The Peptide Side Effects Nobody Warns You About

In this video, I'm breaking down 25 of the most popular peptides, from BPC-157 to redotrutide, and unpacking what's exactly happening inside your cells when things don't go according to plan. And I might be out of line here, but I just want you to be safe. And the best way I know how to do that without taking 1,000 individual consults this week is by sharing this information directly with you. And I'll be honest with you, I'm pretty pro-peptide. I think that's obvious when you look at my channel. But here's the thing. I have never had an informed consent peptide conversation and had to say anything as scary as the rapid-fire side effect readout at the end of the commercials you see for drugs that are approved by the FDA. So in this video, I'm going to break down the side effects across 25 of the most popular peptides that I can think of. The common ones, the notable ones, and the just-in-case red flags that you might need. And a quick disclaimer here, I am a doctor on YouTube, but I am not your doctor. And this isn't medical advice. And also, I am only one provider with 2 ears and I can't know everything. And so if you've had a side effect from a peptide that you think is worth people knowing about, go ahead and drop it in the comments. Before we jump into the master list that I have today, we have to explore a foundational question. What actually is a side effect? Well, in the simplest terms possible, a side effect is just any action a substance takes in your body that you didn't intend for it to do. And in biology, there's really no such thing as a side effect. effect. There are only effects. When you take a peptide or any medication, it distributes throughout your system and interacts with whatever cells or receptors it can, including the ones that you don't want it to. But the key still fits the lock. Think of side effects as like an overheard conversation between 2 adults, but there are kids in the backseat. They overhear the message and sometimes they misinterpret what it means and react. So sometimes they overreact. This is really easily demonstrated with the drug Benadryl. You take it for a rash, but an hour later you can barely keep your eyes open because there are histamine receptors in your brain that just overheard the exact same message you sent to your immune system. And that's all a side effect is, a completely normal biological response heard by a part of you that you didn't mean to talk to. I also need to be clear about something else. What about allergic reactions? Are those side effects? Well, no. If a side effect is like a kid overhearing a conversation, an allergic reaction is more like your home security alarm suddenly going off because your immune system thinks that an intruder broke in. So side effects are predictable extensions of receptor biology, and allergic reactions are false alarms from your immune system. That being said, anything we put into our bodies shares a baseline set of potential risks. Especially with injections, like most peptides are. So with any injectable, you can get local redness, swelling, or pain at the injection site. And with any oral peptide or even medication, you can get potential GI side effects like nausea, heartburn, diarrhea, constipation. And believe it or not, there are several peptides in existence like KPV, SS31, ARA290, Humanin, AOD9604, Penelyne, SNAP-8 and thymosin alpha-1, that all have these baseline risks that I just mentioned, injection site irritation, et cetera, but they actually don't have any other common undesired side effects. And this is partially explained by the fact that many peptides are fragments of proteins or compounds that we already make in our bodies, and that they're just chains of amino acids put together in different sequences. Meaning peptides are like little fragments of proteins, and proteins make up a lot of the stuff So let's move past the basics now and look at the side effects of some of the peptides that I think anyone involved with peptides or even thinking about peptides or studying them should know. Let's start with some very popular peptides like the ones in the Glow Stack, used a lot for healing and tissue repair. People tend to think BPC-157 is a magical little healing peptide, or they tend to think it doesn't work at all. But really, according to research, we think it changes the signaling environment around an injury. We think that it lights up tissues that need to heal or are actively trying to heal. We're going to see more and more research on BPC-157 come out because of its popularity and its tendency to help people. And while side effects of BPC-157 seem to be pretty rare, I mean, I've never actually seen someone have a side effect from it. Here's what some people note: head pressure, GI side effects, and strangely, anhedonia, meaning you just don't care about things the way you should. With the head pressure, well, this could be because BPC-157 upregulates nitric oxide synthesis to drive tissue blood flow, which dilates blood vessels, and perhaps that's why there's a feeling of head pressure. It's not very common. And the anhedonia, well, there's a fascinating study in rats showing BPC-157 affecting dopamine and serotonin pathways in the brain. The effects were really positive for the rats, but sometimes, in certain people, messing with dopamine pathways can inadvertently dull pleasure and reward. This also rings true for the GLP-1 drugs, and I'll go over more of their side effects today too. It's also worth mentioning that the big concern about BPC-157 is that because we believe it helps healing by increasing new blood vessel formation by a process called angiogenesis, There's a theoretical risk of bringing new blood flow to tumors in the body that we may or may not know about. Has it been proven in humans or animals? No, but that's a concern. And then there's BPC-157's best friend, TB-500. TB-500 is often paired with BPC-157 in a stack called the Wolverine Stack. The claim is ultimate healing from the pair. If BPC-157 lights up healing tissue, TB-500 likely directs cellular traffic to an injury by regulating actin dynamics inside cells, the dynamic internal scaffolding that helps cells get to where they need to go. Similar things to watch for between BPC-157 and TB-500 are facial flushing, the head pressure, or sudden fatigue right after dosing. And just like with BPC-157, there's scientific community concern that TB-500 could encourage tumor growth. Also not proven. And finishing out the popular purple glow stack— well, actually it's blue, but my eyes see purple— is GHK copper. GHK copper sounds incredible when you list its benefits, like influencing genes towards repair and downregulating inflammation, increasing collagen's ability to remodel and repair, and encouraging wound healing and hair follicle regeneration. But it becomes considerably less glamorous when it feels like you injected liquid fire into your skin. I call it the gift that keeps on giving. And what I'm saying is that for most people, injecting GHK copper feels real stingy for a while. And this is tolerable for a lot of people, but some people also get pretty brutal pain, like intense burning, redness, and hard knot-like little lumps under the skin that can linger for days. Another concern with GHK copper is that overusing copper without supplementing with zinc to balance it out can lead to copper toxicity, which could cause a metallic taste, severe headaches, and mood swings. Just FYI. But let's leave the world of tissue repair and move upstream to hormonal-driven repair using growth hormone and IGF-1. These are the hormones that are involved in repairing your body after things like intense exercise. They're very popular peptides in this arena. First up are Sermorelin, CJC-1295, and Tesamorelin. These are designed as copycats of a hormone that tells the pituitary to release growth hormone, traditionally used before bed because that's when this hormone, growth hormone-releasing hormone, is naturally highest. Now these all come with a caution of allergic reaction and anaphylaxis. I've seen it more times than I'm comfortable with, and so it needs to be a widespread warning that if you consider a peptide in this class and you try it, if you start to get itchy like in your palms or your feet or your face, Don't tempt fate and try the injection again. Just don't, because the next attempt may cause true anaphylaxis. Now, with the peptide CJC-1295, a very common side effect is pretty immediate head or facial warmth and flushing and head pressure right after injecting, probably because of the peptide's more rapid binding affinity to the target receptors. And with any of these peptides, but mostly with tesamorelin, Fluid retention from increasing growth hormone and its downstream effects can also cause things like ankle swelling or wrist swelling or carpal tunnel-like effects like numbness in the hand. And also, constant stimulation of growth hormone can creep up your fasting blood sugar and drive insulin resistance over time. Growth hormone and insulin are like counter hormones, so if one goes up, the other has to go down. And insulin helps keep blood sugar down, so if you're constantly blunting insulin with growth hormone, Your sugars can go up. Next up are a class of peptides similar to the ones that we just covered, but they help the body release growth hormone via hunger signaling. So when you're not eating and you're in a fasted state, the body has more focus to do its repair work. And these are the ghrelin mimetics: GHRP-2, GHRP-6, hexarelin, and MK-677, which actually isn't a peptide, but we can talk about it here anyway because it goes with the others. A big side effect for these is feeling incredibly hungry also heavy water retention, and sometimes a lot of brain fog. And these peptides can also trigger unwanted spikes in cortisol and prolactin, causing a feeling of anxiety and possibly encouraging you to produce milk. It's because of how they work. They hit receptors that also control cortisol and prolactin. Ipamorelin is also a peptide that mimics ghrelin, but it's unique in that it's very selective to hitting receptors only responsible for growth hormone release. It's fascinating. And this is why it's more popular and why it's often paired with the growth hormone-releasing hormone peptides like Sermorelin, CJC-1295, and Tesamorelin. I have a whole video on ipamorelin if you want to understand this. Just know it's like being able to put earmuffs on the kids in the back so that you can talk to your friend. Let's graduate now to IGF-1 LR3 and Follistatin 344. To put it bluntly, these are peptides that people use for muscle building. And they're not my favorite because they work by bypassing the body's built-in guardrails entirely. It sounds fun until you remember that sometimes our body has limiter capacitors on it for a reason, like the speed governor on your car. Like, it sounds fun to go 200 miles per hour, but I'm sure that wouldn't turn out well if you let me do that. IGF-1 LR3 is a peptide that acts like the hormone IGF-1, which is the downstream effect of growth hormone. It's kind of like taking growth hormone, not quite as potent, but it carries potential for low blood sugars. And if used long-term without being checked, high blood sugar due to insulin resistance, which can lead to diabetes if you're not careful. With follistatin 344, this is a peptide that takes the brakes off of something called myostatin, which is a muscle growth limiter that we all have. There are no commonly cited effects from this one, but there is a caution that using it would cause your muscle tissue to expand much faster than your tendons can structurally handle, basically setting you up for injury pretty easily. Now let's talk about the metabolic powerhouses, the GLP-1s and incretin mimetics. Semaglutide is the easiest one here because it's a peptide that hits one type of receptor in the body, the GLP-1 receptor, but it also has so many side effects. And because of semaglutide, we have learned a lot about the hormone GLP-1. The obvious side effects of semaglutide are nausea, gastric reflux, and constipation. But GLP-1 receptors have been found in the brain, the gut, the pancreas, the heart, the kidneys, and even immune cells. And hitting these receptors acts as like a metabolic governor. In the brain and the gut, GLP-1 slows down GI transit and also the desire for food and other things. And this explains So many things that we've noticed, such as decreased alcohol use and addiction using GLP-1 drugs, but also some people get low motivation or anhedonia because of the role that GLP-1 plays in the brain in dopamine signaling. But in the immune system, GLP-1 actually downregulates inflammation. And then when you add GIP receptor agonism to GLP-1, which is what tirzepatide is, You teach your fat cells to store energy properly. It's protective of bones. It clears out fat out of the liver, and it dials down the nauseating side effects of GLP-1 in the brain. There's really not much downside to adding the GIP piece to GLP-1. Some people can get a very small 2 to 4 beat per minute increase in their resting heart rate and side effects that come from rapid weight loss faster, like gallstones and pancreatitis. But that's really about it. And then we have retatrutide coming out, the triple G: GLP-1, GIP, and glucagon receptor agonism. Adding glucagon receptor targeting cranks up your baseline calorie burn, your metabolic rate. But this addition does come with some more side effects, mainly a risk for an increased heart rate at rest, 5 to 10 beats per minute, and allodynia, where your sensory nerves can become overly sensitive. Feels like you've got a sunburn even if you've been inside all day. Now, all 3 of the GLP-1 agonists can trigger a massive sodium and water dump via the kidneys. They all work to drop insulin levels, and as insulin drops, your kidneys can let go of sodium and water pretty quickly, which can cause fatigue, also an elevated heart rate, dizziness, headaches, and muscle cramps. So as long as your body can tolerate it. I always recommend replacing sodium when somebody is on a GLP-1 agonist. And this is also why I like to ask Element to sponsor videos when I talk about this, because Element is what I personally use. Element products like this packet and this sparkling drink that I like have a scientifically backed ratio of sodium, magnesium, and potassium without adding any sugar or junk. And if you're someone on a weight loss journey Or on a GLP-1 agonist, or you're just like me and you run in 110 degrees for fun, or because you're told to, supplementing with LMNT can save you from things like headaches, muscle cramps, and dehydration. Please always consult with your doctor before doing this, especially if you have a medical condition like hypertension. But if you're needing sodium replenishment, use the link in my description or visit drinkelement.com/frazee to get a free sample pack of their most popular flavors. Like this, with any order. Wrapping up with weight loss, cagrilantide is a regularly explored peptide, and Novo Nordisk is currently researching cagrilantide combined with semaglutide, and that will likely come out as a drug in the near future. Cagrilantide mimics a hormone called amylin, which is a fullness hormone. So really, the side effects noted from this one are just those you would expect with a fullness hormone on overdrive: feeling too full, Bloated, nauseated, and all the other GI effects that come with that. And then there's 5-Amino-1MQ. This is very popular, but also you can buy it on Amazon, which I think is really weird. I'm not encouraging you to do that, FYI. It inhibits the NNMT enzyme, and people like it because it's thought to increase our metabolic rate. And also, obesity causes fat cells to overexpress NNMT, making them the most responsive tissue when the enzyme is blocked. The problem is that the NNMT enzyme affects several body systems, and so side effects are easy to come by, like body temperature increases, sleep issues, and serotonin and other neurotransmitter imbalances. Let's move on to cellular longevity, starting with MOTS-c. MOTS-c is known as exercise in a vial because of its role in the pathway that gets activated after you exercise or when you do something hard to promote cellular adaptation and mitochondrial biogenesis, or the making of new mitochondria, which is what produces our energy. The biggest side effect of this peptide is intense painful welts or hard knots under the skin that can itch for weeks. Why does this happen? Well, MOTS-c is a mitochondrial-derived peptide, meaning the version in our bodies comes from the DNA of mitochondria. But mitochondrial proteins share structural patterns with bacterial signals. So it's thought that when you inject MOTS-c into subcutaneous tissue, the local immune system thinks that there's a bacterial intruder and it starts dumping histamine as if you got a bee sting. And people have claimed to have had anaphylaxis to this peptide. And this is just something you have to take with a grain of salt because anaphylaxis is a full-body reaction. So if the theory about bee sting-like histamine dumps is true, the theory about anaphylaxis could be true, but it's hard to verify this. Go ahead and put it in the comments if it's happened to you. Moving on to the brain. Semax and Selinc are arguably the most commonly used nootropic peptides. They both boost BDNF, brain-derived neurotrophic factor, which helps with neuroplasticity and neuronal adaptation. They have also been researched in calming cortisol responses in the brain. And I'm just sharing what I know, but people tend to use Semax as a focus aid. But the side effects of it can be overstimulation, like feeling anxious or jittery, insomnia, and also temporary hair shedding, probably due to vasoconstriction in the hair follicles. Most people tend to use Selank as a calming peptide. Weirdly, a side effect from this one can be transient alteration of taste. People will report a mild bitter or metallic taste immediately following use, and some people also report emotional blunting with that one. Let's touch on other neurologic-influencing peptides, D-SIP and epithelin. These are not the same, but they do both work partly by resetting circadian rhythms and therefore are also both famous for disrupting sleep patterns and inducing wild or vivid dreams. And some people report headaches with Epithelin in particular. Last, we've got 2 related peptides, PT-141 and Melanotan-2. Starting with PT-141. PT-141 has a fascinating backstory. It's actually an accidental spinoff of Melanotan-2. While testing Melanotan-2 as a sunless tanning agent, researchers realized it was triggering intense sexual arousal. So they isolated that specific compound and created PT-141. But the downside of being intensely aroused using it are nausea and headache. Pretty common. So you just have to ask yourself the question of whether it's worth it. Speaking of melanotan-2, again, researched as the sunless tanning peptide, very popular. Melanotan-2 uses receptors to increase skin pigmentation. Obviously, increased libido is a side effect of this one. But in addition to getting tanner, the byproduct of this is expressing more melanin in freckles and moles. Including ones that are predisposed to becoming cancerous. And there are some case studies of actual melanoma being found shortly after using this peptide. This is actually the one peptide that I'm least in love with for that particular reason. I'm going to stop here because my intention was not to overwhelm people, and I know that that was a lot of information. At the end of the day, my desire was to keep you informed, but also to help you understand and hopefully respect how the body works. When you realize that a side effect is just an overheard conversation that wasn't meant to land there, things make sense. And if this enlightened you and you're a doctor or someone who wants to start prescribing peptides or coaching someone on peptides, especially given the likelihood that many will be prescribable very soon at the time of filming this video, well, that's exactly why I built my Peptide Mastery Course. It takes everything I could find and every bit of knowledge I have on the most popular peptides and lays it out in a Simple, easy-to-digest format, showing you the research and how peptides can potentially apply to human biology. And I'll link that in the description for you. I'm Dr. Ashley Frazee. I just wanted to keep people informed and safe with this one. If you like this video, please hit like for me and subscribe to my channel, and I hope you have the best day.