#620: BPC-157 and Peptide Medications: What Do We Know? – Jordan Feigenbaum, MD

0:00Hello and welcome to Sigma Nutrition Radio. This is episode 620 of the podcast. My name is Danny Lennon and you are very welcome to the show. Today we're going to be taking a look at a topic that has generated a lot of interest, a lot of discussion, a lot of anecdote, and therefore a lot of questions. And hopefully trying to clarify what exactly we know and how people can make best decisions related to this. And of course, we're talking about nominally what people colloquially refer to as peptides in much of these conversations. Now, to be clear, of course, peptides are simply these short chains of amino acids that are found in a whole range of different things.

0:39But the online colloquial phrase when people are talking about the use of peptides now is usually referring to this group of peptide medications. And even within that, we can split them into some of the peptide medications that have been used for a long period of time with a lot of evidence for example insulin or glp1 receptor agonists that have those clear indications dosing etc a bunch of evidence what we're really focusing in on is a different category that relates to a number of these compounds that have been suggested for a variety of outcomes from injury recovery to tissue healing to even longevity or general health benefits that people have now been taking without those medications actually being at the level of full approval and so we're going to be talking on the implications of that what exactly it means and some of the things we can try and glean about what's going on with their use probably one of the most discussed is bpc157 and so we'll be mentioning that maybe specifically but there is a group of several of these that are in a similar boat where people are taking them for a variety of reasons that we'll talk about in the episode and report many positive anecdotes.

1:55And so to go through this particular topic I'm going to be talking to Dr. Jordan Feigenbaum who is the founder of Barbell Medicine who has been previously on the podcast a couple of times and given his expertise in walking this line between being a medical doctor as well as interests in health and performance and the work that they do through barbell medicine i think he's perfectly positioned to walk us through some of the things we know about peptides some of the things that people are reporting and then more importantly what goes into potential decision making both at a broad level for people who maybe are seen to be recommending these and then maybe at an individual level for people who do want to have some type of control and informed consent what they actually should be aware of before making any decisions in either way so hopefully this ends up being useful hopefully this clarifies a number of the outstanding questions you may have or adds a bit of nuance to some of the conversation that can sometimes see one-sided or leaving out some important caveats so if you are a sigma nutrition premium subscriber you will also get a set of detailed study notes to accompany this episode which will go back through everything we discuss in the episode clarify terminology use diagrams and graphs to explain certain concepts and then to add in any of the details we mentioned about any studies etc so that will be found in the description box where you're currently listening if you are listening on the free public feed of the podcast and are interested in getting more out of your podcast listening and using that as an educational tool then check out what we offer with our membership of sigma nutrition premium you get those detailed study notes to our episodes you get a key ideas roundup after each episode interview finishes and you also get a premium exclusive episode every month as well so look at that see if it's of interest see if it's something that can help you in your learning and of course it is the direct way to help the podcast we don't run ads we don't use discount codes for peptides etc and so your support is directly what keeps this podcast going so thank you for anyone who is a premium member and for those of you who are considering that so with all that said you can check out further information about our guests and anything we mention in the episode page which will be linked in the description here.

4:29And for now, let's dive into this conversation between myself and Dr. Jordan Feigenbaum.

4:47Welcome back to the podcast, Dr. Jordan Feigenbaum. Thanks so much for doing this.

4:51Jordan Feigenbaum, MD: Yeah, thanks for having me. Big fan of your content, your work, obviously. And we share this reciprocal respect. So I always feel honored when I get invited back to the Sigma podcast. The honor is very much mine. And I think regular listeners of this podcast will know that we've discussed your work and Barter Bell Medicine's work more broadly a number of occasions. Obviously, you've been on the podcast previously. And you were the first person that I thought would be the best place to talk about the topic at hand today. Not only given that you've had to look into this and you've done a really good job communicating some of the main questions people have had, but also based on your background and experiences across a number of domains.

5:28And so we're going to be talking about what people colloquially are referring to as peptides, again, is a legitimate name. But as we'll mention, when we think about people asking that question, should I be taking peptides? Are peptides good or bad? The term peptides alone is maybe so broad that isn't really from a, think of a research question, isn't very useful to us. And so could you give people who have maybe just came across this type of stuff, maybe have seen people talking nominally online about peptides, what people are most commonly referring to, but then more specifically what peptides as a term really encapsulates just so they can orientate what they're seeing when they hear this term peptides related to health, performance, longevity, etc.

6:15Jordan Feigenbaum, MD: No, that's a, yeah, that's a great question. And I think it actually just kind of shows where you're coming from knowledge-wise, because when you say the word peptides, you're like, okay, what does this actually refer to? Because I do think it's been used in a way where it's almost lost its meaning. In chemistry, peptides refer to a chemical structure that contains amino acids. It's usually a short chain of amino acids. When it gets longer, obviously can be a polypeptide, different sort of lines in the sand, so to speak, that you can draw. And so that means you can have peptides in food, you can have them in supplements, and you can also have them in medications.

6:48Jordan Feigenbaum, MD: People are familiar with GLP-1s. The P stands for peptide. And so online, when people are talking about, quote, peptides, they're not talking about food. They're not talking about supplements. They're talking about medications, or you could call them drugs. I don't describe a moral meaning to drugs versus medications, but I understand sometimes when I call them peptide drugs, they go, well, that means they're bad. I'm like, well, it just refers to the fact that they are something designed to either treat, diagnose, or otherwise alter the structure or function of the body, which is the definition of a medication or a drug.

7:21Jordan Feigenbaum, MD: And so I think that's what most people are talking about when they say peptides and when they're asking, should I take peptides, right? Does that square with you? Is that kind of your understanding here? Yeah, very much so. And I think specifically much of this, they tend to relegate to peptides that are tend to be promoted for things like, as we'll mention a bit later, maybe ligament, tendons, muscle, some other smaller ones that people talk about broadly as longevity, et cetera. But those types of things tend to be the kind of first line of around injury, performance, health, et cetera, as opposed to necessarily a treatment in some way, although we can maybe broaden that out into other things.

8:00So, I mean, they're the primary ones that you see people discussing or? Yeah.

8:04Jordan Feigenbaum, MD: I mean, I think for one of the examples of these peptide medications would be like BPC-157, stands for body protective compound 157. It's mainly billed to be something for injury recovery or post-operatively, for example, also some thoughts about that it might heal the gut. The interesting thing here, and I think maybe where some of the disconnect with the understanding that these are medications versus like, is it really a supplement, is that I think people understand medications and drugs when they're used in medicine to treat a disease, You have a condition, so you could take this as the intervention to hopefully help you feel better, recover, and go into remission, depending on the condition.

8:46Jordan Feigenbaum, MD: Many of these agents, we'll use a third term, aren't really for that. It's almost like living better through chemistry. And so then we don't really have a lot of that in medicine. Like, oh, if you take this, even if you're otherwise healthy, it will improve your quality of life. It will improve what you can do. We don't really have that. We generally refer to those as like PEDs in sport. But like if there were agents that you could take that were, you know, otherwise promoted your lifespan, healthspan or whatever, that's kind of an interesting frontier. And so I think when people are considering taking these, most of the time they're relatively healthy.

9:23Jordan Feigenbaum, MD: And so this is almost like, again, how do I improve my health beyond that health maxers, if you will. I don't say that in a derogatory manner, but like it's different. So I think when people are like, well, it's not a medication I'm taking to cure something or to treat something all the time. It's maybe, again, to live better. And then people can conflate that maybe with a supplement, which is generally what supplements are taken for. So I think that's where some of the confusion comes from, in addition to just like people just say peptides. They never say peptide medications or peptide drugs, even though that's generally what people are talking about.

9:57One of the important things about you being specific with this nomenclature around peptide medications is that once you do that, we have to start thinking about the typical evidential standards we would have for medications as opposed to supplements, right? And so this is where it starts to become interesting because when people hear how commonly they're discussed and the, let's say, the very confident way in which people discuss their potential effects, and then we think that maybe these are medications, there's probably a presumption of how much actual evidence we have around them that can maybe crash against reality.

10:32So maybe let's take BPC-157, because maybe that's one of the most discussed. Using that as an example, can you maybe talk us through the type of evidence that there is behind that relative to the type of evidence or standards you would typically look for a medication?

10:47Jordan Feigenbaum, MD: Yeah. Yeah. BPC-157 was discovered. I can't do air quotes over the air, but it was discovered in Croatia by a research group in the 1990s. And this is a pharmaceutical lab, effectively, right? So a pharmaceutical company developed it, and it kind of languished in animal studies, petri dish sort of studies for the better part of 15 years before the first randomized controlled clinical trial was ran on it. This was 2005, as I recall. And they gave these people enemas of BPC-157 to try to treat ulcerative colitis, which is a condition of the gut. Those results were never published in a journal. They were only communicated at a conference in abstract form.

11:34Jordan Feigenbaum, MD: And so it's really hard to check the methods and whatever else happened. The improvement was not statistically significant, nonetheless, in this abstract. At least two other clinical trials were started and either terminated early or results not published. So for the entire human evidence base period, there's about 30 total human subjects that have been actually published. There's been no randomized controlled trials with fully published data. And so when you think about it like that, it doesn't mean that the medication is bad or that it doesn't work. It's just that it's hard to feel confident about what its safety profile is.

12:09Jordan Feigenbaum, MD: And further, it's hard to be confident that it is efficacious for anything. It doesn't mean that it's not, but like when you say, oh, it works for tendons, it works for joint pain, it works for gut health, right? Again, with problems defining that, we just don't, we don't know. It doesn't mean, again, that people who take it, who have used it and have had a positive experience are making that up. It's just hard to feel confident without these clinical trials. And to your point, most medications that people would agree to take have a rather extensive evidence base. They've gone through phase one, two, three clinical trials, which, you know, is a fancy medical way of saying it.

12:44Jordan Feigenbaum, MD: They've been tested for safety, or at least the characterization of their safety profile, because some medications do have a pretty severe risk profile. They've been compared to at least placebo to see what they do and if they work better than placebo. We know dosing, we know administration stuff through study. And you really do need to do it this way with, again, controlled trials and really well-documented procedures, so that way you kind of feel confident in saying, yep, it's relatively safe, or here is the actual risk benefit profile that the informed consent thing. And so sometimes I've asked folks who are like, I don't care that there's no data.

13:21Jordan Feigenbaum, MD: And I believe them. I believe that. Because I'll ask them then, is the assumption that this is safe and effective? And if so, why? And I have not heard a good answer for that. What do you think about that? You know, people probably do assume, because others have used them, and have had a relatively positive effect, especially they read that online. Do you think that there's an assumption that these have gone through testing, maybe VPC-157 specifically? Well, on any individual case may be difficult to say. There's probably a few things I think might be going on. One, I think at a general level, people value anecdotes far more than they likely should.

13:54They find that very difficult to square away with where that sits relative to other forms of evidence, why we would look for randomized control trials, why it's important to have it compared to placebo. People don't know how to value those types of things or why they might matter. So I think people do increasingly these days, particularly where people turn to for source of information, value a lot of anecdote. And there's no shortage of anecdotes around these. Second is probably a point that I know you've discussed before relates to how many people might view science more broadly for its role and maybe some of the poor communication around that.

14:32And I think this, again, ties into the fact of one of the things I've seen, I'm sure you've seen this online as well of people saying, well, the reason why we don't have any studies is that this has been purposely buried by pharmaceutical companies because they can't make any money off it. And there's various different types of claims. I think there's that kind of distrust of science that for some people buys in. And then as always, people want something to be true. And so when we want something to be true, we tend to lean more heavily on the things that would support that and don't want to listen so much to this doctor over here saying, hey guys, we have zero randomized control trials on this.

15:09Jordan Feigenbaum, MD: Yeah. Look, I would love for all of the things that people are saying about these various peptide medications to be true, because that would put more tools in my toolbox and other clinicians' toolboxes. And we'd have some really powerful tools to use, particularly around injury. You think about it right now, you get injured, right? It's like a chronic overuse tendinopathy type thing, right? And so you have pain, you have some dysfunction, and you're, okay, so it's physical therapy, I got to back off, I have to like find my entry point and build back up. It's not sexy, right? But like, that's kind of the thing.

15:44Jordan Feigenbaum, MD: We just don't have great medications or interventions. Otherwise, even this whole field of what's called orthobiologics, PRP, stem cells, whatever, it's kind of like, it's not that great, the evidence, yet there may be some stuff coming down the pike. So if we had, for example, BPC-157 that showed demonstrable improvement in joint pain, in tendon recovery, in post-operative recovery for soft tissue, particularly of the musculoskeletal system. Oh boy, that'd be huge. I'd love it to be true. But when people are asking my opinion, like, hey, what's the evidence here and what do you think? I'm like, unfortunately, we don't have enough evidence yet.

16:17Jordan Feigenbaum, MD: And then it is interesting though to me that then the subsequent rationalization isn't like, we should get more. We should push for more. We should push industry, the peptide industry for more. They say, well, we can't do it because it can't be patented or can't make money off it. And so I'm fine accepting the risk, which is a personal decision, I understand, but kind of does lead into some ethical questions about, well, really, what should you have access to? Like every experimental agent under the sun or just stuff that has some, at least some safety data on it. Anyway, that's maybe another podcast that would get pretty political pretty quickly, I think.

16:49But that access question is probably something worth clarifying for some people who are maybe just coming across this, that because they're discussed so often online, maybe there's a presumption of these are things I can just go and get that are indicated for me in a local pharmacy as opposed to the reality of how these are actually sold so how are people getting hold of these with the ease of access that we

17:09Jordan Feigenbaum, MD: currently have so there are ones that we would consider like approved medications meaning that they've been through the whole clinical trial gamut all the glp1s for example insulin discovered in the 1920s made one of the original peptide drugs has been approved and used vasopressin oxytocin, noctreotide. There's dozens, if not more, of actual peptide medications that have gone through the process that are approved for use for specific indications, okay, specific diseases and conditions. The majority of these newer peptides, I say newer, again, also in air quotes, because again, some of these are like decades old, have not been through that process or have started that process and otherwise been abandoned either due to a safety signal or lack of effect or some other sort of disinterest from the pharmaceutical industry.

17:54Jordan Feigenbaum, MD: And so, yeah, I think just the, there may be some assumption that because these have been developed by a pharmacy, you know, by industry that they're otherwise safe, which is not true. And so when people go to access them, you really can't get your doctor to prescribe them. Although some have been doing that, whether or not that's legal depends on the, where you live and the regulations around that. Most people seem to be accessing them through a research chemical form. And so for people who are unfamiliar with that, you can consider the traditional way that you would obtain a medication through a pharmacy that your doctor writes a prescription.

18:27Jordan Feigenbaum, MD: Even if it's a generic, you go to the pharmacy, it's on the shelf, they can get it. For medications that are less commonly dispensed, occasionally you'll have to go to a compounding pharmacy, which is a specialized pharmacy that can make the medication. They have the raw materials there and they'll make it. This happens a lot in pediatrics, for example, where like amoxicillin, an antibiotic, it tastes terribly and kids wouldn't drink it. So you mix it with some simple syrup and it goes down nicely. I still have fond memories of the pink stuff from when I was a kid. And so generally speaking, that's the same quality that you would get from a regular pharmacy.

19:02Jordan Feigenbaum, MD: It's just with a specialized medication. And then there's third tier, which is far, there's a Grand Canyon sized gap between compounding pharmacies and regular pharmacies and research chemical grade medications. And they say on the label, not for human use. They are not held to the same standards for purity, for testing, quality control, everything else, dosing. It's just less regulated. But that's kind of the point. You can get them easier, ideally, to run experiments potentially. Apparently, a lot of these are being run on people in real time right now. Unfortunately, that is a really unregulated place.

19:37Jordan Feigenbaum, MD: We don't know the purity. We don't know the dosing. There's little follow-up or monitoring by a trained medical professional. but the attractive part is it's not illegal to obtain them these medications that way they're relatively inexpensive and oh by the way they're becoming more and more common everyone seems to have a discount code in bio or a link in bio where you can go get peptides one of the interesting things you've probably seen this too an influencer or otherwise recognized name in the space will be talking about peptides or whatever and then you go check their bio and there's like a link to some sort of research chemical fight.

20:10Jordan Feigenbaum, MD: Does that, you know, if I did that as a clinician, even though I'm not seeing patients right now, I'd be in a lot of trouble. Can't really do that. But you're an influencer. Ooh, that's fine. What do you think about that? Well, I mean, this is this gray zone where, and is something that I just can't stand, is you have people that have normally science-based platforms through podcasts, YouTube channels, et cetera. And they always give this disclaimer of, I'm not telling people to take this. This is not a personal recommendation. I'm not advocating for I'm just having open conversations with people.

20:39And yet they could have however many number of episodes talking with nominally pro-peptide people about these various hypotheses, make it sound great, have hours and hours of this stuff, also have the link in the episode description of how to get hold of these, but then conflippantly say, well, I'm not telling people to take them. As I, yeah, but most of your material is persuasive to most people listening. And it kind of seems like it's an approval point. and at no point does someone say i wouldn't recommend this based on the lack of randomized control data in humans the lack of safety we have around this just a lack of certainty that even works there's none of that and it's certainly not weighed up in proportion to the speculative parts

21:20Jordan Feigenbaum, MD: yeah it does seem to be generally pro which on the one hand you could argue okay that means a lot of people are having good experiences from them also could be just be survivorship bias the people who are most likely to be have a positive experience are more likely to tell people about that positive experience, particularly on a platform with maybe an incentive to do so. But Andy Galpin had a pretty interesting take on this, or I'll say a reasonable take. He was talking about BPC 157, and he's like, look, there's not really any human evidence here. But anecdotally, it seems like people have good experience and it seems safe.

21:52Jordan Feigenbaum, MD: And I don't think I can push back against any of that, mainly because we don't have data showing that it is harmful. There's no monitoring system in place to like pick that up anyway. So that's where I'm like, I'm not sure, but I can't, by the same token, I can't say, well, it's dangerous. And so I think you can polarize in two different ways. I think both are wrong. One is like just overhyping and saying, look, these work, they're safe. Link in bio. I'm not telling you to take them, but that's what I think. We're just having conversations. Or the other would say, these don't work at all. They're very dangerous.

22:22Jordan Feigenbaum, MD: Don't even think about it. And it's like, okay, now we're fear-mongering. And so I try to take a middle ground most of the time, even though the middle is not always right, it's just kind of where the evidence takes me. And in this case, it's mostly a lack of evidence. And I think people generally don't like that because it's not a concrete stance, right? My stance is more fluid as new evidence comes out. I will update my position, but yeah, it's generally unsatisfying if someone wanted a recommendation, but I can't really make a recommendation at this time. Yeah. I mean, that's just the only thing you can do in that sense of if people are going to make a decision for themselves, at least do that with an accurate sense of what is out there.

23:00And that is that we don't have any real evidence to determine if these things are doing what they're hypothesized to do. And even if we were to grant that, then maybe the other part, which we might have more issue around is maybe the safety profile or even beyond that, how people currently have to go about procuring these means that there is issues around contamination, the dose accuracy, are they getting what they actually think they're getting so even if that we did get later approval of this maybe there is still that risk that's involved and so people need to be aware of all of those things and then also aware of how the limits of anecdote as well that they're maybe useful and can give us some insight to that they seem safe as Andy Galpin said but also the limits of that particularly for some of these outcomes and you more than anyone knows that particularly with resolution of a tendon issue, for example, or something that seemed to be causing a bit of pain that wasn't something incredibly severe, the resolution of that and tying that with the use of anything on an individual perspective is very difficult to attribute how much of it led to that resolution in and of itself.

24:09And so all of these things together means that, yeah, once people are aware of those things, they can make a more informed choice, I guess.

24:16Jordan Feigenbaum, MD: Yeah, if I had to communicate it with somebody who was maybe considering these or at least trying to wrap their arms around like, what are the safety risks to the extent we know them? I think splitting that into a pie, like 50-50. It's the pie chart right down the middle, 50-50. Half of the risk is where you're getting these things from. The research chemical stuff, it doesn't mean all of them are extremely contaminated or impure or otherwise have things that shouldn't be in there. It doesn't mean that. But generally speaking, when they've been studied, very bad. Purity profiles, contamination, dosing, all sorts of stuff.

24:50Jordan Feigenbaum, MD: And this has been shown in SARMs. It's been shown in peptide drugs that are being sold. It's not great. Even the peptide industry's submissions to the FDA for review of some of these compounds, their purity profile submissions were deemed by the FDA to be insufficient. They were like, what are you guys doing? And that's the industry. Okay, so that's half the risk, right? You would think that if these were moved to compounding pharmacies rather than research chemical grade, you would avoid that half of the risk. And I can sign on to that. Okay, for sure. The other half of the risk is what do the drugs do, right?

25:22Jordan Feigenbaum, MD: So you could think about some aglutide. So Ozempic, Wagovi, these GLP-1s. Well, we know the risk benefit profile of that relatively well because it's been studied for a long time through, again, very well done controlled trials. And if you got it through a compounding pharmacy, then ideally you would consider, oh, it's just got to be the semaglutide in this particular dose, so on and so forth. Unfortunately, that hasn't always been the case in the United States. And so there's been some pushback against access to compounding pharmacies. So that's the way I think about risk. I think about sourcing it, which is kind of what we just talked about.

25:55Jordan Feigenbaum, MD: And the other half is like, well, what does the thing do? And in most of these cases, particularly with these newer peptide medications that are out, we just don't know because they haven't really been studied. And so that's where I have concerns. What we should do about those concerns is an open question. And I'm not in the business of making policies. So I don't want to speak to that. But I think people generally, they seem to kind of not be clocking that potential risk, which I understand it's challenging to wrap your arms around that. Sure. Maybe you can clarify one thing for people, because this is something I've seen some confusion that relates to some of the recent communication from the FDA over there in the States and some of the discussions around the compounding of BPC-157 and other peptides, and some people online interpreting that as some type of approval or validation of these peptides directly from the FDA.

26:47Can you maybe explain actually what those discussions were, what they meant, and what they didn't mean? Yeah.

26:53Jordan Feigenbaum, MD: So an FDA-approved medication in the United States basically means that the agent has gone through the appropriate clinical trials and the FDA said, yeah, we think that for these particular indications at these doses, this seems to have some sort of use case there. We have a relatively well-characterized safety profile to the extent it can be known, relatively good efficacy profile, again, to the extent it can be known. But by the way, we're going to monitor this after it's been released onto the market, post-market surveillance. That's actually like a phase four clinical trial, right? It's just always ongoing.

27:28Jordan Feigenbaum, MD: And so it doesn't mean that all FDA approved medications are 100 % safe without risk. It just means that we tend to know more about them. Of course, the FDA has its own problems with like industry influence and not being able to render their opinions in any sort of way that changes what's happening. So for example, the fenfen is a great example. Fenfliramine and fentermine were two separate weight loss medications, each of which separately had been FDA approved. And then they were combined in the 90s for fenfen for weight loss, but they'd never been studied when used together. And so then all these heart issues started coming out.

28:09Jordan Feigenbaum, MD: There were some safety signals prior to release, but the market demand was quite high. But the FDA couldn't do anything about that because they're relatively impotent. Okay. So anyway, the whole point is you can get stuff that's FDA approved that has a risk profile. So I'm not saying that everything's super safe there, but that is the kind of process for FDA approval. What's happened recently, a couple weeks ago, there were a number of these peptide drugs that were on what's called a category two list, which basically means, hey, we don't really have enough data here. We think there's a safety risk here.

28:36Jordan Feigenbaum, MD: We don't really know because, again, lack of evidence. Drugs end up on that if they were submitted by usually industry to the FDA for review. and the FDA was like, we don't know, shoulder shrug. And so they kind of sit there dormant. Compounding pharmacies can't really work with them if they're on that list, at least through legal channels. And so it's kind of no man's land. What happened was the people who originally submitted those medications to the FDA for review withdrew their submissions, withdrew their nominations. So they were removed from the category two list that happened earlier this year.

29:08Jordan Feigenbaum, MD: And then a panel was convened to vote on them whether to move them to category one, which means that compounding pharmacies can work with these drugs like BPC-157. For example, KPV, TB-500, MOTC, some acts, a few other ones. With seven total drugs on this particular panel's vote, there'll be another one in February of 2027, it seems like. The panel voted to move them off Category 2, six of seven, which doesn't mean that compounding pharmacies can work with them right now. They'll have to vote about this again next year, so we'll see. But some people are saying that's FDA approval. Oh, the FDA approved these medications.

29:44Jordan Feigenbaum, MD: Well, no, they just voted to say, yeah, we can keep them off the category two list for now. But they haven't been approved in the same way like GLP-1s are approved or like an antihypertensive medication is approved. It just means, yeah, we're going to vote about this again, which, look, I get it. What I just said is very confusing. There's nothing about these policies and sort of processes that are super straightforward, but that's the way I understand it right now. And yeah, I can understand why people are saying, oh, FDA approved. That's what it means. It's like, oh, not really. It does show how or the direction of travel that needs to take place in order to eventually get that approval to the point where even before thinking about the actual effects that we might get from clinical trials, that even if people are taking these, we know that we have a purity and contamination free product for as much as possible relative to what they might be getting with some of the research grade stuff.

30:36And so that kind of begs the question of, and it maybe varies from person to person, but at least for people who are trying to give a broad number of people advice on this, we need to be then careful about, again, that evidential standards of what we would be comfortable saying, this looks like something that is going to be safe and that has some type of positive benefit. We would need a certain amount of evidence that we're quite a significant amount from to that point.

31:04Jordan Feigenbaum, MD: Yeah, I think that's generally true. If you were to pin people down and say, look, what would make you comfortable taking a medication? I don't think there's one right answer for that because I think the stakes matter, right? Again, if it's kind of just improving your health, not because you're sick right now, but you just want to live better, right? That's probably a different level of stakes than like, look, I've got a terminal condition and there's really nothing for me right now that's helping or that can help. But there's an experimental drug like in the pipeline. you might be more willing to accept more risk in that case.

31:40Jordan Feigenbaum, MD: So I think there's just different stakes depending on what you're looking at here. And so me, when I think about it personally and via a kind of clinician's eye, I'm kind of like I have a relatively high threshold for recommending a medication for pure improvements in health for an otherwise healthy person for good safety data, meaning that something has to be relatively safe and have a decent sized effect for me to even consider it for that purpose. Whereas if it was treating a condition that we really just didn't have good stuff available for it, and their quality of life is severely being compromised, I'm like, well, maybe I'm willing to accept more risk in that case.

32:23Jordan Feigenbaum, MD: The problem here is that when it comes to risks and benefits for most of these medications, we just don't know. And so now you're back in no man's land. You're like, I want to do this informed consent thing, have this conversation, but I can't really do it because I don't know. And the things that would settle it all are some study. So yeah, it's just an absence of evidence, which is problematic. I think if people were to accept that, say, look, I know we don't know. I'm cool with that. Okay. Like that's a personal thing and no judgment for me. I understand that. I think we just have different preferences, which is also fine.

32:57And that's the important thing of making that distinction between, as you say, without doubt, different people are going to have different decision making processes. And there could be situations, not only in this case, but across any type of intervention or supplement, whatever, that we could deem for one person or one group of people. It's probably not worth doing or too risky. In other case, that risk might be worth it. We see this all the time in elite level sport, for example, right? Decision we might make there that we wouldn't do for other people. In this case, though, as you perfectly outline, the problem is we can't make that risk-to-reward analysis because we just don't have data to know what that risk is.

33:34And so without that, it's literally a case of how much you just want to kind of go trial and error on yourself and see what happens. Perfect decision if someone wants to take it, but being clear on all that decision-making process I think is important, which I think is useful for what you've highlighted.

33:50Jordan Feigenbaum, MD: Yeah, people are going to have different risk tolerance profiles, and I think that varies. by what they're experiencing and what their perception is of the perceived benefits. And that's where I really have the problem. It's like if the perceived benefits are overhyped and the perceived risks are like maybe inappropriately suppressed, then even that is like a weird way to go about informed consent, you know? And so I just think if people were better at including us at science communication, perhaps we would feel more comfortable about people making these decisions. But at the same time, it's their decision, not mine.

34:23Jordan Feigenbaum, MD: if the medications are not really able to be obtained through a safe channel, meaning production standard, right? Should people just be able to do whatever they want, take whatever they want, or maybe better characterized, if this vote were to go through and people could get them prescribed via a compound and made via compounding pharmacy, which is what's on the table, should people just be able to have access to whatever medications they want? Oh, that's a great question. If we were living with like perfect information where everyone was aware of that lack of certainty we have, the implications of that lack of certainty of whether it works or not, the safety around it, and people were able to interpret all that information appropriately and then still wanted to make a decision, then fine.

35:09but the worry is that there are people that have a skewed view of well because of the amount of anecdotes we know this stuff works and we know it's not doing them any harm and so it's a difficult one because if you say okay well people should have to take it and then we find through whatever sort of studies that oh there's this real true risk that we weren't aware of that would kind of gone under the radar but at a high enough level within the population once enough people are taking it there's these adverse effects i don't know the best way to navigate that but yeah

35:35Jordan Feigenbaum, MD: I mean, I think ultimately I'm of the opinion if the risk is basically just focused on the individual, meaning that no matter what happens, it doesn't spill over to the rest of society. Then I'm more about, yeah, personal risk management, do your thing. There's limits to that, so nobody nailed me down on that. But that's generally how I feel. but I think that this sort of open access to all medications under the sun, regardless of whether you need them or not, can be problematic when the risks, potential adverse events do spill over to society. For example, look, you got a runny nose, you want an antibiotic.

36:12Jordan Feigenbaum, MD: Everyone gets an antibiotic, all right, now we got a superbug, potentially, right? Or a medication does have a severe adverse profile. Who pays for that? Society ends up paying for that on some level. And so in the States, we have this sort of right to try policy wherein if you have a medication that's cleared phase one clinical trials and the company agrees to provide it to you, you can take this experimental medication in certain circumstances. And so I think I'm around some level of regulation with respect to access, but I don't think that I should be being the parental figure and wagging my finger at folks about it.

36:54Jordan Feigenbaum, MD: It's just, yeah, it's a tough decision to make. I think, especially when you view the risk again, through kind of two different parts of the same pie. One is the thing you're getting what you think it is. And is it pure? Right. And then, okay, what is the actual nature of the safety of the thing itself? And unfortunately it's just not yet known. Yeah. And I mean, that's the thing. Once you open it off to enough people, it does kind of still give that veneer of, this is kind of approved basically, right? That in the same way right now, Now, if we took various different anabolic steroids and just said like anyone who wants them, you can go and just ask in your pharmacy and we'll just give you whatever you want.

37:29That's very different to saying, well, everyone knows that they're commonly used. People have ways of getting onto them, but at least there's enough of a barrier where you're not like promoting that. Any 16-year-old kid can walk into a pharmacy and get them right. And so if the question was more, okay, how would I feel about an elite level athlete that could have a potentially career threatening injury that related to like a tendinopathy and like, do you want to just like throw the kitchen sink at everything given that there could be some risks? Then I'm not going to lose my mind if someone says, yeah, like I'm going to try everything, but that's a different thing as just opening out.

38:01I think it does sometimes give the veneer of a kind of pseudo approval for lack of a better term.

38:07Jordan Feigenbaum, MD: Yeah. Look, if you can get it in like a blister pack, right. And it looks like it came from a lab that corresponds to ways that you've either seen other medications or received other medications. who it's under this auspice of this is probably legit, right? And then we've also normalized injecting ourselves with the various medications, particularly like since the rise of GLP-1s. So yeah, like it's all been kind of normalized and I think the perception can be, we know a lot about these things or enough, plus all these people have had good experiences, it's probably safe. I kind of, Dr. Baraki has coined this phrase.

38:41Jordan Feigenbaum, MD: He hasn't said it in a while, and so maybe I'm outing him here a little bit. He's like, it's really hard to kill 20, 20, 20 somethings. And so we see this in bodybuilding and powerlifting, whatever, people using a lot of PEDs, for example, tend to be younger or whatever. And they're like, look, I did this and nothing bad happened. I'm like, well, relatively healthy right now. No medical comorbidities. You're usually not taking other medications. And also the monitoring can be suspect. No value judgment on any of that. It's just that tends to be the case. But where I worry is, look, if you have somebody in their 40s or 50s and maybe they notice they've lost a step and they've got some, they've had some pains over the years.

39:16Jordan Feigenbaum, MD: And so now they're like, and they hear about peptides, right? From their trainer or from their favorite fitness influencer. And they start taking them and they've got other medical conditions. And so there's some sort of, I don't know, interaction with the current medications they're taking or their specific conditions or otherwise vulnerabilities genetic genetically for other conditions they may develop in the future. And that sets off some sort of unwanted adverse event. It's like, well, it'd be nice to know what risks to monitor for through previous study that again, currently don't exist, which is, yeah, it's very challenging to communicate thing one and then thing two for the public to understand.

39:50Jordan Feigenbaum, MD: And I think ultimately the lack here of communication from trusted resources has been problematic. It's like very lopsided. There's a lot of pro-peptide people and then the anti, we'll call them anti-peptide, but I don't lump myself into the anti-peptide medication person face but they're just saying don't do it and even worse like sometimes there's very much a anti-peptide movement that is very much in a just like a let's make a joke of it right that anyone that's taking it's like a kind of idea right and again i have no love at all for this like hyper optimization kind of culture thing and i will make jokes about some of aspects of that but i think there could be this pushback of it of not explaining or even really looking into the the peptide issue itself and instead just claiming that everyone doing it is just like a a meathead idiot which is clearly not the case as opposed to addressing as you said that we have just have something where we don't have good evidence for if people were to have that clear understanding there is a lack of evidence but as you said what we were not saying is that we could find that these are completely safe and are very efficacious and that would be great and i hope that comes along that is very much possible but currently we just don't have that evidence what i think the problem is and where we see a difference here with the example we just gave with peds for example is that most people that take peds can very explicitly tell you that there are risks and they're very aware of them and they know all of them and they do their best generally i would say not everyone some people take them maybe just without doing due diligence but people that have been doing that a while do that in a way to try and mitigate as much as possible accept that there is downside and risk and then try and just maximize their health broadly beyond that if they can.

41:35In general, I see that's a kind of pattern. What sometimes is happening with the peptide stuff is there is a complete denial that there could be those risks. And as we've said, maybe that is the case. Maybe there is zero risk. But to say right now that there's zero risk is a step beyond what we can actually say. As you've said a few times, we can say we don't know. They seem kind of safe, but we don't know for sure. And I think there's maybe an overconfidence in that potential downside.

42:02Jordan Feigenbaum, MD: Yeah, yeah, that's well said. And I think people, you know, I posted about this. Generally, these posts seem to go viral. So I am incentivized to talk about these more, even though I don't know. I don't know if I'm going viral for the right reasons. People say, oh, well, I got blood work done and my blood work looks better. And I'm like, hey, that's great. I love that. But I don't know that blood work, broadly speaking, is sufficient to monitor for these particular side effects. And further, if you did experience a side effect, for example, right, and you happen to pop up on my post and say, oh, I experienced this.

42:34Jordan Feigenbaum, MD: I also would want to know, well, do controls, people getting placebos have that same side effect? There's some base rate, for example, of all these conditions. And so just as if somebody said I had this bad experience, I can't chalk that up to the medication necessarily. I can't chalk up a good experience to the medication without some proper study, which I mean, people are listening to this are like, dude, we get it. you want the studies. Well, why aren't there studies? And I'm like, that to me is a more complicated question. Why haven't there been studies? And to the extent that they have been studied, why were they stopped?

43:07Jordan Feigenbaum, MD: Because I'll pose this to you. Most all, all of these peptide medications were developed by pharmaceutical companies. And I've got little love for pharmaceutical companies. Generally speaking, they're incentivized to make money. Although you would hope that they're in the business of helping people. Why did they kind of give up on most of these? They've either done phase one or phase two clinical trials and you can read them and like either there's a safety signal there or maybe the indication that they were being evaluated for didn't really pan out as like BPC-157 with ulcerative colitis didn't really seem to make a big difference.

43:41Jordan Feigenbaum, MD: And so then you wonder, well, why did pharma abandon them? Because if they paid the money to develop them, millions of dollars, right? And they started to study them and then they stopped. You're saying that they're not interested in getting the ROI, their return on their investment from creating and subsequently trying to test these. I think pharma is generally more persistent than that. And also like some people or teams of people are really trying to maximize revenue. It seems unlikely that they would just give up because they said, you know what, this works too well. This works too well and it's too safe and we can't do it.

44:14Jordan Feigenbaum, MD: It's like they're going to find a way to patent it or to otherwise have market protection, which are available even outside of patents and for a condition like pain, injury, post-op recovery for like BPC 157, that is a huge market that, again, we don't really have a lot of good stuff for. So you, again, would think like if there was a way to make some money here that they would be interested in doing so. And I think that's where it just raises some red flags for me. It doesn't mean again that these aren't safe, that they aren't effective, but then why have they given up? That's a more interesting question.

44:45Maybe it comes back to what we said earlier that maybe we don't want to address that we want to hold out hope that all is good and it's a bit too uncomfortable again we would have to speculate on why that might be we have no way of actually knowing maybe it's a maybe it's a nothing but it is an interesting to think of why wouldn't there be even in the case that you said where there's no patent available even in those cases just doing that trial and being kind of the first to market has its own advantages to get your money back and more so just get that money and go but uh yeah it's interesting one to think about and again And maybe it's worth some people pondering on that for a while.

45:19But here's fingers crossed for more studies.

45:22Jordan Feigenbaum, MD: Yeah. Yeah. I think what people will say is that, well, because you can't patent it, it's not patentable. These aren't patentable because they're, quote, naturally occurring, for example. And they're peptides. So just short chain of amino acids. You can't patent them. And because pharma can't make money on them, that's why they abandon them. That's like the general explanation that you get. Well, many peptide medications that are formed in the body or naturally are found in nature have been patented. Various forms of insulin, GLP-1s, for example, all sorts of other, the dozens of other peptide drugs that we currently have approved.

45:59Jordan Feigenbaum, MD: DPC-157 has been patented before. There are ways to modify the agent to be patentable. Again, and there are also patent-free market protections. And so I don't know, I would just direct this ire about why there's no studies. to the pharmaceutical industry, and then on top of that, to the black market. Because the more these are made available via the black market, it is my opinion, the less likely they are to be properly studied. Because if you can get these, and the main source of these things is through channels that don't pay somebody, or at least one sort of centralized either company or group, who's going to study them?

46:38Jordan Feigenbaum, MD: There's a trial recruiting right now. Actually, this is kind of interesting. This company out of China has eight pre-registered trials right now for various peptide medications. In about half of them, they say, look, this is a fictional study, like literally on the clinical trial, the pre-registration. The other half reads like a normal clinical trial. And so it's unclear if this is like AI generated stuff or if it's like a translation issue or whatever. A few people try to reach out to like the PI and say, hey, like what's going on here? No response. And so, but like the one in BPC-157 is for people with, I believe it's hamstring strain.

47:12Jordan Feigenbaum, MD: They verify this on MRI and then people have pain symptoms and otherwise limited performance. And so they're recruiting people and they're going to give them BPC-157 or a placebo and then see how they do, right? Both subjective and objective markers of improvement. Now, if people could otherwise get this medication through channels that don't require any sort of approval or safety data or whatever, what is the incentive to do the study? If you really want the evidence, I think we should do that first before making them widely available. But maybe tell me what you think about this. Because the other argument I hear after saying something like that is, well, look, that's all well and good.

47:49Jordan Feigenbaum, MD: We want evidence. We're with you on that. But because we can't get it, at least let's make the stuff that people are buying safe. It's harm reduction. If they can get it through a compounding pharmacy rather than research chemicals, you said yourself, that's half of the risk pie. Isn't that better? And so my thought on that is generally speaking, harm reduction programs and protocols do not increase the market size, do not increase the amount of people using them. A needle exchange, for example, generally doesn't increase use of agents that require needle injection. Whereas if a large company were to start selling these peptides over the internet, telemedicine or whatever, now there's advertising, easier ways to get them, that does increase the amount of people being used.

48:32Jordan Feigenbaum, MD: And generally, it's not what happens with harm reduction. So do you buy that sort of line of reasoning that, look, we're not going to get the damn studies. So let's just make the stuff that people are getting safer as a form of harm reduction, despite the market increasing. Do you buy that? Am I out on left field? No, I think you've touched on it very right. If it's something that's aimed with the idea that it will increase market uptake of that and more people will start doing it. I think that's where we run into the same issue we said before. It's a pseudo form of approval, right? Because for the average person, they're not going to look at, oh, has there been trials done in it now?

49:05Or has it passed a certain level of approval? They're just going to see more advertising around it from legitimate sources, from big telehealth places and so on. And so it will just give that veneer of, oh, now it's gone mainstream. Now it's legitimate. Now I can go and get it from these places. So why not? It's kind of a green light. And I just don't think most people would look beyond that to think nothing much has changed apart from now that you don't have to go and source it from this research grade level. But in terms of our actual evidence base, it hasn't changed. So I think the risk is the same as we mentioned earlier, this kind of pseudo approval that explodes the market.

49:44And then, hey, it's hard to walk that back once we do detect something or whatever.

49:49Jordan Feigenbaum, MD: Yeah, that's the whole thing, right? I think the idea that you're going to make access safer, that is likely true. If in February, whenever they vote on this to put them to category one, where compounding pharmacies can work with these drugs in the United States, that is going to reduce the risk from research grade chemicals, which I am in favor of. I'm not in favor though, then of taking the people who are using this from, let's just use a round number of 10 million to 50 million. Because I'm like, well, I don't know that I'd want more people using it without existing safety data. And to drive this home, when this was voted on recently to move them off of the category two list so that they could be voted on for approval on the category one list later, of the seven agents, none of them have human randomized controlled trial data for the indications that they were evaluated for.

50:43Jordan Feigenbaum, MD: And that's just, these are just seven. There are other ones. And so when you think about it like that, you're like, well, shoot, how, what are they using for evidentiary standards to actually vote on this? And then you look who's on the panel and you've got about a half dozen of FDA's career scientists, right? These are people with a lot of expertise in pharmacology and clinical trials, clinical research, whatever. And then you have another seven or eight people who are in industry, the peptide industry. And you're like, I don't know. That's necessarily what I would want, Even though it does happen all the time at the FDA, again, I'm not telling you that the FDA is like infallible.

51:21Jordan Feigenbaum, MD: My general position is that the FDA is impotent in many ways, but an FDA-approved medication is generally better than an unapproved medication. And so anyway, I just think if your gripe here is like, well, there's not evidence, but we want to make it safer for people to obtain. I'm with you, but man, I have some real concerns about kind of pushing it access up higher despite lack of evidence here. With that, maybe we've pulled it all down to something practical, Jordan. Let us know what is the Barbell Medicine recommended peptide stack that people should take? Yeah, yeah. Some whey protein if you need it.

51:58Jordan Feigenbaum, MD: No. Yeah. I mean, there are, again, this is no hate on peptide medications as a class. We have very powerful and safe ones that are available. GLP-1s we've talked about for a long time now, particularly breaking down some of the stigma around use there, insulin and other agents. So my thought is this, if you are more likely to benefit from any medication compared to the risks that are knowable at the time, and you're on board with that, I'm on board with you. We're aligned. The problem here with these understudied drugs is that we just don't know. It's kind of a cloud on both sides for risks and benefits.

52:33Jordan Feigenbaum, MD: And so because we can't really make an informed decision, I can't tell you what to do. And I have concerns about people DIYing it. And that's really where my concern is. I'm not trying to instill additional fear that's unnecessary. I'm more just trying to be honest about where my kind of perspective lies. And some people don't like that because when I tell them this sort of thing, they go, oh, so you just think I'm stupid for using a peptide medication that's not approved yet. And I'm like, well no look I get it you tell me I can be bigger faster stronger sleep better sexier whatever it is I'm here for it you know I want it I just think that we should go into it with open eyes and unfortunately there's a cover over our eyes where we've got blinders on right now because there's just not data here but there could be and I'm optimistic that there will be at some point I'm in the same boat I look forward to that coming out and knowing one way or the other but fingers crossed that there's something positive there so with that Jordan but before I get to the very final question I always end the podcast on for people that want to keep up with you, the work that you're doing, any other projects that you've gotten on with Barbell Medicine, tell people where they should go on the internet, anything you want to let them know about.

53:41I can do that now.

53:42Jordan Feigenbaum, MD: Yeah. If you search Barbell Medicine in the Google machine, you will find all of our stuff. We're on Instagram, we're on YouTube. We've got a podcast with 470 something episodes now, which I think is embarrassing to say because it's like, what are we doing here? But in our website, a bunch of articles and resources there for folks. We did just release our first book. It's called Signal, What Testosterone Is Telling You About Your Health. It is kind of the intersection between influencers and what they say about testosterone and also the current clinical evidence, which is nuanced. For example, you may have heard that masculinity is declining.

54:17Jordan Feigenbaum, MD: Testosterone levels are dropping. If you're a 20-year-old today, you've got a testosterone level the same as your grandfather did or your grandfather does, something like that. it turns out that testosterone levels haven't really gone down over the last 30 or so years it's just been a testing artifact for example if people are interested in that we talk about all of that in the book you can get that on our website check us out on youtube leave us comments so we can push some of this good information to the top of the algorithm all of that will be linked up in the description for everyone listening please do go and check that out i think you'll very much enjoy that with that jordan we come to the final question i always end the podcast on And it's simply if you could advise people to do one thing each day that might have a positive impact on any area of their life, what might that one thing be?

54:59Jordan Feigenbaum, MD: That's a great question. I thought about this because, again, I remember being on the podcast before. And I feel like I don't know what I said last time. It's probably something like exercise, whatever. Look, we're Barbell Medicine. We want people to lift weights. We want people to eat a health-promoting dietary pattern. Yeah, you guys all know that. But one thing I found, and this is maybe a little more woo, maybe more woo than people would generally associate with the Barbell Medicine with myself. I think that interpersonal relationships are extremely important for health and quality of life.

55:24Jordan Feigenbaum, MD: I don't think that's very controversial. So one thing I like to do personally and something that I, if I'm giving advice to somebody who's asking, once per day, send a message or tell somebody something that you admire about them. Generally, just making this connection with people and kind of showing them not only that you care, but that you actually see them for who they are in a positive light. And I think that comes back to you in spades and ultimately just tightens your social connections. That's what that would be my recommendation, even if that's not an evidence based sort of practice. Dr.

55:57Jordan Feigenbaum, thank you so much for, first of all, taking the time to come and talk to me for going through all this in such meticulous detail and for the ongoing excellent work that you do. It's very much appreciated. So thanks for doing this.

56:07Jordan Feigenbaum, MD: Thanks for having me. Appreciate it.

56:21Before you go, I just wanted to remind you about Sigma Nutrition Premium. At the core of the subscription is our detailed study notes full of useful descriptions, background context, diagrams, charts, etc. to allow you to more deeply understand some of the concepts that were mentioned throughout that particular episode, as well as in linking them back to previous episodes. You also get the segments at the end of each episode where I recap certain key ideas. You get a number of premium-only episodes. Some of them might be Ask Me Anything sessions where we answer your questions that you submitted directly, or they could be a variety of other episodes that you may have seen previews to in the public feed.

57:02So for full details on this, then check out the link in the description box wherever you're currently listening right now, or just go to sigmanutrition.com and you can see all the details there. and of course your support is what keeps sigma nutrition going we don't run ads we don't sell supplements anything like that so your support is what allows me to continue to do this so thank you for that i hope you do come back for the next episode regardless and until then have a great week and take care