In this educational monologue, board‑certified primary‑care physician Dr. Ashley Frazee discusses three investigational compounds that target mitochondria—SS31 (elamipretide), the endogenous peptide MOTS‑c, and the synthetic small‑molecule SLU‑PP‑332. She begins by framing chronic fatigue as a common clinical problem and explains why mitochondrial health is a promising therapeutic frontier. For each compound she outlines the molecular mechanism (SS31 stabilizes cardiolipin in the inner mitochondrial membrane; MOTS‑c activates AMPK leading to PGC‑1α‑driven biogenesis; SLU‑PP‑332 is an ERRα agonist that directly switches on genes for mitochondrial biogenesis and fatty‑acid oxidation), summarizes pre‑clinical and limited human data on ATP production, endurance, organ function, and metabolic benefits, and notes side‑effects and safety concerns, especially the potential for estrogen‑related receptor activation to promote cancer growth. She emphasizes that none of these agents are FDA‑approved for performance enhancement, provides a disclaimer, and encourages viewers to consult a physician before considering them. The video concludes with a brief promotion of her direct‑primary‑care practice and a call to subscribe for more content on emerging medical topics.
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I'm a board-certified primary care doctor, and lately I've been obsessed with mitochondria. Why? Because I run into people all the time who are so tired, and I'm getting tired of not having better answers for them. But what if I told you that there are compounds that are being studied right now that seem to repair and recharge mitochondria, making the body more efficient, resilient, and maybe even extending lifespans? Well, today I'm talking about 3 of the most talked about mitochondrial enhancers in the research world: SS31, MOTS- What they do, how they work, and what you should think about before you try them. This is the kind of stuff that makes me stop in my tracks and say, why are we not talking about these things more? Now, before we dive in, a crucial disclaimer: I am discussing active research. None of these compounds are FDA approved for performance enhancement or well-being. This video is for educational purposes only and is not medical advice. Always consult your doctor before considering any investigational compound. All right, I'm done with that. Let's start with the compound that's actually been tested in humans. What is NMN? It's not tested in humans, but for some very specific mitochondrial diseases. SS31, also called elamipretide. This peptide doesn't actually work on a cell receptor like most peptides do. It has a mission, and it goes inside your cells into the mitochondrial inner membrane and stabilizes it. The inner mitochondrial membrane is where the electron transport chain happens, where your energy is made. Now here's a boiled-down version of what SS31 does. Inside the mitochondrial membrane lives a special lipid called cardiolipin. When cardiolipin gets damaged by aging or oxidative damage or stress, the inner mitochondrial membrane gets unfolded and the electron transport chain just doesn't work anymore. So you don't make energy from that mitochondria. You also end up making more oxidative stress or free radicals. Now SS31 actually binds to cardiolipin and Stabilizes it. It basically props up the mitochondrial membrane so it stays intact. The result is more ATP, more cellular energy, and less oxidative damage. Now, in clinical trials, SS31 has improved endurance and restored heart and kidney function in aging mice models. So in short, SS31 isn't helping you to boost your energy. It's repairing the literal engines that make your energy. So when people throw around phrases like you need to repair your mitochondria, this is a way that it can be done. Now, what are the downsides to SS31? Not a ton, to be honest. It may actually be the safest compound on my list today. The most common side effect in trials was injection site pain, swelling, redness, et cetera. But in clinical trials, it failed to show outcomes that they were looking for, like improving endurance. Some researchers think that it may only improve endurance when you have actual damaged mitochondria. And for healthy individuals whose mitochondria Mitochondria is just fine, the effect might be minimal or negligible. A sealing effect, if you will. But it kind of seems like something worth trying if you're into trying things. You know, maybe we don't need more energy drinks. Maybe we need to be repairing the literal blueprint of how our cells make energy. All right, let's move on. We're going to talk about MOTS-c. This is a very popular peptide, and rightfully so. It is very cool. It's a naturally occurring mitochondrial peptide that you make, and it's released when your cells are under metabolic stress, like during exercise or fasting. Its job— it activates something called AMPK, and this is the same energy-sensing pathway that gets triggered during exercise. Now I want you to see this in a sequence here, so come with me for a second. What I'm showing you is that exercise increases metabolic stress. Your energy load goes down because you've used it, which activates something called AMPK. AMPK activation increases something called PGC-1 alpha. PGC-1 alpha activates something called estrogen-related receptors. The activation of estrogen-related receptors increases mitochondrial biogenesis, increased fatty acid oxidation, angiogenesis, and muscular endurance. MOTS-c allows for this AMPK activation, turning up PGC-1 alpha to allow this whole process to happen. So hopefully that made sense to you. In my studies, MOTS-c actually improves exercise endurance, increases fat And even protected mice against obesity and insulin resistance. But human data is very limited, and there are some side effects that are reported, such as palpitations or insomnia. But there's actually a concern that activating estrogen-related receptors can drive tumor growth because some cancer cells have estrogen-related receptors on them as well. But in actuality, there's an article out there that shows that ovarian cancer cells tend to thrive when there's lower MOTS-c in them, and increasing MOTS-c into the cancer cells Actually inhibited their growth, which is very exciting. Bottom line, MOTS-c is like your body's built-in backup metabolic plan. And the fact that we can now study it or even supplement with it is wild. Now let's talk about SLUPP332, because now you'll understand how potent it is after going through the progression of how exercise leads to activation of estrogen-related receptors, leading to mitochondrial biogenesis, fatty acid oxidation, and switching of muscle fibers from fast twitch to slow twitch, Which basically increases their endurance capacity. Now, MOTS-c came in before estrogen-related receptor activation, but SLUPP332 is literally an estrogen-related receptor alpha agonist. It fits right into that receptor site. Now, it's actually not a peptide, it's a synthetic small molecule, just so you know. But the cool thing is that it activates that alpha-type receptor, and the ERR alpha has the most bang for its buck. It's basically like the master switch that directly binds to and turns on the genes for mitochondrial biogenesis, fat burning, and endurance. So you see, SLU-PP-332 goes straight to the source and flips the switch on and does all of the good things that supposedly MOTS-c does. And you can see these things happening in the research that they've done on mice: increased muscular endurance, increased fat burning, more energy. And this is why people are calling SLU-PP-332 exercise in a bottle. You literally just have to take it to get all of those effects. Now hold up, Because it sounds amazing. So why isn't it readily available to the masses? Well, here's the catch, and I told you this before. Estrogen-related receptor alpha is also active in several types of cancer cells because they crave energy. So pushing that switch too long or too hard could potentially cause cancer cells to grow. And if you don't know that you have a cancer in your body, this could be scary. Well, there you have it. That's a really quick and dirty comparison of 3 mitochondrial compounds that I think could literally change lives. But it's hard for me to promote something that could cause cancer growth, so you understand. In essence, SS31 helps you repair your mitochondria. MOTS-c is a messenger to help you build new ones. SLUPP332 literally turns on that switch to do so. All 3 are being studied as potential breakthroughs for energy, endurance, aging, and even chronic disease. So this is the frontier of mitochondrial medicine, and I am here for it. If you like this video, hit like for me and subscribe to my channel, and I'll keep making videos on topics That people are really interested in, but sometimes are pretty confusing. I'm Dr. Ashley Frazee. I run a direct primary care clinic in Mesa, Arizona. It's where I don't bill insurance. My patients pay me directly. If you want to know more, there are links in my description. You have the best day. Bye.
