What's the deal with peptides?

23:25Exactly.

23:26Emily Oster:And just to give a sense of like the diversity of peptides, I've told you there's infinite. But because the shape is really what dictates the function of molecules in your body, here's some other examples. So GLP ones you said. Aspartame, the artificial sweetener. Like in Diet Coke. Yeah, I'm not sure which one is in Diet Coke. But yes, the one that people actually, a lot of wellness influencers are worried about. Aspartame is a peptide. It's two amino acids stuck together. They just happen to make a shape that stimulates the sugar receptor on your tongue. So it just like makes you think it's sweet, but it's not.

24:00Emily Oster:It's just a peptide. Bee venom, for example, the main protein in bee venom is called melatonin, and that's a peptide. So that can be something that really hurts when you inject it, for example, right? And so one of my concerns, and actually, I'd like to play you a clip, is people suggesting that peptides are really safe because of their sort of nature of being something like a protein. So take a listen to this. Peptides are sequences of amino acids. And why is that important? Because your body recognizes these. It can break them down. They're called metabolites and it can get rid of the waste.

24:38Emily Oster:When we put chemicals, synthetics and pharmaceuticals into our body, there's no natural way for our body to break them down and get rid of them. So Emily, here we have, you know, someone being like, hey, these are just amino acids. Like your body knows what to do with that. Therefore, safe. What do you think? Uh, that doesn't sound right. To me, I mean, I think the fact that something is naturally occurring in the world and is an amino acid definitely does not mean that it is safe. It clearly doesn't, right? Like snake venom has peptides in it, right? There's lots of things. But I think people, one of the reasons that peptides are exploding and actually one of the regulatory reasons you can get your hands on these things even is because of this idea that like, well, they're just made of amino acids after all.

25:25Right. All right. So let's talk about whether these actually matter for anything. And I actually want to start with a place where I think the evidence is the best, which is in the space of collagen. So I hear people talk about collagen peptides, both for your face and for your joint health. So this comes up actually a lot in endurance sports. People talk about, you know, like, I need my joints to not be so elderly and creaky. And so I should take these collagen peptides in a lot of endurance sports drinks. It's a thing. And so my sense is that the evidence on this is at least reasonably good in the case of your skin.

26:07So we have some meta-analyses of trials in which using collagen peptides typically in a kind of topical way can have significant improvements in your skin hydration and elasticity. Now, okay, in that particular meta-analysis, there was a subtlety, which is that when you only looked at studies that were not sponsored by industry, the effects were not there. So capitalism. But I'm curious whether you, like, if you were interested in improving your already lovely skin elasticity, would you use a collagen peptide?

26:44Emily Oster:I mean, maybe. I don't care that much about it. But whatever, I'm a 46-year-old man. So I know that there's some differing opinions here. I mean, the interesting thing about collagen peptides is that they're basically the only peptide to exist in a regulatory landscape that makes it easy and safe to get. Because the FDA has recognized that collagen itself is safe. They call it generally recognized as safe, which means you can be a supplement company and you can put collagen in a pill and you can give it to people. Collagen peptides, all it is, is they take collagen and they digest it with an enzyme.

27:20Emily Oster:So collagen is a big protein with thousands, literally thousands of amino acids. And then they just digest it down into kind of manageable pieces, very similar, honestly, to what your digestive system does when you eat a big protein. But that said, the collagen peptides are, because they're smaller, absorb through the skin a little bit better, absorb through the GI I track a little bit better. And you're delivering in that sense, you're delivering some of these proteins, some of these constituents of the stuff that makes your skin, you know, firm and elastic directly to the site that you want them to be delivered.

27:54Emily Oster:And to me, that seems fine. You know, this is one of those things I tell people, listen, it's not terribly expensive. If you feel like trying it, try it, you know, try to be honest with yourself if you think you really look better, if you don't save your money. Yes. Save your money is perhaps a good advice in general, in everything we hear about on social media. So beyond collagen, I think there are actually a couple of other things where a couple of other FDA approved peptides, which treat actually somewhat unusual things. So one of them is for tanning and one is for improving female sexual desire.

28:34Did I get that right?

28:35Emily Oster:Sort of. Yeah, the one for tanning called atha melanotide. It's not FDA approved to get you tan, but it does get you tan. It's approved for a very rare condition called erythropoietic protoporphyria, which very few people have, but it does stimulate the melanin receptor, which is what makes you tan. And so people who receive this drug do get tan. And it's worth thinking about just because there is a pathway for peptides to go through the same approval process that every other drug has to go through, the same purity standards, the same testing, the same manufacturing practices. And they can do really interesting things.

29:15Emily Oster:Like it's true, the female hypoactive sexual desire disorder, which Emily, we definitely need to do a whole show about this because it's fascinating. That's a peptide product called Vilisi, which was approved to treat this condition. It does apparently increase sexual desire in women. It also causes nausea in 40 % of people who take it, which I don't know how those two things are compatible, but apparently they are. Well, you don't know. It could be the 60 % of people who are not nauseous. You know, it's straight up. Fair enough. Yeah. You're flipping an interesting coin there. And, of course, you mentioned already the GLP-1 receptors are peptides.

29:56Emily Oster:Of course, insulin, which is maybe saved more lives than any other injectable drug that we've ever created, is also a peptide product. So there is a pathway. But I think there's a lot of people who are trying to kind of jump that evidence gun and potentially taking on more risk than they know that they are taking on. What about the evidence on joint pain? Most of this evidence is in athletes. Some of it's in older people. Yeah, it's there. It's there. I mean, so we do have another meta-analysis. And for everyone, a meta-analysis is just a study of studies. So it's a study that aggregates data from multiple other studies that have been done to try to kind of average out the variability and things like that.

30:38Emily Oster:There was some evidence in this meta-analysis of 15 randomized trials of collagen peptides for joint pain, 12 of which were in athletes that showed some improvement in joint pain. There was really no evidence for muscle building, which is the other thing that people sometimes suggest this being used for. Again, one of the problems we have when the outcome of a trial is subjective, like pain or fatigue or even depression. How your skin looks. How your skin looks is that it is very susceptible to what we call placebo effects, like the idea that you're taking something. Now, a randomized controlled trial is going to have placebo controls, but just even because you have a placebo doesn't mean people can't figure out what they're getting.

31:26Emily Oster:Sometimes they taste a little bit different. They look a little bit different, things like that. So, you know, again, for joint pain, it's like, it's, it's relatively safe. It's not going to hurt you. It's they're non-toxic. If it helps, that's great. I mean, some, I don't even care if it's a placebo, right? Like if it helps and then you feel like it helps, you feel like it helps, it helps go for it. Yeah. I mean, this is an example of a place where I think we sort of bring together like often what we're looking for when we try to argue for causality. The question of like, is it biologically plausible?

31:56I think the answer in the collagen peptide case is, yeah, it's biologically plausible that, you know, this could have some, this could make some difference. And then we're looking for, you know, do we have evidence, either randomized evidence or even observational evidence, but here it's randomized that suggests that we do see some impacts. I will say I take away from this, like this is small. There are many other things one might do to address joint pain, like strength training and other things where collagen could be like a little helpful, but it's probably not the be all and end all. And sort of similarly, my guess is the overall variation in skin elasticity across people is much greater than the treatment effect of a collagen peptide.

32:40Like when you see someone on the internet and their skin is amazing and they tell you they took collagen, I'm telling you, it's that they have good genetics and or are using a filter, not that they are taking collagen.

32:53Emily Oster:And are really good at makeup. Like when I was looking at all the peptide stuff on Instagram and things, these videos, all I was like, oh my God, these people are just beautiful. Like that's the, that is the requirement apparently to be an influencer is to like look really good on camera, you know, which is why I'm glad this is an audio podcast. No one has to look at my unfiltered face. Everyone would love it. Okay. So let's talk about the sort of third piece of the peptide conversation, which is the idea of using injected peptides for like longevity, wound healing. And this is a much bigger space than And then narrow, like I'm taking some collagen to improve my face.

33:39It's like, you know, BPC-157. There's a thing called the Wolverine stack, basically, Perry. There's a thing called the Wolverine stack. And I guess, do we want it? Say more.

33:52Emily Oster:Well, OK. Emily, let's take it from the highest authority in the land, Joe Rogan himself. Well, that's the thing about peptides, too. The Wolverine stack, BP-157 and TB-500. I don't know if you ever get injured. If you ever get injured, get immediately on BP-157 and TB-500. I didn't hear about TB-500. What's that one? Thymus and Beta 500. Oh, yeah. In conjunction with BPC-157, it is a phenomenal stack. And it just really helps injuries. I didn't know they called it the Wolverine stack. That's what they call it, the Wolverine stack. For healing? Yeah. Because you heal incredibly well. Like, quickly.

34:27I was talking to a pro football player who pulled his hamstring.

34:29Emily Oster:He's like, dude, I shot that right into my hamstring for two weeks and I was right back on the field. Wow. I was like, that's nuts. So first of all, Joe Rogan, Ben Affleck, Matt Damon in that clip. I mean, we are really blowing against the wind here, Emily. I mean, I don't know that we can compete. No, totally not. I mean, Matt, yeah. All right. But let's, I think BPC-157, because of Joe Rogan, honestly, and the Wolverine stack is BPC-157 combined with TB-500, which is another injectable peptide. I think it's really emblematic of the space. And so, no, we are not, I have to apologize to our listeners.

35:07Emily Oster:There are like hundreds and hundreds of marketed peptides out there. We just simply can't get to all of them and like whether they work and how they work. But I think there's some real big principles here that BPC-157 sort of teaches us. So let's start there and kind of walk through it. Totally. So BPC-157, this is a peptide that was initially isolated from human gastric juices, which is weird. Okay. But fine. But, you know, as you said, you can get peptides from anywhere. Why not from your gastric juices? Sure. But, you know, because it's being promoted for healing and everything, you kind of, I was like, oh, it must have been isolated from like healing cells or something, whatever.

35:51Emily Oster:But, you know, hey, the gastric mucosa is a hostile environment. So maybe there's some biologic plausibility there. The data for BPC-157 is essentially entirely in mice and rats. So you injure a rat, like you sever. This is cruel a little bit, but this is how science works. All research in rats and mice is cruel. I know. So trigger warning for pet rat owners. They will like sever part of a rat's Achilles tendon. and then they either inject this stuff or they inject a placebo and then they see how fast the Achilles tendon heals. And some of those studies in mice and rats do show accelerated healing with PPC-157.

36:35Okay. I just want to pause on the question of mice and rat studies because I feel like a tremendous amount of the data that we have in the world about all kinds of different treatments come from mice and rats because mice and rats are really easy to experiment on. You can do all kinds of stuff with them, like cut their Achilles and do other things and look in their brains and kill them and do all kinds of things, which may be sad, but are effective for learning. And we always then have the question of how do we take the evidence from mice and rats into humans? And, you know, there, there, I think are really good learnings, but someone said to me the other day, you know, if we were mice, we would have solved like everything.

37:16Because actually in mice, you know, you can really titrate and be careful. And there's a lot of things that work in mice. But then when we bring them into humans, it doesn't work or the effect size is totally different or just this doesn't port over.

37:29Emily Oster:Yeah, we're just not the same creatures. But there's even bigger issues than that, particularly when it comes to the longevity space because mice and rats don't live as long as people. In their natural states, you know, mice might live a year or two. Rats might live a little bit longer. But you know what? In these research studies, they're not letting these mice live to a ripe old age, right? What you do is, you know, you do your little Achilles tendon thing and then you watch them for a couple weeks as they heal. And then you, the euphemism is sacrifice the mice, you know, humanely. That's the euphemism?

38:04Emily Oster:The euphemism is sacrifice. You kill the mice in as humane a way as possible. And there are protocols for that. And then, you know, you can extract their organs and look at them under the microscope and do all that stuff. So even if we're like, oh, yeah, this appears to heal Achilles tendons, the larger scale questions of like, what happens if you're doing this repeatedly on a weekly basis for years and years and years? Like, we're not even close to knowing that. And there are some concerns here. So BPC-157, thanks to the mice, we know a little bit about how it might work, aside from the general magic of being a gastric juice peptide.

38:42Emily Oster:BPC-157 appears to bind a receptor called VEGF or vascular endothelial growth factor, which promotes the growth of blood vessels into tissues. And sure, that makes sense. If you're talking about healing, you want a lot of blood flow, like that's no doubt a good thing. One of the problems, actually, you probably can guess the problem, Emily. What's wrong if we promote blood vessel growth into tissues too much? I actually, I feel like this is like when my 14-year-old asked me about her biology homework. And I feel like I'm just, no, I don't know. Cancer is begging for blood vessels to come into the tumors.

39:21Emily Oster:And one of our main therapies to treat cancer is blocking VEGF because it turns off that signal that the cancer is saying like, oh, give me blood, grow blood vessels into me. and then the cancer starves and dies. And so there is a theoretical concern that's, you know, ongoing stimulation of receptors like this could lead to cancer. And we have no idea if that's true because you kill the mouse, you know, a week after you give the injection. So just something to be aware of there. When we look at this particular thing in people, I would say my read is that like, we don't have much evidence in any direction that this is effective in people.

39:56We don't have any randomized control trials. We don't have a lot of, we just don't have anything.

40:00Emily Oster:Correct. Only anecdote, which is unfortunately the problem. Yeah. Yeah. Anecdote is not data. I mean, this whole space, this Wolverine stack, all of the other stacks, the different things really has the feel of like there's an interesting potential, something to explore based on the animal data, but nothing in the people data that would say this should be widely adopted based on efficacy, foundation. and then we are worried about some of the potential risks to using such a treatment. Absolutely right. And I think that's the prudent point. But we also have to realize that, A, there are a lot of people out there that are potentially suffering with something.

40:48Emily Oster:And a lot of times the medical establishment that I'm a part of does a poor job of this, right? They've got joint pain. They have something, you know, yes, sure. They were told to do physical therapy. They're told to do strength training and things just aren't working. So there's a desperation there. Like this does fulfill a need that I think some people have. And then there's a whole group of people, you know, the kind of biohackers who are like, yeah, yeah, yeah. I understand in theory that we would like to have a large randomized trial to prove that this works, but I'm not going to wait for that.

41:15Emily Oster:Like this stuff seems great. My buddy says it's great. This guy online says it's perfectly safe. You know, LFG, like let's go and I'll sort of throw caution to the wind. And I think as much as we can say like, well, guys, I don't know, there's no hard data, it's still going to happen. And so I think anticipating that this stuff is out there, we might want to try to give people some like tools to be able to separate at least what is potentially safe from what is potentially not safe, even if we throw evidence out the window. Yeah. So I want to start with actually the just noting that the – okay, so let's kind of back up.

41:53When we think about peptides, there are some peptides that people take orally. Other than some of these collagen peptides, generally oral peptides are totally ineffective because they break down in your stomach and are not therefore absorbed. So if somebody is telling you here are some gummies with this amazing peptide, like that's just a money toilet, like you're just putting your money in a money toilet and flushing it away, correct?

42:18Emily Oster:I think broadly, yes, there are ways to make peptides more stable in the GI tract. oral peptide consumption is basically going to be safe, you know, even if you are ingesting like bee venom. Because it's not effective. It's safe because it's useless. Your stomach is eating it. Correct. And so I don't worry too much about people, you know, wasting their money on things. You know, I'm a libertarian in that sense. No, I will say I worry about that because I feel like exactly to the point you had before, which is, you know, people are struggling with this. They want to get help. And then online, someone's telling them, oh, just take this gummy bee venom and it's going to fix all of your problems.

42:58I actually think that really gets in the way of people finding solutions that might actually work for them. So I am more worried than you are about the kind of, I'm buying this unapproved thing that somebody on TikTok told me about, even if it is not actually unsafe. Although I agree with you, it's worse if there's a potential safety risk.

43:16Emily Oster:Yeah. I mean, the trick here is being honest with yourself and really trying to determine whether this thing that you tried, if you're going to try it, helped you or not. Like, is your life better or not? Is it worth the expense or not? I agree with you. It probably isn't most of the time. Okay. But then there are these products that you're injecting. So most of these peptides would be delivered to the extent they could be efficacious at all. They are delivered through an injection like a GLP-1. But these, unlike the GLP-1s, are not in an FDA approved product category. So generally the FDA does not approve these peptides, which are made by compounding pharmacies and are not regulated because the FDA has actually now said they are illegal to compound.

44:05That includes this BPC-157 and all of these other ones. And so if you're getting these, they are not from an FDA approved supplier.

44:13Emily Oster:I think this is such an important point. And I want to play a clip here about someone who's trying to talk about safe sourcing of peptides. So today you and I are going to have a little chit chat about where you're getting your peptides from. There are a couple of different ways that you can get your hands on peptides. One is going to your doctor and getting a pharmaceutical prescription for it. Option number two, compound pharmacy. But there are two split offs that come up when we talk about compound pharmacies. So one is going to be pharmaceutical grade, human grade, made for human beings. The other is research grade.

44:46This is the one that I am telling my clients to stay away from. There's not the same amount of oversight. We don't have third party testing.

44:53Emily Oster:So I really do think because, you know, if you're listening to this and you're like, well, I don't know, Joe Rogan says BPC-157 is good. Like, I want to get my hands on some BPC-157. It is important to know what the regulatory landscape is here. Compounding pharmacies are pharmacies that have a license to mix drugs. That's what compounding is. They can make their own concoctions under specific conditions, ideally sterile conditions that they can then sell for injections and things like that. Compounding pharmacies are regulated at the state, not the federal level, which gives this whole crazy patchwork of what's legal across the country.

45:33Emily Oster:And because you can ship these things from state to state, it basically is like a lowest common denominator of what the compounding pharmacy can do. Many of the peptides that you'll see out there on Instagram are able to be made in compounded pharmacies, but many of the most popular ones, as you said, Emily, are not. So BPC-157, this Wolverine stack peptide out of Joe Rogan fame, was classified by the FDA as a category two substance, which is one that has significant evidence for harm. And compounding pharmacies are not allowed to synthesize or create anything that is category two, or they lose their license, that's illegal.

46:10Emily Oster:So if you're getting BPC-157, you're actually not getting it from a compounding pharmacy. You're getting it from overseas almost certainly, and most of it comes from China. So again, BPC-157, I think is like the poster child for this set of problems. It's marketed aggressively. It's got a, I mean, Wolverine stack like that is Sounds amazing. Totally. Awesome. Like I'm a superhero fan. Like that is great marketing. It's got really impressive influencers. Things come out of your hand. I mean, I would do it. I would do it if you show me. You've got these impressive influencers talking about it. You have, you know, anecdotal evidence or anecdotal stories, I should say, from people saying how great it is.

46:50Emily Oster:But it's actually like deemed unsafe. You have to source it from some external country. And we have no idea what its actual effects are. And that's sort of the space right now. It's like, it's pretty much the Wild West. And when it comes to eating something, you know, I'm more experimental when it comes to injecting things into your body, like you don't really want the Wild West. Yeah. And I mean, there are all kinds of examples in the past of things that were injectable that turn out bad. I was looking at this Scientific American article from a number of years ago about stem cells where someone had like injected some stem cells to try to fix some eyelid problem.

47:24and they ended up growing tiny bones in their eyelid, which need to be removed. I'm not saying that's going to happen here.

47:31Emily Oster:That is worse than the substance. It is somewhat worse. Well, I don't, I don't, I know you may not have watched the substance. That's pretty gross. It's pretty gross. But I mean, I feel like there is a general sense that injecting yourself with things, it runs a risk of infection. And it is just a much more extreme approach to this than, say, eating something, which again, I don't think that makes sense in this context for almost any of these peptides. Let me give you two more risks of injecting things into your body as if we don't have enough. Number one, allergy. As you may know, when we eat things, we have this whole immune system in our gut that surveils them for allergens and gives us tolerance to the things we eat.

48:15Emily Oster:This is why, like Emily, I'm sure you've talked about, it's actually good for little kids to like get kind of dirty and put dirt in their mouths and stuff like that so that they have less allergic reactions, right? That's what our GI tract does. When we get what are called antigens, which are peptides or proteins or other things via another route, like the injection or sometimes the inhalation route, a whole different immune reaction occurs. And that is an allergen forming immune reaction. It is worth noting that the first time you get stung by a bee is not when you have the anaphylactic response to a bee sting if you're allergic to bees.

48:50Emily Oster:It's the second time. The first time the allergy starts to get learned and woken up essentially, and then the second time you get stung, you have the anaphylactic shock. As I said, there's infinite peptides you could theoretically inject into you, and it is likely that some at the very least will cause severe allergies in some people. So be aware of that. Number two is what we call autoimmunity. So your immune system is this amazing thing that surveils all the cells in your body and decides, is this me or is this something else? And in general, if you're healthy, it looks at your cells and says, oh yeah, this is me.

49:26Emily Oster:I don't need to attack this. This is myself. We're okay. Autoimmunity is when the immune system starts to recognize something in your own body that is you, but it doesn't recognize it as you anymore. So it attacks it. And lupus, for example, is the prototypical autoimmune syndrome where your immune system is attacking these various cells in your body. When you inject a protein into yourself, you form antibodies to that protein. That is how vaccines work. When we inject a COVID vaccine, antibodies form against the spike protein. And that works because the spike protein is not you. And so when the immune system sees the spike protein again, it can attack that.

50:07Emily Oster:Many of these peptides are derived from human proteins. And if your immune system starts to recognize those peptides as foreign, there's a chance that they might start to attack your own proteins that contain those peptides as foreign. And that could be really bad. It could almost do the opposite of what you want these things to do, right? Because you want these peptides to stimulate this system. And now all of a sudden you have antibodies that are directly attacking the system. That could be an issue in the long term. That does seem like an issue in the long term. Okay. So Perry, I honestly feel like we could just list all of these peptides that exist in the world and just talk about why there's no evidence for them.

50:47There's TB500, there's GHKCU. There are a million of these peptides. And if we talked about every one, in nearly all cases, what we would say was, maybe there's a little bit of suggestive something in mice and there's nothing to say in people. And there are these risks of injecting yourself with random things, which you want to be careful about. So I do want to acknowledge the people who are listening, who are like, I hear you about this, but it sounds good. I'm interested in trying. And so if someone came, you know, your doctor, somebody comes to you and they're like, look, I'm really interested in trying to inject myself with a bunch of different peptides.

51:29I just feel like it's like, that's for me this week. Is there any way to ameliorate some of the concerns that you have about such activities?

51:40Emily Oster:Yeah. I mean, so, you know, you're probably not going to get them from me directly because I don't think the risk benefit calculus is there. But yeah, just to understand, let's accept the fact that people are going to do this. Like, you know, we cannot fight the ties. Ben Affleck comes to you and asks for some advice. What's the advice? All right. Ben, what was up with Gigli? Did you need to do that? Like, was she pressuring you? Okay. If you're going to do it, okay, realize that if someone tells you that they're getting some of these peptides like GPC-157 from a compounding pharmacy, they're not.

52:14Emily Oster:It's not legal. So it's coming from outside of the U.S. So be a little skeptical of, you know, wherever you're getting them from. If you are getting that, and there are places that do a better job of trying to be reputable in this space. And what they do is they farm out the substance to an independent testing laboratory, which issues what's called a certificate of analysis, which basically says, like, we tested the stuff in here. And yes, it is what it says it is. The things you're looking for on a certificate of analysis, number one is purity. Is it actually, you know, is it clean? Is it the stuff you want?

52:49Emily Oster:You want basically greater than 98 % purity to feel comfortable. Number two, you want testing for something called endotoxin. This is a bacterial byproduct that causes sepsis and inflammation. You do not want endotoxin in anything you inject into your body. It's also the thing that causes toxic shock syndrome. You want heavy metal testing. So a lot of these that have come from China and other countries are contaminated with lead and other heavy metals. So you want the certificate of analysis to demonstrate there's no heavy metals there. You want sterility testing. So they've confirmed that it's sterile.

53:22Emily Oster:It doesn't contain bacteria or anything. And finally, you want to check the certificate analysis, which should list the batch number and the lot number against the one on the thing you're injecting or else, right, it could just be referring to some other one that was tested years ago. And I know that sounds insane, and maybe that more than anything else is going to convince people not to use these things. But I do think if all of these pieces are in place, you may be okay. I would not recommend long-term use, though, because we really just don't know the effects. And I am quite concerned about allergy and autoimmunity with repeated dosing.

53:58Emily Oster:All right, Emily. Talked a lot here. What's your one thing about peptides? Don't inject something in yourself that's not FDA approved just because it worked on a rat. That's a good thing. What about you? I'm not ready to give up on this, but there's some serious snake oil vibes here. Fair enough. All right. That's enough about peptides. Possibly too much. Who knows? Stay tuned after the break for our listener mailbag.

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56:53Emily Oster:Hi, I'm Liam Perry. This is Eric from Cambridge, Massachusetts. I'm 44 and keep hearing about the so-called age clip. You know, like in your mid-40s, you wake up one day and everything feels harder. Workouts just don't work. Weight creeps up. Sleep gets weird. And recovery just takes forever. Is this actually a thing or just a mix of lifestyle changes, stress and not moving as much as we used to? What's actually happening, like hormonally, metabolically around this age? Should I start wearing my pants higher now? All right. So as a 46-year-old man, boy, does this question resonate with me. It's referring, just so everyone knows, this 44 is referring to a study that appeared in Nature Medicine of about 100 people, if I'm remembering correctly, across a range of ages.

57:39Emily Oster:And it measured hundreds and hundreds of things in their blood, DNA, methylation, and all these things that are supposed to change with age. And what they were looking for is like, is there a linear decline in any of these things over time or in all of these things over time. That was the expectation. What they actually found was that there's kind of a linear decline over time and then a more abrupt decline at around age 44 that then kind of levels out and then another abrupt decline at age 60. And this has gotten sort of blown up to be like, these are the cliffs, like age 44 and age 60. That's the baseline.

58:12Emily Oster:Emily's rolling her eyes. What's the truth, Emily? I mean, I think there is almost nothing in biology that falls off a cliff like this. Like we have, there are so many things where people quote them as falling off a cliff. Your fertility falls off a cliff at 35, this and that. But like fundamentally, that is not usually how biology works. This is also not, in my view, a large enough sample size to like really sort of definitively draw some kind of cutoff in this way. So I guess for me, like my prior is everything just gets worse slowly over time. and I'm not sure I update very much on that prior based on this fairly limited data.

58:51It is true that as we age, everything gets worse. Slow decline.

58:56Emily Oster:I have one other thought. Okay. Which is that this is based on personal experience that this is the age, like the mid forties when our kids are kind of old enough to fend for themselves a little bit more. And I like, we all start kind of venturing out more. Like I'm doing more activities. I'm like playing golf and I'm lifting weights, which I didn't do before. And I'm like definitely injuring myself. And I wonder if it's just actually the fact that like, we're doing, we're actually doing a little bit more than we would have used to. I don't know. Yeah. This is the age where all of the men in my, I am also 46 and all of the, the sort of men in my social group have decided to like start playing soccer and lacrosse again.

59:35And like, you know, if somebody is like, I'm going to play lacrosse, you know, the next time you see them, they're going to have a broken foot. And And it's just like really, really consistent.

59:44Emily Oster:Exactly. That's the actual cliff. I don't think that there is an age cliff in its way. But the fact that as you age through your mid 40s, things start to feel harder, like that's true. And it's probably a time people have to think more about, you know, how to prioritize their sleep and so on. I do have a secret peptide that only I know that stops the aging cliff. but you have to subscribe to my expensive newsletter. Like and subscribe. I had one mailbag follow-up from last week that I just, I want for the purposes of being honest with our listeners. So in last week's episode, the question was asked, you know, what is something you do that's not based on evidence?

1:00:27And I said, you know, everything I do is based on evidence. And at dinner, my husband, hi, Jesse, listened to it. And at dinner was like, I can't believe you said that. So much of what you do is not based on evidence. And so I just wanted to say that I then started reflecting on some of my behaviors. And I think he may be right. So for example, I'm having some sciatica. And so I am now routinely using a machine that like electrically stimulates the glute muscles to try to fix my sciatica. And I do have to admit, I don't think that's based on evidence. So I apologize for not coming up with that last week.

1:01:09Emily Oster:An immense amount of transparency and honesty from the Wellness Actually podcast separating us from all other people in this space who never back down from anything they say ever. All right, that's it for us for today. Stick with us next week when we'll ask, what's the deal with cold plunges and saunas? wellness actually is produced in association with iheart media our senior producer is tamar avishai our executive producer is jennifer bassett our theme music is by eric deutsch and our content is for educational purposes only if you like the show help other people find us leave a rating and review on apple podcasts or your podcatcher of choice and help us spread the word about the show don't give the tiktokers all the power and don't forget we want to hear from you.

1:02:00Emily Oster:Head over to wellnessactually.fm and leave us a question for our mailbag or suggest a topic for a future show. We'll let the influencers have the last word. I've gotten a ton of questions about what a peptide even is. So let me make this stupid simple. Peptides are short chain amino acids, fragments of protein. They're not steroids or drugs or some fairy dust that some influencer talks about. So imagine your body is like my 911 Turbo S. Now imagine somebody handed you the upgrade file, the tuning file that gets your car to use all the stuff that it already has, but forgot was even there. That's what a peptide is.

1:02:35Emily Oster:It's not forcing anything. It's saying, hey, you know all this hidden horsepower? Yeah, do that. Peptides are like voice commands for your biology. They walk into the pit, crewed your body, and they say, fire up the factory.

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1:04:33Emily Oster:This episode is brought to you by Choiceology, an original podcast from Charles Schwab, hosted by Katie Milkman, an award-winning behavioral scientist and author of the best-selling book, How to Change, Choiceology is a show about the psychology and economics behind our decisions. Hear true stories from Nobel laureates, authors, athletes, and everyday people about why we make the choices we do and how to make better ones to help avoid costly mistakes. Listen to Choiceology at schwab.com slash podcast or wherever you listen.

1:05:39Emily Oster:We'll be right back. We'll see.