Tired But Wired? You're Stuck in THIS Loop

I eat perfectly. I exercise 6 times a week. I try to get to bed on time and sleep. I'm feeling depleted. And I think people are in this state and they don't have a name for it, but you call it the sympathetic spiral of doom.

And it's a loop. You have sympathetic activation, which is your fight or flight, your nervous system being activated. You have mitochondrial dysfunction. The challenge is anytime you try to downregulate your nervous system, it actually might make you feel like you're crashing. People feel like they crash when they go down and try to do their breathwork, try to do their meditation. Oftentimes They feel terrible when they try to do it, if they can even do it in the first place. You've only been able to function because you've been at that high of a state.

You can't meditate your way out of this, like, physiological stress to your cells and mitochondria is what you're saying, right? So what do we do if someone's stuck? What's the first step to getting out of this loop? Today on the podcast, I'm joined by Dr. Scott Scher. He is a board-certified physician and a pioneer in health optimization medicine. As an expert in mitochondrial function and the chief medical officer of Troscriptions, he's helping people break the sympathetic stress loop to rapidly restore energy, focus, and resilience. Hey, it's Dr. Hyman. I'm so excited to share this episode with you today, but before we dive in, I wanna get your help. Please take a minute to hit that subscribe button, whether you're watching here on YouTube or listening on your favorite podcast platform. It truly means the world to me, and it helps my team and I bring you this podcast every single week. Plus, I don't want you to miss a thing. So thanks so much for being part of this community, and I'm glad you're here. Welcome back to the podcast, Scott. So good to have you.

Well, thanks for having me, Mark. Last time it was online. Today it's in person.

Yeah, it was online. We talked about hyperbaric oxygen and today we're going to talk about a really important topic, which honestly affects so many people, including me. And I never heard it quite described like this, but you call it the sympathetic spiral of doom. Ba-da-ba-da-bum.

Yes, exactly. It needs music after it.

And at first I was like, ah, that's kind of hyperbolic, whatever. And then I started reading about it. I'm like, oh, this is what it is. It's basically the way in which your system breaks down from too much stress from your life and your psychology, but also too much stress from the environment.

Yes.

You call this top-down, bottom-up. So environment would be toxins and infections and all the stuff that we're exposed to.

Right.

And it creates a breakdown in our ability to regulate our nervous system. And then it influences our mitochondrial function, which kind of makes it worse. So the body's this big web network where everything's connected. And so you're kind of untangling the web to telling this story in kind of a new way. It's an old story. We all know that stress is bad for us, right? But like, this is a very different frame of it. And I love it. And I think it's going to help a lot of people because you have to be systematic about it. And a lot of us are feeling burned out. Like we're doing everything. Like I eat perfectly. I exercise 6 times a week. I try to get to bed on time and sleep. And it's just, you know, but sometimes I just I'm, I'm feeling depleted. And I think a lot of people out there are probably feeling that. And I think people are in this state and they don't have a name for it and they just feel like crap and they don't know what's going on. They're exhausted. They're wired. They're anxious. They're burned out. And today I really want to like have people who are listening to understand, you know, what, what is going on with their, their energy? What is going on with stress? What are the psychological and the physiological causes of stress? And how do we start kind of navigating this from a therapeutic perspective, because like we all want out of this. I, as soon as like, yeah, I'm in this empathetic spiral of doom and I want the hell out of this thing. So what is it? Explain it to us. Unpack it for us.

Well, thanks again for having me, Mark. And you know what I, what I like to just describe here is it's not a diagnosis for people. This is more of a pattern. As you mentioned, it's an age-old pattern, but I realized recently that it was really a significant discovery for me to understand that it's a spiral and it's a loop. You have sympathetic activation, which is your fight or flight, your nervous system being activated. You have mitochondrial dysfunction. Mitochondrial dysfunction, mitochondria, as all your listeners know, is a part of their cells that make energy. The combination of sympathetic activation and mitochondrial dysfunction is a loop. And what happens here is that this loop can either start with mitochondrial dysfunction directly. That's what I call bottom up, or it can start with sympathetic activation from outside stressors. Say it's your job, your relationship, you have a snoring partner that is snoring and you can't get to sleep at night. Outside stresses, or even worse things like trauma or things that happen when you were younger that have maintained you in this place where you can't stay safe. Either way, whether it starts with mitochondrial dysfunction directly or it starts with sympathetic activation externally, or for most people it's both. Yeah. And then it's something that just makes you fall off a cliff.

It could be, well, let me pause you for a sec.

Yeah.

Just define sympathetic activation.

Yeah.

Because people are like, what is that? And define like a little bit better mitochondria. Sure. Because these are central to your thesis of the sympathetic response. For sure. Yeah. So let's get our terms right.

'Cause I think if people are like, well, otherwise I'd be just be talking doctor stuff.

I'm sympathetic, I'm sympathetic. No, no, no, it's not that.

Yeah, no, good point. So yeah, so I feel sympathetic to those that are in sympathetic. The sympathetic nervous system. So sympathetic is your fight or flight.

Yes.

Part of your nervous system. So it's your, it's running away from the proverbial saber-toothed tiger, as we somehow always refer to it.

I know, right?

I don't know why, but you're getting chased by something.

Yeah.

But unfortunately, we're getting chased all the time in modern society.

Yeah.

Whether it's with our phones that are actively in our faces all the time.

Yeah.

And doom scrolling at 3 o'clock in the morning going, why is this the way it is? Or it's outside things like your job or your relationship. But we're not, we don't reward people resting and relaxing. So the sympathetic nervous system is part of your autonomic nervous system. You have your sympathetic branch, which is your activation, fight or light, and you have your parasympathetic, which is your rest, digest, detoxify, and heal. But modern society doesn't reward that side, right? It rewards the hustle. I mean, in medical school, my friends and I had shirts that said, sleep is for quitters.

Yeah.

Not surprising.

Right.

I grew up in New York.

Surgeons don't have lunch. That was ours. Yeah.

There you go. Same kind of thing. Like you just, you hustle, right? You go and you grind, right? That's what we reward. And then unfortunately, that's how society has created this stress externally for us that we have to perform, we have to have more meetings, we have to do more, do more, do more all the time. And so instead of just running away from the saber-tooth tiger and then, you know, hanging out the rest of the day because hopefully we lived, maybe we probably didn't, but in some cases we did, right? Then you would have the time to relax because your nervous system would be activated and then it'd be shut off. But that's not how modern society works anymore. As you know, we're constantly stressed, constantly on pressure, constantly on meetings, and that's that sympathetic activation. And most of us kind of think we thrive in that environment. And we can for a little while. But the problem is that when you're sympathetic all the time, you're releasing hormones like cortisol, your neurotransmitters like norepinephrine and epinephrine, adrenaline, and adrenaline. Yes, noradrenaline and adrenaline that are stimulating the whole system to work harder. Because if you're in that sympathetic nervous system activation all the time, I call it sympathetic overdrive, you're just shoving all those neurotransmitters and hormones out all the time. And that causes deterioration in immune system function, in hormone function, and in your mitochondria itself. So to define mitochondria, which we can do now, Yeah. The mitochondria are part of the cell that helps make energy, right? When I was in high school, my, my daughter is in 9th grade, she learned, she's got the basic cell. She just learned, she's like, dad, check out the basic cell. It's got a nucleus, it's got cytoplasm, it's got Golgi bodies, and it's got this one little cool organelle called a mitochondria.

Mm-hmm.

I'm like, huh, this is what I learned when I was probably that age too.

Yeah.

You learn that the cell has one mitochondria, but that is far from the case, right?

There's like thousands.

Some cells in our body have thousands of mitochondria per cell, and some cells, actually there's one human cell that has zero. And that's the red blood cell.

Yeah. The red blood cell.

Right. But most mitochondria per cell are in our reproductive organs. Eggs, oocytes, sperm are the number one in our body.

You gotta swim pretty, you need a lot of energy to swim.

Yeah. And the eggs have more though. Women have to, you know, create and make the baby. And so they have more. But then just behind that is your brain, your heart, your liver, your musculoskeletal tissue. So detox, everybody is hugely energetically intensive.

Yeah.

Liver is, people don't realize that is like, if you need it, if you're gonna be able to detox, you have to have a huge amount of mitochondrial energy. And so we have thousands of mitochondria in our brain, for example, as I mentioned. The problem is, and the statistics are crazy, it's like 94% of US adults have some element of metabolic dysfunction, right? And if you have metabolic dysfunction, you also have mitochondrial dysfunction, which means that you can't make energy effectively. Our cells are like gasoline-powered cars, right? We make ATP, as you know, we make also carbon dioxide, we make water, and we also make what are called reactive oxygen species.

Free radicals.

Free radicals. Yes, exactly. And so we need those. But if we have too many, or if we're stimulated for such a long time or a period of time, like you're sympathetically overdriven, right? You're stimulating the mitochondria to make so much energy, or trying to. And what happens over time is that the mitochondria can't keep up. They can't keep up with energy production. They can't keep it up with the detoxification required because you don't have enough antioxidants around. And then the mitochondria become under significant amounts of stress. Yeah. And so you're in this place now where you have sympathetic overdrive, mitochondrial dysfunction in the majority of people. And it's a spectrum now, but all of these peo— everybody, so many of us are on this sympathetic spiral as a result of that.

And what's really interesting is the connection between the stress response, which we all can relate to.

Yeah.

And our mitochondrial function, which is, which is basically something that, you know, most of us don't think about.

Yeah.

And by the way, most doctors don't know much about. That we learned basically in biochemistry in the first semester of medical school, how to, you know, food and oxygen go through our little Krebs cycle mitochondria.

You memorize all the intermediates, right?

And we memorize it for 5 minutes before the test and we forget about it. But mitochondria are central to almost every single disease that we see in chronic illness, whether it's dementia or cancer or heart disease or obesity or diabetes or all the neurodegenerative diseases. It's just quite profoundly important. And you're right. If you, if you are in this stress response and then you're also exposed to all the stresses of being in the modern world with microplastics and pesticides and heavy metals and latent viruses, infections, long COVID, tick infections, mold exposure, insulin resistance, insulin, like the whole thing.

Yeah.

And then of course our, our ultra sort of processed diet that I was getting to that, you know, our highly sugary processed diet. So You know, we all are stressing our stress response cuz you, you're, by the way, eating crap makes your body stressed even if you don't psychologically feel stressed.

Right.

And also it stresses your mitochondria. So then you get all these insults. You talk about this sort of metabolic stress.

Yeah.

You know, what, what are like the main symptoms people are in this sympathetic spiral are doing? Like how would people listening, you know, I have this.

So when it comes down to when the mitochondria are so stressed, they shift over from being, make, being able to make energy effectively instead of making energy like with oxygen, they actually shift over into something called the glycolytic state, which is making less energy because they're trying to protect themselves from all the stress that they're on. And when that happens, there's an overcompensation of the sympathetic nervous system. The sympathetic overdrive gets even higher because you physically feel worse. And these are the symptoms you're talking about. We're talking about feeling tired but wired, feeling like you can't recover anymore from anything that was pretty small before. Something small now, it takes you 2 or 3 days. Like you go to the gym, you don't feel like you really recover for 2 or 3 days, or you go on an airplane, don't recover much longer, or you have a bad night of sleep and you feel terrible the next day, or your mood is all over the place. It used to be pretty stable throughout the day, barring going through perimenopause or something like that. It used to be stable and now it's all over the place. You also can find that just overall your energy level is just kind of up and down throughout the day. Like you're relying on things like caffeine and stimulants to try to give you enough energy, give you enough brain function. And the challenge oftentimes, and I have patients like this, it's like, Doc, I just need to feel better. I need more stimulation. I need more energy. And oftentimes it's not about giving them more energy. It's actually about calming down the whole system, this whole loop, this spiral, and then allowing them to get back to making energy more effectively. And so there's a spectrum here, Mark, and you and I know this. We have people that are super, you know, complex and they've been sick for a long time and have, you know, very significant mitochondrial issues. And then you have people that are on the other side of the spectrum where they just don't feel very good anymore. Like they're just not waking up feeling like they have energy. Their energy is waning throughout the day. Their recovery is not as good. And like oftentimes with those people that it's something often happens where they feel like they just fall off a cliff.

Yeah.

It's like that extra little stress that just did it. And then all of a sudden the things go down.

Yeah. They kind of manage along and then just, they crash. Yeah.

Yeah.

And it's common. A lot of people I've had this. Super common. Yeah. And if you look at it as a spectrum, you know, some, most of us are somewhere in that spectrum.

Yeah.

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Yeah.

So, so this is, you talk about this feedback loop between the nervous system and the mitochondria. Yeah. Because I think it's, it's a, it's a little bit hard conceptually for people to understand. Well, how does that work? You know, you got your nervous system. Yeah. Your sympathetic, parasympathetic, and your stress response, your relaxation response. But how does that relate to your mitochondria and your energy system? And how, what is that connection and loop feedback loop?

One of the main hormones that's being vilified right now is cortisol. Cortisol is your stress steroid hormone. As you know, when you're under fight or flight, when you're in sympathetic overdrive all the time, you're pumping out cortisol. All the time. We're supposed to have cortisol rise when we wake up in the morning. It helps us wake up from being asleep, and then it's supposed to slowly go down throughout the day.

Yeah.

The challenge is that most people do not have that pattern anymore. And what cortisol does is it stimulates the production of— it's a steroid hormone. It also stimulates and initiates the norepinephrine and epinephrine. So norepinephrine, noradrenaline, and adrenaline in the system too. And what happens when you have a lot of cortisol around and a lot of those neurotransmitters is that you are just telling your mitochondria that you're under stress, you need energy now. And as a result of that, it is going to your mitochondria and saying, mitochondria, you need to make more energy now because you're under a lot of stress. This cortisol is high. And as a result of that, you're getting the mitochondria that are like, we can't keep up. There's too much energy requirements that you're giving us. And so that's why it flips over into this something called the cell danger response, which I know you know about, which is when the cell says we have to protect ourselves and the mitochondria says we're sensing too much stress. We can't actually keep up. And so what it does is it tries to protect itself, but that when that happens, you start making less energy. And when you start making less energy, you start feeling like you're not able to compensate. You're not actually able to show up the way you're tired. You're tired. This is the tired but wired kind of feeling.

The ability of the mitochondria to kind of like register this danger is interesting. And you know, you talked about this, this, this new concept, this cell danger response. But if you actually look in the medical literature, there's a lot of scientific papers about this. It's not just some woo-woo thing. Thing. It sounds kind of a little crazy, but if you actually look at it, and I think most physicians don't understand what it is.

No.

So, so, you know, it's what I'm just hearing is you say is when you have chronic stress, either from the top down or bottom up, from, you know, your brain or from, yeah, you know, the toxin crap and shit we're all exposed to, it stresses your mitochondria and then it flips into this cycle, this cell danger response, which is that the same thing as a sympathetic spiral of doom?

That's part of it, right? Because when you're in that sympathetic spiral, you're almost always flipping over into that cell danger response. And so, so unpack what is this cell danger The cell danger response is a natural response that the cells do when they're under stress. There's multiple stages of the CDR and there's a very—

CDR, cell danger response.

Cell danger response. Yes. Sorry. And as a result of having this pattern, we have a way of either going anabolic or catabolic, which means that we can either build up or break down in the system. And what the CDR does when the cell danger response is active, we get into more of a catabolic state. We start breaking down parts of our body to try to protect it. We're in the anabolic state is really when we're building up and getting stronger. That's when you're in a safe space, right? When you're in safe spaces, you're parasympathetic. I call it the parasympathetic edge really. And, and, and we can talk about that, but the idea is when you're in the parasympathetic mode, you're resting, digesting, you can turn off the cell danger response, but you can't turn it off if you're always in stress mode. And the cell danger response is basically protecting you from stress. It's protecting you so that you can survive. It's a survival mode. It's also also activated in the short term when you have acute stress, when you have acute infection, you have acute additional stress outside, external stress, but it's supposed to turn itself off, but it can't turn itself off if it doesn't have that anabolic parasympathetic activation. And that's the challenge. And in addition to that, what happens over time is that you deplete a lot of the intermediates, a lot of the vitamins, minerals, nutrients, and cofactors that are responsible for shifting you out of the cell danger response.

So just the very fact of trying to manage the danger, you're using a lot of nutrients.

Tons of it. Yeah.

And you deplete your nutrients.

Yes.

And then you end up in this vicious cycle where you need the nutrients to fix the problem, but you don't have the nutrients and it depletes them.

And you're still in the stress mode. Yeah. And you're still right. So the, the, the major question is, well, how do you approach it? How do you work on optimizing somebody's capacity and increasing their reserve, getting them out of the sympathetic, but also supporting their capacity to flip out of that cell danger response and support mitochondrial function?

Well, that's an important question. I wanna get into the practical aspects of how do people, end the sympathetic spiral of doom and how do they stop the cell danger response. But before we get to that, I want to kind of unpack a little bit about your top-down, bottom-up idea here. Because it's important because, you know, you can enter into this sympathetic spiral of doom from your psychological state, for sure, from trauma or from your biological state, from things you're exposed to in the environment that you may have no control over or your diet, which you do have control over. So can you kind of walk us through the top-down, bottom-up explanation and where the contributors to the sympathetic expeller of doom and cell danger response. So I think if we understand what those are, we can start to think about how we might approach them.

The top-down part. Let's talk about that first. The top-down part is how are we stressed? What is causing our sympathetic activation? And the amount of things that can be doing this is unlimited in this world. We can talk about it from social media to politics, to what's going around in the world right now with wars and things like that. Two things that are good.

Is there stress in the world right now?

I mean, a little, I mean, a little, I mean, it's not going away.

Yeah.

And we are wired as humans to do two things, survive and reproduce. That's it. That's what we are wired to do because that's what the species requires. And so as a result of that, what do our news media, what does our social media do? It wires you, it's wired or it's created to fit into that, those two patterns, survival and reproduction, mostly survival. So fear, right? Fear is the biggest one. And so there's tons of things that are coming outside out of us all the time that are trying to instill fear in us. It could be everything from the things I mentioned. It could be within your own home, right? If it's a relationship that isn't great, if it's a job that's too hard, if you're not getting enough sleep, that's a huge one because if you're not getting enough sleep, you're not going to be able to regulate your nervous system either. And so that's these, that what I call the top-down aspects. And I could fill in maybe all the psychological stuff.

Give me your childhood trauma.

Yes. And I had, I mean, you've had patients like this too that, you know, they were abused as a child and they never feel safe in their own body. There's no way way they can ever heal. There's no way they can ever really fully, truly be their best self because they're always in this locked-in sympathetic state.

But there's ways for people to come out of that.

100%. Yeah. And we'll talk about that. And then that's exactly what this is all about. It's about understanding the pattern and then seeing how to break it.

So that's the top-down.

That's the top-down. Yeah.

And the bottom-up is—

the bottom, bottom-up is really, you did a great job earlier when we were talking about direct mitochondrial stress, you know, things like infections and—

they're very sensitive. Mitochondria are very sensitive.

They are.

Everything affects them. They do. They do.

It's, I mean, they're a sensitive organelle. There's a lot of them. There's quadrillions of them in our bodies. Huge amounts of them.

That's a big number.

It's huge.

I can't count that.

I can't either, but it's a quad. I know that. I think after that, I can't remember. It's like, I dunno if it's quint after that, I think, but it's, it's after trillions is quadrillions, everybody that's listening. Yeah. Okay. And so it's a lot of mitochondria. And so we need a huge amount of energy. In fact, the, we need to make about 150 pounds of it every single day of ATP to maintain our energy capacity. And as I mentioned, 94% of us can't do this on a regular basis.

Mm-hmm.

And that's because of the things you mentioned. You talked about insulin resistance. And toxins in our environment, medications that we take on a regular basis that actually have a dysfunctional impetus or actually make our mitochondria do worse. Things like metformin, even things like birth control pills, even because they deplete nutrients that help with mitochondrial function. Not to say people should get off their medications, but, you know, but even proton pump inhibitors, which are acid blockers, are a big one.

That's the third leading cause of use of drugs, which is acid blockers from people eating a crappy diet.

Yeah, but statins too. Statins also have significant impact. That's the number one class of drugs.

Drugs.

Yeah.

So number 1 in 3 classes of drugs is causing mitochondrial damage.

Statins. And they have effect on both complex 1 and complex 2, which are the 2 first proteins in the mitochondria to help you make energy. And pesticides do it, infections do it. We talked about it. And then, of course, the sympathetic activation, which can be overarching to everything, but on its own can cause mitochondrial stress. And I think that the way I kind of picture this, and I talk about it with my patients, is that You and I were talking, it's not just one thing, you know, it's often a combination and you're going, you're riding along combo package. Yeah, of course. You know, it's the bundle and like you're riding along, you're doing okay until you hit around, for most people though, it's getting worse now, like around like your mid-30s, late 30s, like early 40s. And then things start going a little, you know, pear-shaped as they say in Ireland. One of my favorite expressions. And they're like, yeah, a little pear-shaped and things kind of go like, why am I not recovering as well? Why do I, need more sleep, or why don't I feel as rested when I wake up in the morning? Or why does when my son comes in, in the, when she, when he gets home at school at 4 o'clock and he says like, hi dad, I go, what do you want? You know, I start like, what's going on there? You know? And so you start noticing these things, but as you said, Mark, it's happening at earlier and earlier ages because of just the amount of toxic exposure that people have on a regular basis, which is crazy.

Yeah, it is a lot. It's a lot. And you know, the truth is we have a lot of mitochondria. But they're fragile.

Yeah.

And they're very sensitive to any insult, even disturbances in your microbiome.

For sure.

And the bacteria in your gut can cause harm.

Yeah.

The microbiome mitochondrial connection, people don't even think about.

Yeah. The inter-kingdom crosstalk stuff is so cool.

It's very impressive.

Yeah.

And you mentioned quickly metformin. I think I want to just quickly double-click on that. This is a drug that's widely being used for diabetes. I've I use it for years in my practice and it can be a good drug for diabetes, but it, but it does have a weird side effect, which is it inhibits mitochondrial complex I. And this is a, yeah, like one of the first steps in producing energy from food and oxygen. And, and one of the studies that most concerned me was they did a randomized controlled trial where they did progressive resistance training, meaning muscle strength training, and in two groups, one taking metformin and one not taking metformin.

Yeah.

And the one taking metformin didn't have any muscle gain. And it inhibited muscle growth. And that concerns me. So it's being used a lot for longevity and aging. I feel strongly that it's not something people should use for that. I think in certain cases, in certain patients, it can be an adjunctive therapy and is a transition to get off of drugs because you can reverse all of it with lifestyle. But like, yeah, I just, I think it's important. So you've got all this top-down, bottom-up stuff. It even gets more interesting than that because a lot of new research, and we've had Chris Palmeron and others talking about the mitochondrial role in mental health.

Oh yeah.

So it's not just that you lose energy and you're tired from the stress. Your, your mitochondria play a big role in dysregulating your mood, right? And your brain function. So talk about that.

Yeah, that's a big piece of it. And I'm glad that you had Chris on. I think it's there. His work is so great looking at metabolic dysfunction and the reversal using the ketogenic diet, for example. And that's a, a big symptom of what we just described here.

That, and by the way, when we talk about metabolic dysfunction as a, it's kind of confusing term. Metabolic dysfunction in this context means How we turn food and oxygen into energy in the mitochondria. That's our metabolism.

Yes. And then I would just add to that, that how we are able to address the stress of making energy as well, in the sense that when we make energy, we make ATP, we're also making waste products, as I mentioned. And that's the other part of metabolic health is that you're able to make energy effectively and you're able to neutralize the stress of making energy. But I love your definition because people get so confused by it. So I appreciate you mentioning it. So when it comes down to brain health, mental health disorders, depression, bipolar, even schizophrenia, and some of the major ones, you see amazing capacity to work on mitochondrial function and see these things get so much better. I mean, people throw around and don't like the word cure, but in some cases, people coming off of medications entirely. And I've seen this, like curing schizophrenia with diet. Yeah, it's amazing. And I have a colleague that's on this with bipolar disorder. Right. And so So I feel like where it comes down to is that this is a mitochondrial dysfunction, at least a significant component of it. There might be neurochemical things for sure, but you and I both know, I learned in medical school that depression was a serotonin deficiency. But we know—

how did that work out?

Not so well.

Wait, wait, depression isn't a Prozac deficiency?

It's a Prozac deficiency, right? And so everybody, we need to put Prozac in the water. That was like, not LSD anymore, but the Prozac.

And we know now that LSD would be better.

100%. Yeah. That would've been an interesting experiment in New York City back in the day. We know that depression is not a serotonin deficiency, and we know the people that have depression have no lower levels of serotonin than people that don't have depression. Right. So I think that, you know, that's an interesting thing that we all learned that's completely wrong. Right. And that's what I learned in medical school is we now know that mitochondrial dysfunction is so much more of the, the actual game here. Now, understanding why people have the mitochondrial dysfunction is absolutely essential. We talked about the top-down, the bottom-up, and how you have to address the causes for sure. But in the essence of this conversation, what I would say to those that are listening is that we can help people right now by working on mitochondrial function and sympathetic activation while long-term trying to figure out what those inputs are that are causing it too.

Yeah.

But seeing mitochondrial function improve and then all of a sudden depression, anxiety, insomnia. Yeah. Get better is, it's been transformative to people that I work with.

No, it's huge. And I think, I think just people should stay tuned to the end of this podcast. So we're gonna get to, yeah, fix this, but I have a few more.

No, I'm sorry. I keep, I I keep foreshadowing.

No, no, it's good. It's good.

It's good.

We're going to get there. At 66, I pay close attention to how my body feels, especially my energy, my strength, and my resilience. And aging doesn't mean we have to slow down or stop doing things we love. And that's why I'm genuinely excited about Timeline powered by Mitopure. And I've been talking about it for years. Since adding it to my daily routine, I have personally noticed a real positive difference in my energy, In fact, I've recommended it to many of the important women in my life because mitochondrial health becomes especially important for women in midlife when changes in hormones can affect energy, muscle health, and metabolism. And what I like about Mitopure is that it's backed by serious science. As a functional medicine doc, I found that Mitopure is one of the simplest ways to support mitochondrial health, which is critically important as you age because our mitochondria become damaged over time, and that results in a noticeable loss of energy, of strength, and resilience. Now, Mitopure MitoPure restores damaged mitochondria in a way no other supplement can, helping you feel more like yourself at any age. Now, if you've been hearing me talk about MitoPure for a while and have been meaning to try it, this is the moment because Timeline's clinically proven formula is now available at a new lower price. MitoPure now starts as low as $79 with the exact same science and formula. Timeline powered by MitoPure has just slashed this price and you can get an additional 20% off your first month if you order now when you go to timeline.com/drhyman. That's timeline.com/drhyman to get 20% off their new low price. One of the most fascinating areas of research in functional medicine right now is red light therapy. Now, specific wavelengths of red light have been shown to support mitochondrial function, essentially helping your cells produce more energy. And when your cells have more energy, your body is better able to support natural recovery processes. And that's why I've been using products from Bone Shark. They're a wellness brand focused on science-backed tools that help counter the stressors of modern living. Everything from blue light blocking glasses to circadian lighting and red light therapy. One product I really like is their red light cap. It uses 650 nanometer red light to deliver targeted light energy directly to the scalp, encouraging natural hair follicle activity to promote hair growth in both men and women. It's incredibly easy to use. Just wear the cap for about 10 minutes while reading, cleaning, or answering emails. The high irradiance LEDs deliver targeted red light therapy in a comfortable, lightweight design you can use right at home. Buncharge ships worldwide, offers free shipping on the red light cap, a 12-month warranty, and it's even HSA and FSA eligible. So head to buncharge.com/hyman and use the code HYMAN for 15% off today. That's B-U-N-C-H-A-R-G-E.com/hyman and use the code HYMAN. One of the ways, you know, as people are listening, I imagine they're thinking is, well, you know, Okay. I know how to activate my parasympathetic system. I can meditate, I can do breathwork, I can do yoga, I can maybe exercise to improve my mitochondria, but, hmm, you know, cold plunges, saunas, whatever. But you said something which is interesting. You said you can't parasympathetic your way out of cell danger. What does that mean?

So this is the thing, right?

Because you can't meditate your way out of this like physiological stress to your cells and mitochondria is what you're saying, right?

Yeah, you can't. I mean, because you're in this sympathetic locked-in kind of mode. And the challenge is anytime you try to downregulate your nervous system, it actually might make you feel like you're crashing. Because when you try to get yourself outta sympathetic and get into parasympathetic, but you've been in sympathetic for a long period of time, so you're in that fight or flight, your mitochondria, as we've been talking about, have been under a lot of stress for a while and we've depleted vitamins, minerals, nutrients. We're in that cell danger response location of, of your cell spectrum of capacity to make energy. And then you're trying to bring down the nervous system. But what can happen when you do that is that you've only been able to function because you've been at that high of a state. And when you bring down the nervous system without enough support on the mitochondrial side, especially immune system will really be helpful too. You'll see that you have this crash. People feel like they crash when they go down and try to do their breathwork, try to do their meditation. Oftentimes they feel terrible when they try to do it, if they can even do it in the first place. Because the other challenge of this too, Mark, is that people don't even know what it feels like to be back in parasympathetic mode. They don't even remember what it felt like to calm down their nervous system. And so it can be very difficult to do breathwork or tell somebody to meditate, or the last thing you want to do is to tell them to calm down, of course, right? That doesn't work. If anybody's married or has a partner, they know rule number one of being married is that you don't tell your partner to calm down, right? It doesn't work. I was talking to my son who's 8, and he's like, Dad— he has 3 sisters, 3 other sisters, and my wife— and he's like, Dad, what are the things you never tell a girl? I'm like, number one, do not tell them to calm down.

Good advice.

Yeah, yeah. But so that's the thing, right? If you're in locked in state where you're in this metabolic dysfunction related to being in this cell danger response, not being able to make enough energy, you can't just breathe your way out of it.

And so you've gotta really deal with those root causes. Like, you know, you say if you're mercury poisoned or you're betrothed to fish and your thyroid's not working, it's hard to get enlightened. You know, you gotta like, you gotta deal with those biological things.

Yes.

And then the, often the psychological things or the physiological stress gets better, but it takes time. And, and you know, it's interesting. I really sort of fascinated when you came up with this, cuz I I, I've noticed this for years in my practice. I was like, gosh, when people have a physical stress, meaning a toxin, an allergen infection, it's poor diet, whatever, it actually causes a, a, uh, like a, a trouble with the whole system. Like it's not just, it's not just causing like a mental stress causing stress. It's, it's physiological stress. It creates the same fight or flight, the same sympathetic activation, the same, even if you, even if you're kind of cool and everything's fine, you can still feel stressed because of having mercury in your system.

100%. For example. Yeah.

And I think that's something people don't realize. So it's not just psychological, it can be biological causes of psychological stress.

100%. And that's what I tell my patients all the time. It doesn't have to start with that sympathetic activation, but it begins somewhere. And then at some point they both often, they both have to be addressed, right? Which is you can't just address the mercury exposure if you don't address also the sympathetic activation that was caused by the mercury exposure. Even if it wasn't a top-down issue, before, maybe had some mild things in that, in that were stressful but not too bad, but all of a sudden you're mercury toxic. That's a different story. So when you work on mercury toxicity, you also have to work on the sympathetic activation too. 'Cause if you don't do them both, you're still gonna be left in a place where you're still sympathetically activated. And you know how it is, like you've worked with patients like this, you know that if somebody's so fight or flight dominant, there's no healing that you can do with these patients.

No, it's true.

It's impossible. And and it's really difficult. It's like the one time I agree with our conventional colleagues that if you're giving them supplements, it's like giving them expensive urine, right? If you're not addressing the root cause, the sympathetic activation along with the root cause, if it was mitochondrial first, right? Yeah. And so that's why it's so nuanced here. And, but it's so important to kind of piece this out as you are and discuss it.

But then even like if the mitochondria are stressed from toxins or whatever, it actually makes the body stay in fight or flight.

Yeah.

So how to explain that connection between the mitochondrial stress from things that are just insults that you didn't have to do, do it like that are not mental insults, right? So causing this, you to be in this mental state of fight or flight, right?

So the idea is that when you have a lot of mitochondrial stress, you're not making enough energy. Okay. And when you're not making enough energy, the system goes, oh no, I need more energy. And what it does is tries to compensate by increasing your sympathetic nervous system, increasing your capacity to find out psychologically how you can help the situation. So it's almost like it's a bottom-up where you have these sensations and activation of inflammatory pathways and et cetera in the body related to mitochondrial dysfunction that overtly psychologically this manifests in you trying to figure out why this is happening or trying to give you more energy.

Yeah.

So to maintain the capacity that you need to make any energy at all. And so you get in this loop where it doesn't have to be any of that overt sympathetic activation from outside sources. All of a sudden it's just mitochondria itself that are not making enough energy and then causing the system to compensate for that. Okay.

So let me see if I get this straight. You, we've got this, this thing that you've described, which is something that I think most of us who practice this way for years have already seen. We never called it this, but the sympathetic spiral of doom, which can come from the top down, bottom up. It's a lot of mitochondrial dysfunction and stress, a lot of inability to produce energy in our cells, which runs everything. And we end up in this cell danger response. So we've got like sympathetic spiral of doom, cell danger response. Response. So people listening go, yeah, that's me. Right? I'm listening. Go, yeah, that's kind of me. So like, what do we do? Like what if someone's stuck? How do, what's the first step to getting out of this, this loop? The first step is spiral of doom.

Spiral is, is to escape the spiral. That's what you want to do over the long term. But initially you want to figure out ways to help somebody now to help break the spiral and get them additional support so they actually can maintain and benefit from long-term support. So the idea is that you're a functional medicine expert. You've founded the field basically with Jeff and others. You know that working with people and optimizing their health, vitamins, minerals, nutrients, optimizing their gut, their neurotransmitters, that can take a long time to do, right?

Yeah.

And if you're in this spiral, it's very difficult to do as well because again, you're clamped down, you're sympathetically activated. So the goal of breaking the spiral is to support the mitochondria now as much as possible. And at the same time, slowly start downregulating the sympathetic activation, slowly downregulating the nervous system so it can calm down. But you have to do it in that order. You have to start off with supporting mitochondrial first, mitochondrial function first.

So it's not meditate first and then— no, it's fix your mitochondria first, then meditate.

Because what can happen is if you go too soon on the parasympathetic side, trying to calm down the nervous system without having mitochondrial support, that's when you get into trouble too, because you're physically and mentally can't compensate because you don't have enough energy capacity. And so your energy capacity is still low. You've downregulated your nervous system and now the sympathetic activation, the fight or flight is down. You're trying to calm down the nervous system and, but you don't have energy that you can make. You don't have enough energy. And so as a result of that, you crash. And I've seen this in, in my practice all the time where if you start working on the nervous system too soon, people crash. And so the key is to work on mitochondrial function now and give immediate support so that when you start downregulating meditating and calming down that this nervous system has enough capacity. The whole system has enough capacity because the mitochondria are supported.

Okay. So let's talk about that. How, how do we fix mitochondria? Because it certainly wasn't something that we all learned in medical school. It's, it's something that's one of the central features of functional medicine, which is understanding how to diagnose and treat mitochondrial dysfunction.

Right.

It's a little bit tricky cuz you know, the best way to look at mitochondria is do a muscle biopsy. Yeah. But that's not fun.

Yeah. No.

But there are other, other tests. How, how do you, how do you think about approaching mitochondrial dysfunction? Cuz yes, it's gotta be focusing on the causes. Like if you're eating something that's bad or if you're got exposures to toxins, but let's assume you're, you're, you're working on those cuz you have to. What else can you do to revive these little poor baby little mitochondria that don't feel so good?

Well, I think you're kind of alluding to the idea of testing to see how mitochondria are working. And there are new tests out there that are working on than giving you a direct sense of what's happening in the mitochondria. And there maybe there are, there are a number of them that are on the market already. Some of them might be more ready for primetime than others. What, what do you think is the, the, well, I mean, there's, there's a couple out there. I mean, the ones that I use are more the indirect measures like you do, like organic acid testing, for example, looking at the intermediates that are associated with making energy and also oxidative stress markers, inflammatory markers. Right. Like those are really good indicators really.

Yeah.

Of mitochondrial function. There's things like MiScreen and MitoSwab and others that are out there that I think are I think they're new.

Yeah.

In the end, what I see here is they're, it's really nice to have the data for sure. Because then you can get a sense of how people do over time. Yeah. But so much of this, as you know, Mark, is subjective. I do know how they feel. If you, even guys who are not as good as women, as we know about telling you how they feel, like, well, how did you feel last, you know, 5 years ago? Tell me about your energy now versus 5 years ago. Like, oh yeah, I had a lot of energy. I had no issues. And now I get brain fog. I get that dip during the day and I feel terrible. Like people can typically give you a sense. So subjectively, such a big part of this, and I know that's hard bit, but it's so important because it's how you feel on some level. But what it comes down to is that when you're looking at optimizing mitochondrial function, it is giving the mitochondria what it needs to make energy effectively and to address the stress of making energy.

Okay.

Vitamins, minerals, nutrients, antioxidants, getting rid of heavy metals. This is your work. This is my work. The challenge with all of that though is that it takes time. Time. Yeah, it doesn't happen overnight. And so I've kind of fallen in love with a compound called methylene blue that you know of. Yeah, that is a very novel compound in some respects, but it's been around for a long time. But it's one of the most effective ways at supporting mitochondrial function right now. And the reason is that it works on the energy production cycle of things. It helps with energy production, and it also works works directly like an antioxidant. So our cells are like gasoline-powered cars. Methylene blue at low doses, as long as it's a clean source, 4 milligrams to 25 milligrams or so, works both as an energy enhancer and as a detoxifier. So it more like an electric power vehicle rather than a gasoline-powered one. And so it's become one of these big levers that I can pull with patients to be a bridge, to be that bridge. I like a picture. I often will put up a picture of the Brooklyn Bridge. I love the Brooklyn Bridge. I grew up in New York. and it's this bridge where you can help people right now while they're on that path. So if you're starting at like letter A through H or something in the alphabet on your path to optimizing your health, that first beginning can be really hard, really hard because you don't have energy to, to go take a walk around the block. You don't have enough energy to make your own food. You don't have enough energy to maybe get out of a relationship that's toxic, right? But once you start giving people enough energy, supporting that capacity without causing stress on the system, that's when they can make huge gains across the alphabet in my analogy here, getting them to L M O or whatever. And then they're able to start really making changes that they really wanna make. And so I see methylene blue as a fantastic bridge for so many people on this path to their own health optimization journey.

You know, and the mechanism of action is really interesting, right? It, it kind of acts as an electron carrier.

Yeah.

Which is what electrons are really what goes through through this little mitochondrial, you know, assembly line to make energy, to make ATP. Mm-hmm. And it kind of bypasses some of the complexes like 2 and 3 that are kind of in the way. So if there's mitochondrial dysfunction, it kind of like leapfrogs over it a little bit, right?

Yep. It bypasses it.

And then you get more ATP and you get less oxidative stress. In my practice, you know, one of the doctors was sharing with me how they were doing intravenous methylene blue and how they had a Parkinson's patient and they immediately improved their symptoms. Mm-hmm. And, and I don't know if it was a long-lasting effect, but it was an incredible interesting because we know that Parkinson's is fundamentally a mitochondrial disease in the part of the brain that has to do with motor function, right? And so can you kind of explain how that might all be possible?

Yeah. So in the end, neurocognitive disease, metabolic, as we've been talking about, everything has these parts of the cell called the mitochondria that help make energy, your immune system, everything. And so if your mitochondria aren't working well, you have significant incapacity in the areas that have the most mitochondria that are affected. And so in Parkinson's, you know, it's in the substantia nigra in the brain, for example. So one cool about methylene blue I should mention is that it is highly bioavailable, which means that orally absorption, oral absorption of methylene blue is almost as good as IV. The only difference with IV is that how fast it gets in the body. But most people don't need IV. Most people can use oral and get the same mitochondrial benefits. And so what you were describing on, on what's called the electron transport chain in the mitochondria. So the mitochondria has these proteins that are all kind of lined up and electrons that we get from our food, mostly carbohydrates and fat, they get donated to these chain using something called NAD and FAD, which people know NAD these days, right? That's a hot topic, I know. So you get these carriers, electron carriers, NAD and FAD, that bring electrons into the mitochondria. So what happens is if you have those first couple proteins not working very well, complex 1 or complex 2, the whole rest of the system breaks down. You don't have capacity to make energy. And most of the mitochondrial toxins out there are affecting complex 1 and complex 2. We talked about statins, we talked about metformin, infections, pesticides more are affecting those first 4 complexes, those first 2 complexes, excuse me. And so if those first couple complexes aren't working, the rest of the system breaks down. So what methylene blue can do is it can come in, it can bypass the complexes that aren't working very well and donate electrons directly up the chain. So all of a sudden you're able to start making energy in these cells.

It's almost like a bypass road. If there's a broken road, you just kind of go around it.

Yes. And it also can recycle things like NAD and FAD so those can maintain their capacity. Capacity to take electrons from your food, even if those particular complexes aren't working as well as they needed to. So it's this amazing capacity to bypass and compensate for almost any capacity or incapacity of the electron transport chain to work. And that even to the much as so as it's actually the antidote for cyanide poisoning. So cyanide, right, is actually a—

kills you by stopping your mitochondria from working.

Complex IV. So the fourth complex in the mitochondria, Complex IV, is destroyed by cyanide. And what methylene blue can do is it does these ninja moves of going across membranes and being an electron acceptor so you can maintain electron flow through those protein complexes even if you're poisoned by cyanide. And so that's just demonstrating the power of this particular—

Yeah. And it is, it's actually how I learned about it was in the emergency room.

Yeah.

As the emergency room doctor, if someone comes with cyanide poisoning, this is the drug that you give to cure people.

Like, right. So it's not common, but it's there. There's another one called methemoglobinemia, which is more common, and that's also also why it's used in emergency rooms all over the country.

That's from carbon monoxide poisoning.

Carbon monoxide poisoning. And also if you've like the huffing glue or like the, that stuff. Yeah. If you have too much of that, that gives you the incapacity to carry oxygen on your red blood cells and methylene blue changes the, the, the, the, the iron state to make sure that you can. Yeah.

I mean, and it also, it also acts as a, an MAO inhibitor, which is MAO is like a monoamine oxidase. It's really regulates neurotransmitter function, but you got higher serotonin, dopamine, norepinephrine, it can have improved mood, neurocognitive effects, right?

So it's dose dependent. So lower doses of methylene blue will increase norepinephrine and serotonin. Mm-hmm. Higher doses will also increase dopamine once you get to about 100 milligrams or so. The key, as I mentioned, is that it's dose dependent.

Mm-hmm.

Meaning that a little bit will do a little bit of that and more of it will do more. So there are people that have talked about how methylene blue just helps people feel better because it increases serotonin, but that's not the case at all. Yeah. Right. We're talking about small amounts compared to the huge effect on mitochondrial function. People listening at 100.

To take it. Like, you know, what are the doses like? How do you do it? You know, I see a lot of people like sucking on these lozenges. It makes their tongue all blue.

They can just swallow it. It's okay.

You can swallow it. You can swallow it, right?

Yeah. Because as I mentioned, it's almost 100% bioavailable, which means if you ingest it, whether you dissolve in the mouth as a trochee or if you swallow it, you can get the same mitochondrial benefits. The key here, Mark, and I think this is important for your audience to know, is that methylene blue is not a natural compound. It doesn't come from the earth. It's a synthetic ingredient. And as a result, As a result of that, it can be sometimes contaminated with heavy metals, things like lead, mercury, cadmium, and arsenic. Okay. In the manufacturing, in the manufacturing process. And so to take the synthetic thing just for a minute, 'cause I know some people don't like the idea of taking anything synthetic. The way I like to talk about this is that not everything natural is good for us. Okay.

You can forage arsenic, mushrooms will kill you, right?

Mushrooms. Like I was in medical school and I saw 2 people die of liver failure because of foraging for the wrong mushrooms. For example. So, and of course the dose makes the poison, right? So you can have low doses of natural products that can be okay, but high doses of nicotine, for example, can kill somebody, right? And so on the other side of things, synthetic argument, not everything synthetic is bad for us is what it comes down to. We live in synthetic worlds. We have lots of synthetic things all around us, right? My son, when he was 4, he had a tracking cellulitis or a skin infection up his leg, and I was looking at it go up his leg in front of me. And so I took him to the hospital and I got him antibiotics, which are synthetic. Okay. And if you're taking insulin right Right now, as a diabetic, if you have type 1 diabetes or type 2, it's a synthetic ingredient. It's not from a pig anymore. Right, right. And so there are reasons why we need synthetic things. And I think methylene blue falls into this category where it's a synthetic compound that can help so much, especially in the short term. And then I think over the long term, as you get more optimized, you don't need it as much.

And do you use it in conjunction with other mitochondrial support? So in functional medicine, we talked about CoQ10 and creatine and carnitine and yes, epoic acid and N-acetylcysteine and riboflavin and, you know, all, you know, magnesium, potassium, aspartate and all these wonderful, yes, ribose that can be supportive. And I've used them in my practice to great benefit, often, you know, together with, you know, even things like heart failure.

Of course.

But, um, you have to use them in conjunction with Methylene Blue or not as much?

It works better when it's being used in more of a synergistic mutual way as you just described it. Because not only, so Methylene Blue, what it's gonna do is increase metabolic rate cuz it's gonna increase the amount of energy you're making. Mm-hmm. So low doses are very supportive. They don't cause a huge amount of stress, but it is much better to have it as a full ecosystem that you're creating in the mitochondria. So you're creating all the substrate, meaning you have the capacity from vitamins, minerals, nutrients, like all the things that you just mentioned to support mitochondrial function and use the methylene blue. It's like a supercharge because the things you mentioned do a great job with mitochondrial function, but it takes time for all of those to work. Whereas you give some methylene blue in the system, within about 3 days, once you find the right dose, you will feel a difference. It's not something that happens 30 days or a month later, which can happen with many of the things that you mentioned, which I love and I use in my clinical practice too, and they're so supportive and necessary. But what methylene blue can do is in that short term give you the boost that you need. And so that you start feeling the difference much sooner.

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I found it's the fastest tool to be able to do it from a mitochondrial perspective, right? Because you want to be able to support the mitochondria to help it relax. And a good example of this, it's okay to take it every day. So in the beginning, yeah. As long as you're keeping the dose low, my sense of this is that what does the dose low mean? Right. So usually a milligram gram amount? So typically, milligram dose that I find that's really great for the mitochondria is somewhere between 8 to about 25 milligrams a day. If you're keeping the dose less than 30 milligrams per day, you don't even have to take a day off and you can take it every day. If you're getting, if you're taking above 70 or 80 or 100 milligrams of methylene blue, then you do need to take more days off. So the thing about it, methylene blue kind of has this sort of bimodal capacity. What I mean by that is like low doses of it around what I just described as a range, fantastic mitochondrial mitochondrial function, sometimes a little bit higher than that. But when you get to about a milligram per kilogram, which is around 50 to 70 milligrams of methylene blue and above, what happens then is it becomes more of an anti-infective. Actually, it's a fantastic antimicrobial at higher doses. And it does that because it produces something in the body called hydrogen peroxide. And hydrogen peroxide, you know, you can buy at the store.

It's actually what your white blood cells produce to kill infections.

Exactly. And so what methylene blue does is it creates more of a hydrogen peroxide capacity and you kill bugs easier and you also enhance your antioxidant systems if you have the capacity. And that's the key. And that's why if you have an acute infection, I use it all the time at high doses. But if you have a chronic infection, chronic Lyme, chronic mold, I use it at the higher doses, but I ramp them up. I don't start them. Yes. Because you're, because if you give somebody a high dose of methylene blue right off the gate and they have chronic Lyme, they're not gonna feel good if you give them 50 or 100 milligrams right away. So slowly increasing their dose, mitochondrial support, and then higher doses can be fantastically effective for chronic Lyme, for chronic mold, for even people with spike protein seen some interesting things as well. And also, it's just as a result of that, even viral infections as well. I've seen some really interesting things, but the majority of people are going to be using lower doses for mitochondrial function. That being said, some people have these chronic infections that are causing significant infection or significant mitochondrial dysfunction. But I was going to say, I was going to tell a patient a story about a friend of mine. He's a colleague. He's like, Doc, I've had anxiety for my whole life. I started taking methylene blue. And it's gone. Wow. You ask, well, why is that the case? Right? Is that because we changed his neurochemical stuff? No, it's because we gave him significant mitochondrial support immediately. And then he's like, I've never felt this good. Like, what did— and as a result of having enough mitochondrial support, his system started being able to unclench itself.

Yeah.

And because now you're making enough energy and now the system can start healing. Amazing. And I found my methylene blue at these low doses to be fantastically effective, Mark. And I don't I haven't, and initially I was very skeptical, you know, because I was like, this is a compound that doesn't come from the ground. And my dad's a chiropractor for 45 years. Like in the beginning he was militantly against Western medicine. Mm-hmm. But over the years he now knows that it's important to use too. But so I was blown away the first couple years when we started using it. People, I had this, we had this one lady with mild cognitive impairment. She started telling stories about her childhood that nobody in her family had ever heard of before. Her brain came back online. I had another lady that had chronic mold, done all the remediation in her house, in her body, still felt terrible. Started giving her some methylene blue. She was back to work in 2 weeks. It was crazy. And then I had another lady with chronic ankylosing spondylitis, like severe pain disorder in the back, inflammatory issues. Nothing had ever worked. She started taking methylene blue and her pain just went away. And I was like, this is back in 2020. So we were the first people to really pioneer this back then in 2020 at the company, at our company. And so So we've seen gigantic amounts of anecdotal data. And then there's researchers that have been doing this and showing that these are models of Alzheimer's, models of Parkinson's, you know, others looking at it in traumatic brain injury, looking at it in stroke. And so it's just, it's a fantastic compound that, you know, has gotten more popular over the last couple of years, which is great. But understanding what you're doing, like dosing-wise and making sure you're getting good quality stuff is absolutely essential. Like the stuff on Amazon is garbage mostly. Most liquids out there are not as potent, even if it says it on the label, it's, you know, it's a huge deal. And so I'm very much a proponent of using it, but using the right company stuff, the right products and the right dosing is absolutely crucial.

And you know, just to be transparent, you have created a company called Prescriptions, which I use, but it, you provide methylene blue and you have different forms of it, but you run through all third-party testing and make sure it's the right dose. And that there's no contaminants. And so is there, is there like a, is there a method that you've kind of developed that actually you're able to do that?

So at Transcriptions, which is our company, we decided to make this company, by the way, Mark, we did, we actually evolved it out of a nonprofit organization. So we have a nonprofit called Health Optimization Medicine and Practice. You've met Dr. Ted in the past, who's our founder, Dr. Ted Archakoso. And the idea with the nonprofit was to create an ecosystem for practitioners for training and for, for learning how to optimize health rather than focus on disease and very much aligned with functional medicine. And out of that we birthed the transcription company because you wanted to help people right now along that path. And Transcriptions was the first company to come out with a commercial product of methylene blue using it in 2020. I thought Ted was crazy at the time. I'm like, what are people going to— they're going to want their urine to be blue because your urine will turn blue.

By the way. Yeah. You make sure you're in green or blue.

Exactly. You're dying. It concentrates in the urine. Urine. So you gotta, you gotta watch out for that. And you have to, so you don't stain your clothes. Yes. You gotta be very careful. And so we came out with the first commercial product in 2020, and I was a little bit hesitant, to be honest, because I was like, I saw the research, it was very compelling. But then the other issue that I was very hesitant about is that it took us about a year and a half longer to launch the company to find a good source of methylene blue. Even when it said pharmaceutical grade, US grade, it was contaminated with heavy metals or it was not as potent as it said on the label. The challenge is, and you know this, you get a compound from another country. We got, we get ours from Japan and Korea and even China. I mean, it doesn't matter where you're getting it from, you're gonna get what's called a certificate of analysis with your product, with, with the ingredient itself. That certificate analysis is technically supposed to be a third-party assessment of that particular ingredient. But can you trust that that's coming from another country?

No.

Right.

China is, is China policing itself, right?

I'm not even throwing China under the bus. Any, any other country, right? And so what we do, which most companies don't do, unfortunately, you know this in the supplement world, even across the board, is that we test it again once it comes into the United States with another independent lab to make sure that it's safe, to make sure that it meets our specifications. And only then do we put it in our products. And then we test it again, final product, to make sure it's the exact amount of milligram dosage. And we've tested a lot of things on the market. But in the end, I didn't get into get into this to sell methylene blue. I get into this because treating patients, I saw this pattern. Yeah. I didn't know, I didn't name it.

And yeah, you can use it in conjunction with your other areas of expertise like hyperbaric oxygen, red light therapy, which kind of also help modify mitochondrial function, right?

100%. Yeah. This is not just a zero-sum game. It's not like one thing. What I find with methylene blue, it's just a fantastic supercharger accelerator bridge for our patients that are just stuck. And then all of a sudden we unstick them, they could become unstuck, I guess. And then we can actually let them finally heal, finally maximize their potential. Because you can't heal when your mitochondria are stuck and you can't heal.

I agree. It's, it's one of the, it's one of the sticky issues in functional medicine is how do you unburden someone's mitochondria? How do you get 'em out of this cell danger response and this, what you call the sympathetic spiral of doom? So, so let's kind of talk a little bit about what you call the parasympathetic edge. Yeah. What is that? Why is it important? And it's, you know, A lot of people talk about, you know, pushing hard and just going through and, you know, going through the barriers that you feel and kind of overcoming resistance, but you're saying maybe that's not the best way. So what is the parasympathetic edge?

So this is the opposite of the sympathetic spiral. This is the parasympathetic edge, but the deal, I have a friend of mine, he's the only Olympic skier and former wide receiver on the Philadelphia Eagles. His name's Jeremy. And he told me when he first started doing his competitions, he would listen to like Metallica and like hard metal. But by the time he was Olympic level, he was listening to Mozart and Beethoven. Why? He didn't need his nervous system to be functioning at a sympathetic level. He needed to drop down just a little bit to find that edge so that he was right in there. And you talk about people that are high performers, they are not in sympathetic overload. They are just below that in a place place where they can maintain their capacity. Navy SEALs are famous for this, right? They can find ways when they're in, when they're actually in operations, they're not sympathetically dominant. They've done training so much. Like a Michael Phelps is a great example of this too, right? You have trained so much for every eventuality that nothing is going to make your nervous system go too high. Because if it goes too high, we can't function that high up. We don't do well. And this is where like the classic example is like you have that dream where you're supposed to give a speech and you can't remember lines. Because when your sympathetic nervous system's so high on such high alert, you actually lose blood flow to the front of your brain, which is where you have what's called your executive function, your capacity to maintain things, come bring things from your long-term memory. Like you go blank, you go blank. That's sympathetic activation. And so we want to have people learn is that when we downregulate the nervous system, you're going to function better than you're even thinking that you're functioning at a higher capacity when you're at sympathetic dominance. Because when you teach teach people that you can bring people down and have them function at a better level, it is like night and day. I mean, the main good example of this, another one just to give another example is, is recovery. Like we're now in 2026, people care about recovery, right? We were kind of like, oh, but you know, 5 or 10 years ago, if you were an athlete in the professional sports, nobody gave a crap about recovery, right? Until people were burning out, they were getting injured and things like that. But now if you Focus on knowing you can strength train 3 times a week at most, and it's better than strength training 5 times a week. Why? It's the same deal because are you gonna exercise optimally? That is sympathetic. But as soon as you finish exercise, you need to drop yourself down into parasympathetic to actually gain muscle and actually build because you build most of your muscle when you're out of the gym.

Right. Because cortisol actually causes you to lose muscle, right?

Yes. It's, it's, it's catabolic.

Yeah.

But the system, and that's the system that is involved in calming down the brain. GABA is your primary inhibitory neurotransmitter. That is your neurotransmitter that puts the brakes on your firing, calms down your nervous system, and it's enhanced when you have increased insulin, for example. So when, after you eat, your GABA levels go up, for example. But GABA is deficient in so many of our patients, in some people, so many people, because of the lives that we We live with stress all over the place. So GABA deficiency is actually more associated with depression, anxiety, insomnia than any serotonergic issues that you could ever imagine.

But, but you say that you're taking GABA cuz you can buy GABA supplements over the counter, right?

So GABA as a supplement is not a good idea.

Yeah.

Yeah.

But you're saying there's another compound that comes from the toxic mushroom, the Amanita muscaria mushroom. Yeah. Which is, I agarin.

Yeah. Agarin. Yeah. Agarin. Yeah.

Agarin.

Yeah. And so what it comes down to, like to break it down and just briefly, so GABA, again, your brakes of your brain, right? If most of us are running around GABA deficient because of the sympathetic activation, the spiral that we've been talking about, the challenge is that if you go to your regular doctor and you say, I have anxiety, I have stress, I have depression, they're probably going to give you an SSRI. Maybe they'll give you a benzo, which they don't want to give you, but they might give you a short amount of it. Now, when it comes to benzos and alcohol, that's benzos like Valium or like Valium, Ativan, Spanish, right? So those medications and alcohol, they all bind to the GABA receptor, but they vastly deplete GABA in the process, giving you more GABA issues over time and more anxiety, more stress. And then you have more tolerance to those drugs, you need to take more of them, et cetera. And so GABA supplements sounds like a good idea, right? But the problem with the GABA supplement is that GABA is too big of a molecule to get into the brain. If you take GABA and it works for you, you have a leaky brain. Leaky brain, meaning that your blood-brain barrier is not doing what it's supposed to, keeping things out. And so, well, what do you really have there? Oftentimes you have a leaky gut, as you know. So if you optimize the gut, I've had patients like this where GABA works for them beautifully. They feel nice and calm and relaxed. We optimize their gut, seal it up, GABA supplements stop working. And when I first started talking about this a number of years ago, I had a number of clinicians that came up to me and said, GABA supplements, if they work for my patients, it's diagnostic. They have have a leaky brain. And I was like, this is interesting. And I started learning more about it and seeing it in my own clinical practice. When you optimize the gut, which I do in practice all the time, the brain gets better. So GABA supplements don't work. If they do work, go see a practitioner.

But there's something else you can take, which is from the mushroom.

Yeah, the mushroom has, so the amanita mushroom has a very cool compound called agarin or agarin, and it's a long-acting molecule that works on the GABA receptor binding to where GABA GABA would bind. The cool thing about the GABA receptor is that there's a— there's— it's 5-subunit receptor, not getting too technical, but you have a place where GABA binds itself and then you have separate sites called, you know, separate sites or allosteric sites where other things can bind.

Yeah.

Where agarin binds is where directly where GABA would bind. So when you take it, you're not depleting GABA in the process. The thing is, if you're binding something on a separate site to the GABA receptor, say it's kava, for example, or CBD or CBG or magnolia Golia bark or valerian. These are all binding to separate sites, increasing the amount of GABA to bind. But if you don't have enough GABA around, all that's not going to comp— what's going to happen is over time, those aren't going to work very well for you. They're going to stop working.

Scott, so this is really fascinating stuff. And I think that, you know, getting a parasympathetic edge is key. Ending the sympathetic spiral is key. How do you kind of support people to kind of maintain that they'd sort of broken the cycle a little bit? And we're going to refer you to resources. Approaches. I know you've written a lot about this and I wanna ask you where people can find out more information, but how do you maintain a more stable state rather than keep falling into the sympathetic spiral of doom?

Yeah, I think the first place is to know what it feels like to not be in that state, right? Because when you know that the system is now calmed down, you're going to feel better. You may not feel 100% better right away because you still need a lot of long-term support. You need support with, you know, your vitamins, your minerals, your nutrients, your diet. These things can take time as you know, and be difficult, and then you fall off the wagon and come back up and things like that. So, but I I think what it comes down to for me is that you need to have short-term ways to intervene, right? Short-term way for me is methylene blue is just a great capacity enhancer in the mitochondria. Optimizing the GABA system can be great, and Transcriptions does have some products there. We have something called Tro Calm and Trozy that can be helpful. You don't have to go product. You can also learn how to meditate and do breathwork and start taking more walks in nature, get better sunlight. These are all going to be helpful too. It doesn't matter where people are on that, on their level of capacity to start doing something, right? Sometimes it's helpful, I've found, is to give them something like something that downregulates the nervous system, something that's GABAergic, that works on the GABA system, to give them the experience of what it feels like to not be in that sympathetic state and doing it in a very supportive way. So their mitochondria supported typically is what I try to do first, as I mentioned, and then I'll give them the experience. You can still get some reactive anxiety when that happens because you're used to being at a certain level. So that's short-term. So short-term, giving people the experience of where there is. We talk about in meditation, there's no there there, but in parasympathetic edge, there absolutely is a there there. So knowing what that feels like, and then you can try to modulate that in various things that you're doing in your day-to-day life.

Powerful.

And, but that's the thing, like your day-to-day life becomes your meditation, becomes your life, right? You have to find ways during your day to break down, not break down, but calm down the system, right? Taking more breaks, getting outside in the sunlight. And then that's more medium-term. Long-term is like, okay, why are you so sympathetically activated? We talked about this. Is it external stuff? Is it the top-down? Do you need to get out of a bad marriage? Do you need to sleep in a different room to just get a sleep divorce from your partner? I think about 50% of US couples sleep in different beds, different rooms. This is not, it's not that's not a small thing. They have a more PC word of like sleep union or something like that now instead of sleep divorce and make it doesn't sound as bad. But if you need to sleep in a different room so you get better sleep, you should. But that can be hard, right? So trauma, you mentioned this as well, and this is where things become harder, right? This is where your experiences with psychedelics specifically are very interesting, right? Because like looking at psychedelics like ketamine and MDMA and ibogaine like you did, right? Like these are huge. And I know you've already, you've spoken openly about this, which I really commend you on because I'm very often sending my patients to go get ketamine with our friend, you know, Dave Raben and, and, and others that are out there that are really good at creating a huge neuroplastic response to these, these medicines. And that's where the real healing is going to occur long-term. We can give the people the experience. Of downregulating their nervous system. Now we can give them modes of operation at a day-to-day basis, but if there's elephants that are hanging around in the room, those are still there, you know? And we have to address those. And from the mitochondrial side, it's the same thing, right? We have to address the mercury toxicity. We have to address the toxic exposures or the practice functional medicine, basically. Exactly. Yeah. Yes, exactly.

Like that's the system.

Yeah. You have to be, the system is, and your system is fantastic. For that, right? That's what you do. Yeah. And that's what's beautiful. But that takes longer.

Yeah. It takes longer. So can people stand methylene blue long-term or is it, is it like a maintenance thing?

What I've had people typically do is that find your right dose. What I, my main way of doing that is start off at a low dose somewhere at 4 or 8 milligrams and which is a quarter or half one of our troches and then increase your dose every 3 to 5 days. See how you feel at one dose. Take it in the morning.

Typically one whole troche is 16.

Yeah, one whole troche is 16. Then one quarter is 4 milligrams. So take 4 milligrams in the morning. See how you feel. Take it on an empty stomach. You don't have to dissolve in the mouth. Okay. You can if you like, but your mouth is going to be blue. That's okay too. It's a little bit, it works faster up here, but the same amount of methylene blue is going to get in the body. See how you feel for about 3 days. Take it in the morning. Don't feel much. Go to 8 milligrams. See how you feel. Take it on an empty stomach in the morning. If you don't feel much, go to 12, then go to 16. But somewhere between 8 and 16 for most people is when they're going to start feeling, wow, I do have more energy. Wow, my brain's functioning a little bit better. I don't have as much brain fog. I'm not getting that energy dip in the middle of the day. My inflammation is better. My— even my pain might be better. My mood seems to be more regulated. You will know. And that's what I find is that— and then when you start increasing the dose more from there, you don't typically see as much return on your investment. Usually there's like a sweet spot for people. And once you find that right dose, how long or how often should you take it? Depends on what you're taking it for. If you're taking it as a bridge, you're kind of early on in your process, you might need to take it every day. And I have patients that are on it every day for a while, but over time the goal is always to come on it less or use it less, only needing it when you— only using it when you need it. So for example, when you get more optimized, you're still gonna have mitochondrial stress, you know? And the question is, when do you use it? So a good example is when you're traveling. On an airplane. On an airplane, you're going from about 21% oxygen in the air that you're breathing at sea level to about 18% relatively on a plane. That's a huge hypoxic stress, low oxygen stress on an airplane because you're pressurized to about 8,000 feet above sea level. The best jet lag hack that I've ever found, Mark, is to move to Colorado because I live at 5,500 feet. And so when I go on an airplane, it's 8,000 feet pressurization. Then I come to Austin to visit you. I'm I'm at sea level, I feel great because I know I've been at, I've been at altitude for a while and I was just at 8,500 feet in, in Montana and I felt it. You need Methylene Blue for that, man. Because then actually what I have is anybody that's coming to visit me, I always give them Methylene Blue before they get on the plane. And then I was actually with our nonprofit, Dr. Ted and Boomer, who's our CEO at Transcriptions and HomeHope. We were in Tibet and we were at Mount Everest base camp at 17,000 17,000. It was very, very high. We didn't have, we had intermittent oxygen. We had oxygen canisters, but we were using methylene blue. It was game-changing.

Really?

That's, that wasn't the only thing we used.

We used Diamox and we used, I got, I got, I got pretty significant altitude sickness when I was in Bolivia. We drove right up to 16,000 feet. Like there was no acclimatization.

That's, yeah.

And there was a hotel there and my oxygen saturations were down in the seventies.

I'm sure. Yeah. And Ted's were low too and we had him on oxygen.

Yeah.

But we were using Diamox, which is a drug for altitude. We're using Viagra as well. Yeah. Right. Cause it helps with nitric oxide and blood flow. and then we're using methylene blue. So as you get more optimized, Mark, you don't need it as much and you don't need it as often. And that's— but I have everybody, all of my patients have a higher strength methylene blue in their medicine cabinet just in case, which is like, which is, which is 50 milligrams in strength. So we have something called Tro Plus Blue, which is available to practitioners. So if you're a practitioner listening, we have a practitioner.

And why would you use the 50?

So the 50s are great for acute infection, acute stress overall. And so So I use it for acute infection, acute stress. So if somebody has like a concussion or has a acute injury, I give them higher doses for a short period of time. Yeah, for a short period of time. And sometimes I combine it with antibiotics. So my mom, for example, was bitten by a Lyme tick in New York. She's around 70. And so, sorry, Mom, I gave away your age, but I gave her methylene blue about 2 milligrams per kilogram, about 150 milligrams for 5 days. And she also took doxy. Doxy at the same time. We wanted to give her doxy because she's in New York. Lyme ticks are everywhere, right? But her, we checked her Lyme titers 4 weeks later, they were negative, right? So, and so it's not like it's the only thing sometimes, but it's also being used as monotherapy for urinary tract infections as well at these higher doses. So I give higher doses.

That's amazing.

Intermittently, but it's the lower doses that I use and maintain. So for me, I'll use it about 3 times a week, 4 milligrams every day, every 4 milligrams at a time, sometimes twice daily. You can dose it in the morning. Sometimes I'll dose it again early in the afternoon as well because it doesn't typically keep you up. It's not like caffeine or a stimulant. It should just give you more energy. Feel like you can just kind of go, you know?

Yeah.

That's the idea. And then when you find that right dose, often you'll know it if you're pretty well optimized. You can also use it for endurance. I have guys that use it because it increases aerobic capacity.

Oh, good.

Okay. So I have cyclists that use it.

I have a bike trip this summer.

I'm gonna do that. Yeah, exactly. And then I have ultra marathons that I use it.

Amazing.

I know you've, you've used it as well and had some experience. Yeah.

Experience as well.

Yeah.

This has been such a great conversation. Where can people learn more about your work, about the sympathetic spiral of doom?

Yeah.

Your cell danger, all that stuff.

A couple different places. And thank you for having me, Mark. So my personal website is my name. It's my name, drscottsher.com. The company that makes some of the products we've been talking about today is called Troscriptions. It's the word troche and prescriptions mashed up into Troscriptions. Transcriptions. We are pharmaceutical grade. We're physicians that run the company and we have precision dosing with all of our products. I really care about all of that. So does Dr. Ted. You can check it out at troscriptions.com. We have Just Blue, which is our pure methylene blue. We have something called Blue Canotine, which is a combination with methylene blue, nicotine, caffeine, and CBD, which is fantastic for focus. It's more for stimulation, but great as a stimulant. Then we have Tro Calm and Tro Zzz, which are more on that GABA side, turning that brain off that GABAergic side. So Tro Calm and Tro Zzz. And then we hold, we have a whole practitioner ecosystem.

Tro Zzz is for sleep.

Tro Zzz is about the most comprehensive sleep formula that I've seen on the planet. It's got 8 different ingredients, including the GABA system. So Tro Zzz is fantastic. And we also have a practitioner ecosystem. So if you're a practitioner, you can sign up for our practitioner account. You can either buy for your office or we have direct shipping. We have a huge portal and ecosystem that I've developed over the years with my team. So that's at truscriptions.com. Transcriptions.com. And then the nonprofit is called Health Optimization Medicine and Practice, or HomeHope for short. It's homehope.org. And there you can find, if you're interested in training, we have CME-certified courses. We have a whole ecosystem there that's very much aligned with functional medicine as well. And then where else? I think, you know, on our website, on the Transcriptions website, there's a lot of information on the sympathetic spiral of doom. I've been talking a lot about more, a lot more about this, and I will continue to be doing it as well. And again, this is not a diagnosis, it's a pattern that you and I have seen in clinical practice for years, Mark. But the key I think is the sequence here is mitochondrial support first, then sympathetic downregulation. And in that order is the key. And then we break the spiral, we escape from it long-term using the work that you do and that I do in clinical practice.

Amazing. Well, thank you. Thanks for doing it, Scott. Thanks for always helping me when I reach out to you on the hypercarbogen stuff.

Oh yeah. And then finally I have one other company called OneBase Health, and that's a company that's involved in the hyperbaric space. I know you have a chamber now and yeah, yeah, you had some good experiences too.

So thanks, Scott. Thanks for what you do and just bringing the science to everybody and being dedicated to helping people live a healthier, better life.

Right back at you, Mark. Thanks for having me.

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