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

23:58What 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 the 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 you know ever so slightly yeah um 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.

24:32They'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 transmuted through the surface. Exactly. So how does that apply to human health and biology?

25:08Because I think maybe people are a little lost by what you're saying. The point is - Because I'm a smart guy. I'm getting a little lost. So help me out here. The conductive medium that allows the metronomes to come into sync and to, 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.

25:49Inside the mitochondria become charged like little batteries. This is where the lightning bolt you know, both calculations come from. And then they start to talk to one another. And mitochondria are these, you know, like an intracellular brain, pretty much. Mitochondria can receive information from hormones, from metabolites and from - Immune system, from the microbiome, right? Yes, 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. There are many different forms.

26:23And this comes, you know, from the tree, which is really crystallized energy from the sun. Yeah. 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 piece of food, it's like stored energy from the sun in some version, right? That's something what it is. They're growing the plants and eating the plants themselves or eating the animals that ate the plants.

26:55And 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 to use technical language, right? You have one thing and then how many branches, how many different ways can it go? Yeah. Is, is, you know. Yeah. Yeah. With the number of cells we have, the number of genes we have, the number of proteins. It's infinitely complex. Yes. You know, the, 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?

27:37Do I do that? Well, I just want to stop you there because what you said, it just, 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 i personally really unfortunately understand mitochondria on a cellular level myself, because my mitochondria have been so screwed up so many times that I've had to really understand how to recreate a healthy energy system in my body.

28:18And I do that with my patients and it's, it's, it's kind of miraculous. The miraculous thing about it is, is what we see in nature every day, right? Like the, our ability to heal and to, and to build and sustain health is what we see in nature, right? Like you, 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, and 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 incapacitated. I was in bed.

28:53I 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 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.

29:35And this weekend I was in Aspen and I hadn't really been doing a lot of cardio, I've been 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. You might've caught you're working 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 is that it was a new idea to me, one of these fundamental laws of biology that you've uncovered called the energy resistance principle.

30:20And most people probably have never heard of it. Most doctors haven't heard of it. I steeped in this stuff and I never heard of it until I read your stuff. I think it's something that you, you kind of discovered. Hopefully you get the Nobel prize. I want to 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 conagerie, I think they're like the canaries in the coal mine, You know, the canarian coal mine was a canary.

30:56They put a coal mine and if it died, the coal miners knew the air was bad, get the hell out of there. So the mitochondria are the first kind of sensitive little organelles inside our cells 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? Because 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.

31:44And 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 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 34 years ago, Jeffrey Bland came up with this idea of mitochondrial resuscitation.

32:21How 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 in this energy resistance principle to understand what's happening and then what to do about it? I think the reason why energy 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?

32:55And you look at which diseases are there evidence for that mitochondria are impaired in some way. And it turns out every disease. Pretty much, pretty much. So why is that, is your question. 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 way. Yeah. I'm an energy healer. Yeah. Right. Right. There might be something to that, but 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?

33:38That 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 the 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?

34:13The 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 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 going to start burning a ton of energy.

34:59and 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 the this thing this organism needs to manage an economy of energy right and 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 they're like the resting metabolic rate or you mean? Resting is when you're not doing anything, right?

35:38But then 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 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 was this remarkable discovery a few years ago by Herman Ponser. He went to work with Hadzahs in Africa. Yeah, I've been there.

36:10He 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. And 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 type wiggle. Really, how is that? How is that? Exactly. This is, that's a, it's a mystery. It's a bit of a mystery for, there are many evolutionary reasons why that could be the case.

36:51imagine you're, you know, a caveman back, you know, 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 going to not, I'm not going to sleep and I'm going to just be very active. And then I'm just going to eat more food, right. Because 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.

37:27So 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 know, on the treadmill or, you know, your cycle ergometer, you see 300 calories.

38:05So 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 going to save it somewhere else. So the 1500 is going to end up shrinking. It's called metabolic compensation. So the organism is going to 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.

38:42Yeah. 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 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.

39:30There'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 with type 2 diabetes and in their first degree relatives, even if they don't have diabetes. 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 pgc1 alpha regulates the amount of mitochondria so if pgc1 alpha goes down then you the that happens if you stop exercising right or if you're bedridden for some reason or if you break a a leg and it's in a cast right the muscles are going to atrophy it's also going to 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 cell the muscle cells are going to say shit this this this is costing me a lot of energy.

40:30I need to build the machinery to support that energy flow. And then it makes more mitochondria by turning out PGC-1 Alpha. So PGC-1 Alpha regulates the amount of mitochondria. And there's a few reasons why - You can get more and you can get more fish in mitochondria. Yes. There's much more wiggle room in the amount of mitochondria you have. 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.

41:02But 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'll 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, and for some physiological system - It's more efficient.

41:39Actually, 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. Yeah. 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. Yeah, so 20 beats. Like 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.

42:13Now 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 want to i want to explain that i want to and then i want to 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 like how how do we then begin to apply this in new science?

42:51And even, you know, 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.

43:32Fundamentally, 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 change 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 you're, you know, 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, you know, ametal or some, you know, 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?

44:01There'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 i'm tired i'm tired that study was done in flies it was like you know 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 yeah and the way it arises is because energy is basically facing more resistance it's like you're flowing water through a pipe right or through a hose if you squeeze a hose, right?

44:41You increase a pressure, you increase a 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, right? 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, 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, your laptop, what you need is resistance in the circuit.

45:23Energy 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. Then 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?

46:00That energy, electromagnetic energy hits a green leaf and then it's transformed into something else. A different form of it. 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, the sun, energy. You can feel the energy. If you go out in the sun, you can feel it. That is transformed by plants into energy and food. Yeah. And it's kind of a miracle. And the body is kind of the reverse. So mitochondria are the human kind of - They do the opposite.

46:36Like 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.

47:14And 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 are like the two poles in this electrical energetic circuit.

47:48So 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 into energy. They store it. We eat it. We reorganize it and 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, it can explain most chronic diseases at some level or another. Correct. When we think about healthy aging, we often think about our external appearance.

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49:58Because 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 omnis that I have 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.

50:43Boom, 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 help us understand 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 when things go wrong, does it cause human disease?

51:19And then how do we fix the mitochondria? Because, you know, I was saying earlier, in medicine, it's pretty much ignored after first year biochemistry. And yet in functional medicine, we have, I think, somewhat crude tools to assess the functioning of mitochondria through looking at Krebs 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. So I think the way I think about it, just to explain to people is mitochondria is like you kind of put energy in and it's kind of, this is not actually how it happened.

52:02Like 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 to 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. So it's like, we're, 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.

52:35But when those go awry, you end up with more mitochondrial damage and more trouble with your mitochondria and less ability to produce energy. and that leads to all the diseases like the mental health issues, the metabolic diseases like diabetes, the cardiovascular issues, and psychiatric even like neurodegenerative issues like Parkinson's, Alzheimer's, autism. So kind of walk us through how we start to think about when measuring what's going on, like are there clinical tools? And there's one that you talk about like this GDF-15, which is a new blood test, a biomarker that can help you understand how this energy resistance principle is working?

53:11Are you good or bad? And what other tools can we use to measure? And then, you know, how do we begin to 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. uh in other words they they are things that go wrong that are fundamental to all age-related diseases and yet we're treating all the diseases except 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 they all converge on the hallmarks of aging right and so the hallmarks of aging i wrote about and and one of the key hallmarks is mitochondrial dysfunction and a lot of the longevity therapies work on what I call the longevity switches.

54:08These are the things that regulate in part mitochondrial function, the creation of new 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 sirtuins, 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 talk about how hallmarks of aging are good and they're useful framework, but they don't go far enough because they don't ask the question, why?

54:45Functional 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 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. My hair rises because it's so misleading. And it kind of locks us into this old idea, mitochondria are powerhouses. You gave a nice story of how mitochondria kind of are this little ATP producing 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.

55:32And 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.

56:07So anytime I hear a mitochondrial function, I... Wow. Because it's reduced to just ATP for most people. Yes. It's like... Yes. And if you say mitochondrial 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 the biochemical type of energy gets dematerialized. and then it makes is adenosine triphosphate. So three phosphate molecules. And that's kind of what's happening with sparklers inside your cells.

57:04Interesting. 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.

57:49And 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? In a hose, at some point, something's going to 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, to break down.

58:27And 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 CoQ10 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.

59:13If 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 - 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 not 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 their mitochondrial DNA that we get from her mom, they have a mutation and they feel tired all the time.

59:46Many 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 pretty angry that this is not reimbursed. 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. Yeah. 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.

1:00:24You 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 anhedonia 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.

1:01:03GDF15. What does it stand for? Growth differentiation factor of 15. And you can measure it in a blood test. You can measure it 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 be a research scientist. You do. The Mayo Clinic has a clinical test for GDF-15 that they use to diagnose mitochondrial disease. Yeah. GDF-15, interestingly, was discovered completely separately in different fields of medicine. So it was discovered in mitochondrial disease. Like if you want to know, does this person have mitochondrial disease or not?

1:01:32They're always tired. They have this symptom, neurological issues, cardiac issues. And these are rare genetic mutations that are very rare and that are well-recognized in medicine. They usually be diagnosed by muscle biopsy. Correct. 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. They're 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 that change their microbiome, our nutrition plays a huge role in the function of our mitochondria.

1:02:11I mean, that's why ultra processed food is so bad because there's no nutrients in there and it creates a lot of inflammation. Why? Why does it create inflammation? Good question. I mean, I have a theory, but I would love to 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.

1:02:47Like 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 mitokines to myokines.

1:03:17I mean, every kind of communication. It's so fascinating and it's happening at fantastical speeds, constantly in the body. And when those communication systems are awry, that's when disease arises. If everything is going well in your body and your cells are 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 you know lives uh harmoniously you know as part of the social contract like every cell works with every other cell and no one cell is going to go on their own to in a selfish way that's what cancer is but if every cell is okay and and is functioning harmoniously the whole organism you don't need to secrete cytokines right because the cells are are working the way they should when something's wrong then you if you're a cell and you're experiencing excess energy resistance because your mitochondria are not working properly.

1:04:20Maybe 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 going to 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.

1:04:57We 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. over time. And then during the exercise, I felt so great afterwards. 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.

1:05:29So 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 relate 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?

1:06:02And 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? Because people that are, when they're in the manic phase, they don't feel tired, right? No, it's crazy. You feel like so much energy. They can stay up all day for like 10 days in a row and they're - Yeah, you don't feel like sleeping. I think they're Jesus. You don't feel this. Yes, 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.

1:06:39But 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 a weight that's too heavy for you, and then it starts to burn, right? What is that burning? It's lactate. It's not. It's not. That was debunked. Oh, really? When I was a student.

1:07:12What 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. You can still contract, but you feel the burning. Well, I'm doing pull-ups. There's one point I just can't get another pull-up in, right? What is that? I think that's a mixture of there's acidity and there's buildup of product. 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.

1:07:45Then 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. When blood can't flow to the heart anymore, like the pain of this, my dad went through this a few years ago. 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?

1:08:21Elephant sitting on 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, 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 like, Hey, 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, have any one of these conditions that may be related to the mitochondria, where do I start?

1:09:03Like 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.

1:09:42You make your new mitochondria when you're resting, right? And that's a key element of energy resistance principle. You need to increase your resistance when you're biking or you're out of breath 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, you know, the great thinkers, you know, the creative writers will tell you, like you need to like obsess with something, but then you need to like go. You go for a nap or you shower and then the idea comes, right?

1:10:17It's when you relax, it's when you relax that you get the benefit from having, you know, the increased resistance. So the chronic exhaustion, you know, 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. Yeah. I think part of the core philosophy for functional medicine, right? How do you - Restore function.

1:10:55Yes. How do you restore function? How do you allow the organism to heal itself, to do what nature just naturally does, what life naturally does? And I think key pieces that we know are generally true across people, but I just want to 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 want to know if something works, the gold standard in science is 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 Did I move the average, right?

1:11:45Did I move the needle? So you measure something and you're a group of 100 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 you 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 up 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?

1:12:20And 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 salutary. 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.

1:13:00And 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 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 talk 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?

1:13:30How well are they working? What's impairing them? How do I help their mitochondria work better? How is that going to 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 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 based on the diseases?

1:14:02And 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 function that she 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, how do we take this and practical, practicalize it if that's a word?

1:14:36Yes. How do we touch human lives with this wonderful scientific knowledge? Yeah. Yeah. I want you to spend the rest of time talking about that. Cause we're kind of did a lot of science stuff and I want to get, if you can, and if you can just tell me, I'll, like, I'll, 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, right?

1:15:11Which 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 right like is your organism able to flow energy through the mitochondria the way it should um and i think that's why perturbing the system like doing a stress test i think you've used vo2 max as as a way of like testing the system and seeing how the mitochondria are they capable vo2 max is basically a test of how how much energy can you flow how quickly can you flow energy um 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.

1:16:02GDF-15, 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 consilience, 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… So measuring that's important.

1:16:43The 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 have it. Mayo Clinic doesn't. If I'm a doctor, can I send my blood of my patients to Mayo Clinic now? I think so. Yeah. Yeah, I think so. Yeah. They've used it only, I think. For these severe diseases. For mitochondrial diseases. Yes. These like rare genetic disorders.

1:17:13Yeah, they don't think too much about the continuum of disease from asymptomatic to full-blown pathology. Yeah, correct. But there's this new study in the UK, the UK Biobank. It's 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 3 ,000 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?

1:17:49And then you go down the list. GDF-15 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 ideology. That's amazing. So we got to get this test commercially available like ASAP. That would be very useful, I think. That protein marker we know also goes ballistic in pregnancy and might 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 GDF-15.

1:18:32So that's too much energy resistance. Right. And how do you fix that? In this case, the energy resistance comes for the placenta, right? This is, we think is the placenta trying to protect the mom against the baby's really low energy resistance. So a core principle in 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 goes up here and goes down here, where's the water going to go? Down, right? Because it's a path of least resistance. For the water to go up, they would need to be like pushed or there'd be a lot of resistance.

1:19:11So energy flows the same way in the body. So if there's something in the body that has really low energy resistance, energy is going to go that direction. We think that 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.

1:19:46And there's this thing called the placenta that filters energy and everything else from the mom into the baby. And then there's a tiny little cable that connects the baby to the mom, right? They're not like fused. There's kind of a limited channel for communication. for feeding. So GDF-15 comes from the placenta. The placenta makes tremendous amount of GDF-15, you know, hundreds or thousands of orders of fold more than... 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 GDF-15. What do I do about it? Like clinically, what do I do?

1:20:31Like 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? Because I've, I've, you know, 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, 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.

1:21:06Exercise, but then good periods of rest. And we need to cherish the rest period as much as we cherish the intent. Yeah. My aura ring said rest today. I'm like, all right, fine. I won't exercise. This is so important. I learned to feel this. I call this mitoception, right? Like, you know, interoception. Yeah. Right? 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, not through great sensitivity to my, to my subtle energy. But through exercise, I learned, you know, I started running a few years ago, but if I run every day, then I get injured, you know, and like Achilles or knee or like, so if I run every other day for me, that's, that's the right dose.

1:21:51Right. And I don't run 20 miles. I run, you know, for, I don't know, 20 minutes. And that's, to me, that's like the right dose the right intensity um so mitoception 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 you know pop your journal open and ask like what brought me energy today what really energized me what inspired me uh and then then you do the other the 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.

1:22:30What things in your life, right, 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, right, to that and kind of train your awareness, your energetic awareness. And I call this through mitoception. So that's one thing I threw this practice. Yeah, it's so interesting because I used to teach these workshops around, you know, 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?

1:23:03What 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 states of mind, And 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?

1:23:42And 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 beautiful. who 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.

1:24:30And 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 seem to be enhanced or that seem to have a greater ability to transform energy. That's fascinating because I call myself a pathological optimist. Yeah, that's, it's probably good. I've been through a lot of hardship in my life, both physical, emotional, psychological, and yet I always come out optimistic. Whether it's foolish or not, I don't know.

1:25:10But the joke is optimists live longer, even if they're wrong. I think it's true. And, you know, these difficult life experiences is really what shape us. Yeah. And they shape us energetically. So how is this being used clinically in medicine now? Like where are the pockets? I mentioned a few like Brian, I mean, like Suzanne Goh or Chris Palmer or Sabani Seti 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.

1:25:43We 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. You know, I mentioned moving, right? Like exercise and then resting as essential for building that, 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 you know if you do this to a child and i think you traumatize you know child the art the art of education is really to tailor the right you know pattern of resistance you need to say no sometimes but you need to also let the energy of that you know young creature flow um so too much resistance in the mind not good feels terrible nobody likes a job where they can't you know be themselves and do what they want to do.

1:26:43And, but then not enough resistance, you know, feels ungrounded and probably feels like, um, you know, psychotic disorders or. That's good. So it's remarkable because these metabolic therapies, you say they're not quite in the clinic yet, but I would kind of disagree with you because, you know. Metabolic therapies are, no, no, I like ketogenic diet, 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.

1:27:20The 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 than 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 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, you know, the electrons on the ketones get to oxygen with less resistance than the electrons on glucose.

1:28:11There's glucose has to go through this crazy path, very, um, indirect to get on, on oxygen. So burning fat actually can help the mitochondria work better. I mean, 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, I put this woman on a ketogenic diet it. 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, um, yeah, I've experienced also greater clarity of mind from not having sugar. And I think I'm one of those like lean hyper responders. I think they're called, uh, if I eat too much sugar, too much fat, I can't put on weight.

1:28:51Like I'm pathologically, you know, doomed to be lean, uh, which, which is pretty bad because then if there's too much food substrate, so much sugar or fat in my blood, then it ends up being deposited ectopically, right? In my liver, in 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, you know, like intermittent fasting for like 16 hours, I feel much better. And then, so it goes back to mitoception, 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 going to be most useful not as a one-time thing where you go to your doctor, 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.

1:29:45What 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 - 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.

1:30:22Yeah, exactly. I think it boils down to changes in energy resistance. And if you were exercising, 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 mitochondrion is a little, you know, 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?

1:30:57And then your whole organism can live in a more comfortable way and a more energetically efficient way. So this is almost like kind of a unified field 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, 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.

1:31:26And there are these, in functional medicine, there's these lenses, like there's seven basically lenses we look through. and we basically look at what are the things that, in the simplified terms, like energy gain, energy drain, what is too much we need to get rid of or 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 are all influenced by mitochondria, but they all are influenced by each other.

1:32:01And there's a network phenomena. The glue between them, I would say, is energy. 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 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 is, comes down to mitochondrial health, right?

1:32:36Maybe I can tell the story that you talked about earlier, like finding a virus. And last year over New Year's on, on December 31st, I was, 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, and that night was like terrible. Next day I felt, I felt depressed. yeah like my 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 uh spring 2027 okay it's a while so yeah i was thinking i should be writing about this like this is this is my immune system burning energy so much that it's draining my will to live and it was during 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.

1:33:36My experience of like being energetically depleted by this virus. I wanted to record this, but I don't care enough. And now think about this in my normal state of mind. 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 the immune system we know this from a lot of good work uh 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 cells are running a marathon yes and and you know on on overdrive and then the body is warm right if you have a fever that that costs energy uh and then just like going to the bathroom like you're moving every muscle contraction was painful and this is all like really adaptive this is the brain saying shit we're running here this slow down rest yeah there's something that's costing a lot of energy we're going we're going to go bankrupt if we 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 yeah uh shut down your thyroid hormones which also can that's interesting because when i was really sick.

1:34:52My 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.

1:35:24So 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, this, this thing, this guy doesn't move, right? 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 yeah 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 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.

1:36:14But that terrible feeling was nothing else, I think, than 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 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 resilient, right? So the mitochondria are these flow channels that are there to support the demands of energy flowing.

1:36:57And my heart was beating much faster, right? So again, not my mitochondria broken or like needing something, but 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 Goldilocks effect is important, but at a deeper level, our bodies need to have the stress response in order to become more resilient. Correct.

1:37:34So when you exercise or lift weights, or when I was riding my bike up the mountain, like I was huffing and puffing. I was, it was hard, right? You should, yeah. And that was increasing stress in my system. Correct. But it was temporary. And there's this concept we've talked about on 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 had this theory that the molecules in 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.

1:38:13And then our bodies use them to say, oh, let me build a more resilient system. And so ultimately what you're saying is that, you know, 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? Right. So then in response to that, the body will mount responses. We call it stress responses. Like when you adapt after exercise, you make more mitochondria. That's a stress response. But then the result of having, the product of having more mitochondria in your body and your muscles is lower energy resistance.

1:38:51So 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. 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. That's an oversimplification. what really needs to happen is you increase energy resistance, right?

1:39:29And 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 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 ultimately, 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 plunger all these people do to kind of an interaction with another person where like moves your energy that might actually increase energy resistance yeah but then ultimately then it once it stops you become more resilient and you activate these longevity pathways you know that's amazing you know for example, during the day, you'll study, right?

1:40:23Or 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 like who you are as an energetic organism is during sleep, right? 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, it's 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.

1:41:03And 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 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 like everything in nature like the sun rises and it sets right and then it's it's like trees you know they have leaves and then they fall and the yin and yang.

1:41:45It's like the ancient Chinese figure out, the yin and yang, right? The way your heart works, you know, contracts. Breath in, breath out. Day and night, right? Sleep, 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 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. And that's why we have such a burden of chronic 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.

1:42:16And 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 was my teacher when I studied holistic medicine. And I had a part-time practice back in Montreal for five years when I was doing my PhD, learning about mitochondria during the week. And then one day a week on Fridays was, Vendredi, pas de mitochondria. So no mitochondria on Friday. And that's where I was seeing clients in the clinic. And this connected me with that level of human experience. And people describing not being well and dis-ease, not necessarily because of a disease diagnosis, but just the dis-ease that traditional medicine has no answer to.

1:43:02So 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, My 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 the microbiome these are just the fundamental things that our mindset that can, yeah, they deplete our energy if we don't do them right.

1:44:04And that if we actually learn about how the 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. High or low energy resistance. High or 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 Goldilocks of energy resistance.

1:44:53Too 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.

1:45:31You know, 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, you know, which is physics that Einstein was trying to get to. But there are these natural laws of biology that we haven't discovered. And my gut 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?

1:46:06Pierre 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. Human 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. We're kind of looking through kind of like almost like, you know, the first X-ray, you know, you can barely kind of see anything. And now we have these high resolution three Tesla imaging machines where you can see everything.

1:46:47I think we're going to get there. I think, you know, hopefully we don't have to do muscle boxing and everybody to find out their mitochondria. 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, I have high energy. There's a reason and there's a pathway to understand how to assess it and to treat it.

1:47:22And 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 going to 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.

1:47:59So I just want to 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, want to geek out a little bit, go in there. You can throw the paper in chat. GPT have it summarized it for you. So meet this in eighth grade reading level, you know, or like whatever you want. And, and I think, uh, your book is coming out, which, uh, is going to be all about energy in 2027. I'm going to 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.

1:48:30This is not, you know, some crazy hippie in some clinic and, you know, like in Berkeley, this is actually in the halls of academia where, and I'm nothing against hippies in Berkeley, trust me. But I mean, 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 going to keep up with your work.

1:49:06I have you back on the podcast when we get your book coming out. And again, just congratulations. And I've 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 and for video versions of this podcast and more.

1:49:36Thank 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 guests' 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.

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1:50:37Thanks so much again for listening.