In this video Dr. Ashley Frazee explains cortisol (glucocorticoid) receptor resistance—when cells stop responding to cortisol’s anti‑inflammatory signal— and how it creates a cascade of metabolic dysfunction. She describes how chronic cortisol elevation burns out mitochondria, disrupts thyroid conversion, sex‑hormone production, and insulin sensitivity, leading to persistent inflammation, brain fog, anxiety, and poor sleep. The core problem is a “biological doom loop” where damaged mitochondria further blunt cortisol signaling. Dr. Frazee then offers ten evidence‑based, biologically‑focused strategies to break the loop: (1) get morning sunlight or light‑therapy, (2) consume adequate protein early, (3) set a caffeine curfew, (4) practice cold exposure, (5) exercise to stimulate mitochondrial biogenesis, (6) stop doom‑scrolling, (7) establish emotional boundaries, (8) train the brain to shut off (meditation/short breaks), (9) use targeted adaptogens (rhodiola or phosphatidylserine) to modulate cortisol response, and (10) explore experimental mitochondrial peptides (SS31, MOTS‑c, Humanin, SLUPP‑332). She emphasizes that repairing healthy mitochondria is essential to restore cortisol sensitivity and improve energy, mood, metabolism, and sleep. The video ends with a call to like, subscribe, and watch her related mitochondrial video.
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Stop if this is you. You're anxious, inflamed, exhausted, and knocking back energy drinks like they're candy. So you ask your doctor to test your cortisol levels. The problem is, what exactly do you expect your doctor to do about it? You see, I am a doctor, so I should have the answer, right? Well, I never really did. Not until recently, at least. So let me tell you what I've learned. Your cortisol level might be high, but your cortisol is not the issue. If you can't function in the morning without caffeine, but your brain suddenly turns into a motivational speaker between 2 and 4 in the morning, you've probably been pumping out cortisol so much and so often that your body has stopped responding to it properly. Your cortisol is screaming, but your cells have muted the signal. This is cortisol resistance. Scientifically, it's called glucocorticoid receptor resistance, and I have a whole video breaking that down if you want to watch that next. But if you feel like hot garbage all the time and you can't sleep, you might be living in that cortisol-resistant state. And your mitochondria, your cells, little powerhouses, have basically been forced into doing cortisol's job, and they're over it, and they're burnt out too. Your body's just putting up strike signals all over the place. Okay, let me break this down really simply. You see, cortisol is supposed to be your inflammatory brake pedal. So when your cells get tired and stop responding to cortisol, you basically lose the brakes on your body's inflammatory response. Cortisol is there and it's supposed to be keeping those brakes on, but your body can't hear it anymore, or it just doesn't want to. So inflammation just keeps climbing and climbing and you feel worse and worse and worse. Now, as if that's not enough, cortisol doesn't actually break your body alone. It drags 3 major other systems down with it. It pushes the brakes on thyroid conversion. It dumbs down your sex hormone production, not because cortisol is stealing anything from you. Your body just picks survival over fertility. And cortisol resistance begets insulin resistance. And so when you're not responding to cortisol the way that you should, you actually don't respond to insulin the way that you should either. So then what happens when you eat is your blood sugar goes up, but you don't have the insulin response to put the sugar into the cells for use. So you end up still feeling hungry, tired, Sluggish and irritable. Okay, so what can we do to fix this hot mess that you started? Well, here are some things that research actually shows, and this is the stuff that blows my mind, and it changed how I think about stress. So hopefully it helps you as well. You see, research shows that glucocorticoids, which cortisol is one of them, binds to receptors on your mitochondria and have the ability to change the mitochondrial DNA expression, which basically means that your stress hormone is directly You see, if you're a little bit stressed every once in a while, your mitochondria boost energy output. But with chronic stress all the time, your mitochondria are trying to put out more energy, but they start to burn out, and then they leak out inflammatory substances, reactive oxygen species, and your cortisol receptors start to get damaged. And that's when you start to feel stressed out. just get even more dysfunctional and downregulated. You see, it's a vicious cycle. Chronic cortisol elevation starts to burn out your mitochondria, and then your receptors get downregulated. And so you've got elevated cortisol all the time and damaged mitochondria. And the real problem is here is that it takes healthy mitochondria in order to reverse cortisol resistance. And damaged mitochondria just make cortisol resistance worse. See, it's a full biological doom loop. And your brain, The hippocampus in your brain actually gets slammed the hardest, which leads to brain fog, memory issues, anxiety, irritability, insomnia, your thinking not being able to turn off when you want it to. It's just full cellular mutiny. And here's where we cue the reset. Okay, so normal advice just doesn't seem to be working for this. You know, I'm all for journaling and bubble baths, but you just can't bubble bath your way out of Cortisol receptor resistance. I think that's maybe where I come in as a doctor. You know, I'm not a therapist. I'm not somebody who can work with you for an hour at a time on your mental health, but there are some biological things that we can do. So I'm going to give you a list of 10 things that I think are the fastest ways to biologically crush your cortisol resistance. All right. Number 1, get sunlight. I don't care if you don't have sunlight, like where I grew up, it was raining 9 months out of the year. If it's cold and stormy and dark outside in the morning, get a sun lamp. They actually work to stimulate your body to feel the sunlight and improve your mood and wake you up in the morning. Number 2, get plenty of protein early if you can, but if you're somebody who likes to intermittent fast, then I understand completely. But if you eat enough protein, you end up stabilizing your blood sugar and this can stabilize your cortisol, which can stabilize you. Number 3, give caffeine a curfew. Listen, I drink like a pot of coffee in the morning and an energy drink most days, so I understand. We're the same. But if you drink caffeine after 2:00 PM, you are robbing yourself of the chance to shut your brain off when you need to. If you're somebody who has an issue shutting your brain off at night or falling asleep or staying asleep and nothing else is working, at least try to remove caffeine from your day by 2:00 PM. Just Full stop. Number 4, cold exposure. This is something that I talk about a lot because I'm a huge fan of cold plunges. But when you expose your body to extreme cold for, you know, a period of 3 minutes, and you can develop this ability to shut your mind off and breathe through it and let your body know that it's okay, when you get out of the cold, your brain starts dumping dopamine and norepinephrine out like it's no tomorrow to try and kind of rebalance what you just went through. It is an amazing And it makes you feel motivated and ready to go. And this is a very good strategy to get you out of that brain foggy cortisol resistant pattern, but it also trains your brain and your body to be able to withstand stressful environments better as well, which is a huge biohacking trick if you ask me. Number 5, I can't go without talking about exercise, but hear me out. And I'm sure you've heard this before. I'll just reiterate it for you. Exercise has the ability to close the cortisol loop. So when you think about stress, And cortisol release. Back when we were hunters and gatherers, when we got stressed out, it was generally because of some sort of threat to your life. And so your body pumps out cortisol and then you run for your life in order to get away from the threat. But these days, if we're stressed out, generally we're sitting at a desk or we're having an argument with someone or we're driving in the car. And when we get stressed, our cortisol goes up, our blood sugar goes up. We're not actually running from anything or moving our bodies the way that we were meant And I get it. I understand that you can't always be moving all the time or exercising all the time, but when you do go and exercise, especially the days that you have a lot of stress, you're able to close that loop where you were meant to be running from a tiger in the jungle that day, but you couldn't at the moment. So at least you did it later and you're able to close the stress loop the way that you were meant to. And exercise also activates the pathways that allow you to make fresh new mitochondria, which allow you to get out of that cortisol-resistant pattern. It's so good for you. All right, number 6, stop doom scrolling. I'm serious. Every time you get on social media, if you're flipping through what other people are doing, you actually create these micro cortisol spikes because there's something about seeing everybody's perfect life and their achievements all the time that makes you feel less than. If that's not you and all you watch are funny reels, okay, this is not for you. Let's move on. But if you do find yourself comparing to other people on social media when you get on, turn it off for a couple of weeks and see how you feel, especially if social media is what you're doing in order to try and wind down, but it's not actually winding you down. Number 7, I thought about pulling this out, but I'm just going to say it. You are not responsible for other people's emotions. Put up some emotional boundaries. If you feel like you're responsible for everyone else around you, you're not. And even if you are, you can put up some boundaries around the way that you react to everybody else. You are responsible for you and not the reactions of everyone else around you. Number 8, train your brain to turn off. Now I know you don't want to hear me tell you to meditate, but I'm gonna do it anyway. Just training your mind to turn off for, you know, 30 seconds and then maybe 45 seconds the next time and then 60 seconds the next time. If you find that your mind is racing all the time and you can't turn it off, Then force it to. You have to have these periods where your brain stops thinking about everything going on or everything that you have to get done in order to get good sleep. And if you want a trick to this, try stretching before bed and turning your mind off while you do that. It kind of keeps your mind mildly preoccupied with the thing that you're doing in order to stop thinking. Just try it and let me know if it was helpful. All right, number 9, pick 1 or 2 Supplements, not a hardware store of adaptogens. If your mornings are sucky and you feel like you can't get out of bed, try taking rhodiola, 200 milligrams in the morning. Rhodiola has actually been shown in human studies that are targeted towards fatigue and burnout to normalize or reduce the exaggerated peak of the cortisol awakening response, meaning that it helps the body manage the stress of waking up. Or if you deal with situational stress, try phosphatidylserine. Phosphatidylserine is one of the most well-studied supplements specifically for managing the effect of cortisol. It has the ability to reduce the rise in circulating cortisol that occurs in your body in response to an acute stressor. You know, say like you're having to have a big meeting or a big test and you stress out a lot before those things. Studies suggest that taking phosphatidylserine before you do these things can actually help that cortisol response kind of come back to baseline after the stressor has moved on. In general, taking 200 milligrams before bed has been shown to blunt that overthinking problem that people have that leads to issues with falling asleep. And then doses of 300 milligrams taken around an acute stressor helps blunt that response. All right, number 10. This is biohacking stuff. This is all theoretical and in no way medical advice here because we all know the gray zone that peptides live in. But I love them so much because the mechanisms just make so much sense when you think about them. You see, there's SS31. This is a mitochondrial peptide that goes in and stabilizes the inner membrane of your mitochondria so that they don't burn out as easily and you can keep them working the way that they should be. There's MOTS-c, which basically boosts Boosts your metabolic resilience and activates the same pathways that fasting and exercise do, leading to fresh new baby mitochondria. See, theoretically, if a person couldn't exercise every day but they could take a peptide like MOTS-c and then go for a walk, it might have similar benefits as getting a heavy gym session in. That's all theory, of course. Humanin. Humanin is a small mitochondrial peptide that your mitochondria actually send out to Fight back against chronic stress and cortisol damage. This peptide is a massive protective factor. It can stop cellular death. It can shield your brain cells and cleans up oxidative mess before it gets bad. It boosts mitochondrial quality and helps with insulin resistance. We think it's a big player in cellular longevity. There's also a newer compound that's out called SLUPP-332. Now this one doesn't have enough research behind it to show that it's safe for human consumption yet. But if you circle back to the good things that MOTS-c does in your body, SLUPP332 could be a little more potent because it actually goes in and hits a specific receptor in your cells called estrogen-related receptors that turn on mitochondrial biogenesis. Quite amazing and fascinating in my opinion. So I hope you understand why I get kind of excited about this stuff, because if stress is damaging your mitochondria and mitochondrial therapy could undo the damage, And kickstart you back to a point where you can actually get back up and fight a little bit, I honestly think it's worth looking into. And if you want more on mitochondria, I made a video on that too. When cortisol stops screaming at you and your mitochondria stop waving their white little flags, you basically could possibly get your energy back, your sleep, your metabolism, your mood, your focus. Sometimes your nervous system just deserves a little break, and I'm here to try and help you get that. If you like this video, Please hit like for me and subscribe to my channel, and I'll try my best to keep giving you tips like this. I'm Dr. Ashley Frazee. I run a direct primary care clinic in Mesa, Arizona, where I'm just trying my best to be a doctor that gets down to the bottom of things. You guys have a great day. Bye.
