Tired But Wired? The Hidden Loop Destroying Your Energy | Dr. Scott Sherr, MD

Summary

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The Dr. Hyman Show

Episode: Tired But Wired? The Hidden Loop Destroying Your Energy
Guest: Dr. Scott Sherr, MD
Date: April 15, 2026

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Episode Overview

In this episode, Dr. Mark Hyman sits down with Dr. Scott Sherr, a board-certified physician and leader in health optimization medicine, to unravel the complex web of chronic stress, mitochondrial dysfunction, and persistent feelings of being "tired but wired." Together, they introduce and dive deep into the concept of the “Sympathetic Spiral of Doom”—a destructive feedback loop between stress and cellular energy systems. With practical insights and emerging clinical tools like methylene blue, they offer hope for breaking this cycle and restoring vibrant health.

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Key Discussion Points & Insights

1. The “Sympathetic Spiral of Doom”: What It Is and Why It Matters

• Definition: A feedback loop where chronic sympathetic (fight or flight) activation leads to mitochondrial dysfunction (cellular energy breakdown), which in turn worsens stress response and perpetuates burnout ([00:14], [03:34], [05:43]).
• Multi-factorial Causes: The spiral can start from psychological stress (top-down) or physiological insults like toxins, infections, and poor diet (bottom-up), and usually involves a mix of both ([04:03]–[06:46]).

Quote:
“You have sympathetic activation—which is your fight or flight, your nervous system being activated. You have mitochondrial dysfunction. The challenge is, any time you try to down-regulate your nervous system, it might make you feel like you're crashing...you've only been able to function because you've been at that high of a state.”
— Dr. Scott Sherr [00:14]

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2. Understanding Sympathetic vs. Parasympathetic

• Sympathetic: Mobilizes the body in response to stress; overdrive leads to hormone and neurotransmitter imbalances, immune dysfunction, and cellular damage ([07:08]–[10:09]).
• Parasympathetic: The ‘rest and digest’ system essential for recovery, healing, and energy restoration; undervalued in modern society ([08:39]).

Quote:
"Modern society doesn't reward [rest]. It rewards the hustle. I mean, in medical school, my friends and I had shirts that said sleep is for quitters."
— Dr. Scott Sherr [08:39]

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3. Mitochondrial Dysfunction: The Cellular Root of Modern Malaise

• Role of Mitochondria: Central to energy production, especially in high-demand organs (brain, heart, liver, muscle) ([10:10]).
• Stats: 94% of U.S. adults have some element of metabolic—and by extension, mitochondrial—dysfunction ([11:03]).
• Symptoms: Fatigue, brain fog, mood instability, poor recovery from stressors, reliance on stimulants, and the crash-and-burn cycle ([13:44]–[15:42]).

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4. The Top-Down and Bottom-Up Stress Model

• Top-Down: Psychological stressors—news, relationships, trauma, lack of sleep. Much of modern life is lived in a state of chronic sympathetic activation ([23:59]–[25:42]).
• Bottom-Up: Biological insults—toxins, infections, medications (e.g. statins, metformin), poor diet—all can directly damage mitochondria and induce stress ([25:44]–[29:21]).

Notable Point:
Mitochondrial stress from toxins or metabolic insults can generate psychological symptoms without obvious emotional triggers ([35:24]–[36:00]).

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5. Why You “Can’t Meditate Your Way Out” of Biological Burnout

• Critical Insight: In severe cases of this feedback loop, calming the nervous system with meditation or breathwork can actually worsen symptoms unless cellular energy is first restored ([33:11]–[35:05]).
• Nuance: Addressing both root psychological and physiological (mitochondrial) stress is essential for true healing ([36:07]–[36:52]).

Quote:
"You can't parasympathetic your way out of cell danger... 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, you’ll crash."
— Dr. Scott Sherr [33:11]

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6. The Cell Danger Response

• Concept: The cell “flips” into a protective, energy-conserving mode when overwhelmed, halting recovery even if stress is reduced ([21:21]–[23:00]).
• Downside: This state depletes nutrients, making it even harder to recover, establishing a vicious circle ([22:50]).
• Link to Disease: Mitochondrial dysfunction and the cell danger response underlie many chronic conditions, neurodegenerative and mood disorders included ([29:51]–[32:37]).

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7. Breaking the Cycle: A Practical Sequence for Healing

A. Support Mitochondria First

• Supplements: Classic mitochondrial supports (CoQ10, carnitine, lipoic acid, riboflavin, magnesium, etc.)
• Targeted Tool: Methylene Blue
  • Acts as an electron carrier, bypasses damaged complexes in mitochondria, rapidly boosts cellular energy, and reduces oxidative stress ([41:39]–[47:26]).
  • Potent both for brain and body; supporting symptoms in neurodegenerative disease, chronic fatigue, infections, altitude, and more ([45:41]–[47:57]).
  • Oral forms are as effective as IV for most people ([45:41]).

Quote:
"Methylene blue 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.”
— Dr. Scott Sherr [47:26]

B. Gradually Downshift the Nervous System

Once energy returns, begin restorative practices: meditation, breathwork, time in nature, sleep hygiene, and trauma work ([69:50]–[70:30]).

C. Customizing Dosing and Protocols

• Typical starting methylene blue dose: 4–25mg per day; titrate until improvements are felt ([55:45], [73:53]).
• For infections/acute stress, higher doses temporarily and under clinical supervision ([76:56]–[77:48]).
• Combine with nutrients and adjunct therapies as needed ([54:00]–[55:26], [62:22]).

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8. The Parasympathetic Edge

• Performance Insight: True recovery, muscle building, and optimal brain function occur in a slightly ‘downregulated’ (parasympathetic) state—not chronic overdrive ([63:25]–[65:54]).
• GABA System: Chronic stress depletes calming neurotransmitters like GABA. Dr. Sherr discusses why GABA supplements are often ineffective and introduces agarin (from Amanita mushrooms) as a tool to directly support GABAergic tone ([66:35]–[68:55]).

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9. Maintenance & Long-Term Strategies

• Short-term hacks: Methylene blue “bridges” to restore energy quickly so longer-term diet, sleep, and lifestyle changes become doable ([41:39]–[44:54], [69:50]).
• Medium/long-term: Address root exposures (toxins, infections), trauma, and optimize nutrition and relationships ([69:50]–[73:35]).
• Dosing wisdom: Use daily at first; decrease as health stabilizes. Have on hand for known mitochondrial stressors (e.g., air travel, illness) ([73:35]–[78:23]).
• Synergy: Integrate with therapies like hyperbaric oxygen and red light for optimal results ([62:22]).

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Notable Quotes & Moments

• "If you’re giving them supplements, it’s like giving expensive urine. If you’re not addressing the root cause, the sympathetic activation along with the root cause… it’s so nuanced here, but it’s so important."
  — Dr. Scott Sherr [36:53]

• “The key is the sequence here: mitochondrial support first, then sympathetic downregulation—and in that order is the key.”
  — Dr. Scott Sherr [80:19]

• “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.”
  — Dr. Scott Sherr [32:07]

• “High performers… are not in sympathetic overload. They are just below that, in a place where they can maintain their capacity.”
  — Dr. Scott Sherr [64:10]

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Key Timestamps by Topic

• Intro/context: [00:00]–[03:29]
• Defining "sympathetic spiral": [03:34]–[06:46]
• Sympathetic vs parasympathetic explained: [07:08]–[10:09]
• Role and vulnerability of mitochondria: [10:10]–[13:44]
• Symptoms of the spiral: [13:44]–[15:42]
• Feedback loop between stress and mitochondria: [18:40]–[21:19]
• Cell danger response: [21:21]–[23:17]
• Top-down vs. bottom-up stressors: [23:44]–[29:21]
• Link to mental illness: [29:51]–[32:37]
• Why calming alone often fails: [33:11]–[35:16]
• Breaking the spiral: practical protocol: [39:05]–[41:39]
• Methylene blue deep dive: [41:39]–[48:51]
• MAOI effects, safety, sourcing methylene blue: [51:28]–[62:53]
• The parasympathetic edge: [63:03]–[66:42]
• Restoring GABA, supplements, and agarin: [66:42]–[69:22]
• Short/medium/long-term recovery tips: [69:32]–[73:35]
• Dosing strategies: [73:35]–[78:23]
• Resources and where to learn more: [78:26]–[80:53]

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Resources and Where to Learn More

• Dr. Scott Sherr’s website: drscottsherr.com
• Troscriptions (methylene blue, GABAergic formulas): troscriptions.com
• Nonprofit training (Health Optimization Medicine and Practice): homehope.org
• More from Dr. Mark Hyman: @DrMarkHyman (all platforms), drhyman.com

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Bottom Line

If you’re tired but wired, and nothing seems to fix it, you may be caught in the sympathetic spiral of doom. The answer isn’t just more willpower, meditation, or better sleep—but targeted support to repair your mitochondria, break the danger response, and reclaim your body’s energy edge.

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For complete protocols, clinical supervision is advised. This episode is not a substitute for personalized medical care.

Transcript

[Dr. Mark Hyman]

I eat perfectly, I exercise six times a week. I try to get to bed on time and sleep. I'm feeling depleted.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And I think people are in this state and they don't have a name for it.

[Dr. Mark Hyman]

But you call it the sympathetic spiral of doom.

[Dr. Scott Sherr]

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 down regulate 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 breath work, 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.

[Dr. Mark Hyman]

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?

[Podcast Host/Announcer]

Today on the podcast, I'm joined by Dr. Scott Sher.

[Dr. Scott Sherr]

He is a board certified physician and

[Dr. Mark Hyman]

a pioneer in health optimization medicine.

[Podcast Host/Announcer]

As an expert in mitochondrial function and the chief medical officer of transcriptions, he's helping people break the sympathetic stress loop to rapidly restore energy, focus and resilience.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

I wanted to share something personal about my own health journey now. A while back, I went through a period where I was recovering physically and working hard to rebuild my strength. I was doing all the right things, eating well, exercising. I was focusing on sleep and recovery. But I started looking more closely at how the body actually uses protein as we age. And here's the thing, our bodies don't always utilize protein as efficiently as we get older. So even when you're eating well, you may not always be getting the essential amino acids your body needs to support muscle repair and recovery. And that's when I started using perfect aminos. Now, I want to be clear, this isn't about replacing whole food protein. I'm a huge believer in getting high quality protein from real food. But perfect amino can be a very convenient way to complement your diet and to help make sure you're getting the essential amino acids your body relies on. The essential amino acids are nine amino acids your body cannot make on its own. So you have to get them from food or supplements. And they play a key role in processes like building and repairing muscle, supporting your recovery and maintaining overall metabolic health. For me, it's become a helpful part of my personal routine while focusing on recovery, strength and maintaining muscle as I age, especially alongside resistance training and of course a nutrient dense diet. So to get your perfect amino today, head over to bodyhealth.com and get 20% off your first order with the code HYMAN20. That's b o d y health.com and use the code HYMAN20. For years, my diet and my fitness were pretty dialed in and yet I still felt like something was missing, especially during the darker months. And light was the variable I struggled to get right. And Chorus, the makers of Oyo, have spent years and millions in research and development to solve this. They didn't just build a light bulb. They figured out how to bring the sun indoors. Backed by more than 530 patents in Nobel level science, Oyo by Chorus removes stimulating blue wavelengths at night so your body can do what it was designed to do. Rest and recover. And when your circadian rhythm resets, everything improves. Your sleep deepens, your energy sharpens, even your immune system responds. I've seen what happens when people fix their light. They don't just sleep better, they feel clearer, more grounded and more alive. If you're making one change this year that touches everything, start with your light. Learn [e-mail] Dr. And enjoy 15% off their newest product, Oyosphere, with the code HYMANSPHERE15 that's K O R R US.com SPHERE and use the code HYMANSPHERE 15.

[Dr. Mark Hyman]

Welcome back to the podcast, Scott. So good to have you.

[Dr. Scott Sherr]

Thanks for having me, Mark. Last time it was online, today it's in person.

[Dr. Mark Hyman]

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 you know, I never heard it quite described like this, but you call it the sympathetic spiral of doom.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Bada bada bump.

[Dr. Scott Sherr]

Yes, exactly. It needs music after.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And you know, at first I was

[Dr. Mark Hyman]

like, ah, that's kind of hyperbolic. Whatever.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And then I started reading about it. Yeah, I'm like, oh, this is what it is.

[Dr. Mark Hyman]

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

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And it creates a breakdown in our ability to regulate our nervous system and

[Dr. Mark Hyman]

then it influences our mitochondrial function, which kind of makes it worse.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

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.

[Dr. Mark Hyman]

We all know that stress is bad for us, right? But this is a very different frame

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

of it and I love it and

[Dr. Mark Hyman]

I think it's going to help a lot of people because even have to

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

be systematic about it, right?

[Dr. Mark Hyman]

And a lot of us are feeling

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

burned out, like we're doing everything.

[Dr. Mark Hyman]

Like I eat perfectly, I exercise six 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, right? And I think a lot of people out there are probably feeling that.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And I think people are in this state and they don't have a name for it and they just feel like

[Dr. Mark Hyman]

crap and they don't know what's going on. They're exhausted, they're wired, they're anxious, they're burned out.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And today I really want to like

[Dr. Mark Hyman]

have people who are listening to understand, you know what, what is going with their, their energy, what is going on with stress? What, what are the psychological and the physiological cause 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, what is it? Explain it to us.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Unpack it for us.

[Dr. Scott Sherr]

Well, thanks again for having me, Mark. And, 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 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 our 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 stressors or even like 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.

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

And then it's something that just makes you fall off a cliff. It could be.

[Dr. Mark Hyman]

Well, let me pause you for a sec. Yes, define sympathetic activation because people are like.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

What is that?

[Dr. Mark Hyman]

And define like a little bit better. Mitochondria, because these are, these are central to your thesis. Sympathetic. So let's get our terms right because I think people are like, well otherwise

[Dr. Scott Sherr]

I'll be, just be talking doctors.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

Yeah, 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 part of your nervous system. So it's your, it's running away from the proverbial saber tooth tiger as we somehow always refer to. 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. Whether it's with our phones that are actively in our faces all the time 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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

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[Dr. Scott Sherr]

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.

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

Not surprising. I grew up in New York.

[Dr. Mark Hyman]

Surgeons don't have lunch. That was ours.

[Dr. Scott Sherr]

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 toothed 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, 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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Yeah.

[Dr. Scott Sherr]

The mitochondria are part of the cell that helps make energy. Right. When I was in high school, my daughter is in ninth grade, she learned, she's got the basic cell. She just learned, she's like, dad, check out the basic cell. It nucleus. It's got cytoplasm, it's got golgi bodies, and it's got this one little cool organelle called the mitochondria. I'm like, huh? This is what I learned when I was probably that age too. You learned that the cell has one mitochondria, but that is far from the case. Right.

[Dr. Mark Hyman]

We have thousands.

[Dr. Scott Sherr]

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.

[Dr. Mark Hyman]

Yeah, the red blood cell.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

and number two, swim. They had let,

[Dr. Scott Sherr]

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 genetically intense.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Liver.

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

Liver people don't realize that is like if you need it, if you're going to 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 you can't make energy effects. 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.

[Dr. Mark Hyman]

Free radicals.

[Dr. Scott Sherr]

Yes, exactly. And so we need those. But if we have too many or if we're stimulated for such a, 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. 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 people, everybody, so many of us are on this sympathetic spiral as a result of that.

[Dr. Mark Hyman]

And what's really interesting is the connection between the stress response, which we all can relate to in our mitochondrial function, which is, which is basically something that, you know, most of us don't think about. And by the way, most doctors don't know much about that. We didn't. We learned basically biochemistry in the first semester of medical school, how to, you know, food and oxygen go through our little Krebs cycle.

[Dr. Scott Sherr]

Mitochondria, you memorize all the intermediates.

[Dr. Mark Hyman]

And we memorize it for five minutes

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

before the test and we forget about it.

[Dr. Mark Hyman]

But mitochondria are central to almost every single disease that we see in chronic illness, whether it's dementia, dementia or cancer or heart disease or obesity or diabetes or all the, all the neurodegenerative diseases. It's just quite, it's quite profoundly important.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And you're right.

[Dr. Mark Hyman]

Like if you are in this stress response and then you're also exposed to

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

all the stresses of being in the

[Dr. Mark Hyman]

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. And then of course, our ultra sort of processed diet that I was getting to that.

[Dr. Scott Sherr]

Yeah, yeah.

[Dr. Mark Hyman]

You know, our highly sugary processed diet. So, you know, we all are stressing our stress response because you, you're by the way, eating crap makes your body stressed even if you don't psychologically feel stressed.

[Dr. Scott Sherr]

Right.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

You know, what, what are like the main symptoms? People are in this sympathetic spiral doom. Like how would people.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Listening. I have this.

[Dr. Scott Sherr]

So when it comes down to when the mitochondria are so stressed and 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 two or three days. Like you go to the gym, you don't feel like you really could recover for two or three days, or you go on an airplane, don't recover for 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, 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. It's like that extra little stress that just did it. And then all of a sudden the things go down.

[Dr. Mark Hyman]

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

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

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[Dr. Mark Hyman]

A lot of people I have this super common. And if you look at it as spectrum, most of us are somewhere in that spectrum.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

So you talk about this feedback loop

[Dr. Mark Hyman]

between the nervous system and the mitochondria because I think it's a little bit hard conceptually for people to understand. Well, how does that work? You've got your nervous system, your sympathetic parasympathetic and your stress response, your relaxation response. But how does that relate to your mitochondria and your energy system and what is that connection and loop. Feedback loop.

[Dr. Scott Sherr]

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. The challenge is that most people do not have that pattern anymore. And what cortisol does does is it stimulates the production of it's A steroid hormone. It also stimulates and initiates the norepinephrine, 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. You're tired, you're tired. This is the tired but wired kind of feeling.

[Dr. Mark Hyman]

The ability the mitochondria to kind of like register this danger is interesting. And you know, you talked about this new concept, this cell danger response, but if you actually look in the medical literature, it's there. There's a lot of scientific papers about this. It's not just some woo woo 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.

[Dr. Scott Sherr]

No.

[Dr. Mark Hyman]

So. So you know, what I'm just hearing, as you say, is when you have chronic stress, either from a top down or bottom up, from, you know, your brain or from the toxin crap and shit, we're. 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?

[Dr. Scott Sherr]

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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And so unpack.

[Dr. Mark Hyman]

What is this cell danger response?

[Dr. Scott Sherr]

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.

[Dr. Mark Hyman]

Still dangerous response.

[Dr. Scott Sherr]

Still dangerous response, yes. Sorry. And as a result of, 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. Where 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 we can talk about that. But the idea is when you're in the parasympathetic mode, you're rest, 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, 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 CO factors that are responsible for shifting you out of the cell danger response.

[Dr. Mark Hyman]

So just the very fact of trying to manage the danger. You're using a lot of nutrients, tons of it, and you deplete your nutrients.

[Dr. Scott Sherr]

Yes.

[Dr. Mark Hyman]

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 in it to please them.

[Dr. Scott Sherr]

And you're still in the stress mode and you're still right. So the major question is, well, how do you, 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?

[Dr. Mark Hyman]

Well, that's an important question. I want to get into the practical aspects of how do people end the sympathetic spiral room and how do they stop the cell danger response? 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 can enter into this sympathetic spiral doom from your psychological state for short term trauma, or from your biological state, from things you're exposed to in the environment that

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

you may have control over, or your

[Dr. Mark Hyman]

diet, which you do have control over. So can you kind of walk us through the top down, bottom up explanation

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

and where are the contributors to the

[Dr. Mark Hyman]

sympathetic spiral 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.

[Dr. Scott Sherr]

The top down part, 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 sport. 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, to things that

[Dr. Mark Hyman]

are stressed in the world right now.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

And, 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 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 of us all the time that are trying to instill still 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 what I call the top down aspects. And I could fill in maybe all the psychological stuff. Give me your childhood trauma and I mean you've had patients like this too, that they were abused as a child and they never feel safe in their own body. There's no 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.

[Dr. Mark Hyman]

But there's ways for people to come

[Dr. Scott Sherr]

out of that a hundred percent. Yeah, 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.

[Dr. Mark Hyman]

So that's the top down.

[Dr. Scott Sherr]

That's the top down.

[Dr. Mark Hyman]

And the bottom up is.

[Dr. Scott Sherr]

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.

[Dr. Mark Hyman]

Very sensitive.

[Dr. Scott Sherr]

They are.

[Dr. Mark Hyman]

Everything affects them.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

That's a big number.

[Dr. Scott Sherr]

It's huge.

[Dr. Mark Hyman]

I can't count that.

[Dr. Scott Sherr]

I. I can't either. But it's a quad. I know that. I think after that, I can't remember. It's like. I don't know. It's quint after that, I think. But it's. It's after trillions is quadrillions. Everybody that's listening. 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. And that's because of the things you mentioned. You talked about insulin resistance and toxins in 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

[Dr. Mark Hyman]

acid blockers, are a big one. That's thoroughly in cause of use of drugs, which is acid blockers from people eating a crappy diet.

[Dr. Scott Sherr]

Yeah. But statins, too. Statins also have significant impact.

[Dr. Mark Hyman]

And that's the number one class of drugs.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

So number one in three class of

[Dr. Scott Sherr]

drugs is causing mitochondrial statins, and they have effect on both complex 1 and complex 2, which are the two 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 package. Yeah. Of course, you know, it's the bundle and like you're riding long, 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 when, 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, in earlier ages because of just the amount of toxic exposure that people have on a regular basis. Which is crazy.

[Dr. Mark Hyman]

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.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

And they're very sensitive to any insult. Even like disturbances in your microbiome for sure. And the bacteria in your gut can cause, cause harm.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

You know, the microbiome mitochondrial connection, people don't even think about.

[Dr. Scott Sherr]

Yeah. The inter kingdom crosstalk stuff is so cool.

[Dr. Mark Hyman]

Very impressive.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

And you know, you mentioned quickly metformin. I think I wanna just quickly double click on that. This is a drug that's widely being used for diabetes. I've used it for years in my practice and it can be a good drug for diabetes. But it does have a weird side effect which is inhibits mitochondrial complex 1. And this is like one of the first steps in producing energy from food and oxygen. And one of the studies I'm most concern me was they did a randomized control trial where they did progressive resistance training, meaning muscle training in two groups, one taking metformin and one not taking metformin. And the one taking metformin didn't have any muscle gains and it inhibited muscle growth.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And that concerns me.

[Dr. Mark Hyman]

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, reverse all of it with lifestyle. But like. Yeah, I just, I think it's important. So, so you've got, 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 Pomeran and others talking about the mitochondrial role in mental health.

[Dr. Scott Sherr]

Oh, yeah.

[Dr. Mark Hyman]

So it's not just that you lose

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

energy and you're tired from the stress.

[Dr. Mark Hyman]

Your, your mitochondria play a big role

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

in dysregulating your mood. Right.

[Dr. Mark Hyman]

And your brain function.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

So talk about that.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

And by the way, when we talk about metabolic dysfunction, it's kind of confusing term. Metabolic dysfunction in this context means how we turn food and oxygen into energy in the mitochondria.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

That's our metabolism.

[Dr. Scott Sherr]

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 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 and mental health disorders, depression, bipolar, even schizophrenia, and some of the major ones, like 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 like entirely. And I've seen, seen this like curing

[Dr. Mark Hyman]

schizophrenia with diet and keto diet.

[Dr. Scott Sherr]

It's amazing. And I, you know, I have a colleague that's on this with bipolar disorder. Right. And 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 know, you and I both know, I learned in medical school that depression was a serotonin deficiency.

[Dr. Mark Hyman]

But we know how did that work out?

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Not.

[Dr. Mark Hyman]

So wait, wait. Depression isn't a Prozac deficiency.

[Dr. Scott Sherr]

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 LSD would be better. A hundred percent. Yeah. That would have been an interesting experiment in New York City back in the day. We know that depression is not a serotonin deficiency and we know that people that have depression have no lower levels of serotonin than people that don't have depression.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Right.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

No, it's huge. And I think, I think just people should stay tuned. The end of this podcast. We're going to get to fix this. But I have a few more.

[Dr. Scott Sherr]

No, I keep, I keep foreshadowing.

[Dr. Mark Hyman]

No, no, it's good, it's good, it's good. We're going to get there. One of the ways, you know, is as people are listening, I imagine they're thinking as well, you know, okay, I know how to activate my parasympathetic system. I can meditate, I can do breath work, I can do yoga, I can maybe exercise to improve my mitochondria. But 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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

What does that mean?

[Dr. Scott Sherr]

So this is the thing, right?

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

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 down regulate your nervous system system, it actually might make you feel like you're crashing. Because when you try to get yourself out of 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 your cell spectrum of capacity to make energy. And then you're trying to bring down the nervous system, 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 breath work, 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 breath work 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, 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 three sisters, three older sisters, and my wife, 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.

[Dr. Mark Hyman]

Good advice.

[Dr. Scott Sherr]

Yeah, yeah. But so that's the thing, right? If you're in that, this 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.

[Dr. Mark Hyman]

And so you've got to really deal

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

with those root causes.

[Dr. Mark Hyman]

Like, you know, we say if you're mercury poisoned or you're B12 deficient, your thighs aren't working, it's hard to get enlightened. You know, you gotta like, you gotta deal with those biological things.

[Dr. Scott Sherr]

Yes.

[Dr. Mark Hyman]

And then the, often the psychological things or the physiological stress gets better, but it takes time. And you know, it's interesting, I, I, I, I really sort of fascinated when

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

you came up with this because I,

[Dr. Mark Hyman]

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, like a, a trouble with the whole system. Like it's not just. Yeah, 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

[Dr. Scott Sherr]

in your system, 100%, for example. Yeah.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

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 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 exposure. Even if it wasn't a top down issue before, maybe you had some mild things that were stressful but not too bad, but all of a sudden your mercury toxic, that's a different story. So when you work on mercury toxicity, you also have to work on the sympathetic activation too. Because 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.

[Dr. Mark Hyman]

No, it's true.

[Dr. Scott Sherr]

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. You know, if you're not addressing the root cause, the sympathetic activation along with the root cause, if it was mitochondrial first. Right. And so that's why it's so nuanced here. But it's so important to kind of piece this out as you are and discuss it.

[Dr. Mark Hyman]

But then even like if the mitochondria are stressed from toxins or whatever, it actually makes the body stay in fight or flight. So how to explain that connection between the mitochondrial stress, stress from things that are just insults that you didn't have to do do it like that. Are not mental insults causing this you to be in this mental state of fight or flight.

[Dr. Scott Sherr]

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 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' the mitochondria itself that are not making enough energy and then causing the system to compensate for that.

[Dr. Mark Hyman]

Okay, so let me see if I get this straight. We've got this thing that you described, which is something 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, 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 biogeum 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?

[Dr. Scott Sherr]

The first step, the 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, can maintain and benefit from long term support. So the idea is that you were, 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, the neurotransmitters that can take a long time to do right. 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 mitochondrion now as much as possible and at the same time time slowly start downregulating the Sympathetic activation slowly down regulating 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.

[Dr. Mark Hyman]

So it's not meditate first and then it's fix your mitochondria first, then meditate.

[Dr. Scott Sherr]

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, you physically and mentally can't compensate because you don't have enough energy capacity. And so your energy capacity is still low. You've down regulated your nervous system and now the sympathetic activation, the fight or flight is down. You're trying to calm down the nervous system, 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 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 down regulating and calming down, that this nervous system has enough capacity, the whole system has enough capacity because the mitochondria is supported.

[Dr. Mark Hyman]

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.

[Dr. Scott Sherr]

Right.

[Dr. Mark Hyman]

It's a little bit tricky because you know, the best way to look at mitochondria is doing muscle biopsy. But that's not fun. Yeah, no, um, but there are other, other tests.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

How, how do you, how do you

[Dr. Mark Hyman]

think about approaching mitochondrial dysfunction? Because, yes, it's gotta be focusing on the causes, like if you're eating something that's bad or if you're got exposure to toxins. But let's assuming you're, you're, you're working on those because you have to, what else can you do to revive these little, poor baby, little mitochondria that don't feel so good.

[Dr. Scott Sherr]

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, on giving you a direct sense of what's happening in the mitochondria. And there maybe there are a number of them that are on the market already. Some of them might Be more ready for primetime than others.

[Dr. Mark Hyman]

What do you think is the.

[Dr. Scott Sherr]

Well, I mean 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. Those are really good indicators really of mitochondrial function. There's things like miscreen and mitoswab and others that are out there that I think are in. Interesting. I think they're. They're new.

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

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. But so much of this, as you know, Mark, is subjective. But people really 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, five years ago? Tell me about your energy now versus five years ago. Like, oh yeah, I had a lot of energy. I had no issues. And now I, I get brain fog. I get that dip during the day and I feel terrible. Like people can typically give you a sense sense so subjectively such a big part of this. I know when that's hard, 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. Vitamins, minerals, nutrients, antioxidants, getting rid of heavy metals. This is your work? This is my work. The challenge with all that though is that it takes takes time. It doesn't happen overnight. And so I've kind of fallen in love with a compound called methylene blue that you know of. 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, 4mg to 25mg or so, works both as an energy enhancer and as a detoxifier. So it's 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. 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 the energy 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 LMO or whatever, and then they're able to start really making changes that they really want to make. And so I see methylene blue as a fantastic bridge for so many people on this path to their own health optimization journey.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

Which is electrons are really what goes for through this little mitochondrial assembly line to make energy, to make ATP. 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?

[Dr. Scott Sherr]

Yep. It bypasses and then you get more

[Dr. Mark Hyman]

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. And I don't know if it was a long lasting effect, but it was an incredible thing because we know that Parkinson's is fundamentally a mitochondrial disease in the part of the brain that has to do with motor function.

[Dr. Scott Sherr]

Right.

[Dr. Mark Hyman]

And so can you kind of explain how that might all be possible?

[Dr. Scott Sherr]

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 co thing 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 at 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 what's called the electron transport chain in the mitochondria. So the mitochondria has these proteins that are all kind of aligned up and electrons that we get from our food, mostly carbohydrates and food fat, they get donated to this 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 one or complex two, 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 four complexes. Those first two 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.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

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 is actually a.

[Dr. Mark Hyman]

Kills you by stopping your mitochondria from working complex 4.

[Dr. Scott Sherr]

So the fourth complex in the mitochondria complex 4 for 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 molecule.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And it's actually how I learned about

[Dr. Mark Hyman]

it was in the emergency room. As an emergency room doctor, if someone comes with cyanide poisoning, this is the drug that you give to cure people, right?

[Dr. Scott Sherr]

So it's not common, but it's there. There's another one called methemoglobal anemia which is more common and that's also why it's used in emergency rooms all over the country. Carbon monoxide poisoning. And also if you've like the huffing glue or like the bad stuff, 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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

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[Dr. Mark Hyman]

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 get higher serotonin, dopamine, norepinephrine. It can have improved mood neurocognitive effects. Right.

[Dr. Scott Sherr]

So it's dose dependent. So lower doses of methylene blue will increase norepinephrine and serotonin. 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, 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. Right. We're talking about small amounts compared to the huge effect on mitochondrial function.

[Dr. Mark Hyman]

People listening wanna know how 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.

[Dr. Scott Sherr]

They can just swallow it. It's okay.

[Dr. Mark Hyman]

They can swallow it.

[Dr. Scott Sherr]

Swallow it, right? Yeah. Because as I ment, 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 of that, it can be sometimes contaminated with heavy metals, things like lead, mercury, cadmium, and arsenic. Okay.

[Dr. Mark Hyman]

In the manufacturing.

[Dr. Scott Sherr]

In the manufacturing process. And so to take the synthetic thing just for a minute, because I know some people don't like the idea of taking any. Anything synthetic. The way I like to talk about this is that not. Not everything natural is good for us, okay? You can forage.

[Dr. Mark Hyman]

Arsenic is. Yeah. Arsenic will kill you.

[Dr. Scott Sherr]

Right. Mushrooms. Like, I was in medical school and I saw two people die of liver failure because of foraging for the wrong mushrooms, for example. So, 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. 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 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 boot 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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

And do you use it in conjunction

[Dr. Mark Hyman]

with other mitochondrial support. So in functional medicine, we talked about CoQ10 and creatine and carnitine and poic acid and nthly cysteine and riboflavin and, you know, magnesium, potassium, aspartate, and all these wonderful, wonderful.

[Dr. Scott Sherr]

Yes.

[Dr. Mark Hyman]

Ribose, that can be supportive. And I've used them in my practice to great benefit often, you know, together with, you know, thinking things like heart failure, of course. But you have to use them in conjunction with methylene blue or not as much.

[Dr. Scott Sherr]

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 going to do is increase metabolic rate because it's going to increase the amount of energy you're making. 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 grading 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 three 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.

[Dr. Mark Hyman]

So this is the most important tool for getting out of this sympathetic spiral of doom.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

okay to take it every day.

[Dr. Scott Sherr]

So in the beginning, yeah, as long as you're keeping the dose low, my sense of this is that what does

[Dr. Mark Hyman]

the dose low mean?

[Dr. Scott Sherr]

Right. So usually milligram 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 giving. If you're taking above seventy or eighty or a hundred 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. As a range. Fantastic. Mitochondrial, mitochondrial function, sometimes a little bit higher than that, but up to 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 can buy at the store.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

It's actually what your white blood cells

[Dr. Mark Hyman]

produce to kill infections.

[Dr. Scott Sherr]

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 antioxidants 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 in 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 going to 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. I've seen some interesting things as well. And also, you know, 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 using lower doses for mitochondrial function. That being said, some people have these chronic infections that are causing significant, you know, 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, you know, my whole life. I started taking methylene blue and it's gone. 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. And because now you're making enough energy and now the system can start healing. And I found my methylene blue at these low doses to be fantastically effective, Mark and I. And 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, 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 two 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 you know, we were the first people to really pioneer this back then in 2020 at the company, at our company. And 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. 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 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. Yeah, 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.

[Dr. Mark Hyman]

And you know, just to be transparent, you. You have created a company. Yeah, we have subscriptions.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

Which I use. But. But it. You provide methylene blue.

[Dr. Scott Sherr]

Yeah.

[Dr. Mark Hyman]

And you have different forms of it, but you run through all third party testing and make sure it's the right dose and right. That there's no contaminants. And so is, is there, is there like a, is there a method that you've kind of developed that actually able to do that?

[Dr. Scott Sherr]

Which is our company, we decided to make this company, by the way, Mark. 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 Articoso. And the idea with the nonprofit was to create an ecosystem for practitioners, for training and 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 we wanted to help people right now along that path.

[Dr. Mark Hyman]

And.

[Dr. Scott Sherr]

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, what are people gonna, they're gonna want their urine to be blue. Because your urine.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Well, by the way.

[Dr. Mark Hyman]

Yeah, you make sure your urine green or blue or you're like.

[Dr. Scott Sherr]

Exactly. The concentrates in the urine. So you gotta, you gotta watch out for that. And you have to.

[Dr. Mark Hyman]

So you don't stain your clothes.

[Dr. Scott Sherr]

Yes. You gotta be very careful. And so we came out with the first commercial product in 2020. And I was looking 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, USP 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 going to get what's called a certificate of, 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.

[Dr. Mark Hyman]

Right.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

China's.

[Dr. Mark Hyman]

Is China policing itself?

[Dr. Scott Sherr]

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 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 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 in.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

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 can 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 is stuck. And you can't.

[Dr. Mark Hyman]

I agree. It's one of the sticky issues in functional medicine is how do you unburden someone's mitochondria? How do you get them out of this cell? Danger response. And this what you call the sympathetic spiral of doom.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

So. So let's kind of talk a little

[Dr. Mark Hyman]

bit about what you call the parasympathetic edge. What is that? Why is it important? And it's. You know, 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?

[Dr. Scott Sherr]

So this is the opposite of the sympathetic parasympathetic 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 is 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 drive, 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 where they can maintain their capacity. Navy seals are.

[Dr. Mark Hyman]

Are.

[Dr. Scott Sherr]

Are famous for this. Right. They can find ways when they're in the. 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. 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 don't. We can't function that high. We don't do well. And this is where like the, the classic example is like you have that dream where you're supposed to give a speech and you can't remember your lines because when your sympathetic nervous system's been 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. Things come, bring things from your long term memory. Like you go blank, you go blank. That's, 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 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 example is, is recovery. Like we're now in 20, 26. People care about recovery, right? We're kind of like, oh, but you know, five or 10 years ago, if you were an athlete in the professional sports, nobody gave a crap about recovery, right? And so people were burning out, they were getting injured and things like that. But now if you focus on knowing you can strength train three times a week at most, and it's better than strength training five 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.

[Dr. Mark Hyman]

Because cortisol actually causes you to lose muscle, right?

[Dr. Scott Sherr]

Yes, it's catabolic, but the GABA system, and that's the system that is involved in calming down the brain. GABA is your primary inhibitory neurotransmitter transmitter. 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 GAB is deficient in so many of our, in some people, so many people, because of the lives that we live with stress all over the place. So GABA deficiency is actually more associated with depression, anxiety, influence, insomnia than any serotonergic issues that you could ever imagine.

[Dr. Mark Hyman]

But you say that you're taking GABA because you can buy GABA supplements over the counter.

[Dr. Scott Sherr]

Right? So GABA as a supplement is not a good idea.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Yeah, yeah.

[Dr. Mark Hyman]

But you're saying there's another compound that comes from the toxic mushroom, the amini muscarium mushroom, which is Agarin.

[Dr. Scott Sherr]

Yeah, Agarin, Yeah, Agarin, yeah, yeah. And so what it comes down to, like, to break it down just briefly. So gaba, again, your brain breaks of your brain.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Right.

[Dr. Scott Sherr]

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, you know, they don't want to give you, but they might give you a short amount of it. Now, when it comes to benzos and

[Dr. Mark Hyman]

alcohol, benzo like Valium or.

[Dr. Scott Sherr]

Like Valium, 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 a 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. 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 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 opt in, optimize the gut, which you and 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.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

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 would bind. The cool thing about the GABA receptor is that it's 5 subunit receptor. Not getting too technical, but you have a place where GABA binds itself and then you have separate subunits sites called, you know, separate sites or allosteric sites where other things combine.

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

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 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, what's going to happen is over time, those aren't going to work very well for you. They're going to, to stop working.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

Scott so this is really fascinating stuff

[Dr. Mark Hyman]

and I think that, you know, getting a parasympathetic edge is key. Getting the sympathetic spiral doom is key.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

How do, how do you kind of

[Dr. Mark Hyman]

support people to kind of maintain they've sort of broken the cycle a little bit. And we're going to refer you to resources. I know you've written a lot about this and I want to ask you kind of 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?

[Dr. Scott Sherr]

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 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 like called Trocom and Trozi they can be helpful. You don't have to go product. You can also learn how to meditate and do breath work 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 their level of capacity to start doing something right. Sometimes it's helpful, I found, is to give them something, something like something that down regulates the nervous system. Something that, 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 have given 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 working 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 sympath, right? We talked about this. Is it external stuff? Is it the, is 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 a small thing. They have a more PC word. If they're like sleep union or something like that. Now instead of sleep divorce, 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? 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 Rabin and others that are out there that are really good at coffee, 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 on 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 from the mitochondrial side. It's the same thing, right? We have to address the mercury toxicity, we have to address the toxic exposures

[Dr. Mark Hyman]

or practice functional medicine, basically.

[Dr. Scott Sherr]

Exactly, yeah. Yes, exactly. Like that's work the system. Yeah, you have to be. The system is. And your system is fantastic for that. Right? That's what you do and that's what's beautiful. But that takes longer.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

What I'd have 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, increase your dose every three to five days. See how you feel at one dose. Take it in the morning.

[Dr. Mark Hyman]

Typically one whole troche is 16.

[Dr. Scott Sherr]

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 three days. Take it in the, the morning, don't feel much. Go to 8mg, 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 gonna 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. 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 trying to. 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 8,000ft above sea level. The best jet lag hack that I've ever found, Mark, is to move to Colorado, because I live at 5,500ft. And so when I go on an airplane, it's 8,000ft pressurization. Then I come to Austin to visit you. I'm at sea level. I feel great because I've been at. I've been at altitude for a while,

[Dr. Mark Hyman]

and I was just at 8,500ft in. In Montana, and I felt it.

[Dr. Scott Sherr]

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 Home Hope. We were in Tibet, and we were at Mount Everest Base Camp at 17,800ft. 17,000. It was very, very high. We didn't have. We had intermittent oxygen. We had oxygen canisters, but we're using methylene blue. It was game changing, really. That wasn't the only thing we used. We used Diamox and we used.

[Dr. Mark Hyman]

I got. I got. I got pretty significant altitude sickness. When I was in Bolivia, we drove right up to 16,000ft. There's no acclimatization.

[Dr. Scott Sherr]

That's.

[Dr. Mark Hyman]

Yeah, there was a hotel there, and my oxygen saturations were down in the 70s, I'm sure.

[Dr. Scott Sherr]

Yeah. Teds were low, too. And we had them on oxygen.

[Dr. Mark Hyman]

Yeah.

[Dr. Scott Sherr]

But we were using Diamox, which is a drug for altitude. We're using Viagra as well.

[Dr. Mark Hyman]

Yeah, right.

[Dr. Scott Sherr]

Because 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.

[Dr. Mark Hyman]

And why would you use the 50?

[Dr. Scott Sherr]

So the 50s are great for acute infection, acute stress overall. And so I use it for acute infection, acute stress. So if somebody has, like a concussion or has a, you know, 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. I gave her methylene blue about 2 milligrams per kilogram, about 150 milligrams for. For five days. And she also took 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. Four 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.

[Dr. Mark Hyman]

That's amazing.

[Dr. Scott Sherr]

Intermittently. But it's the lower doses that I use and maintain. So for me, I'll use it about three, three times a week. Four milligrams every day. Every four 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, 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.

[Dr. Mark Hyman]

Oh, good. Okay.

[Dr. Scott Sherr]

So I have cyclists that use it.

[Dr. Mark Hyman]

I have a bike trip this summer. I'm gonna do that.

[Dr. Scott Sherr]

Yeah, exactly. And I have ultra marathons that I use it.

[Dr. Mark Hyman]

Amazing.

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

A couple different places. And thank you for having me, Mark. So my personal website is my name. It's my name, Dr. Scott Sher-R S C-O T T S H-E-R R dot com. The company that makes some of the products we've been talking about today is called Troscriptions. It's the word trochee and proscriptions mashed up into tro scriptions. 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 that. So does Dr. Ted. And you can check it [e-mail] we have just blue, which is our pure methylene blue. We have something called blue canadine, 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 Trocom and Troz, which are more on that GABA side. Trojan turning that brain off that GABAergic side. So trocomb and Trozi and then we hold, we have a whole practitioner.

[Dr. Mark Hyman]

Troz is for sleep.

[Dr. Scott Sherr]

Troz is about the most comprehensive sleep formula that I've seen on the planet. It's got eight different ingredients, including the GABA system. So Trozy 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 a trisco. And then the nonprofit is called Health Optimization Medicine and Practice or Home Hope 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, with functional medicine as well. And then where else? I think, you know, on our website, on 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, 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 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.

[Dr. Mark Hyman]

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

[Dr. Scott Sherr]

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

[Dr. Mark Hyman]

Well, thanks God, thanks for you do. Just bringing the science to everybody and being dedicated to helping people live a healthier, better life.

[Dr. Scott Sherr]

Right back at you Mark. Thanks for having me.

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If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review and subscribe to the Dr. Hyman show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on the Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness center, my work at Cleveland Clinic and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my 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.

[Dr. Mark Hyman (Sponsor/Personal Story Segment)]

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[Podcast Host/Announcer]

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