Ben Greenfield [00:00:00]: Welcome to this best of the best episode on peptides. If you go to BenGreenfieldLife.com/BestOfpeptides, you can access the juicy show notes for this one. I have selected some of my favorite conversations about this somewhat controversial topic of peptides and put them all together for you in this one mighty podcast episode.

Ben Greenfield [00:00:23]: So enjoy.

Ben Greenfield [00:00:23]: And again, the shownotes are at BenGreenfieldLife.com/peptides. Eelcome to the Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist and nutritionist, and I'm passionate about helping you discover unparalleled levels of health, fitness, longevity and beyond. In this first snippet from my interview with the great Jay Campbell, we get into peptide sourcing and purity, ipamorelin and tesamorelin, their effects on muscle growth, fat loss and sleep. Very interesting for growth hormone, the fear of injections and what you can do about needle anxiety and why peptides are becoming mainstream and what you can expect in this industry. So let's listen to what Jay has to say. Back to peptides.

Ben Greenfield [00:01:15]: Jay, you know, you sent me this package and I've never really ordered peptides from the Internet because, you know, the general consensus, at least to my understanding, has been issues with purity, issues with some of these pharmacies, and issues with you potentially emptying your pocketbook on what could be very expensive peptides with low efficacy or impurities, yet saline. You, you swore to me that what you were about to send me was, you know, the equivalent or, or safe or, you know, what I could be getting currently through a physician, which is obviously a little less convenient than just being able to go order your peptides from the Internet or, you know, from something like this, this new website, what's it called? Limitless Life. Limitless Life website that you've made. So, so what, what is going on exactly with this ability to be able to now order peptides from the Internet?

J. Campbell [00:02:10]: Yeah, so, I mean, like, so first off, I just want to say I agree with you, you know, so for my personal perspective, as I told you, I've been using peptides since 2004. I always, in the beginning, I mean, first off, in 2004, doctors weren't prescribing peptides anyway. There was no, nobody knew anything about peptides unless you were (insulin). Yeah, I mean, exactly. But I mean, from a standpoint of, you know, from a clinical compounding pharmacy prescribing peptides as they have in the, let's say the last six or seven years, there was nobody that was involved in peptides. And you got it from like basically being in underground forums, you know, bodybuilding, new Usenet groups and stuff like that. And so my first foray into peptides was using ipamorelin in 2004. And it's really funny because I, I think you know this.

J. Campbell [00:02:56]: I did a podcast in early March on our friends, our mutual friends, Mind Pump, you know, Sal, Adam, Doug and all those guys. And we went really, really deep on peptides. And it was an amazing podcast, you know, for the, for the public and of course for their audience and for a lot of people.

Ben Greenfield [00:03:12]: But I'll include the show notes. They're great, the Mind Pump guys.

J. Campbell [00:03:16]: They are, dude. And it was an amazing podcast. Yeah, I definitely point to that. It'd be really helpful for a lot of people. But a lot of people that listen to that, to their audience heard me talk about Southern Research Co. And this was the company in Texas that I and everybody else that was using peptides, you know, which there was obviously a very rogue small group of humans back then that were using it. But like, there were people in that audience that heard that and they were like, this guy's legit. And they messaged me and they're like, whatever happened to them? And I'm like, man, your guess is as good as my guess.

J. Campbell [00:03:50]: But again, 2004 through 2006, I was using ipamorelin through Southern Research Company in Texas, whoever they were. And obviously again, they were back. I mean, I know who they were without getting anybody in trouble. They were basically the back office operation of a compound pharmacy that was just selling these things on the Internet through bodybuilding magazines and underground forums. And dude, ipamorelin was the most profound thing at the time that I had ever used. I mean, next to testosterone. And then as you know, and we can go deeper on this, and obviously I write about this in the book with the God stack and all these other things, testosterone and growth hormone inducing peptides and of course human growth hormone itself have a synergistic effect.

J. Campbell [00:04:28]: And so when you're using a surgically precise dose of testosterone and growth hormone, or any peptide inducing growth hormone like ipamorelin and tesamorelin and CJC, we'll talk about those. They're just amazing together. So when I started using ipamorelin, I was like, wow, I got leaner. I put on maybe three to five pounds of muscle. My training was better, my sleep was incredible. But to originally your question, it's weird because again, with compounding pharmacies, selling peptides through prescriptions with doctors in the last six or seven years. And then previous with my experience using research chemical companies, I was reluctant, like you, you know, to talk about research chemical companies. But Limitless Life Nootropics.

J. Campbell [00:05:11]: The owner, who I'm obviously a very close personal friend with, Chris Mercer, he actually does certificates of authenticity on all of his peptides. He also is the only guy I know in the industry and again, I'll mention names, you know, there's obviously Peptide Sciences is a big and great company. They've been selling peptides for close to I think a decade now, somewhere between eight and 10 years. And they're by far the biggest outfit from a, you know, gross revenue standpoint in the industry for peptides. But they're not testing their peptides. And Chris came to me two years ago and was like, look man, I follow you, I think you're awesome, blah blah, blah. Would you be interested in promoting my peptides? There's a reason I want you to. And here's the reason.

J. Campbell [00:05:52]: And then him and I obviously became really good friends. So fast forward to now. Obviously since the book launched, I have affiliate links in the book, of course to Limitless and Limitless has exploded. I mean they went from, you know, doing, I mean they're basically doing seven to eight times revenue a month than they were doing before the book launched. And obviously the Mind Pump podcast helped. There's, the book is selling like crazy on, on Amazon. Of course a lot of people, Ben, are looking.

Ben Greenfield [00:06:20]: What's the name of the book?

J. Campbell [00:06:22]: It's called Optimize Your Health for Therapeutic Peptides.

Ben Greenfield [00:06:25]: Okay.

J. Campbell [00:06:26]: Yeah, and then there's a subtitle.

Ben Greenfield [00:06:27]: And so, so these Limitless Life peptides, they have a certificate of authenticity. Are they doing something different that other compounding pharmacists aren't that allow them to maintain that purity?

J. Campbell [00:06:40]: I mean, not really from a standpoint. I mean it's hard for me to answer that because I don't know. This is what I'll say. I don't know of any compounder or research chemical company. We can talk about the difference between research chemical companies and compound pharmacies if you want. I'm happy to, but I don't know anybody that's actually going out on the line and paying an independent third party company to test their peptides because it costs money. One, and number two, they're using an FDA registered DEA certified lab to do it. Right.

J. Campbell [00:07:16]: So whether they're a compounder or a research chemical company, who's actually doing that now again, the compound people will hear this podcast and they'll say, Ben, that's just part of the deal if you're a compounder. Well, is it? I mean, again, who's testing the compounders?

Ben Greenfield [00:07:30]: Yeah, yeah, that makes sense. Well, I can tell you that I began to use what you sent last week and I had forgotten, you know, you brought up ipamorelin. You sent me ipamorelin and tesamorelin. You actually asked me about a few of the things that I'd want to try. And I named those two because I did a stint of them a couple of years ago. I think I did two different 8 to 12 week stints of them during the year and saw profound increases in lean muscle gain and fat loss despite no significant changes in diet and exercise. And you know, my sleep score has been like 92 to 95% for the past week since I started doing that little. I actually do the ipamorelin injection in the morning and the tesamorelin in the evening.

Ben Greenfield [00:08:18]: And yeah, I had forgotten how unstoppable you feel when you're taking these things. And so the ipamorelin and the tesamorelin. Why is it that that compound or that or that that stack seems to work so well?

J. Campbell [00:08:32]: That is a really good question. So I, obviously we wrote about that in the book, so I know, you know, you already mentioned Nick, you know, Nick Andrews and I were involved in writing the book. We obviously produced the course which you were so grateful, I mean, gracious to promote for us last year. And then we're going to talk about a new course that's coming that's going to be for babies. And then let's just take a step back before I answer your question. I think you know, this, you know, your audience is a lot bigger than mine. I mean, the reality is, is that peptides represent this like new form of, let's call it quantum healing in medicine. Right? And in the last three years, regardless of our opinions of what have happened, a lot of people feel burned.

J. Campbell [00:09:09]: They have lost trust in allopathic medicine, they've lost trust in, you know, let's call it the system. And so what's happening right now is a lot of people are coming into, you know, let's just call it collective awakening or mass consciousness. And they're like peptides. And I don't want to ravenhole and talk to them about bioregulators, but I know we're going to be talking about that because that's even a bigger thing coming because they're orals and non injectables, but the biggest issue with peptides, as you know, and you just said it, you're like, oh, I injected this at night and this in the morning. Then that literally eliminates from our, you know, internal Jay Campbell teams test, not testimonials, but surveys and questionnaires that we do. 85% of people are still too afraid to inject themselves. Right. Like you and I can sit there and we can show them that it's a 32 or 31 gauge insulin needle and you can jab yourself.

Ben Greenfield [00:09:56]: Millions of diabetics do daily.

J. Campbell [00:09:59]: Exactly. But again, it's a hang up. It's actually called tyrannophobia, which is a fear of needles, needle phobia, but it's called tyrannophobia. Fear of injection.

Ben Greenfield [00:10:07]: Yes, that was a fear of dinosaurs, but makes sense.

J. Campbell [00:10:10]: It's the craziest name what it means. Yeah, me too, tyrannophobia. But the reality is, is that you got 85% of the public that will not inject themselves. So like we can sit up here and we can talk about how amazing these things are, but there's still this like level of fear that the consumer, the end user, has to overcome. And once they do, I mean, obviously it's simple, right? It's like brushing your teeth. But it's very interesting because that's the biggest bugaboo as I've gotten so deep into this. And honestly, as I told you four months ago, and you were obviously very gracious to write the foreword for the book and I'm very grateful about that and I appreciate you guys always say, man, I truly love this book.

Ben Greenfield [00:10:49]: Embarrassingly, live on the podcast. Could not remember the title of the book I wrote the foreword for, but I remember it was quite good.

J. Campbell [00:10:55]: You talked to a lot of people, bro. It's okay. But no, but seriously, truthfully, it's crazy to see how big peptides are becoming right now in the mass consciousness. I mean I cannot handle, my assistants, cannot handle the emails and the messages that I'm getting. And so I'm letting you know forewarning as when this podcast runs, man, you are going to be getting so many people message you asking you questions. Not that you don't already, but you know about this because this is just such a big thing right now. But at the end of the day, injecting yourself is, like I said, brushing your teeth after you do it once, perhaps twice, you're never going to be afraid of it. You're not going to have fear of it.

J. Campbell [00:11:41]: It's something that's very easy to do it doesn't require any kind of skill. Watch one video, listen to me and you talk about it. The next course that I have coming, which is called Peptides Demystified, is going to be a basic intro newbies, total neophyte level course on how to do this with all of the questions that people have that you and I take for granted. Again, how to prepare your needle, how to use bacterial static water, how to inject a peptide, all this kind of stu. So it's going to be much more helpful. And you know, I will apologize to the audience, not your audience, but the world at large, and say, you know, I really took for granted a lot of the basics because I've been using peptides for so long. But, you know, most people have no familiarity with them at all. So I'm really grateful now that there's, you know, obviously you giving me this forum and obviously the Mind Pump guys too, to really talk this, because I'm telling you, man, it's mind blowing.

J. Campbell [00:12:33]: How many people are Interested in peptides.

Ben Greenfield [00:12:35]: GLP1 glucagon, like peptides, these small molecules that help you not eat and in some people result in what they call ozempic phase. Yep, we're going to talk about those next. So get ready to hear Pendulum's Colleen Cutcliffe's take on GLP1.

Ben Greenfield [00:12:53]: What's GLP1 stand for?

Colleen Cutcliffe [00:12:55]: GLP1 stands for glucagon, like peptide. And essentially it is a small molecule that stimulates insulin response, and it actually does more than that. So on the one hand, it stimulates insulin response to help clear out the sugar in your blood after you've eaten a meal. But it also appears to have a very strong tie to our brains and our cravings and our food cravings. And so people who, you know, take these GLP1 drugs, which are designed for people with type 2 diabetes, not only see that their sugars are metabolized in their blood more effectively by releasing insulin, but they also find that they have increased the. So they just really don't crave foods as much. And so that combination leads to kind of a really nice positive cycle in which you are metabolizing sugars better and then you're also craving less of the foods that kind of cause these high sugar spikes. And so GLP1 drugs like ozempic and things like that, that's how they function.

Colleen Cutcliffe [00:13:52]: And they're extremely effective in helping to lower blood glucose spikes and lower food cravings.

Ben Greenfield [00:14:00]: Would you ever take those? I think they call them semaglutide peptides. Because now I know where I've heard that term GLP1 before, because everybody's dropping that as the way that these drugs like, or peptides, if you want to call them, like Ozempic, actually work.

Ben Greenfield [00:14:12]: What do you think of those?

Colleen Cutcliffe [00:14:16]: I personally would not take them. And the reason is because, first of all, they were designed for people with type 2 diabetes who are people that are actually unable to produce the right amount of GLP1 in order to manage their blood glucose spikes. So you're talking about people that have a disease that a drug was designed for. And if you're a healthy person and you're able to make GLP1, kind of adding a drug on top of that, in general, there's going to be side effects that you're going to experience. But maybe more importantly is physiologically what GLP1, how it's supposed to work? So how it's supposed to work is that, you know, you eat food, your microbiome digests that food and it tells your body, we just ate a bunch of food, we need to clear the blood, we need to clear the glucose out of the blood. So it stimulates GLP1. GLP1 gets released, it tells your body to release insulin.

Colleen Cutcliffe [00:15:08]: You clear the sugar out of your bloodstream. So actually the levels of GLP1 in your blood go like this, kind of similar to blood glucose spikes. When your body eats food, GLP1 gets spiked in your bloodstream to tell your body to metabolize that sugar, and then it goes away. And then when you eat again, it does the same thing. And so you're supposed to have this cycle of GLP1. What the GLP1 drugs do is they increase GLP1 consistently. So you no longer have this cycle that your body is supposed to have. It's just high levels of GLP1 all the time.

Colleen Cutcliffe [00:15:43]: And while that can result in really nice immediate results, it's not the way your body's supposed to physiologically work. And so when you disrupt cycles like that in your physiology and all kinds of other biochemical systems get disrupted. And so for me, since I don't have diabetes, I wouldn't personally take them.

Ben Greenfield [00:16:05]: So if you had the GLP1 constantly being stimulated by these semaglutide peptides, would you have constantly high insulin levels or low insulin levels?

Colleen Cutcliffe [00:16:16]: You would be high. So basically you're, you're trying to, your body is constantly trying to metabolize all the sugar in your bloodstream, even when they're, even when you haven't eaten.

Ben Greenfield [00:16:26]: Huh. So you could almost like induce kind of like chronic hyperinsulinemia with these.

Colleen Cutcliffe [00:16:32]: And not only that, but these beta cells which are producing insulin, you're constantly stimulating them and having them going. And so eventually those betas, and this is actually quite well known for people with type 2 diabetes, when you keep stimulating those beta cells that produce insulin, over time the drugs become less effective because you're basically. It's like if someone were yelling in your ear all day long in the beginning, you might have a reaction, but after a while you're going to start to tune it out. And our cells have a similar feedback loop, which is to say that under constant stimulation, eventually they become less responsive. And so you're, that's what you're doing to your body. You're overstimulating a process all the time that's not supposed to be turned on all the time.

Ben Greenfield [00:17:10]: Huh? Well, I mean, even though like obviously being overweight or obese might have more risks than something like this peptide might present, sounds to me like we would have to see like a lot better long term safety data on something like pancreatic function or insulin sensitivity before saying that the average, I don't know, fitness enthusiast who wants to lose a few pounds or one of these anti aging enthusiasts who wants to keep blood sugar regulated effectively should use something like this.

Colleen Cutcliffe [00:17:42]: 100%. I mean, the long term effects and safety of long term use of the drugs in healthy people really hasn't been explored. They were developed for people with diabetes.

Ben Greenfield [00:17:53]: Yeah. And in contrast, it's my understanding that a lot of these so called blood glucose disposal agents that a lot of people talk about, like berberine or bitter melon extract or apple cider vinegar, or I suppose like a pharmaceutical like metformin, those are acting differently, right? Those are triggering the, from what I understand, the cell surface receptor, the glute transporter that would allow for glucose to be taken up into something like muscle rather than hanging around the bloodstream. It's a different mechanism of action, isn't it?

Colleen Cutcliffe [00:18:24]: Well, to be honest with you, even though metformin has been out for a long time, I think there's still things being uncovered about it. And actually there's a pretty strong set of hypotheses around metformin impacting the gut microbiome and that being one of its mechanisms of action too. And actually a lot of people theorize about apple cider vinegar as having kind of a similar thing. So you're introducing something more acidic into the microbiome, you're potentially changing the composition of the microbes that are there. But ultimately, the microbiome is your natural way to metabolize these fibers and to help your body metabolize sugars and carbs by stimulating GLP1. That's kind of the natural system. And so that's where the microbiome becomes really interesting, because what people found is that people with obesity and type 2 diabetes are low or entirely missing these microbes that stimulate GLP1. And so that's where you start to have really interesting intervention opportunities.

Ben Greenfield [00:19:20]: So rather than taking GLP1, you're actually allowing the bacteria in your gut to naturally produce GLP1 all on its own. What kind of bacteria would actually do that?

Colleen Cutcliffe [00:19:31]: Well, there's actually only one strain so far that's been known to do that. So as I mentioned, there are these short chain fatty acids like butyrate that get produced by the microbiome. And there's been evidence suggests that butyrate can stimulate GLP1 production. There's actually only one bacterial strain that's ever been shown to directly be able to stimulate GLP1, and it's a strain called Akkermansia mucinophila. This is a strain that you're really not going to see on labels, and certainly probably most people haven't heard of it, but it is emerging as a keystone strain in the gut because it is the only strain that we know of right now that literally lives in your gut lining. And its job all day and all night is to keep that gut lining regulated. And it also is the only strain that is known to be able to stimulate GLP1. And so it really is becoming clear that this strain is super important.

Colleen Cutcliffe [00:20:21]: And maybe I'd say, moreover, the way Akkermansia started to make its way into this keystone strain status is because there are a wide variety of diseases in which people are low in Akkermansia. So there's obesity, type 2 diabetes, type 1 diabetes, actually bipolar disorder, inflammatory diseases, immune diseases. So you start to say, like, well, gee, all these diseases that people have and they're also low, they're correlatively low in Akkermansia. Why would that be? And really what's starting to emerge is that Akkermansia is just playing a really core role in the gut lining as well, well as the production of GLP1. And that's how it's having all these outsized effects when you don't have enough of it.

Ben Greenfield [00:21:07]: From the episode the coolest, craziest peptides.

Ben Greenfield [00:21:09]: You've never heard of, and one of my favorite guys in the supplement industry, Kyal Van Der Leest from Level Up Health. We're going to talk about oral bioavailability of peptides and what you need to know about the risks of contamination with injectable peptides and a whole lot more. All right, here we go.

Ben Greenfield [00:21:27]: What's the state of the peptide industry in Australia right now? Is it similar to the US where it's under increasing scrutiny, particularly the injectables?

Kyal Van Der Leest [00:21:36]: Well, prior to the September ban from compounding chemists last year, Australia was stricter than America. A lot of them were banned already because we had this thing called the peptide scandal back in the 2000s, where a professional sporting team were just shooting up AOD and TB500 and none of the regulatory bodies for in Australia knew what these were. And they kind of made them look silly because all these 20, 30 athletes taking to the field looking like super soldiers and winning games and doing fantastic. So. But you know, they were doing something that wasn't approved. So a lot of those players ended up getting banned. One of them was the MVP for the league for that season. He got stripped of that title after they found out that they were doing peptides.

Kyal Van Der Leest [00:22:23]: And as a reactionary step, they banned and put a lot of stigma around peptides within Australia. So, yeah, ones like TB500 are still banned today. A lot. AOD9604, I believe, banned as well. And basically everything they took, they put on the banned list in Australia.

Ben Greenfield [00:22:45]: So, and, and, and by, by the way, Kyal, was that both the oral and the injectable versions?

Kyal Van Der Leest [00:22:48]: Just injectable versions is what they were doing. A lot of the players would slander the other players by like mimicking the injectable, like doing an injection on the field. That was how the other teams were kind of like pettily mocking them for doing these actually highly advanced biohacking protocols. Like credit to the team for doing that. I know as well they were doing things like hyperbaric oxygen and red light therapy all the way back in like 2006. So they were pushing the envelope then, but maybe a bit too far ahead of the curve. But for as far as the bans and stuff, I think it's actually a bit more relaxed here comparative to America, because you guys now have the FDA ban for compounding chemists. That's the big thing I need to clarify is the ban on this list of 19 peptides is exclusively for these compounding chemists.

Kyal Van Der Leest [00:23:41]: And I'm concerned about that because there doesn't seem to be any good justification for why they've done that and they've also cut the head off. The most purest source of these peptides. There's a lot of vendors of these online now that have popped up like mushrooms and that's almost reactionary to the compounding chemists that do have the FDA approval. The quality has to be perfect. It's like you've taken away the most pure and the cleanest source of these peptides with this regulation and now people who need them are going to go without them and people who still want them are going to get them elsewhere.

Ben Greenfield [00:24:20]: Right from, from a tainted source. Potentially.

Kyal Van Der Leest [00:24:23]: Potentially. That's the issue when you sort of, when the dollar dictates where you get your peptides. There are really cheap options out there. Like I can, I can see it, I've seen it myself. But these things aren't cheap. Like they are custom synthesized. A lot of the time as a manufacturer, you know how much these cost and then you see companies selling them for less than your cost price. It just doesn't make any sense at all.

Kyal Van Der Leest [00:24:47]: And that's sort of where it's a bit of a. There's like a lot of landmines you can, you can step on when you're using peptides, especially the injectable ones. Like the purity of those needs to be perfect, the quality testing needs to be there. There needs to be no bacterial contamination, no LPS, no metals. All these things that are so important and cost money to test for. As far as I can tell, a lot of these sort of fly by night vendors that have popped up aren't doing any of that required testing. And I just don't feel like it's a good thing that they've done that. These regulatory bans, I hope there's backlash and they, they reverse that decision and give it back to the compounding chemists.

Kyal Van Der Leest [00:25:25]: But from a policy perspective, the fact that they've done that really concerns me because they should be in the spotlight, they should be investigated, they should be studied in universities for what they can do. The biggest knock on peptides that I see, and I have to acknowledge is there is a very clear lack of human evidence. There's a lot of animal evidence, but human evidence, it's just not being done because they're not patentable. Well, instead of banning them, let's fund them, let's get this happening, you know, like they are helping people. Without that robust evidence base, there's no doubt about the effects of these peptides now people use them and they feel really good on them and then they don't want to go back to not using them. So rather than take them away because there might be some concern over it and taking it away from the best people making them, they really just should put this into studies. They should be funded for like armed services and veterans. Any sport where there's a risk of a brain injury, they should be used already proactively or veterans returning with brain injuries or something like that.

Kyal Van Der Leest [00:26:30]: This is where they should, this is where the attention should be. Not on like, oh, we don't like them because we don't know what they are or we don't like them because they're competing with the existing pharmaceutical drugs that are out there. So that's my big spiel about what's going on. It's a bit long winded, but I'm really passionate about this because these things have been called the future of medicine and it's for freaking good reason. They are so pleotropic in their benefits. They're so safe in their safety profile. They don't interact with the liver, so there's very little risk of toxicity. There's a little bit higher risk with some of these synthetic derivatives that don't come from the body.

Kyal Van Der Leest [00:27:07]: There are peptides that are naturally based and ones that are synthetic, but for the most part they are broken down in circulation and by the kidneys. So there's very low risk, there's very high safety profile on these. And there's so many other things out there that should be under scrutiny, not these peptides.

Ben Greenfield [00:27:26]: When you were listing some of the things that would be potential concern for contamination, particularly an injectable peptide, you mentioned LPS You're referring to lipopolysaccharides and if so, how do those even get into an injectable?

Kyal Van Der Leest [00:27:39]: Yeah, well they shouldn't be in there. That's the, the fact of the matter. But yeah, lipopolysaccharide is from the cell wall of gram negative bacteria. It's highly inflammatory and it only would get in there with poor manufacturing processes and lack of sterility. And yeah, just those two things and it really, there's no chance it should be in there. If a company has done the testing and has followed good manufacturing GMP facility protocols, which, yeah, majority of them out there do. There's a lot of good vendors online that do follow these practices. And if you're going to buy, make sure you buy from someone who has the testing or if they don't have the testing, they can prove that they do it not just for LPS.

Kyal Van Der Leest [00:28:19]: But for heavy metal contamination.

Ben Greenfield [00:28:22]: For oral peptides with the pass through on the kidney, are you concerned at all for people who might have compromised kidney function? Or are there certain people for whom these wouldn't be a fit?

Kyal Van Der Leest [00:28:29]: When I say they come out of the kidney, it's like the metabolites of those peptides. Most of the time, peptides are broken down just by proteolytic enzymes within your body. Like hydrolase enzymes. The main one, a lot of the oral ones are only short chain. So the amino acid chain is usually between three and 10amino acids long. And they're all just one of the 20amino acids that are found in the diet anyway. So once that bond is broken and that tertiary structure or that folding structure of the peptide is broken, then you're just left with amino acids. It's not too dissimilar to if you just took like an essential amino acid and you've just got them as single form in the end.

Kyal Van Der Leest [00:29:07]: It's not like you're left with a toxic metabolite. You are just left with an amino acid which can then go on and incorporate itself into your muscle or go wherever it's needed. So the breakdowns of these things is just peptides are just amino acids. So there's another added layer to the safety profile of these things.

Ben Greenfield [00:29:24]: Now based on the fact that they're hydrolyzed in that manner. Would it make sense from a formulation standpoint or a stacking standpoint to take some kind of a digestive enzyme if you were to consume an oral peptide? Or are they broken down easily enough without that?

Kyal Van Der Leest [00:29:38]: Well, taking a digestive enzyme alongside a peptide is actually a contraindicated point for when you consume them. Yeah, if you take it side by side with your peptides, you're not really giving them a good chance because that's one of the things with the formulations I do is I buffer against those enzymes by putting things like bicarbonate or celca prosate sodium. These things buffer the stomach acid and prevent that pepsin pepsinogen to pepsin conversion in the stomach, because pepsin's the main proteolytic enzyme in the stomach that will break down oral peptides. So taking your peptides away from proteolytic or any digestive enzymes is important because you've got the protein and the pac man next to each other. You want to kind of keep them apart or your own endogenous pacman, so to speak. Enzymes. Buffering them and keeping them sort of away from the main ones is a great way to make sure that they get systemic. Once systemic, they do last about three to six hours.

Kyal Van Der Leest [00:30:35]: It is a very short half life. And that's why certain things like the Follistatin therapy, if you just take Follistatin by itself, again, you have to take it daily, day after day after day, versus the ones that you've. I think you've done it with Adeel Khan.

Ben Greenfield [00:30:50]: Yeah. You mean the intramuscular injection, the Follistatin gene therapy intramuscular, yeah.

Kyal Van Der Leest [00:30:55]: So the gene therapy versus just taking Follistatin, your body's making that Follistatin all the time, versus you'd have to inject it daily, probably two or three times.

Ben Greenfield [00:31:05]: Okay, so if I were to go up and have lunch after this and take your gut repair formula with lunch, would that mean I shouldn't take digestive enzymes at the same time from having a meal with gut repair formula?

Kyal Van Der Leest [00:31:15]: Yeah. So when I advise people how to take the products, I always say, if you can tolerate in that GI repair formula the zinc carnosine in the high dose, then have it away from food. But if you do get a bit nauseous from zinc, which people, ironically, the ones who are most deficient in zinc tend to get the most nauseous from zinc. So, yeah, if you do get nauseous from that zinc in that formula, take it with food. Otherwise it's best to take your peptides away from food, especially if it's a high protein meal, because those, you know, endogenous enzymes that are being upregulated and the stomach acid that's being churned out in preparation or in reaction to you consuming your meal will compromise the ability of the peptides to be absorbed. Ones like the BPC157 are a bit more resistant because that's where they're made, in the stomach acid. They kind of are the exception to a lot of the rules that we apply to. These are orally bioavailable peptides in that it's made there and it's resistant.

Kyal Van Der Leest [00:32:12]: But. But ones like KPV or GHK copper or the TB4 fragments, they're more fragile. And that's why we have to be intelligent in how we take them and how we buffer them or also how we deliver them. So, yeah, don't take your enzymes with your peptides would be my recommendation.

Ben Greenfield [00:32:32]: That's really good to know. Actually, I didn't know that. So the gut repair formula, by the way, which we've mentioned a couple times, for people who didn't hear our first episode, this might help them wrap their head around your formulation approach. What all is in that?

Kyal Van Der Leest [00:32:44]: Oh, that one's a tripeptide formula. It's got KPV, lorazotide and BPC. Those three peptides are really amazing. All of them? All three of them for repairing the gut lining.

Ben Greenfield [00:32:57]: Can you break down what each of those are and how they work?

Kyal Van Der Leest [00:32:59]: Sure. So BPC157, everyone's favorite peptide at the moment. If you're into peptides. Pleiotropic. Pleiotropic peptide. Multiple benefits, mainly centered around wound healing and restoration of the epithelial layer of the gut. It's really good for repairing hyperpermeability of the gut, as is the lorazotide, which is they work in synergy together. One sort of heLPS with the collagen networks.

Kyal Van Der Leest [00:33:28]: It helps upregulate the growth factors required for wound healing. And the lorazotide is a zonulin antagonist. So it brings together the, the lining of the epithelial wall layer. And yeah, together with KPV, which is an antimicrobial anti inflammatory peptide, they work really well in synergy to basically fast track your gut healing as, as best they can.

Ben Greenfield [00:33:54]: Now what would be the difference between the oral bioavailability and the injectable bioavailability?

Kyal Van Der Leest [00:34:00]: Yep. So injectable is always going to be the gold standard for bioavailability. 100 of what you inject ends up in circulation. That's just how it is. Injectables often come as raw or lyophilized and then you have to reconstitute with water and then inject. That is what it is. That's great. Purity is important for those, as we mentioned, the LPS and then the heavy metals versus the oral forms.

Kyal Van Der Leest [00:34:29]: Oral forms tend to be limited by the size of the amino acid chain. The most common example of a peptide that needs to be injected that everyone says is insulin. Insulin's a 51amino acid chain long peptide.

Ben Greenfield [00:34:45]: Yeah, so. So it's pretty big.

Kyal Van Der Leest [00:34:47]: And that's why all diabetics, you don't see them popping peptide or insulin capsules when they need to regulate their blood sugars. It's just too large. The, the kilo Dalton size and the chain lengths are too large for oral absorption. But if you get around the 10amino acid chain, long mark and below, then these are called small chain peptides and they have a much better chance of being absorbed orally. The smaller they get, the better. As a rule, it's, you know, not solid rule, but as a rule, the smaller the and Shorter the amino acid chain, the better the chance that will be able to be absorbed. And anything under 10, with the exception of BPC 157 which is 15, but anything under 10, you do have that ability for it to cross the intestinal epithelium and end up in circulation. Every peptide has a different profile of how well it will be absorbed and they tend to be, depending on the, the peptide, about the 15 to 20% mark if you just take them as a raw peptide without sort of buffering it.

Kyal Van Der Leest [00:35:50]: And if that peptide is less than 10amino acids long. So like KPV, that's a three chain peptide. It's derived from alpha MSH, the parent peptide of that. From MSH you also have melanotan which has KPV it as well. But melanotan is too large. Alpha MSH is too large, but KPV being that 3amino acid peptide is small enough that if you buffer it with something like a delayed release capsule, something like bicarbonate, to prevent the pepsinogen to pepsin breakdown of the peptide, you don't take it with enzymes, then it will make it pass and through your stomach acid well enough that you will end up absorbing it orally and it will end up in circulation where it can have its powerful anti inflammatory effects, it's anti microbials, it's anti candida and Lyme effects.

Ben Greenfield [00:36:40]: Well, well, KPV has some pretty cool analgesic, painkilling and mood enhancing properties too, right?

Kyal Van Der Leest [00:36:46]: That was the, that's the PEA portion of the products I use. So.

Ben Greenfield [00:36:50]: Okay.

Kyal Van Der Leest [00:36:50]: Yeah, that's palmitool ethanolamide. That's one of these new age or cutting edge supplements that I, I really like to recommend to people. It's essentially cannabis oil for its purpose and its effect. It works on the CB1, CB2 receptors. It has the analgesic effect that you mentioned before for painkilling. It's a COX2 inhibitor and it really just helps with inflammation. It's kind of like a turmeric and a cannabis oil combined without any of the cannabinoids and any of the things that people worry about with CBD. So I really love that ingredient as a functional filler in my products.

Kyal Van Der Leest [00:37:29]: I don't ever use things like rice flour or just cellulose as a filler in the products. I think that's such a missed opportunity when you know the peptides are only usually in microgram quantities. So you are left with, if it's a 700 milligram capsule, you're left with like 699 milligrams to do something to synergize with the peptides. And that's in every formula I do. That's what I try and utilize. If people are taking a capsule, let's just get the most out of that capsule.

Ben Greenfield [00:38:00]: I know your capsules are pretty jam packed, man. It's crazy. And the PEA based on the effects in the endocannabinoid system, would that also assist with sleep or sleep architecture?

Kyal Van Der Leest [00:38:10]: Yeah, it can definitely do that. It can also reduce your neuro inflammation levels. And because PEA is actually a fatty acid, it has an affinity for the brain and for the heart. So it's a fantastic one for anyone who has any cardiac inflammation, but also any neuroinflammation. So that the PEA and the magnesium threonate I was using together when I was living really close to a cell phone tower years ago, before I knew any better. And they really sort of helped me get through that along with things like methylene blue.

Ben Greenfield [00:38:40]: Yeah, the GHK copper peptide, you sent me that one. Now what would be the time or the reason to take that orally?

Kyal Van Der Leest [00:38:48]: So GHK is one that has that low bioavailability that I spoke of. And most people will inject it, which as a copper thing to inject it can actually be quite painful. But you take the GHK because it's fantastic for anti aging. It upregulates a heap of your longevity genes, it helps activate your stem cells. And even if you take it orally and it will end up systemic, the way I formulated it, and then it has just fantastic effects for, for your skin, for the stem cells of your skin, but also for the stem cells of your gut. So in maybe three or four months time, I'm going to actually be adding it to the GI repair formula because I've just found so much literature on it helping with the gut that at the moment I, with that large dose of zinc, I balance it out with copper citrate. Well, I'm just going to swap that copper citrate for the GHK copper. That way I'm still maintaining a good zinc to copper balance.

Kyal Van Der Leest [00:39:43]: But you know, we're adding a very, very functional synergistic peptide rather than just a bit of token copper to balance those ratios out.

Ben Greenfield [00:39:51]: Yeah. And you have this peptide cheat sheet. And again, I'll put this at BenGreenfieldLife.com/PeptidePower if people want to check it out.

Ben Greenfield [00:39:58]: I had a Q and A episode called Cheap Hacks to Reverse Aging. And whether or not peptides could cause cancer. Well, let's dive in and hear what I had to say. All right. The first question comes from Bay Area 1976 and M. Bogey 8000. I don't know how somebody as two people asked a question, but they figured it out beyond me. I'm a Luddite, so they say, can BPC157 feed polyp growth in the colon due to the creation of new blood vessels? Wow, this is interesting.

Ben Greenfield [00:40:28]: This reminds me of the questions I got a few months ago when the study came out showing that NAD could accelerate the growth of cancer. Turns out it's true. If you already have a pre existing tumor, in this case breast cancer supplementing with NAD or NR NMN may cause tumor growth. It would mean that if you have cancer, you may want to think twice about using NAD, particularly breast cancer. This is also something that came up in that old book by I think T. Colin Campbell called the China Study in which he suggested that excess protein intake could cause cancer. Well, it turns out that in rats who had been given a toxin that caused tumor growth, that once a tumor was present, a high protein diet could accelerate tumor growth and put that tumor in a pro anabolic state. No surprises there.

Ben Greenfield [00:41:17]: Right? So it's kind of one of those things where does this cause cancer or does this, if you already have cancer, have the potential to cause accelerated growth? You always have to ask yourself that because the media misses that part. They're like, well, it's associated with tumor growth so it must cause cancer. As a matter of fact, many of these things that cause cancer, tumor growth in a state in which cancer is already present may actually be preventive in other cases. And we'll get into that. So for those of you who are unfamiliar with BPC157, it's a peptide. It's technically called a pentadecapeptide. So that's a fancy term for a series of 15amino acids held together by peptide bonds. It's also known as body protection compound.

Ben Greenfield [00:41:55]: It's known as PL10, it's known as PL14736. It's known as what else bepecin. It's got a lot of different names, but it's most popularly known as BPC157. We've known about it since the early 90s. It's not found in many places, but in your gut it actually is made as a, as a body protecting compound. That's exactly what it does. It protects and it heals tissue. Now it's made synthetically Right.

Ben Greenfield [00:42:20]: It's derived from a protein found in the human gut, but it's just one part of that protein that's naturally produced in the digestive system. So then they synthesize this peptide. So a lot of people use it for healing up tissue for oral consumption, which the FDA has not cracked down on, by the way. They've only cracked down on the injectable version of BPC157. But the oral version a lot of people will use for gut issues and systemically for inflammation system wide, until the injectable version began to become less and less available. Thank you, FDA. I used to inject it into joints subcutaneously into abdominal tissue after like a plane flight or any other situation, which I was a little bit more inflamed. And in addition to all of its beneficial healing effects, it's also a strong.

Ben Greenfield [00:43:03]: And this is particularly relevant to cancer. It's a strong angiomodulatory agent. Angiomodulatory means it affects how blood vessels are made. So research suggests that BPC can help to heal tissue by increasing blood flow. And one of the ways it does this is through what's called angiogenesis and vasculogenesis. That basically means it helps to create new arteries and new veins, right? Angiogenesis, new arteries, vasculogenesis, new veins. But here's probably why my two astute listeners asked this question. Blood vessels are involved in the creation of tumors as well, right? And some researchers have speculated that by helping create new blood vessels to tissue, BPC157 could also help supply the blood that supports cancerous tissue growth.

Ben Greenfield [00:43:47]: Now, no studies have shown that I'm aware of and that I can find that BPC157 can actually support cancerous tissue growth. But there's a suggested mechanism of action that dictates that maybe it's helping to feed blood vessels into tumors. But then you could also look at studies that have have been done on BPC's potential protective effects against can cer. So, for example, if you have lesions and ulcers and stomach lining damage, and particularly schizophrenia, can be found to cause damage to the stomach lining, BPC 157 can prevent those lesions from forming. And in one study, they gave mice what's called haloperidol, which forms stomach lesions. And the BPC157 significantly reduced the size of those stomach lesions. And that means it's helping to prevent the damage to the stomach that could lead to cancerous tumors or cancerous stomach ulcers. In addition, They've shown that BPC157 can have an inhibitory effect on skin cancer cell growth.

Ben Greenfield [00:44:51]: So there's two feathers in the cap, so to speak, for BPC157 for actually not causing cancer and in fact controlling formation of stomach cancer or skin cancer. Now, it might also help to treat some of the side effects of the drugs used to treat cancer. You take a chemotherapy drug like cyclophosphamide. Cyclophosphamide is a chemotherapy drug. It's very effective at killing cancer cells. But it has some unfortunate side effects. And one of those is that it causes lesions to the stomach. See where I'm going here? And they've actually looked at the effects of BPC157 in rats given this cyclophosphamide chemotherapeutic agent.

Ben Greenfield [00:45:25]: And they found that the rats that were given the BPC had much smaller stomach lesions than the rats that were not given BPC157. And the researchers concluded in that study that BPC157 is a very safe anti ulcer peptide. Now, BPC may also, and I think the same thing about amino acids in general, be helpful in treating cancer. Cachexia. So cachexia is also known as wasting syndrome.

Ben Greenfield [00:45:48]: Okay?

Ben Greenfield [00:45:49]: This is where somebody gets cancer and they lose body mass, including muscle and fat. It can be caused by cancer. It could also be caused by aids. And almost half of cancer patients suffer from cachexia at some point. And cachexia is a problem because that leads to a lot of frailty, complications, including death. And some estimates go as high as 20% of cancer deaths being more related to cachexia than directly to the cancer itself. However, BPC157 could help in the treatment of cachexia resulting from cancer. Now, when you look at all the other things that BPC157 can do, improve inflammatory bowel disease, improve the ability for ligaments and tendons to heal, for muscles to heal, for bones to heal, for skin to regrow, to regenerate spinal tissue in some studies in rodent models.

Ben Greenfield [00:46:33]: But still, it has a lot going for it, and it seems to be very safe. It may even help to cure periodontitis, which is periodontal disease, basically, and wound healing, even from burns and significant skin wounds. So here's the thing. I'm not that concerned about its potential for causing polyp growth in the colon due to creation of new blood vessels. I'm not going to say that's ironclad and that we don't still have a need for long term human clinical research on the association between any peptide including BPC157 and cancer. However, it's very safe, it's very simple and I'm personally comfortable using it. I probably, if I had a tumor, would not. Let's say I go in for my colonoscopy tomorrow and I find a bunch of polyps growing.

Ben Greenfield [00:47:24]: I would probably restrict my intake of anything anabolic for a while. IGF1 or. IGF1 Precursors or peptides, BPC157, anything that could assist with the creation of new blood vessels. I mean if I had, I have a whole list of things I would do if I got cancer. But you know, I would be having a very polyphenol and flavanol forward ketogenic based diet and I would be doing, you know, a lot of fasting, a lot of grounding and earthing and movement and ozone and hyperbaric and you know, there, there's a whole list of things. I had a whole podcast about cancer a few weeks ago and I'll link to that one in the show notes because I went on for like 45 minutes in terms of all the different treatments out there. But anyways, long story short is I wouldn't worry that much about BPC157. It's still available orally if you want to try it.

Ben Greenfield [00:48:07]: There's a, there's a few sources out there. I still have a stock in my refrigerator of the injectable stuff. If you want to know more about the FDA cracking down on it. I have a series of videos on Instagram right now about peptides that you can go watch. They're at instagram.com/BenGreenfieldFitness. All right, so another great practical question from Big Sexy KG. Does boiling hot coffee over collagen peptides denature the peptides at all? Boiling? Well, this is relevant because a lot of people are into putting collagen in their coffee. It doesn't have to be with but with or without butter, right? Collagen can be put in your coffee and a lot of people really like that because collagen can be very protective to joints. It can assist with sarcopenia that occurs with age.

Ben Greenfield [00:48:52]: I have many people who are aging and who are also health enthusiasts. Mark Sisson's probably the guy who first turned me onto this. 40 grams of collagen a day. Now I do 40 grams of amino acids per day. I also drink bone broth. I do a little gelatin obviously here and there from my massive jello projects. But collagen it is a legitimate question, because collagen supplements contain what are called hydrolyzed collagen peptides. Now, hydrolyzed collagen peptides are what you get when collagen protein is broken down to smaller portions.

Ben Greenfield [00:49:21]: So the collagen can be easily broken down and used by the body. Now, the process uses heat for the extraction of those peptides, and that heat is typically no hotter than 190 degrees, because exposing collagen peptides to higher temperatures can result in degradation. Now, although heat can render the collagen powder less useful, if you actually have collagen peptides and you want to degrade them to the point where they're no longer functional at all, you have to get above 300 degrees Fahrenheit. And if you're drinking your coffee at above 300 degrees Fahrenheit, you're a mad scientist, you have a lot of pain tolerance, or you have no skin left on your lips or your mouth, because coffee is typically brewed at 200 degrees Fahrenheit or less. Now, if you're putting collagen your coffee and you want to play it safe, only heat your hot water if you have one of those electronic water heaters to 190. And that'd be the safest way to go. But you gotta get close to 300 to really start to make the collagen so denatured that you're not gonna get any benefits out of it. Now, this is important to know, because dietary collagen cannot be absorbed, it has to be broken down to individual amino acids, which are the building blocks for proteins for your body to use.

Ben Greenfield [00:50:34]: And because of this, if you're just relying on collagen rich foods and chewing the knuckles off of the chicken and having some bone marrow here and there or some bone broth, the collagen is not actually broken down. It's less absorbable. It's not going to hurt you, but you're not going to get all the benefits of a broken down collagen peptide or hydrolyzed collagen. So when you hydrolyze it, it can actually increase its absorptability. And there are things like vitamin C that you can include. Like a match made in heaven is some collagen coffee and a handful of blueberries, for example. Because vitamin C rich foods help to boost collagen levels. Now, you could also add vitamin C to your coffee.

Ben Greenfield [00:51:11]: There's no reason you can't do that. Or take some liposomal vitamin C before you have your coffee with the collagen in it. Now for the collagen to be absorbed, the proteins in it need to be denatured to alter their structure and that puts them into a pre digested form that allows them to be more easily absorbed. And that's done using heat. We've established it's only 190 degrees and you don't have to get much hotter than that. So long story short is it's pretty rare that you're going to be cooking with collagen above 200 degrees. But if you are making, I don't know, collagen bread or collagen casserole or collagen turkey or whatever and you are doing higher temperatures, you are going to denature the collagen to a certain extent and render it possibly somewhat a little bit less beneficial for you. Well, hopefully you enjoyed this episode.

Ben Greenfield [00:51:56]: Again, you can access all the show notes at BenGreenfieldLife.com/BestOfPeptides. That's BenGreenfieldLife.com/BestOfPeptides. Thanks for listening. To discover even more tips, tricks, hacks and content to become the most complete, boundless version of you, visit BenGreenfieldLife.com.

Ben Greenfield [00:52:23]: In.

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