the list. GDF15 is by far the best marker for most diseases. Most diseases. Most diseases. So it's a pan disease, right? The technical term is a pan disease biomarker. Why the hell is that? The energy resistance principle says it's because all of these diseases have an energetic etiology. That's amazing. So we gotta get this test commercially available like ASAP. That'll be very useful, I think. That protein marker we know also goes ballistic in pregnancy. And I'd actually be driving nausea, right? You mentioned that, right, in your research. Yeah, so there's a new paper that came out showing that morning sickness in first trimester pregnancy is driven by excess of GDF15. So that's too much energy resistance. And how do you fix that? In this case, the energy resistance comes for the placenta, right? This is, you know, we think is the placenta trying to protect the mom against the baby's really low energy resistance. So the core principle in like the way energy works in the world is that it will flow down the path of least resistance. So if you have water streaming down a river and then the terrain, you know, goes up here and goes down here, where's the water gonna go? Down, right? Because it's a path of least resistance. If for the water to go up, then we need to be like pushed or there'd be a lot of resistance. So energy flows the same way in the body. So if there's something in the body that has really low energy resistance, energy is gonna go that direction. We think that stem, stemness in your stem cells, like the developing embryo, like the fetus, it's probably really low energy resistance. But then if the mother wasn't protected against that, right? If there wasn't kind of a shell of high energy resistance around it, then all the energy from the mom would be going to the baby and then that would be actually bad for the mom. So the solution that the human species found is to shelter the baby into a little pocket. And there's this thing called the placenta that filters, you know, energy and everything else from the mom into the baby. And then there's a tiny little like cable that connects the baby to the mom, right? They're not like fused. There's kind of a limited channel for communication and for feeding. So GD15 comes from the placenta. The placenta makes tremendous amount of GD15, you know, hundreds or thousands of orders of fold more than the rest. So let's say I'm a doctor and I have a patient who's got fatigue or any one of the conditions that I earlier mentioned and I measure this GD15, what do I do about it? Clinically, what do I do? Like what are the therapies that are currently available from lifestyle, from stress management, from diet, from exercise, from supplements, from medications? Like what's out there that can be used? Cause I've been using these principles of mitochondrial resuscitation for a long time. But I'm just wondering from your perspective as an expert in this, like what's here now and what's coming down the pike? What can we use to decrease energy resistance and allow energy to flow more freely in the body so the body can heal itself? Moving, physical activity, right? You increase energy resistance and then you relax. Exercise. Exercise but then good periods of rest. And we need to cherish the rest period as much as we cherish the intent. Yeah, my auring said rest today. I'm like, all right, fine, I want exercise. This is so important. I learned to feel this, I call this mitoseption, right? Like, you know, interoseption. Yeah, it's like awareness of your mitochondria. Exactly. If you tune into your energy to your mitochondria, then you can know, yeah, I should be resting, right? And I've learned to feel this through injuries. Not through great sensitivity to my subtle energy. But through exercise I learned, I started running a few years ago, but if I run every day, then I get injured, and like Achilles or knee or like a... So if I run every other day for me, that's the right dose, right? And I don't run 20 miles, I run for 20 minutes and that's to me, that's like the right dose, the right intensity. So mitoseption, kind of feeling into your mitochondria and using these energetic signals that we all get at the end of the day. And at the end of the day, you can actually sit down, maybe pop your journal open and ask, like, what brought me energy today? What really energized me? What inspired me? And then you do the other, the flip side, you say, what drained me today? Like that conversation with that guy was really draining. I don't want to do that again. What things in your life are sucking your energy? And I would say which things in your life are increasing energy resistance in your body? So you can learn to become sensitive to that and kind of train your awareness, your energetic awareness, through mitoseption. So that's one thing I threw this practice... Yeah, it's so interesting. Cause I used to teach these workshops around kind of healing repair. And one of the exercises I had people do was go through and create a list of energy drain and energy gain. What are the things that drain your energy and get rid of them? What are the things that help you gain energy and add those things? It's interesting, that's what you're talking about. Yeah, I think it's profound because that's actually the best way you have, right? To keep a tab, not on how the machine of your body is working on how you, the energetic process is doing. And emotions, right? And our state's of mind, emotions really are energy in motion. Right? We feel emotions when energy is stuck somewhere, when it flows, right? Emotions are energetically charged and they mean so much. Like the content of your mind is the best instrument you have, right? And kind of feeling into how you feel is the best instrument you have to know whether the content of your life is aligned with who you are as a person. That's beautiful, that's what you said. But you're also in your work of psychobiology, as you call it. Talk about how states of stress will actually directly be transduced or communicated to the mitochondria that then change the way they work in a detrimental way. And it's not just like an idea, it's actually biology. Yes, your mind can actually change your mitochondria. And this was a hypothesis 10 years ago. Now, we know this is true. And we've done a few studies in the lab and brains of people after they pass away. And on whom we had information before they died about how they felt about life, about themselves, about the world around them. And we found that people who felt more optimistic, who felt more connected to other human beings or something greater than themselves, people who felt like they had a purpose in life, they have more mitochondria in the prefrontal cortex. And more specifically of mitochondria that seemed to be enhanced or that seemed to have a greater ability to transform energy. That's fascinating because I call myself a pathological optimist. It's probably good. I've been through a lot of hardship in my life, both physical, emotional and psychological. And yet I always come out optimistic, whether it's foolish or not, I don't know. But the joke is optimists live longer, even if they're wrong. I think it's true. And these difficult life experiences is really what shape us. And they shape us energetically. So how is this being used clinically in medicine now? Where are the pockets? I mentioned if you like Brian, I mean like a Suzanne Goh or Chris Palmer or Simone Setti and other places, where are you seeing this actually emerge in a clinical practical sense for people? I don't think it's there yet, but I hope in five years it will. And I think right now we're still thinking about mitochondria as little machines, little powerhouses. We still think about the body as a machine that we need to fix, that we need to supplement with something. I think there's a deeper reality that where the mind plays a much bigger role than we anticipated. I mentioned moving, exercise and then resting as essential for finding that sweet spot, helping your body find this Goldilocks zone of energy resistance requires that you push it and then you let it rest. Same thing mentally, psychologically. Like we need to have something to work towards. The mind needs resistance as well. Too much resistance, if you put too much resistance on the mind, then you feel stifled and you feel, if you do this to a child, then I think you traumatize a child. The art of education is really to tailor the right pattern of resistance. You need to say no sometimes, but you need to also let the energy of that young creature flow. So too much resistance in the mind, not good, feels terrible. Nobody likes a job where they can't be themselves and do what they wanna do. But then not enough resistance feels ungrounded and probably feels like psychotic disorders or... That's good, but it's remarkable because these metabolic therapies, you say they're not quite in the clinic yet, but I would kinda disagree with you because... Metabolic therapies are, no, like ketogenic diet, do you mean? Yeah, ketogenic diets or even mitochondrial supplements that are used to improve mitochondrial function, whether CoQ10 or NAD or NMN or the B vitamins or... If there's a deficiency in the mitochondria, those things can be life saving and life changing. The ketogenic diet, I've tried it myself. I've met and feel so grateful to have had people share their experiences with me, their lived experience of going through terrible times of schizophrenia or bipolar, then going on a ketogenic diet and seeing their lives completely transformed and finding the energy, finding the capacity to do things in a way that they hadn't in years. This is like remarkable and I think that works in part because the ketogenic diet reduces energy resistance in the body. If you have ketones in your blood, ketones enter the brain and then they're oxidized. They get, the electrons on the ketones get to oxygen with less resistance than the electrons on glucose. Glucose has to go through this crazy path, very indirect to get on oxygen. So burning fat actually can help the mitochondria work better. I've had patients with Alzheimer's who I was treating and helping them improve and then they would have a dip and I would put this one moment on a ketogenic diet and it was like the lights came on and it was like, holy crap. Yes, I've seen that many times now. This is remarkable. And I've experienced also greater clarity of mind from not having sugar. I think I'm one of those like lean hyper responders. I think they're called. If I eat too much sugar, too much fat, I can't put on weight. Like I'm pathologically doomed to be lean, which is pretty bad because then if there's too much food substrate, too much sugar or fat in my blood, then it ends up being deposited ectopically in my liver and my muscles and maybe other places. So I don't have a great tolerance to like excess food. And I've noticed like if I fast for intermittent fasting for like 16 hours, I feel much better. And then so it goes back to my deception, like feeling what's right for you. And my hunch is once we have a GDF-15, marker of energy resistance, accessible and available to people, it's gonna be most useful not as a one time thing where you go to your doctor, where you get GDF-15 measured. And then, you know, oh, my energy resistance is higher than it's supposed to be for someone my age. What can be most useful is when you have your GDF-15 measured every day, maybe you have a continuous monitor, like a CGM, but for energy resistance. And then- Is that realistic? Is that coming? I think it's coming in a few years. But then you could know for you, right? For you, Mark, if you eat this thing, when you have your almonds in the morning, your energy resistance drops by 5%, which is amazing, right? If you eat this like cheesecake for lunch, It goes up. It goes up 15%, bad news. That's why you feel crappy if you go good for a second while you eat the cheesecake and then a little bit later, you feel like crap. Yeah, exactly. I might have to, I think it boils down to changes in energy resistance. And if you go for, if you were exercising, right? During the exercise, energy resistance would creep up. And then after the exercise, it would go down. And then as you make more mitochondria, because the more mitochondria you have in your body and in your muscles, the more flow channels there is for energy, right? Every mitochondria is a little channel. Fascinating. So then you can live at lower level of energy resistance. And then if there's lower resistance, like lower blood pressure, for example, then the heart doesn't need to work as hard, right? And then your whole organism can live in a more comfortable way and a more energetically efficient way. It's almost like kind of a unified feel theory for human health in a sense, right? I think it is, yeah. It's like when you keep going upstream, upstream, upstream, why, why, why, why, why, why, why, this is the medicine of why is functional medicine. You come to a conclusion that there's these fundamental biological processes. And I know you're focused on mitochondria, but I think there's other things that are really playing a role here, like microbiome and nutrient sensing and other things that immune dysregulation. And there are these, in functional medicine, there's these lenses. Like there's seven, basically, lenses we look through. And we basically look at one of the things that in the simplified terms, like energy gain, energy drain, where it's too much, we need to get rid of our too little that we need to get. That's kind of the principle. And it affects these seven physiological network systems, right? Your microbiome and gut, your immune system, your energy system, which is your focus, your detoxification system, your transport and circulation, and communication systems, and your structural system. And they all influence by mitochondria. But they're all influenced by each other. And there's a network phenomena. The glue between them, I would say, is energy. And energy flow is what connects all of them. And mitochondria is part of it. It's kind of the hardware, right? It's like a microchip, a distributed microchip that through which energy flows to power the immune system, to feed the gut and to interconnect everything. So what you're saying essentially is that sort of the future of medicine is mitochondrial medicine, in a sense. Like it's really understanding how that plays a role in so much chronic disease. I think the future of medicine is understanding energy. Energy, which comes down to mitochondrial health, right? Maybe I can tell the story that you talked about earlier, like finding a virus. And last year, over a few years, on December 31st, I was starting to feel a little like scratchy throat. And I went to the New Year's dinner, but then I came home early, went to bed feeling terrible. And that night was like terrible. Next day, I felt depressed. Like my immune system was probably in full force. I had fever, like pretty high fever. And then my state of mind changed. And then I thought, I should be writing about this. I'm writing a book on energy. Yeah, yeah. When's it coming out? Spring, 2027. Okay, it's a while. So I was thinking, I should be writing about this. Like this is my immune system burning energy so much that it's draining my will to live. And it was draining, I couldn't have motivation. I couldn't like care about the things I normally care about. I couldn't, you know, I thought I could just like prop myself up in the bed, like pull my laptop and like write about what I'm feeling, my experience of like being energetically depleted by this virus. I think I wanted to record this, but I don't, I care enough. And now thinking about this in my normal state of mind, I like, this is crazy. This was such an opportunity to capture this human experience of like being drained of energy. What was happening is not that my mitochondria were broken or that, you know, I was missing a supplement or something. What was happening was that the immune system, we know this from a lot of good work, was consuming so much energy, right? You have immune cells that have recognized the virus and now they need to multiply. So you have one immune cell that knows what the problem is. It's like your immune cells are running a marathon. Yes. And, you know, on overdrive, and then the body is warm, right? If you have a fever, that costs energy. And then just like going to the bathroom, like, you know, moving every muscle contraction was painful. And this is all like really adaptive. This is the brain saying, shit, we're running here. This really- Slow down, rest. Yeah. There's something that's costing a lot of energy. We're going to go bankrupt if we don't shut things down, right? And then the brain has this amazing ability to shut down testosterone, for example, which is, which costs a lot of energy. To shut down your thyroid hormones, which also can cost a lot of- That's interesting because when I was really sick, my testosterone went down dramatically. My thyroid- Energy saving. Energy conservation. Yeah, my thyroid hormones shut down. And I was like, I felt horrible and I just had to rest. We understand this as energy conservation, right? The brain is receiving the signal from the immune system, cytokines, GDF-15 is one of them, but not only GDF-15. Goes to the brain, the brain says, shit, something in the body, the brain might not know what is causing energy, but it's receiving the signal through the cytokines. Something is over-consuming energy big time. If we don't do something, we're going to die, like literally. So then the brain says, okay, will to live down, motivation down, desire to interact with other human beings down, sensitivity to pain, alledonia, right? Or to your skin, way up. So that this thing, this guy doesn't move, right? Yeah. Make sure this guy doesn't go running, for example, right? So then you make the whole body uncomfortable. The brain could be engineering all of this. The same thing with aging. The brain could be shutting down testosterone and thyroid hormones and all of the endocrine deficits. We know even like hair grain, like could be a way of saving energy, because it costs energy to put pigment, put color in your hair. So what was happening there in this like terrible experience, and it lasts about 48 hours, where I felt like I was actually scared. I didn't go to the hospital, but I felt scared because I don't remember feeling that terrible. But that terrible feeling was nothing else, I think. Then my brain feeling like we're running out of energy. Like I was running out of energy. The flow of energy that I am was compromised. And if I didn't have the resources, which are my mitochondria and my little fat stores and like other glycogen that I had stored, you know, places, then I could have died, right? And maybe that same infection or that same situation, if I was 90 years old, that might have been the enemy, right? But because I have more mitochondria than- More resilient. Yeah, more resilience, right? So the mitochondria, these flow channels that are there to support the demands of energy flowing. And my heart was beating much faster, right? So again, not my mitochondria broken or like needing something, but it was the energy was being diverted. And I think that's what chronic stress is. The reason stress is bad for us, the reason stress makes us tired, and ends up damaging our organs and ends up aging us faster is because it steals energy from the things that keep us healthy. Okay, so let me get this straight, Martin. What you're basically saying is the goalie locks effects is important, but at a deeper level, our bodies need to have the stress response in order to become more resilient. Correct. So when you exercise or lift weights, or when I was riding my bike up the mountain, like I was huffing and puffing, it was hard, right? You should, yeah. I was increasing stress in my system, correct? But it was temporary. And there's this concept we've talked about in the podcast called Hormesis, which is basically a stress that doesn't kill you, but makes you stronger. That's why calorie restriction increases longevity. That's why things like various inputs that are even supplements may increase the kind of little stress in the body. I have this theory that the molecules and plants, these phytochemicals that we consume when we eat colorful fruits and vegetables, are actually the plant's defense mechanism, but they're little mini-poisons. And then our bodies use them to say, oh, let me build a more resilient system. And so ultimately what you're saying is that, the energy resistance when it gets high can actually induce longevity pathway. It's a danger. If energy resistance creeps up in your body, it's dangerous. So then, if it stays elevated forever, right? So then in response to that, the body will mount responses because stress responses, when you adapt after exercise, you make more mitochondria. That's a stress response. But then the product of having more mitochondria in your body and your muscles is lower energy resistance. So then you can spend, you spend an hour exercising, huffing and puffing at high energy resistance, and that's uncomfortable. That was two hours, but yeah. Two hours. And then you spend 22 hours at lower energy resistance. That's a net gain. This is such a key point because it's not that energy resistance is bad or good. It's just understanding how to play with it so that you're not in a constant state of energy resistance, which is what happens when you're chronically ill. Exactly. And the key point here, and we talked about the Goldilocks level of energy resistance, it's an oversimplification. What really needs to happen is you increase energy resistance, right? And then you decrease energy resistance. So it's like a pendulum, or maybe it's more like in three dimension, it's more like an infinity sign. But there's, you go to high energy resistance, you exercise, but then you spend some time in low energy resistance. But you need that in order to actually create resilience and health. Exactly. So that's the key here. I think people need to walk away with this. We can start to look at how we're doing. And in ultimate, what we're saying is this, at GDF 15, if we could continuously measure, like a glucose monitor, would go up if we're doing stressful things like hyperbaric oxygen or doing exercise or a sauna or a cold plunge, all these people would do to kind of... Or an interaction with another person where it moves your energy. That might actually increase energy resistance. But then ultimately, then once it stops, you become more resilient and you activate these longevity pathways. That's amazing. For example, during the day, you'll study, right? Or you'll learn something, you listen to a podcast. But then what really, when that knowledge really sets in and kind of gets incorporated into the corpus of your knowledge and into who you are as an energetic organism, is during sleep. And sleep is maybe the... It's a daily period of very low energy resistance. When you sleep, energy resistance, right? It's like the... You measure how much energy the body burns during the day is like this. And then you have a meal and then you actually burn a bit more energy to digest your food. Then if you go on a bike ride, you get a big spike, then when you go to bed, there's this beautiful decrease, this hypometabolic state. And then stress hormones, right? The same hormones that kind of mount these hormetic responses like cortisol and testosterone, they go down when you sleep. And then that's when repair happens. That's when healing happens. So it's in the period of low energy resistance, right? And then before you wake up, you start to have those hormones that go up again. And then waking up is a stressor. Waking up is a stressor. And then it costs energy. You can see this. We've done studies of sleeping people. And when they wake up, there's this beautiful spike of energy resistance or energy expenditure, which is driven by the energy resistance. But this runs through everything in nature. The sun rises and it sets, right? And then it's the trees, they have leaves and then they fall and they fall. It's like the ancient Chinese figured out the yin and yang, right? The way your heart works, you know, contract and then it will contract. Breath in, breath out. Day, night, right? Sleep, breath, wake, right? It's actually true. And that's really a key principle of life, which is on, off, on, off, on, off constantly. And then getting a balance right is important. And unfortunately, most of the way we live in the society today is just on, on, on, on, on, on. And that's why we have such a burden of product disease. So wow, what a conversation. I mean, this could go on for hours. I just want to kind of summarize what we talked about because it's a lot. And I think that, you know, what your work is discovering, and you sort of came up with this energy resistance principle, right? This is your- It came up with a wonderful friend of mine who's, who was my teacher when I studied holistic medicine and I had a part-time practice in back in Montreal for five years when I was doing my PhD, learning about mitochondria and on, you know, during the week and then one day a week on Fridays was vendredi pas de mitocondri. So no Friday, no mitochondria on Friday. And that's where I was seeing clients in the clinic and this connected me with, you know, that level of human experience and people describing, you know, not being well, then, you know, this ease, not necessarily because of like a disease diagnosis, but like just the dis-ease that traditional medicine has no, you know, answer to. So that was kind of my- So we're kind of looking in the wrong place for the answers. And what your work is really helping elucidate is that by thinking upstream, by thinking of what are the common links between all these diseases that we see, that we've talked about, that are affecting us so desperately from mental health issues to metabolic issues, to neurodegenerative issues, to immune issues, I mean, all of it, that there's kind of a sort of a common link and the common link is energy. And that many of us know on a symptomatic level that we don't have enough energy. And that we now understand what are those things that impair energy production and their poor diet, stress, lack of exercise, lack of sleep, inadequate nutrients that run our energy system, toxins, allergens, microbes, microbiome, these are just the fundamental things that our mindset can impa- Yeah, they deplete our energy if we don't do them right. And that if we actually learn about how they function and how the mitochondria work, we can actually start to improve our energy by taking away the things that impair it and adding in the things that help it. And there's a laundry list of things that do that. The beautiful thing that you're talking about is finally soon being able to have a clinical biomarker, a blood test that is sort of universally applicable to understand where you are in the cycle of energy gain or energy drain in simple layman's language. Yep, higher low energy resistance. Higher low energy resistance. And then we can modify our lifestyle, our way of being, our diet, our supplements, our sleep in order to actually help improve and help us get to the goal deluxe of energy resistance. Too much is bad, too little is bad. And that the future of medicine will be, I think increasingly be able to understand how we measure mitochondrial function, how we measure energy, right? The GDF-15, which is, I think one, I think there probably will be others. And how we then can sort of use this to treat a whole range of different diseases. And where this is happening already, because you say it's not quite clinically there, I think I disagree with you. I think it is clinically there. I mean, metabolic minds is an organization that funds research at Mayo Clinic and other institutions like yours to help understand the role of mitochondria and mental health. The autism work of Suzanne Go, the metabolic health work of Sabani Seti and others around diabetes and metabolic health, these are changing how we think about health completely. And it's kind of like I kind of joked about the unified field theory, which is physics and Einstein was trying to get to, but there are these natural laws of biology that we haven't discovered. And I might get feeling after having this long, long conversation is that this energy resistance principle is one of those things. It's one of these fundamental laws that you've uncovered that can help us explain a whole range of things, right? Pierre Laplace said that a small number of general laws can explain an enormous number of complicated and complex phenomena. Through a small number of general laws of physics, we can launch a spaceship to Mars. It's complicated. Humor biology is far more complex than that and is kind of an unknowable, but there are like directionally things that we can do to optimize that. And I've been doing this clinically for years. It's crude, I would admit, or kind of looking through kind of like almost like the first X-ray, and you can barely kind of see anything. And now we have these high resolution three Tesla imaging machines where you can see everything. I think we're gonna get there. I think, hopefully we're gonna have to do muscle bobs and everything, but find out their mitochondrial. But I think there's a lot of doorways to activate this. And I think there's a lot of things that we can do from a lifestyle and diet and supplement perspective that help with these pathways. And I've written a lot about it. I've talked a lot about it. You're leading the science in the way on this. I think it's an incredible field. So everybody listening understands energy. They know, I don't feel good. I have low energy, high energy. There's a reason and there's a pathway to understand how to assess it and to treat it. And I've written a lot about this in my books. I talk about it a lot, but I think personally I've experienced this on a cellular level, so I understand it. And I've treated thousands of patients this way. And I've seen really miraculous things happen that are beyond our comprehension with our current model of medicine. And so I'm just so grateful for your work. I'm so grateful that you're leading this. You're a young guy, which is great because a lot of years ahead of you to kind of help us kind of unpack all this. Lots to do. And then turn into something that's gonna really help humanity at scale and to really change the way we think about health and medicine and to move us from this disease-centric model to a health-centric model. So I just wanna thank you for your work. I want people to learn about it. I am going to link to all these articles in the show notes. So I want you to really kind of, if you're listening, wanna geek out a little bit, go in there, you can throw the paper in chat, GPD have a summarizer for you. So make this an eighth grade reading level, or like whatever you want. And I think your book is coming out, which is gonna be all about energy in 2027. I'm gonna keep an eye for that. We'll certainly promote it. I love that you're creating the science of health program at Columbia, at your Columbia University. This is not some crazy hippie in some clinic. And like in Berkeley, this is actually in the halls of academia where, and I'm not thinking as hippies in Berkeley, trust me, but I was one once. But I think that it's so inspiring to me that scientists are saying, wait a minute, we got this wrong and we're thinking about disease wrong. And we need to shift our thinking and look for root causes and look upstream and look at how we begin to reimagine medicine from the perspective of health, not disease. So Martin, thank you for coming all the way to Austin to talk to me. I think we're gonna keep up with your work. Have you back on the podcast when we get your book coming out. And again, just congratulations and I've been learned so much from you already. So thanks for being on the podcast. Thank you, my pleasure. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review and subscribe to the Dr. Hyman show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on the Dr. Hyman show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my guest's opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. 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