Dr. Scott Sherr on Mitochondria, Stress, and Midlife Fatigue

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We are overstressed and we're under so much physical, emotional, cognitive stress that not only is having an effect on our nervous system, but it's also having an effect on our capacity to make energy at the same time. And so the sympathetic spiral of doom is this combination of having sympathetic nervous system that's on all the time. So your sympathetic nervous system is the one that's supposed to be on when you're getting chased by something, or something's very serious and you need to like get out of the way, or the proverbial saber-toothed tiger is running after you kind of deal. But modern society doesn't really have those things anymore. All it has now is these small but very sympathetically active things that we're doing all the time. Scrolling on our phone, going to meetings, doing the things that we're just going, going, going, going, going. So that sympathetic nervous system is, is active all the time. And we have the mitochondria, the part of our cells that make energy. That part of the cell is very, very important. We have a huge amount of energy requirements on a day-to-day basis. We make about 150 pounds of the energy currency in our body called ATP. And if we are not meeting our energy demands, the system starts going, oh no, I need to make more energy. You need to give me more capacity. And so the mitochondria, when they're trying to make more energy but can't, start putting out signals and say, hey, we can't make enough energy. You need to rev up even more than you already are. And then you get to this place where you're revving up more, but you don't have enough capacity anymore. Your, your reserve is so low because you're already at this high stress level, right? And, you know, society rewards this stuff. It rewards women and men that go, go, go. I mean, when I was in medical school, my friends and I had shirts that said, sleep is for quitters, right?

I grew up in New York.

The hustle, right? It's all something that people want because that's what's acknowledged and rewarded in our society. Then as a female, when you're getting toward midlife and your hormones are changing, And all of a sudden you can't meet those kinds of demands anymore because your estrogen levels are lower. Your mitochondrial function is now lower because of that. Your progesterone levels are lower, and all of a sudden you can't sleep as well. And so you're like, why is everything kind of falling off when I was feeling okay a couple years ago? And so the sympathetic spiral of doom is this chronic sympathetic activation with chronic mitochondrial dysfunction that is happening without us knowing it. And then all of a sudden we feel like the wheels have fall off, fallen off, and we don't know what to do.

I don't really know how a, especially a woman, now I must speak from a woman's point of view because guess what?

It makes sense, yes.

I know us well, but you look at it and not only are we, I always say, I always joke that we have, you know, two jobs or two careers 'cause we have our career and then we come home and we have our career. Right. And then we have our kids and then we have our parents and, you know, there's very few husbands.

Mm-hmm.

I'm gonna make a blanket statement, but I think most of the case this is correct, that are thinking about their kids' dental appointments or birthday parties or what they're gonna wear to school. It just, doesn't happen.

I'm guilty of this too. I have 4 kids and yes, my wife works full-time and yes.

Yeah, but yet, you know, I was like working full-time, primary breadwinner and putting on the birthday parties and like, and, and, and, and, you know, and I woke up at one point, I went, I didn't sign up for this. I don't wanna be, 'cause for a while you feel really good about it. Just like you said, you're like, look at all the things I can do. And I go, I don't wanna do all these things. And I just wonder how many women are like, God, you know, I'm feeling like crap, my metabolism's tanking, I feel like I'm aging faster, and it's because— and they're looking outside of all the things, getting their labs done, et cetera. And a lot of this stuff, I don't know how you'd even see it on a lab test.

A lot of it's gonna look like it's normal, yeah.

So, I mean, how big of an issue do you think this is?

I think it's a much bigger issue than we realize. And I think, you know, just to kind of reflect back what you said about women and responsibilities, I remember when I was in California and I saw a billboard and it had a father and a son, and all it said on the, on the, on the billboard was, Dad, just show up. Like, that's all that dads are expected to do, kind of, right? Like, all they need to do is be there, and then women do everything else.

Yeah. It's like, Mom, pack my lunch, get my clothes.

I was with my wife in the car. She was so pissed when she saw that sign. Yeah. You know, and I have 4 kids, and so there's a lot that I do to help the kids. But you're right. Birthday parties, dental appointments, the dermatologist, all that stuff is happening because my wife makes the appointments. And I just don't think about it. I always tell her it's like doing laundry. It's like, I think about doing laundry, but I thought about it 2 weeks from now when you thought about it today. Right? And so it's like, you know, women's minds are, have amazing capacity overall. But what is happening, I think, is that the capacity is, is at a, a certain level that they don't realize it's such a reserve is so low as a result. And then as a result of different changes that happen in midlife, all of a sudden that capacity goes down and then the signs become obvious in the sense that you can't recover anymore. You're gaining weight. Your energy is just all over the place. Your mood is all over the place.

Versus insulin thing where everyone's focused on fasting blood sugar. Why aren't we looking at fasting insulin? We'll fix this, figure it out way early. Yeah, yeah. I see the same challenge here. We don't have these early warning signs as far as I can tell. There's not a lab you're taking for it, so, right, so doctors would miss it. They're not getting trained on it likely. Are you getting trained on nervous system regulation and med school? No, no, no. Like, was it considered a woo thing? Like, or just—

I think we only learned pathophysiology. That's all I remember. Like, in medical school, you learn anatomy and physiology for a semester, like your first semester. So you're in the cadaver lab, you're, you know, looking at all the organs and all the things, all the tissues. You learn physiology, not normal physiology, maybe for a semester. Then the rest is just disease, right? They're not focused on keeping people healthy because the medical system is basically saying, you know what? We can't do anything about people getting sick. We are just gonna treat, treat them when they're sick and then hopefully help them a little bit.

Right. So what would these signs be then for someone, since this is such a major problem that's overlooked?

Right.

What could be some of the early signs or symptoms that things are not going well that you, cuz, cuz again, like you said, it's a badge of honor to be stressed out and overworked, right?

Yeah. So you can look at it from an objective perspective and you look at more from a subjective perspective. Objectively, what I typically do with patients is I work on a whole battery of things that, of laboratory testing that you wouldn't get if you went to your normal doctor. You know this very well. It's sort of like the functional integrative world. Mm-hmm. The framework is called health optimization medicine, and it's a framework that was developed by a colleague and mentor named Dr. Ted, who said like, let's see if we can keep people healthy so that we can optimize them over the long term and prevent a lot of these things from happening. That's in the ideal case, of course, right? If you look at foundational biomarkers like vitamins, minerals, nutrients, and cofactors and gut health and neurotransmitters and hormones, you can get signs of things falling off the wheels or falling off, you know, the wheels falling off the truck or whatever, way before it actually, you actually see it. And I remember I was working with a couple people where actually elite athletes that had the worst looking foundational biomarkers, but they were at the top of their game.

Wow.

This is not uncommon because the body can compensate for a long time until it can't. Yeah. And, and that's what it comes down to is like we have these amazing machines that compensate as long as they can until the wheels fall off. And then I keep using that analogy for some reason. And we are like, well, what just happened? How, how could I feel? So poorly all of a sudden. And, and I think what it comes down to, JJ, is that when you're thinking about sympathetic activation and mitochondrial dysfunction, this loop, the way I kind of approach it with my patients is like, look, think about it from a top-down and a bottom-up approach where top-down means that you have a lot of things that are happening to you on a regular basis that are causing sympathetic activation. Is it your job? Is it your kids? Is it your spouse? Do you have a snoring spouse that's keeping you up all night and you're not getting any sleep? Is it, you know, a bad relationship? Or something that happened in your past that you haven't addressed yet. That's all the things that are coming from the outside, right?

Mm-hmm.

And then, and then you have all the things that are happening inside as well, like toxins in our environment, medications that we're taking, infections that we're getting, insulin resistance. You talk about high blood sugars, right? These are all affecting our mitochondrial function. And 94% of US adults have metabolic and mitochondrial dysfunction. Only 6% of US adults are metabolically healthy. So you get this stress that's coming directly at the mitochondria. You have this. And that's the sort of the bottom-up side of things that I call it. And then the top-down is the stuff that's coming outside. And then you, you, you talk to somebody and you're like, you have so many different things that are happening here, both outside and inside that we need to address, right? And so the key is to understand that it's happening. And then from there being able to see, well, where can we start bringing in more support so you can start feeling better? Where I always start with this is not so much on the stress side actually, because if you just decrease somebody's stress, but their mitochondria and their cells and their immune system, their hormones are already tanking, they're not gonna feel very good. And that's because they don't have any reserve and you just, they've been elevated and trying to go and go, go to keep up with what they need to do. But as soon as you take off the, the gas pedal, put on the brakes, they're like, their system starts crashing, right? Yeah.

And, and it's like you always get sick after exams.

Exactly. Right. It's like that stress, stress, stress, and you see crash, right? And it's the same thing if you don't have enough mitochondrial support. So I'm always a big fan.

How do you know if you have enough mitochondria?

Like, yeah.

Where's the mitochondria test?

I know MeScreen's trying to do it, but it's like, yeah, there's a couple people doing it. Yeah.

Where is that? Tests that can tell us this? It would be so amazing, besides a biopsy. Like, how do you know?

So there are a number of tests out there that have come out. The MiScreen is one of them, some other mitochondrial tests. The way I think about this is that if you can take a good clinical history as a practitioner, you should pretty much have an idea. I mean, it could be anything from something overt, like if you have diabetes, high blood pressure, metabolic syndrome, you have metabolic dysfunction, you have mitochondrial dysfunction.

So if you have metabolic dysfunction, you have mitochondrial dysfunction.

And defining that is sometimes helpful for people because metabolic dysfunction Sometimes it's like, what does that mean? So I try, I try to make it super simple. I say, look, can you make energy effectively? And then after you make energy, can you address the stress that happens when we make energy? Because our cells are like gasoline-powered cars. We make ATP, our energy currency. We make a lot of it, 150 pounds every single day, a huge amount. But we also make water, carbon dioxide, which, you know, goes to the plants. They make oxygen, the beautiful cycle of life. And we also make reactive oxygen species. These are small reactive molecules. That come off because of oxygen, and these are signaling molecules. But if you have too many of them, or if they're around for too long and you don't have enough antioxidants to be able to neutralize them, then you get into this place where you get a lot of stress on the system. So metabolic health really is, can you make energy effectively and can you detox from the energy that you make? Do you have enough antioxidant capacity? And if you don't have either one, one or the other, you don't have metabolic health. And that's why it's so important when you address metabolic health. You have to address it both on the energy production side and also on the detoxification side, and not just one or the other. So if you give somebody glutathione, for example, to help them with the detox, but they can't make any energy, right? They're still gonna feel like crap, right? If you give them something that's gonna give them more energy, but they don't give anything on the detox side of things, they're still gonna feel like crap, right? So that's why it's so important to think about this, you know, holistically.

The woman who's feeling exhausted and feels like her metabolism's broken, how does she know Is it hormones? Is it diet? Or is it nervous system? Or is it just all of the above? Do we have— just have to consider that nervous system's always this foundational piece that always needs to be addressed?

I think the nervous system is always a big foundational piece. The question is just the sequence that's best optimized for that particular individual. Because as I mentioned, if you just say like, you know what, you need to calm down.

Oh boy, does that make us mad too.

That makes you really mad. You don't wanna tell a woman that she looks tired. You don't wanna let— tell her it looks stressed that she didn't sleep or something. So you don't wanna say, hey, why don't you just calm down? Right? That, that doesn't work out, right?

Uh, no.

Um, not even just that. You don't wanna work just on working on calming down the nervous system. I was talking to, uh, somebody a couple weeks ago with Lyme and mold and, and what happened was a lot of stress associated with everything else too. And she was given something by her practitioner to calm her down and she just crashed. Right. And that's because she didn't have enough of that mitochondrial support to really do it. And so the way I think about this, JJ, is like, you wanna help somebody now? Right? You wanna help them feel better now. And sequencing usually is mitochondrial support first. And then from there, looking at the, the, the nervous system and, and understanding how to best downregulate that in a safe and intentional way. Over the long term, you wanna optimize their gut. You wanna optimize their hormones, optimize their neurotransmitters, but that may not be enough, you know, and, and that might not be enough right away.

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