In this solo educational video, board‑certified primary‑care physician Dr. Ashley Frazee shares her personal experience of post‑COVID fatigue and outlines a comprehensive approach to “resetting” mitochondrial health to restore energy and reduce chronic fatigue. She begins with a brief overview of mitochondrial biology, emphasizing the role of NAD+ as a cellular battery and the master regulator PGC‑1α that drives mitochondrial biogenesis. Frazee then details the major contributors to mitochondrial damage—including chronic stress and elevated cortisol, poor sleep, a high‑sugar/processed‑food diet, and certain medications (statins, metformin, SSRIs). She proposes lifestyle interventions that activate PGC‑1α and promote repair: regular exercise, adequate sleep, intermittent fasting, cold‑water immersion, sauna use, and exposure to sunlight or red‑light therapy. The core supplement stack she recommends includes NAD+ precursors, carnitine, CoQ10, creatine, alpha‑lipoic acid, PQQ, melatonin, magnesium, and urolithin A, each described with its mechanistic role in energy production or mitochondrial turnover. Frazee also explores frontier compounds—mitochondrial‑derived peptides and experimental molecules such as MOTS‑c, SS31, SLU‑PP‑332, and humanin—highlighting their research‑backed potential to mimic exercise or protect mitochondrial membranes. Throughout, she stresses that the content is informational, not personalized medical advice, and encourages viewers to adopt the discussed practices, like a “reset,” to improve fatigue, weight management, and overall vitality. The video concludes with a brief professional bio, a disclaimer about her direct‑primary‑care model, and a call to like, subscribe, and stay engaged.
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I'm a board-certified primary care doctor, and I see a lot of people who just need a total reset. They're stressed out, fatigued, not sleeping well, can't lose weight, and I just want to shake them out like a dusty rug. And so lately I've been diving into mitochondrial health to see if fixing your mitochondria is what you need in order to get things going again. Most doctors don't know this stuff. It's like we're handed this massive complex machine called the human body, but our training barely scratches the surface on how to keep the energy center of the cell, the mitochondria, running smoothly. And that gap leaves so many people stuck feeling tired. So let's change that. Now, before I get into details on mitochondria, I'm just going to share a personal story with you. Several months ago, I had a bad bout of COVID and it left me feeling really drained. After I had COVID and thought I had recovered, I was in the gym trying to work out, but so fatigued. I was convinced that I had cardiomyopathy, just feeling completely out of shape and dragging every day, which wasn't my norm. So I went on a mission to reset my mitochondria and see if that I used about 4 of the techniques that I'm going to explain in this video, and I finally felt like I had that second gear again. So if you feel like you or someone you know could use a reset, watch this video. And just remember, this is not medical advice from me to you. I am just a doctor on YouTube talking about things that fascinate me. I am not your doctor. All right, let's start with a little background on mitochondria and why you should care. You see, every cell in your body except your red blood cells Have multiple mitochondria. Under a microscope, they look like little beans with squiggly lines in them. And simply put, this is where your energy is made, in the mitochondria. So now let's talk about how that happens. When you eat, food ends up in your cells as NAD+. You can think of NAD+ as like a battery charger for your mitochondria. You get NAD+ from certain nutrients like niacin and tryptophan, plus your body recycles it. Over time, NAD+ levels naturally decline with age, and it's thought that low levels Low levels of NAD+ in the brain can contribute not only to fatigue but to things like age-related dementia. And get this— stress, inflammation, disease, and things like poor sleep all burn through NAD+ faster than your body can make it from food. It's like when you can't find enough wood to keep a fire burning. When NAD+ levels tank, energy production slows, and oxidative stress rises, leading to inflammation and damaged mitochondria. Now, mitochondria don't just lose their charge, they get damaged. How? I've actually got a whole video on that, but long story short, sleep deprivation, not exercising, chronic inflammation, eating a lot of sugar, seed oils, and processed foods are just among the few things that can damage mitochondria. Even some meds like statins, metformin, SSRIs can all have different ways of stealing the substrates that mitochondria make energy from or ways of gumming up the process. Now let's take a quick dive into stress and cortisol levels. You'll want to hear this. Think about cortisol. It's not evil. It's your survival hormone. It makes fuel accessible in emergencies. But when it's always high and you don't necessarily need that energy to run from a tiger in the jungle, it ends up redlining your engine. High cortisol floods your body with free fatty acids, easy fuel, but it's not always used. And over time, unused energy causes something called lipid peroxidation. Think of that like when you have a bottle of oil on the counter and you let it sit there and It goes rancid. You can't use it anymore. Something else happens when you have all this extra energy, but you're not using it. There's something in your body called PGC-1 alpha. It's the master switch of mitochondrial biogenesis. It tells your cells to make more mitochondria. But again, when you've freed up all these fatty acids to burn, but you're not actually exercising or running from something, your PGC-1 alpha just sits there turned off like a light switch collecting dust. And then no new mitochondria are made, and the ones you do have start to get all worn out. And that's how chronic stress literally burns out your mitochondria. It's like having 20 tabs open on 3 different browsers on your computer all the time and expecting it to run efficiently. Okay, so now you understand some basics on mitochondria and how they get burned out. So what can you do about it? Well, first and foremost, most importantly, exercise. If you come to my office, I'm going to tell you 10,000 times till I'm blue in the face, you've got to be exercising. You see, exercise literally turns on the genes that tell your cells to make new mitochondria, that PGC-1 alpha. Well, exercise flips that switch on. If you're able, it's just not negotiable. And sleep— mitochondria literally repair themselves while you're asleep. I shouldn't have to explain that one. Intermittent fasting— I'm actually not a fan of constant intermittent fasting, and yet I don't eat lunch on most days, so maybe I'm a hypocrite. But if you can wait long enough until your body actually needs fuel, you allow certain processes in the body to activate, much like exercising, turning on mitochondrial biogenesis and repair. Cool, right? And cold plunging, my favorite thing. Cold plunging also turns on PGC-1 alpha. It stresses the body enough to say, whoa, I need to adapt. I need to make more energy, more mitochondria for this, for the next time. A fact that I absolutely love about cold plunging is it activates your brown fat. Brown fat is something that adults don't have very much of. Babies have a lot of it, and it's really thermogenically active because it's packed full of mitochondria. And cold plunging literally activates your brown fat to be more thermogenically active, to burn more fat. On the opposite side of temperature extremes, there's sauna therapy. Getting in a sauna also activates PGC-1 alpha. The stress of it is what causes it. You see the pattern here? But saunas also activate something else called heat shock proteins. Which are like your cell's emergency repair team. They refold damaged mitochondrial enzymes, clear out misfolded proteins, and prevent mitochondrial death. And then there's sunlight and red light therapy. These stimulate something called cytochrome c oxidase, which is an enzyme that drives fuel production in mitochondria. Put these kinds of things in your weekly routine and you can literally train your mitochondria like your muscles. This kind of stuff just lights me up. Now let's talk about some supplements that can supercharge your mitochondria. Sometimes all you need is to give the body some raw materials and signals to make your mitochondria more efficient. Remember that NAD battery charger we talked about earlier? Well, you can literally supplement with precursors to NAD or NAD itself if you want to go with injections or IVs, but the oral supplements are precursors to NAD. If you've ever done this and you've noticed more focus or energy when your NAD levels are nice and high, that's literally your mitochondria firing cleaner. And I've experienced this firsthand. Put it in my comments if you have too. Carnitine. Carnitine's like an Uber driver that takes free fatty acids and shuttles them into the mitochondria. And then there's CoQ10. CoQ10's kind of like a spark that lights the fire to burn the fat. Without both of those, you've got all the fuel in the world just kind of sitting in the tank. Creatine. Creatine keeps an energy buffer inside of your cells. The P in ATP is phosphate, and creatine allows for storage of phosphate in your cells so that ATP can regenerate kind of instantly on demand. That's why your brain and your muscles love it. Alpha-lipoic acid, or ALA. If you've seen that on the supplement shelf, this is an antioxidant that can sneak into mitochondria and neutralize free radicals. It's also a cofactor in energy production itself. PQQ. This is one that not a lot of people know about. You get it by eating certain fruits and vegetables, and you can also supplement with it. PQQ is another thing that can turn on PGC-1 alpha. Melatonin. Melatonin is not just for sleep. It also has another superpower. It's a powerful antioxidant that when it raises at night signals to the body that it's safe to repair and regenerate. It also gets delivered straight into the inner mitochondrial membrane, stabilizing it, allowing for better energy production, and it also scavenges free radicals that otherwise would cause inflammation. Is your mind blown yet? Magnesium. Energy production literally can't happen without it. You see, ATP is almost always stored as a complex with magnesium. If you don't have magnesium, you can't store that energy. Urolithin A— this is a natural small molecule that's made in your gut when you have the right microbiome. Bacteria in your gut metabolize things like pomegranate, strawberries, raspberries. You make urolithin A. And it tells your body it's time to take out the trash. It triggers something called mitochondria mitophagy, the recycling of old inefficient mitochondria. And it also triggers our friend PGC-1 alpha. It's kind of like a janitor of mitochondrial health. All right, if you've made it this far, let's talk about some frontier stuff, stuff that I absolutely love to nerd out on. Peptides and other compounds that can kind of force your body into mitochondria-making mode. You see, if you can't do all the things that I just told you about, If you're desperate, consider supporting the research on the following things. This is MOTS-c. This is a mitochondrial-derived peptide that kind of behaves like exercise in a vial. You make it naturally, but there's a lot of research on supplementing it, and the research shows that it improves glucose utilization, endurance, and fat oxidation, basically teaching your mitochondria to be metabolically flexible again. It flips your body's metabolic switch from carbs and sugar all the time to Burning fat, creating the same clean, sustained energy and efficiency that you feel after you do an intense workout. And SS31, this is a peptide that binds to something called cardiolipin, a lipid that sits on the inner mitochondrial membrane. When cardiolipin is not doing well, the mitochondrial membrane unfolds and it doesn't work well. Well, SS31 goes in and stabilizes cardiolipin, allowing for the mitochondria to be more efficient. Basically keeps the mitochondria from short-circuiting. There's a lot of great research on SS31. There's even human data on it. It's actually approved for use in humans for a very specific mitochondrial disease. Then there's SLUPP332. This one's my favorite, but there's not enough research on it to know that it's safe. Not gonna lie. It's basically a compound that goes into the body and literally fits into something called an estrogen-related receptor site. And all that PGC-1 alpha switch flipping we were talking about, well, the downstream effect is the activation of estrogen-related receptors. These literally turn on mitochondrial biogenesis, fatty acid oxidation, and the literal switching of muscular fibers into having more endurance capacity. The same exact downstream effect that exercise gives you, SLU-PP-332 does too. And that's why they're calling it an exercise mimetic. Cool, right? Sure, I'll get a ton of comments on, well, you don't know the side effects, so why would you even consider that? Bring it on. All right, humanin. This is another mitochondrial-derived peptide. It's made by your body. It's a very small peptide that acts like a molecular first responder. Ew. It protects against oxidative damage by blocking pro-death signals and activating pro-survival pathways. Levels of humanin drop as we age, kind of like NAD+. Basically, research is showing that higher humanin levels are correlated with longevity. There's been some amazing studies that have looked at humanin levels and neuroprotection, especially in Alzheimer's disease. All right, I'm gonna have to take a break from the excitement, guys. I just love this stuff, and I wish it was taught to me in training, but it just wasn't. But I am glad to have the training that I got in medical school and residency because it allows me to really understand the science and to also repackage it in a way that hopefully you understand. And to me, that's what doctoring is all about. To others, I know there's different definitions, but this is my lane. I'm Dr. Ashley Frazee. I run a direct primary care clinic in Mesa, Arizona. I'm a regular old doctor, but I don't take insurance, so I get to geek out on stuff like this. If you like this video, please hit like for me, subscribe to my channel, and I'll keep going. You guys have the best day. Bye.
