Dr Reveals What Kills Mitochondria - And How to Fix it

What if you're not tired because you're getting older or because you need more caffeine? What if your mitochondria have decided it's not safe to make energy? Your mitochondria's job is to make energy, and they're constantly making this decision. Do I produce energy or do I protect myself? Today, I'm going to show you the 5 things that force your mitochondria into survival mode, how to tell when it's happening, and what you can do to reverse this process. I'm Dr. Ashley Frazee. I'm a primary care doctor working outside the bounds of insurance. Which gives me a lot of time to learn about things like this, the biology of energy, performance, and aging. Well, first let's go over what mitochondria are and what they do for you. You probably learned that mitochondria are the powerhouses of the cell. They take the food that you eat and the oxygen you breathe and convert them into ATP, the energy currency your body uses to do essentially everything. But here's what we don't learn in high school biology. Mitochondria aren't blindly producing as much energy as possible. When the environment looks safe, they can focus on producing energy, clearing out old mitochondria that no longer work well through mitophagy, and building healthier new ones through mitochondrial biogenesis. But when they detect danger, they shift their priorities. They don't care that you want to lose weight, build muscle, or have enough energy to play with your kids. If they believe they're under attack, survival always comes first. And this is a theme that we see over and over again in human biology. Sometimes fatigue is just a sign that your body is protecting itself. And if that's happening, we can look deeper and figure out if your mitochondria feel threatened and why. So how do you know if your mitochondria are messed up? Now, there are a couple of tests out there that do a cheek swab and give you a report of mitochondrial function that look like this. It's just that these tests cost around $700 and we're not 100% sure of their real-world validity yet. I'll let you know if that changes. But for most people, Simpler data points may be more useful. Things like, do you wake up feeling like you never recovered? Do you crash every afternoon and try to resist it with more caffeine? Are your workouts becoming unusually difficult, or are you struggling to recover from them? And if you're a big data nerd like me, is your HRV going down? Is your resting heart rate going up? Is your VO2 max declining? But if you really want it to be simple, just answer the question: are you more fatigued than you should be given your circumstances? Now, none of the things that I just mentioned prove that you have mitochondrial dysfunction, but if several things are moving in the wrong direction or you just feel flat out tired despite doing all the right things, something may be limiting your ability to produce and use energy efficiently. And if there's a question that it could be rooted in your mitochondria themselves, well, then the next question becomes, what is telling your mitochondria to pump the brakes? And there are a lot of possible causes. I've actually already made this video. It just got really overwhelming for people, I think. So this time I'm going to give you things in 5 broader categories to keep it simple. So here we go. The first thing your mitochondria hate is having too much fuel to process. Picture for me a bunch of cars driving down a 5-lane freeway. Under normal circumstances, on a normal day, the traffic flows smoothly. But what if there's construction and suddenly during rush hour, 5 lanes of traffic have to merge into 2? Everything then becomes congested, right? Well, now imagine the food that you eat as those cars. That fuel is trying to travel through a series of metabolic pathways so your mitochondria can ultimately turn it into energy. But when extra food and fuel keeps arriving faster than your body can process it or use it, the entire system backs up. Inside your mitochondria, electrons that come from your food are supposed to move through the electron transport chain in a nice, Controlled sequence. Think of the electron transport chain like the factory assembly line in which your energy is actually produced. When the system becomes overloaded, some of those electrons leak out and react with nearby oxygen, creating reactive oxygen species, which are like little molecular sparks. A few sparks are fine and typical. You actually need them for cellular signaling and adaptation. But when the sparks start flying everywhere, the factory overheats. And those extra reactive oxygen species begin damaging the mitochondrial membranes and machinery around them. And the system just starts to break down, just like a poorly maintained engine. There's actually some very cool research by a guy named Michael Brownlee who proposed a unifying mechanism of diabetic complications. Diabetes is essentially high blood sugar, too much fuel. So before his proposal, we thought that heart disease, eye disease, kidney disease, etc., were all separate complications of elevated blood sugar or diabetes. But his proposal actually helped explain how chronically elevated blood sugar overloads mitochondrial metabolism and increases the production of a reactive oxygen species, or spark, called superoxide. And this unified the mechanism leading to heart disease, eye disease, and kidney disease with diabetes or high blood sugar. And more important than that, It pointed to the issue being in the mitochondria. In other words, metabolic overload or having too much fuel can become the ignition point to a devastating cascade leading to inflammation that then destroys blood vessels, your heart, your kidneys, and so on. And this isn't just about eating a dessert occasionally. It's about chronically sending in more fuel than your mitochondria can use, especially in the setting of insulin resistance. Which a lot of people have. So too much fuel enters the freeway, the lanes become congested, electrons start escaping, sparks are flying around, and you get things like 10-car pileups. It's just a hot mess. Now let's move on to the second reason mitochondria get messy: damaged membranes. So mitochondria have 2 membranes. There's a relatively smooth outer membrane that allows certain things to move in and out of the mitochondria to get into the factory or get on the freeway. And then there's this inner mitochondrial membrane, which looks like this. It's folded up over and over again. And this is where the factory assembly line, or the electron transport chain, lives, and where most of our ATP, or energy production, happens. But this membrane, the inner mitochondrial membrane, it's constantly exposed to high-energy reactions, which makes it uniquely vulnerable to damage. And the inner mitochondrial membrane contains something called cardiolipin. It's a phospholipid. Cardiolipin basically holds the membrane together. It's like the scaffolding for the factory. But cardiolipin can and does get damaged, and it loses its ability to hold the membrane together. And if this happens, well, your factory assembly line just doesn't work very well. So the membranes are important. You've got the door to the factory, the scaffolding holding it up, and the factory assembly line itself. But these membranes can become damaged. So what damages them? Well, one of the major internal causes is excessive oxidative stress, including the reactive oxygen species created during the metabolic traffic jam that we just discussed. But what you put into your body matters too. Your mitochondrial membranes are partly built from the fats that you consume. So a poor quality diet dominated by ultra-processed foods and easily oxidized fats makes those membranes more vulnerable to damage. When you eat highly processed foods, it's like you're building the foundation of your energy factories out of untreated dry wood instead of reinforced steel. Other things that can damage these membranes include pollution, certain heavy metals, inflammation from infections— viral, bacterial, fungal, etc.— and specific medications like fluoroquinolones or Levaquin or ciprofloxacin, which doesn't mean that they should never be used, but it explains some of their known adverse side effects. Chronic stress contributes as well through persistent cortisol signaling creating inflammation and poor sleep and impaired recovery. And this is why I keep saying that stress management is not optional if you want a healthy lifestyle. And I know that's hard to hear because sometimes that job or your family circumstances just don't allow you the room to de-stress. But stress isn't just something you feel emotionally. Your cells experience it biologically. When mitochondrial damage consistently outpaces repair, you lose power. And eventually you shut down entirely. So speaking of inflammation, this is the 3rd reason mitochondria get messed up: inflammation and infection. So inflammation isn't always bad. If you cut your hand or you catch a virus, inflammation is part of how your body protects and heals you. But here's what can happen at the mitochondrial level. During an immune response, some cells will shift ATP production towards glycolysis, which doesn't happen inside the mitochondria. It happens outside of it. And glycolysis is a very fast but inefficient way to make ATP. You get 2 ATP from this method versus about 30 through the electron transport chain in the mitochondria. But during things like infection, when this shift happens, the mitochondria in those cells are partially repurposed from maximizing energy production to coordinating defense, inflammatory signaling, damage control, and if necessary, cellular death. The factory doesn't shut down, but part of it is converted into a command center and like a weapon system while the cell is relying on its backup generator, glycolysis, to help cover the immediate energy needs. It's just that this becomes a problem when the inflammatory mode backup system never completely switches off. So persistent inflammation, lingering infection, repeated stress, disrupted sleep, or an inability to recover can continue sending the message that the danger hasn't passed And your mitochondria are just acting like battleships now instead of efficient factories. That may be one reason people with lingering issues from viruses and people with chronic inflammatory conditions, or people who feel inflamed all the time, often describe very similar symptoms. Things like fatigue, brain fog, poor exercise tolerance, and slow recovery. Their energy factories may still be diverting resources towards defense. And so in this situation, it becomes a priority to help create an environment in which your mitochondria can safely return to producing energy efficiently. Wave the white flag, right? The war is over. Okay, that was kind of depressing, so let's move on to the next way your mitochondria can get messed up. Number 4 is poor recovery. Your mitochondria aren't only producing energy during the day, they're constantly repairing, recycling, fusing, dividing, and adapting to demand. And adequate sleep supports many of the mitochondrial quality control processes. Think of sleep as the maintenance shift for your cellular factories. And during this shift, our damaged mitochondria choose different paths. So slightly damaged mitochondria can fuse with healthier ones. This is called mitochondrial fusion. It's a little like buddy taping an injured finger to a healthy one so that the injured one can heal. And then mitochondria that are too badly damaged to be rescued get isolated and recycled through a process called— Mitochondrial autophagy. Mitophagy is your cell's internal cleanup system. It's the process of identifying dysfunctional mitochondria, breaking them down, and recycling the usable parts so that they're no longer consuming resources or contributing to cellular stress. Mitophagy is like walking around your house and labeling all the clutter that needs to go, like those random toys my kids bring home from the arcade. But mitochondrial quality control appears to become less efficient as we get older. It is what it is. But if you chronically shortchange your sleep or live in a state of constant stress, you make it even harder for your body to complete this maintenance work. Your damaged factories don't get repaired efficiently and trash begins accumulating. And then you wake up expecting your cells to provide another full day of energy, but they can't. And just FYI, research suggests that this process can happen surprisingly quick. Even short periods of sleep restriction can impair mitochondrial function and antioxidant defenses. More severe sleep deprivation has also been associated with oxidative stress, and signs of muscle damage. So don't run your factory 24 hours a day, never shutting it down for maintenance like you did when you were in college. Without proper maintenance, something's just gonna break. And this is where I want to introduce you to a compound that I've been researching a lot called urolithin A. Urolithin A is produced when certain gut bacteria metabolize things found in foods like pomegranates, berries, and walnuts. But here's the problem. Not everyone has the right combination of gut bacteria to produce meaningful amounts of urolithin A. According to research, urolithin A appears to support mitophagy, the process of identifying and recycling damaged mitochondria. And because mitochondrial quality control tends to decline as we age, we have begun studying whether supplementing with urolithin A can support mitochondrial health. A lot of the research on using urolithin A has come from a company called Timeline, Who eerily reached out to me while I was writing this video. I am not even kidding. And so I asked if they would like to sponsor this video, which they are. So Timeline created Mitopure, a highly purified and precisely dosed form of urolithin A that has been studied in multiple human clinical trials, and it's shown to improve and counter age-related mitochondrial and muscular decline. A trial in older adults found improved muscular endurance and mitochondrial biomarkers. And another trial in middle-aged adults reported improvements in muscular strength, exercise performance, and the mitochondrial biomarkers. Later studies expanded this into athletes and other populations. Now, MitoPure did sponsor all of these studies, but they're generally regarded as high-quality, scientifically rigorous studies. And that's why I have started taking the MitoPure gummies myself, and I'm excited to share my experience with you after I've used them consistently for a couple of months. If you want to try MitoPure with me, I've left a link in the description for you. And thank you to Timeline for sponsoring this video and supporting my love of making videos for you guys. All right, moving on to the 5th and final thing your mitochondria hate. And this one might be the simplest of them all: having nothing to do. I mean, I'm all for a good rest day, but not when one rest day turns into days, weeks, months, or years. Your body and cells, down to the mitochondria, adapt to demand. Exercise and physical activity signals to your cells that they need more energy capacity. In response, your body activates pathways that improve mitochondrial function and stimulate the creation of new mitochondria— mitochondrial biogenesis. Take that demand away and your body has no reason to maintain a large energy production system if it doesn't need it. There's no reason to employ 100 people if there's no demand for what the factory is producing. And I want this section to encourage you because your mitochondrial response to increased demand can begin very quickly. Even one workout can substantially increase the activity of something called PGC-1 alpha, a major regulator of mitochondrial biogenesis. But the important point is this: just one workout can begin signaling to your body that it needs greater energy-producing capacity. You do not have to wait 6 months for your cells to notice that something has changed. They notice immediately and get to work. Also consider this: The more muscle mass you have from things like lifting weights or simple resistance training, and I'm talking like just get a band like this. Well, this creates demand too, because muscle is packed with mitochondria. I actually made an entire video about this and never released it because it was way too nerdy. But the more mitochondria you have, the better off you are. So muscle isn't only about strength or looking good. The more metabolically active muscle tissue you maintain and the more consistently you use it, the greater the demand for mitochondria and healthy Mitochondrial function. So your mitochondria are responsive to demand, and it's up to you to give them a reason to change. Now, I've just given you a whole bunch of reasons on how your mitochondria get all messed up. So let me give you some brighter news. Every problem we just discussed gives us a clue about how to fix it. So you just need to be careful about supplying your factories with too much raw material, or at least increase the market for the supply. Be careful about the source of your supplies in order to minimize damage, clear out what's beyond repair, and build new energy capacity. And if you need it as a stepwise progression, follow this: if you continue flooding your mitochondria with excess food or fuel, you're damaging their membranes and surrounding them with constant inflammatory signals. And at that point, no supplement is going to rescue your energy. So start by improving your metabolic environment, or how much you are eating. Give your body defined times to eat instead of constantly carrying snacks around in your purse or sipping a calorie-filled latte. And this is like 90% of the reason why the GLP-1 drugs work so well for people. They just stop the need for constant eating. But when you do eat, build your diet around adequate protein, healthy fats like fish, antioxidants like berries and colorful foods, and just minimize the processed stuff. Provide the raw materials needed for healthier membranes and support your body's antioxidant defenses. Then identify the major stressors that apply to you. Do you have insulin resistance? Are you getting poor sleep? Do you have an inflammatory condition or feel inflamed? Do you have issues from an infection that you never recovered from? Or are you taking a medication affecting mitochondrial function? Are you chronically stressed? You don't need to become afraid of everything here. Just identify the biggest source of stress in your situation and begin there. Next, protect your recovery by prioritizing sleep. I can't tell you how many conversations I have with patients about sleep. If you don't think you get good sleep, start tracking it somehow. So I wore a Whoop for 3 years. I've worn an Oura Ring for 2 years. My husband wears a Garmin. There are so many different things that you can use to track your sleep. Just use the information to identify trends, and if something looks persistently wrong, take it to your doctor and investigate it. And this is also where some supplements may make sense. Urolithin A may support mitophagy and mitochondrial quality control, which is why I introduced Mitopure earlier. CoQ10 is another option. It participates in the electron transport chain, And it helps protect your mitochondrial membranes from oxidation or lipid peroxidation. Statin medications can reduce circulating CoQ10 levels. So people experiencing possible statin-related muscle symptoms like fatigue or muscle aches can or should discuss that with their doctors. Ubiquinone is the oxidized form of CoQ10 and ubiquinol is the reduced form. They're both forms of CoQ10, and for all intents and purposes, either may be used. NAD is a huge mitochondrial support supplement. I have a whole video on that if you want to understand why. And please remember this, I am a doctor on YouTube, but I am not your doctor. Please talk with your own before starting anything new, especially if you have a medical condition or if you take medications. And also, please do not buy every supplement that you hear me mention. Some of you have lists containing 30 supplements, and I've seen them. All right, step 3, just build more mitochondria. But remember, your body won't simply build more mitochondria because you asked nicely. You have to create the demand. Exercise is the clearest and most reliable way to do that, and weightlifting or resistance training will allow you to keep or gain muscle, which allows you to have more mitochondria and more energy-producing capacity. But then there's cold exposure. This is another way to create demand that I personally use. And there's a link to the cold plunge in my backyard if you want to see the one that I have. And there's also things like saunas and red light therapy. Well, these don't directly replace exercise or help to manufacture new mitochondria, but they may activate adaptive pathways that help protect and preserve mitochondrial function and improve their resilience. I have another video explaining how heat, cold, and red light affect mitochondria if you want to go deeper on that. And then there are targeted mitochondrial peptides. Please do not buy random peptides from the internet and start experimenting on yourself though. Find somebody who actually understands what they're doing with it. So there's SS31, known as elamipretide. This interacts with cardiolipin, the thing that helps stabilize the inner mitochondrial membrane. Well, sometimes it gets exposed and damaged and the membrane falls apart. Well, SS31 has this amazing ability to go in and stabilize cardiolipin. cardiolipin, thereby stabilizing the mitochondrial membrane and keeping things working efficiently. MOTS-c is another mitochondria peptide that is actually made in your mitochondria. We already make it, but it participates in the signaling response to energetic stress or demand and aids in the process of mitochondrial biogenesis. And these peptides are amazing and fascinating, but they are advanced tools. Exercise, metabolic health, or good nutrition, sleep, and recovery are still the foundation. And I know you're going to ask this last part, so I'm going to throw it in here. How do you know if any of this is working? Well, feeling better actually does matter here. And I know that's a simple explanation, but if you try some of these things and you have more energy, you recover more quickly, and you don't crash every day, that is meaningful. Even if nobody can hand you a lab report proving exactly what happened inside of your mitochondria, because it just doesn't exist yet. But journal things and look for patterns. Are you becoming more resilient? Can you generate more energy when you generate more demand? And can you recover without feeling destroyed the next 3 days? Those are signs that your system is adapting. So when your mitochondria sense overload, damage, inflammation, or insufficient recovery, they protect themselves. But when you reduce those threats and give them a reason to become stronger, they respond to that too. Your mitochondria are listening to the environment that they're in every day. Give them a reason to make energy again. I'm Dr. Ashley Frazee. I'm just trying to make your biology cool again so you feel motivated to help yourself. If you like this video, please hit like for me and subscribe to my channel. And I hope you have the best day.