The Freshman Mole

Are Peptides Safe? What We Know So Far

Summary: Many peptides are well-established medicines, but experimental peptides currently popular with bodybuilders and “biohackers” are a very different story. For compounds like BPC-157, TB-500, KPV, Epitalon, MOTS-c and Semax, human clinical evidence is limited or absent. Animal experiments (and personal reports – which we cannot use to define national medical practice!) suggest interesting effects. But in humans, they might, or might not, be ineffective or dangerous.
More details in the video and article below.

The article below is based on the content of this video.

Why are peptides now more accessible?

In the last two years, we’ve moved from a “war on peptides” to a situation where public interest is blowing up, gym bros are Wolverine-stack-maxxing to cure their shoulder niggles, and longevity enthusiasts are debating whether Chinese black-market substances might allow them to live 5 days longer. Perversely, some just-trust-me-bro folks even see lack of any proper human efficacy or safety data as a positive.

And now, the Health Secretary RFK Jr has cleared the way for easier compounding of six unapproved peptides. He must have been running quite a successful stack himself as the decision overruled the warnings of FDA scientists.

But what even is compounding and why should we care? And does this decision democratize access to miracles, or is it just another bump in the clown road the world is on? And who are the six chosen peptides – what are their molecular architectures, mechanisms, potential benefits and risks? In this article, we’ll discuss the science, disprove the Wolverine stack with its own line of logic, and check out several crazy stories. We’ll focus on the facts but also read user reports, though I wasn’t too proud of humanity when I read through some of them.

So, let’s get started with drug compounding. You might have heard this term over the last few years in the context of the obesity peptides Ozempic and Wegovy. This was quite a controversial saga itself, as an official drug shortage fueled a booming market for compounded GLP1 drugs.

What is pharmaceutical compounding?

You might have heard this term over the last few years in the context of the obesity peptides Ozempic and Wegovy. This was quite a controversial saga itself, as an official drug shortage fueled a booming market for compounded GLP1 drugs.

Traditionally, drug compounding occurs when patients cannot be treated with an FDA-approved medication. It typically involves an already approved active substance that is tailored to an individual patient’s needs. This can include the preparation of formulations that avoid allergens for specific patients, and is also important for children that need lower doses and easier-to-swallow dosage forms. This is essential for things like pediatric cancers, so compounding can be pretty great.

Compounding happens all the time, and is extended to even more substances in case of drug shortages. For obesity drugs this has quieted down but it wasn’t as temporary as you would think based on the law, probably also because this has proven lucrative for compounders and telehealth companies. There’s no R&D risk involved – just take someone else’s product and undercut them on price. Also, why stop at approved GLP1 drugs, when you can start cooking retatrutide that is not even approved by the FDA yet?

What are the risks of compounded peptide injections?

I hope some alarm bells are ringing for you now. If selling unproven drugs becomes a market, then compounding stops being “pretty great”. We have the example of semaglutide salts here as a different version of a drug, but sometimes it’s also that compounders just don’t prepare or store these drugs as diligently, shipping sterile injectables that actually are not.

This can result in warning letters, enforcement action and the obligatory lawsuit shenanigans. But in the best case, hopefully no patient harm. Grey or black market enthusiasts might want to call me overly cautious, because there has been no catastrophe for obesity peptides, right? Sure, you might get scammed and receive samples with bacterial toxins – but apparently you also have good odds of getting hooked up with more semaglutide than you wanted for some extra gains.

Contaminations and thus risks of compounded drugs can be extremely serious. Actually, it’s behind what the DOJ called the largest public health crisis ever caused by a pharmaceutical product. In 2012, three lots of a steroid drug prepared by a compounding pharmacy were contaminated with a fungus. Across 23 states, as many as 14’000 patients were injected with the contaminated steroid, resulting in over 700 fungal infections and tragically, at least 64 deaths.

Get this – the owner and head pharmacist of the compounding center in question wasn’t only to blame for the authorization of contaminated material, but also for creating fake prescriptions which these morons tagged with celebrity names.

So, all of this tells us that compounding needs to be well regulated, products need to be prepared and distributed with pristine quality, and all the different players need to focus on patients instead of marketing and profits. Well, if that isn’t a lot to ask.

The Story of Makena

What’s that – want another ridiculous story? Compounding was also used as a tool of protest against high prices of a progesterone drug. Prior to official approval in 2011, compounders sold an injection to individual patients for 10-15$. The FDA ran a program that encouraged modern trials of older and repurposed medicines, incentivizing companies with market exclusivity on off-patent drugs. So, a small pharma company ran an accelerated development program and got the drug approved. Oh, and they also jacked up the price hundred-fold to $1.5K per injection. So, the program that the FDA initially encouraged turned out to be an ugly duckling, and they indicated they would not take enforcement action against drug compounders even though it was not legally permissible anymore. The cherry on top is that the approval for this drug was withdrawn a decade later because it turned out that it didn’t even work. What a mess.

In some sense, today’s situation is equally crazy, because we’re now talking about facilitating the compounding of peptides for which there’s no drug shortage, no FDA approval, and in some cases not even published studies in humans.

Why did the FDA flag BCP-157 and other peptides?

To understand the events in 2026, we need to understand what happened three years earlier, and learn a little FDA bureaucracy. Simply put, the agency maintains a list of substances that pharmacies are allowed to use for compounding, and it constantly reviews new candidates that are nominated. While they are reviewing them, the substances get placed into different interim categories. Landing in category 1 is the good spot because they have conditional regulatory leniency, whereas category 2 substances are ones with potential safety risks, and the FDA may go after compounders who distribute these.

Around 2020, many compounders started nominating peptides like crazy, requesting the FDA to review them for the official list. In the interim, they were obviously hoping to land in the category 1 – but in 2023, the FDA threw them into  Category 2. Notice that there were other substances being reviewed, including the peptide LL-37.

The FDA cited significant safety risks, and if we look at LL-37, they might actually be catastrophic. With this peptide, you’re potentially harming your reproductive system and increasing cancer risk. Unfortunately, LL37 has still ended up in some bodybuilding stacks, supposedly helping with gut health. I’d rather eat a yogurt and some fiber. By the way, this Reddit comment again shows us how common mistakes are when people freestyle drug administration.

Anyways – the FDA’s decision in 2023 was pretty logical – but politics and capitalism would like to have a word with us. The decision ruffled the feathers of compounders and some other people, gradually building up pressure on the new Health Secretary who, as we already saw, had been an advocate of peptides anyways.

Why were peptides reviewed in 2026?

This brings us back to July 2026, with the classification of these peptides unsurprisingly back at the table. This is not the HHS announcement, yet, but this time, we got the opinion of the FDA’s Pharmacy Compounding Advisory Committee, hilariously abbreviated as PCAC. We’ve previously discussed similar Advisory Committees when we talked about psychedelics – they are supposed to be independent advisory panels for the FDA, giving non-binding recommendations based on scientific or medical expertise, or patient insights.

Prior to the PCAC, FDA scientists themselves did their homework and published some nice background documents, covering the six peptides in question and a seventh that was one up for debate. We’ll see the details later – but long story short – they recommended against all of them given the evidence is nowhere near sufficient to establish any efficacy or safety.

But by now, we know that the review wasn’t the no-brainer we would expect based on the science. Again – sprinkle in politics and capitalism – and you get a PCAC composed of people with conflicts of interest. You can read about the allegations yourself if you’re interested, but apparently seven of the eleven regular voting members had financial ties to peptide-related businesses or clinics. Another one was the son of a congresswoman who urged HHS to convene the panel. Yikes.

Now, get this. Across all peptides reviewed, all supporting votes came from these eight members. The result was to greenlight the six peptides, basically advocating for the FDA to reverse its actions from 2023. The seventh one, a potential insomnia peptide, actually didn’t make the list due to one single vote. This is particularly ironic because if you look at the number of human studies across all seven, this one actually had among the most data.

But how did an advisory recommendation to the FDA turn into an HHS policy? Well, the disagreement continued behind the scenes. HHS officials initially wanted the FDA to issue formal regulation deeming these peptides safe and good-to-go, probably leveraging the AdCom “expert” input as an argument. The FDA pushed back on this given unexplored safety and lack of data.

What did RFK Jr’s new policy actually change?

So, the HHS apparently decided that the next best thing to do was to simply tell the FDA not to follow its existing rules, and let compounders live in peace. This is called enforcement discretion, and the key argument was harm-reduction: people are already injecting these substances anyway, so better allow them to get them from licensed pharmacies with better quality control than black market mystery syringes. If getting shredded while potentially increasing my overall mortality risk isn’t peak freedom, then I don’t know what is. What do you think about the decision and this argument?

Some would say that this isn’t a carte blanche, because compounders need to collect information on side effects and verify the purity of their ingredients. This sounds like the bare minimum and FDA might not even have the authority to enforce some of the requirements. This is like a enforcement discretion-inception. Also, none of the drugs passed the FDA’s sniff-test in specific indications, but the HHS decision offers flexibility for all uses. So, not only can a doctor write a prescription for a drug with no human safety data, but they can also just cook it up for any use they want.

I recognize that not every compounder and grey-market seller will be a Machiavellian actor, but relaxing control over this field is really problematic, and will not discourage bad actors from causing harm: More and more people will inject themselves with vials labelled ‘not for human consumption’, and spend their money on things that make them less healthy, not more. Like we see here in the retatrutide example, some of the samples might even not contain any peptide at all.

Ironically, that might not be so bad if you’re looking for the peptide LL-37, because at least you’re not harming yourself. But what about the other six peptides? Do we know how they work and if they are harmful, miracle drugs, or maybe just nice placebos?

KPV peptide: The research on inflammation

Let’s start with the simplest molecule on our list – KPV. Every natural sciences student should actually be able to correctly guess its structure. We’re looking at a tripeptide, composed of the three amino acids lysine, proline and valine. This compound is basically the end of a much bigger, thirteen-amino acid peptide produced in the human body, called alpha-MSH. This hormone stimulates the production of melanin, so it is the primary actor behind the pigmentation of skin and hair.

So, why are people excited about the smaller related molecule, KPV? Well, there is research showing it has anti-inflammatory properties, so it might be useful to treat conditions like inflammatory bowel disease. Basically, assuming we mess up the intestine of mice by adding a sugar compound abbreviated as DSS, addition of KPV suppresses cytokines, which are small signaling proteins that guide the immune system and control inflammation. For example, this chart quantifies the mRNA levels of IL6 – so the expression or production of one specific cytokine. Significantly less cytokine in the fourth column implies less inflammatory response, and we also see that the colon of the mice have less cell damage. Importantly, we already have effective drugs against inflammatory bowel disease, so this is not a condition where we are looking for anything to work out of desperation.

You’ll know that cancer is also linked to inflammation, so there is some research suggesting that KPV could also slow down colorectal cancer. OK, this is interesting – but you could find a bazillion substances that potentially look promising in test tubes and mice models. The issue is that we don’t have any data in humans, so it seemed logical for the FDA to be against facilitating compounding of KPV.

Unfortunately, we have built 5 carts before the horse, and people have already started to throw this into their regeneration stacks, hoping that the anti-inflammatory effects translate into superior wound healing or simply general health. But we can’t even say if KPV can significantly penetrate the skin based on literature! If the permeability in human corpse skin is any guide, topical KPV creams or serums might be useless. So, we might be in a situation again where you’re actually not getting any active substance into your body, and you might be better off for it, because we have no data on short- or long-term safety. This nice table speaks for itself.

As always, there are of course positive and negative anecdotal reports, and we obviously cannot base healthcare practices on such data. We don’t know who used what, how and when, what other things they were doing like diet or what additional dubious compounds they were stacking on top of each other, and finally, there is no way to account for placebo effects, or things simply getting better over time.

In my opinion, all of these arguments should bury the case for KPV, at least right now – but what about the infamous BPC-157 and its Wolverine-stack-combo partner TB-500?

BC-157: Can it really heal injuries?

BPC-157 is definitely a larger fella. Count the amino acids and you will realize we’re now at fifteen. We can actually find the same three building blocks of KPV in here again, with even three prolines in a row. BPC-157 is synthetic, but derived from a larger compound originally isolated from human gastric juice. But just like KPV, it holds promise for skin regeneration and all kinds of tissues more broadly – tendons, muscles, bones, potentially even organs. The molecular mechanisms are again complex – this includes “KPV-like” anti-inflammation, but also things like encouraging the formation of new blood vessels.

This wide variety of mechanisms has led to some research that seems promising indeed. For example, BPC-157 seems to help skin burns in mice, help tendon recovery in rats, or heal bones of rabbits.

However, none of these effects have been adequately studied in humans, and it looks like the only real musculoskeletal outcome is one retrospective (so not great) study where seven out of 12 patients reported subjective symptom improvement for their knee pain.

Still, there is the hypothesis that there is nothing that BPC cannot heal, its use exploded in amateurs and even athletes, with the World Anti-Doping Agency banning the substance in 2022. And no, a ban does not mean that the agent is effective, and it definitely doesn’t mean that its safe. As we’ve mentioned for KPV, you can find positive reports but also negative ones – this could even include concerning things like dissociation.

Why should we be so cautious? Well, psychiatric adverse events can be catastrophic in the most extreme cases. I’m reminded of rimonabant, which was one of the first-generation weight loss drugs so it perfectly fits our obesity/peptide theme. If we sometimes cannot even detect such hidden, longer-term risks with properly studied drugs, then how can we without any studies at all?

Speaking of studies, there has been one placebo-controlled study that tested the efficacy of BPC-157. But – hold your horses. First, the study was in ulcerative colitis – so again, inflammatory bowel disease and not musculoskeletal conditions – and the route of administration was a rectal enema. Regenerating your butt hole is probably not what you need for exercise recovery – though this depends on your choice of exercise. Jokes aside, the FDA document nicely explains why this study is not helpful. Most notably, BPC failed to demonstrate statistically significant improvements over placebo and the full data have never been published. Interestingly, there was another phase 1 study a decade later, but we also have no results from that one.

We are back at what is a common theme – we have no good data at all, so we don’t know what the safety risks are. There was one report in the adverse event database of BPC-157 leading to shortness of breath and an ER visit, and another one of hyperpigmentation. We can only hope that cases like these will be monitored well going forward.

Another safety risk might come from the hypothesis that the creation of blood vessels could actually promote tumor growth. This makes sense mechanistically, though we don’t know. Oh and obviously, don’t be this person.

Some of you might wonder, how is BPC-157 made? Most chemists will have heard of solid phase peptide synthesis, or SPPS. This is based on the sequential coupling of amino acids, gradually building a growing peptide chain – kinda like adding pearls to a string. Even though BPC-157 has a decent size of 15 amino acids, you can get an overall yield of >75% based on the first building block. If you want to read how this works in practice, you have two exciting reads: A Chinese military patent, and an article in my favorite Slovenian Chemistry journal (xD). And if you’re done with those and still want another exciting read, you should check out my satire book. It’s not about peptides, but it makes up for that by putting you into a freshman year fever dream.

So, why did I mention peptide synthesis, other than because of my name? Well, bad batches of these peptides can actually include many impurities from the solid phase synthesis process, so there are also risks from chemical contamination, not just the biological risks we discussed earlier.

TB-500: What about the Wolverine stack?

With seven amino acids – and no proline by the way – TB-500 is roughly half the size of BPC-157. It’s our third peptide, and three time’s a charm: this is again a fragment from an endogenous protein produced by the human body. This larger parent peptide is called thymosin beta-4, and is upregulated in response to tissue injury. Compare the mechanisms and pathways, and you’ll realize where the stacking logic with BPC-157 is coming from. The hope is to get a boost in repair and anti-inflammation, but through a complementary or synergistic pathway to BPC.

This is again the part where I show you the slightly prettier skin of a poor mouse with skin burns, and complain about the fact that a compound with no (clinical) human documentation at all is being pushed for everything under the sun. My own hot take is that the most recent research suggests that the Wolverine stack is less than legendary. Here, researchers cut up and then reconstructed the Achilles tendons of rats, and they found that only TB500 increased tendon strength in a statistically significant manner. BPC157 alone or in combination with TB500 didn’t reach significance. So, if we use rat research with a sample size of 4 to guide human medicine, then everyone should actually be taking TB500.

So, nothing useful on TB-500 – but actually, it’s even worse than nothing. The only clinical trial record for this compound is a fictional record with a fake Chinese trial site. I assume this was done to simply allow sellers to claim that ‘human studies are underway’, of course in the name of marketing. Pretty insane.

Epitalon: Can this peptide slow aging?

Next up, we have the smaller Epitalon, perhaps my favorite one. This is a synthetic tetra-peptide, somehow derived of a natural extract of cow brains called epithalamin. This distinction matters because some of the transformational claims behind Epitalon are actually based on research with epithalamin, and apparently we still do not even know what epithalamin actually contains. We know that they are different, but that Epitalon is quote “probably” the active component. Even the pharmacy that nominated epitalon for compounding – so to get it on the official list – said epithalamin is just another name for epitalon. I mean, it would be good to know if I have to inject myself with cow brain serum, or if I have to take the synthetic drug that is quote “probably” the good stuff.

So, what are the transformational claims? Well, it’s apparently the fountain of youth. Although this sounds like the biggest scam of them all, the compound is super interesting. One issue however is that basically all the research was conducted in Russia decades ago, so not all papers are translated and it’s obviously also not the same as if the research was done in the US.

Why is it so interesting? In some experiments, giving epitalon to mice decreased how often they developed solid tumors or leukemia, and even extended their lifespan. This effect wasn’t consistent though. In one set of mice, the average lifespan increased overall, while in another one, only the maximum lifespan of the oldest ones increased. The theory here is that epitalon might elongate the body’s telomeres. These are the protective caps of chromosomes, which shorten each time a cell divides. Over time, they become too short and the cell stops dividing, or simply dies, thus contributing to aging of a tissue. Activation of telomerase enzymes could rebuild these telomeres and rejuvenate the body, so this is where clinics are getting the ‘fountain of youth’ story from.

W e have to give credit where credit is due: beyond the animal studies, it has been given to hundreds of people and supposedly increased the lifespan of elderly people by one year. There are obviously big question marks on what this study actually was, and the sample size of 20 is ridiculous – you’ll notice it used epithalamin and not epitalon – but hey, at least this is more than what we have for the other peptides. Would be great if we could replicate this with today’s trial standards, and finally understand the what frick epithalamin even is.

I won’t cover everything, but one interesting to highlight is that extending telomeres is a double-edged sword – adding too much protection and you risk your cells turning rogue and becoming cancer down the line. So in humans, over long enough timeframe, the apparent reduction in spontaneous tumors might actually reverse. We have no data, so we have no safety information, yada yada you know the Spiel.

MOTS-c: Do we know if it works in metabolic health?

The fifth one is different, but also kinda the same. MOTS-c is a 16-amino-acid peptide that can regulate insulin sensitivity and metabolic homeostasis. So, it’s different in the sense that instead of regenerating your wounds, its promise is to improve your metabolic health and physical capacity. But it’s kinda the same because we again only have mice as our role models. Essentially, mouse on a high-fat diet = bad, but a high-fat diet + MOTS-c = not so bad.

Mice injected with MOTS-c on a daily basis also seem to run longer, so there is an endurance angle to the compound. This treadmill test reminds me a little bit of the non-peptide SLU-PP-332 that we’ve discussed in a previous video, so if this topic is interesting to you, you can check that one out. Unsurprisingly, the mechanism of MOTS-c is poorly understood, but it somehow activates AMPK signalling which puts the metabolism on overdrive, increasing the turnover of glucose and fatty acids.

As for the other peptides, we have no clinical data but have turned the broader population into guinea pigs – with some people say it gave them more energy, others say it zapped them, some say it only works for older people. It doesn’t help that most of these people are also on GLP1 peptides, many on the already unapproved retatrutide, so you cannot really tell who is doing what and what is helping them. Some folks – imagine this – claim it to be ineffective unless you stack-max it with another peptide, SS31 – of course, at your own risk. Again, no human efficacy data, no safety data – so the FDA was wise to be against this compound, and the HHS seems to be less wise, given they also included it in the list for enforcement discretion with the other 5 peptides

Semax: What is the data on this nootropic peptide?

Finally, in number six, we have Semax, a seven-amino-acid peptide. This one does have a surprise. Like epitalon it was primarily studied in Russia, but it’s actually even approved there as a nasal drop for various conditions, including stroke recovery and memory disorders. In the US, the marketing promises are again rather endless, with most people aiming to use Semax as a nootropic to enhance cognition and focus.

One of the proposed indications reviewed by the FDA was migraine, and the best data we have there were 12 subjects that were tested on an ambiguous rating scale with no blinding, control group, etc.. Another indication was recovery from acute brain injury, and there we have an abstract with an unknown number of humans undergoing unknown treatment regimens leading to unknown clinical outcomes. I just hope the approvals in Russia were not based on data like these… We could spend more time on its potential mechanism, but honestly I think the video is already dense enough.

Semax: What is the data on this nootropic peptide?

So, the bottom line is not that these peptides are necessarily useless, or that we should not find new longevity drugs. It’s just that interesting mechanisms, athletic mice and positive user reports are not enough for us to run large-scale experiments on the broader population. I really hope that we’ll see serious clinical trials on peptides in the coming years given the hype, but I also suspect that we’ll also hear about concerning cases – whether from harmful substances, contaminated products, or inadequate patient education. Freel free to hate me in the comments with a positive user anecdote, but whatever you do, please don’t accidently quintuple your dosage.

I hope you learned something new. Stay safe!

Peptides: references

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