Peptide & Hormone Therapies for Health, Performance & Longevity | Dr. Craig Koniver

Andrew Huberman 0:00 (Upbeat music playing) Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Craig Koniver. Dr. Craig Koniver is a medical doctor who did his training at Brown University and Thomas Jefferson University. He is a world expert in what he refers to as performance medicine, which involves the use of peptides and other therapies for improving mental health, physical health, and performance. Now, many of you have perhaps heard of peptide therapies. Perhaps some of you have not. A peptide is simply a small protein, so insulin is a peptide. We have many different thousands of peptides in our brain and body, and they perform a variety of different roles. Dr. Koniver's expertise is in the use of exogenous, that is peptides that one takes, exogenous peptides for activating multiple pathways in the brain and body to augment health. Now, of course, peptides such as insulin have been used for many years now to treat things like diabetes, but today we talk about novel peptides, including GLP-1, so these are glucagon-like peptide analogues, things like Ozempic and Mounjaro, which I realize are a bit controversial. However, today we talk about the microdosing of those peptides. We talk about those peptides combined with other peptides, as well as behavioral practices to offset the muscle loss associated with them, and then we dive into some lesser-known peptides, but ones that are growing in use. For instance, BPC-157, or body protection compound 157, which is used to treat inflammation, to accelerate wound healing, and a variety of other things. Then we discuss the use of peptides specifically to increase growth hormone secretion during sleep, as well as some peptides that can actually increase rapid eye movement sleep dramatically. Today we also discuss testosterone therapies, not just for men but for women. These are growing increasingly popular, as well as things like NAD, as well as specific supplements. Dr. Koniver, as he will soon tell you, is not a huge proponent of supplements, but he does mention several that he feels are of particular use, including things like coenzyme Q10 and some of the methylated B vitamins, and he explains why he takes that stance. So today's discussion is really for anybody interested in mental health, physical health, and performance. And the reason I say that is that even if you aren't considering taking peptides or are already taking peptides, peptides and some of these other compounds I've mentioned sit somewhere between doing nothing except diet and exercise, supplements which I sort of see as the next step up the ladder in terms of augmenting your health approaches, and then, of course, there are a number of prescription drugs, including hormone therapies such as growth hormone therapies, testosterone therapies, and a number of other things that, yes, can modify those hormone pathways, they are in fact hormones, but they actually can shut down one's natural production of those hormone pathways. Peptide therapies sit somewhere between doing nothing and supplementation and those more advanced hormone therapies, and that's why peptide therapies, I believe, are growing in popularity. They can augment specific hormone pathways. They can augment specific, in fact multiple processes within the brain and body to augment health, but they don't tend to operate in that negative feedback cycle by shutting down one's own endogenous production. Now, that doesn't mean that they aren't without some safety concerns, and today we of course discuss the potential side effects and safety concerns of peptides, as well as the critical issue of sourcing clean peptides and working with a board-certified physician if one is going to pursue peptide use. So by the end of today's discussion, you will be right there on the cutting edge of what's happening and where things are going with peptides, and in keeping with that, you'll notice that during today's discussion, we talk a fair amount about what the FDA currently allows in terms of prescription peptides, what the FDA has recently removed from the market in terms of peptides, and as a very recent update, just prior to the release of this episode, I learned that three peptides, CJC-1295, ipamorelin, both of which are in the growth hormone secretagogue family, meaning they promote the release of growth hormone, as well as thymosin beta alpha, which is in the sort of anti-inflammatory and tissue repair pathway, those three are now re-allowed for prescription in the United States. So at the time of recording this episode, we discussed some of those as being recently banned by the FDA. They are now approved again for use in humans by the FDA, so there's a brief and very recent update. So just to summarize this admittedly long introduction, today you're going to learn about this incredible area of science called peptide biology and how it can augment mental health, physical health, and performance, and you're going to do so from one of the world's leading clinical experts.

Andrew Huberman 4:52 Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Joovv. Joovv makes medical-grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, it is the incredible impact that light can have on our biology. Now, in addition to sunlight, red light and near-infrared light sources have been shown to have positive effects on improving numerous aspects of cellular and organ health, including faster muscle recovery, improved skin health and wound healing, improvements in acne, reduced pain and inflammation, even mitochondrial function, and improving vision itself. What sets Joovv lights apart and why they're my preferred red light therapy device is that they use clinically proven wavelengths, meaning specific wavelengths of red light and near-infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Joovv Whole Body Panel about three to four times a week, and I use the Joovv Handheld Light both at home and when I travel.If you'd like to try Joovv, you can go to Joovv, spelled J-O-O-V-V, .com/huberman. Joovv is offering an exclusive discount to all Huberman Lab listeners with up to $400 off Joovv products. Again, that's Joovv, spelled J-O-O-V-V, .com/huberman to get up to $400 off. Today's episode is also brought to us by BetterHelp. BetterHelp offers professional therapy with a licensed therapist carried out entirely online. Therapy is an extremely important component to overall health. In fact, I consider doing regular therapy just as important as getting regular exercise, including cardiovascular exercise and resistance training exercise. Now, there are essentially three things that great therapy provides. First, it provides a good rapport with somebody that you can really trust and talk to about any and all issues that concern you. Second of all, great therapy provides support in the form of emotional support, but also directed guidance, the dos and the not-to-dos. And third, expert therapy can help you arrive at useful insights that you would not have arrived at otherwise, insights that allow you to do better, not just in your emotional life and your relationship life, but also the relationship to yourself and your professional life and all sorts of career goals. With BetterHelp, they make it very easy to find an expert therapist with whom you can really resonate with and provide you with these three benefits that I described. Also, because BetterHelp is carried out entirely online, it's very time efficient and easy to fit into a busy schedule, with no commuting to a therapist's office or sitting in a waiting room or looking for a parking spot. So if you'd like to try BetterHelp, go to betterhelp.com/huberman to get 10% off your first month. Again, that's betterhelp.com/huberman. And now for my discussion with Dr. Craig Koniver.

Andrew Huberman 7:40 Dr. Craig Koniver, welcome.

Craig Koniver 7:43 Thank you, Andrew. I appreciate the invitation to be here.

Andrew Huberman 7:45 I'm thrilled that you're here. We are gonna launch ourselves into the space that is called peptides.

Craig Koniver 7:53 Yeah.

Andrew Huberman 7:53 And it's a, it's an interesting space-

Craig Koniver 7:55 For sure.

Andrew Huberman 7:56 ... because I think, um, most people probably don't know what a peptide is.

Craig Koniver 8:00 Right.

Andrew Huberman 8:00 They should feel no guilt or shame about that.

Craig Koniver 8:02 Right.

Andrew Huberman 8:02 Well, I'm sure you'll, you'll tell us. But this area of medicine that people broadly refer to as peptides is picking up a lot of momentum, even though it's been around for a long time.

Craig Koniver 8:14 Mm-hmm.

Andrew Huberman 8:15 And I find it particularly interesting because, um, there are many people using peptides for very specific purposes. But most people haven't really heard of the various peptides that are out there.

Craig Koniver 8:28 Right.

Andrew Huberman 8:29 And if anything, we can be sure that in the years to come, peptides are going to be increasingly popular. And there's-

Craig Koniver 8:38 Totally agree.

Andrew Huberman 8:38 And there's of course, the incredibly popular peptide of GLP-1 agonist, um-

Craig Koniver 8:45 For sure. Taking over.

Andrew Huberman 8:47 So to drop into this, um, and make sure everyone's on the same page, uh, what is a peptide?

Craig Koniver 8:53 Yeah. I mean, just from a very elementary level, peptides are just chains of amino acids. So amino acids all naturally occurring molecules. We call it a peptide if it's 40 amino acids or less, call it a protein if it's 41 amino acids or more. The body makes, I think, last I read, 300,000 peptides. So it's a massive number. Uh, we've probably therapeutically are using closer to 150 over the years, which is obviously tiny compared to that. So to your point, this is blossoming. We've been using peptides for about eight years, a long time. Um, but still very early in, in our understanding of how best to use peptides and how clinically we're gonna get the most out of them. So it's exciting.

Andrew Huberman 9:37 Maybe just to orient ourselves, we should talk about GLP-1 first.

Craig Koniver 9:42 Okay.

Andrew Huberman 9:42 Um, not because it's necessarily the, uh, category of peptides that, um, I think, uh, people would want to consider for themselves, um, but because most people have probably heard of, uh, semaglutide-

Craig Koniver 9:56 Mm-hmm.

Andrew Huberman 9:57 ... and, um, Mounjaro and things like that.

Craig Koniver 9:59 Sure.

Andrew Huberman 10:00 So, um, how long ago was it that humans started injecting GLP-1 agonists in order to lose weight?

Craig Koniver 10:08 I think the weight loss aspect has only been a couple years. I mean, it's been tremendous how it's accelerated to like literally becoming the number one prescribed in America. Uh, you know, semaglutide, Ozempic w- was approved longer than that for, for type two diabetics, helping with, you know, glucose control and, and helping with glucose utilization. Uh, and what they found, you know, as a side effect was that these people were losing weight, and then that word caught on. And you know, what's interesting, I don't think most people understand this, most of the medicines prescribed, particularly in America, are prescribed off label, meaning they've never ever been approved for what they're used. So-

Andrew Huberman 10:46 Is that right?

Craig Koniver 10:47 Yeah, the vast majority. Yeah. Are never approved. So as a physician, I'm allowed to prescribe any drug for any reason I want, as long as it's been approved for something, right? As long as we're safe, right? We don't wanna be cavalier about this and renegade and do all these things that are not, that are out, out of bounds. But that is the truth. So th- that's, semaglutide is a great example being used for helping people, diabetics, type two diabetics lower their blood sugar. And then it got to, well, now let's help diabetics lose weight, right? Because diabetics struggle with weight, the insulin resistance. And then it became, well, even if you're not a diabetic, could you benefit from losing weight? Well, heck yeah, right? I mean, look at the amount of obesity and people who are overweight and having trouble maintaining healthy weight. It's exorbitant in this country and certainly worldwide. So then it spread. It did eventually get, uh, FDA approval specifically for weight loss.

Andrew Huberman 11:43 Mm-hmm.

Craig Koniver 11:43 But, you know, at first, no, it's been just for type two diabetics to help with glucose utilization. And, you know, we've been using primarily tirzepatide, which is like semaglutide version 2.0 mostly for the past two years.

Andrew Huberman 11:58 Mm-hmm.

Craig Koniver 11:58 Have learned a tremendous amount, and my opinion's actually changed from working with people.

Andrew Huberman 12:04 Yeah, what is your opinion? My understanding is that, um...... well, there's sort of two camps on this, it seems.

Craig Koniver 12:09 Yeah.

Andrew Huberman 12:09 At least two camps. One camp seems really bullish on this, um, they seem very excited about this drug. The other camp seems to, uh, point to the fact that one may be creating a drug dependency.

Craig Koniver 12:21 Mm-hmm.

Andrew Huberman 12:21 Um, that it's very expensive, um, and they point to the also potency of lifestyle factors like exercise and caloric restriction, um, eating mostly non-processed foods, et cetera, as a "better alternative". I'm not necessarily saying that.

Craig Koniver 12:37 Sure.

Andrew Huberman 12:37 I think they both have their place. It's re- to me, it seems very contextual, but as a clinician, I'm curious what you think.

Craig Koniver 12:43 Yeah, I- I agree, both have their place. Um, my philosophy is I want everyone have- to have access to things that are, number one, safe, that propel them to look, feel, and perform their best. And if that means, right, if it was just about if I can exercise my way out of this, eat my way out of this, meaning lose weight-

Andrew Huberman 13:01 Mm-hmm.

Craig Koniver 13:02 ... change my body composition, why do we have an epidemic, you know, of so many people who struggle with that? 'Cause it's really hard, right? And we don't totally understand it. I'm not saying that... Yeah, the processed food thing's a massive problem. I mean, I know that's come to light recently with-

Andrew Huberman 13:18 Mm-hmm.

Craig Koniver 13:19 ... people pushing for us to take a look at food companies and the quality of our food, which is amazing. But if people aren't interested in doing better for themselves, and, you know, the- this is- may not make sense, but I think it does. The analogy I use is I like to help people win the race first, which then helps them motivate to train for the next race, right?

Andrew Huberman 13:39 Mm-hmm.

Craig Koniver 13:39 And this kinda goes against the grain of conventional medicine, which is, you know, if you wanna train for the race, you have to, you know, run a certain number of miles, you have to sleep a certain way, you have to eat a certain way. You have to do all the things, struggle to get there, right? And losing weight is a struggle. And- and the way I look at it, if I can help people lose weight first, literally by using something like tirzepatide, semaglutide, and I've seen this, they're now excited. I mean, I met with a client yesterday here in Los Angeles, and she literally looked at me and said, "You've changed my life." She goes, "I am a super successful woman in my company, with my family, with my kids. Everything's great, but now I love my life. My workouts are better, I look better, my clothes fit better. I am super excited about waking up every morning." Like, she is there, and that is what it's about, right? And so for people, if you can help them achieve their goal first, then they're gonna be motivated. The light bulb turns on, they're gonna be like, "Wow, I want more of this." And that's the aha moment that I love helping people with.

Andrew Huberman 14:36 Mm-hmm.

Craig Koniver 14:36 So at first, I was like, "Oh, we gotta be really cautious with this." Same thinking, like, I don't want people to lose too much weight, like, this is a problem. Are they gonna be dependent? I don't like the notion that you have to take something the rest of your life. (sniffs) And I'm not saying it has to be the rest of their life, but when something works, and as far as I can tell, it's very safe, I think- I think it's worth discussing. And I- I like people having those options, at least.

Andrew Huberman 14:59 Yeah, it sounds like from the, uh, story you just told us that it's not just about, um, an aesthetic change that motivates people to lean into other aspects of their health and life-

Craig Koniver 15:08 Totally.

Andrew Huberman 15:08 ... when they lose some weight, that it's also just the- the sheer l- literal weight, and also that adipose tissue, fat tissue, you know, produces a lot of hormones that-

Craig Koniver 15:18 It does.

Andrew Huberman 15:18 ... we know impact the brain and, um, brain function, which is not to say that there aren't people out there with a lot of adipose tissues who aren't extremely bright and motivated, et cetera. But many people who are carrying excess body fat don't feel good. They report brain fog, et cetera. And I think now, thanks to Chris Palmer and actually at Stanford, there's also a program in metabolic psychiatry, we're starting to see, um, the- or understand and appreciate the link between adipose tissue and brain health-

Craig Koniver 15:46 Yeah.

Andrew Huberman 15:46 ... or lack of brain health in most cases.

Craig Koniver 15:48 Sure.

Andrew Huberman 15:48 So

Andrew Huberman 15:49 in the, um, in the case of GLP-1-

Craig Koniver 15:51 Yeah.

Andrew Huberman 15:51 ... um, people have criticized it saying that a fair percentage of the weight, uh, that's lost is, uh, lean body mass, muscle loss. But it seems to me that can be remedied pretty easily if people just do some resistance training.

Craig Koniver 16:05 I- I think part of that, yeah, resistance training. The other tha- thing I would say is from what we've seen is when people are using the conventional dosages, um, they're losing weight too quickly.

Andrew Huberman 16:16 Mm-hmm.

Craig Koniver 16:16 And so what we do is we get, uh, both semaglutide, mostly tirzepatide compounded, and that allows us to use basically microdosages, and start very s- low in terms of dosage and go slowly with people. And what we found is as long as people are losing less, two pounds or less a week, they're not losing the muscle mass. We certainly encourage a- adequate protein intake, you know, resistance training, but that microdosing has been a game changer, like literally game changer because then people don't feel like, oh my... And I've seen it where we- when we started, people were losing, you know, 15 pounds in three weeks.

Andrew Huberman 16:52 Goodness.

Craig Koniver 16:53 Right? And then they're like excited, but then they're not 'cause then they come off of it and they just gain it right back. Or they lose a lot of weight and they lose that fat in their face and they look like skeletons. And we've seen those called Ozempic faces. We don't like the way that looks, and that fat takes a while to come back. So if we just go slowly with this and we can really dial it in and nuance it, that has had a tremendous impact. And now beyond the weight loss, you know, w- we're seeing cognitive benefits, we're seeing, you know, inflammation benefits and a lot of people with autoimmune disease who their inflammation markers are coming down and that's the only thing we can think is working.

Andrew Huberman 17:27 Is that a direct effect of, um, Ozempic on the immune system and pathways related to inflammation? Or is it indirect through the loss of adipose tissue, body fat, which then lowers, uh, lowers inflammation?

Craig Koniver 17:42 Great question. O- or I could say, is it the positive thoughts that come from looking yourself in the mirror and feeling good, right? Which transcends to feeling better about yourself and that feeds forward to the momentum that you put forth in the world. All of those things. I think it's all of the above. You know, I think that's gonna be hard to dissect, but it's real. I mean, I have a patient, she's 50, she has Hashimoto's thyroiditis, meaning she attacks her thyroid. She doesn't, you know, make enough thyroid hormone. So she takes thyroid hormone. Well, one of the challenges with that is they make a lot of thyroid antibodies, this antibody called thyroid peroxidase antibody. And when you have an elevated thyroid peroxidase antibody, you don't feel good, you feel inflamed, your joints hurt, you get rashes. Life is just not easy. And it's a challenge to get that number down. I mean, certainly a challenge for me. You know, we traditionally use probiotics, a lot of things to help bolster the immune system. Well, now we're starting to use the GLP-1s and we're seeing that those antibody levels come down.... and I, I don't have a great way of explaining it, but there's something going on that's very positive.

Andrew Huberman 18:41 Mm-hmm. Very interesting.

Andrew Huberman 18:43 Well, I suppose moving from, uh, most widely known, um, peptides are still fairly unknown to most people, even the concept-

Craig Koniver 18:52 Yeah.

Andrew Huberman 18:52 ... but that's why you're here. Uh, you're changing that right now. Um, but moving from things like GLP-1 to what I would probably call the second most popular peptide, the one that we're hearing more and more about all the time, um, and that's BPC-157-

Craig Koniver 19:09 Yeah.

Andrew Huberman 19:09 ... Body Protection Compound 157.

Craig Koniver 19:11 Yeah.

Andrew Huberman 19:12 Um, which to my understanding, there are a lot of animal data-

Craig Koniver 19:17 Yes.

Andrew Huberman 19:17 ... very few, if any, clinical studies on humans.

Craig Koniver 19:19 Agreed.

Andrew Huberman 19:20 But a lot of people now taking BPC in various forms.

Craig Koniver 19:23 Yeah.

Andrew Huberman 19:23 Um, what are some known uses for BPC, let's just say within your clinic?

Craig Koniver 19:30 Sure.

Andrew Huberman 19:31 Um, and then we'll get around to the fact that BPC has, let's hope temporarily, been taken off market-

Craig Koniver 19:37 Yep.

Andrew Huberman 19:37 ... um, and what some of the alternatives are. But, um, what is BPC? What instances or people have you found it useful for?

Craig Koniver 19:45 So many. So I think with BPC, for me, kind of the most utilized peptide that we've used, so we like to use BPC a- almost with every patient. It is very anti-inflammatory, right? And so just from a very general perspective, you know, most people walking around who are adults, you know, they're stiff, they're sore as they get older, they work out. We work with le- uh, athletes of all levels. There's that element of inflammation. Maybe they have some chronic disease, diabetes, heart disease, autoimmune disease. Inflammation is paramount, we understand that. And BPC, I, you know, observe with so many patients, we're talking thousands upon thousands of patients where their inflammation comes down. So they feel better, they're not as stiff, they're not as sore, their knee doesn't hurt as much, their shoulder's improved. So we've learned, you know, that we start with a dose, you know, based upon these, like you said, animal studies, um, which is conservative, make sure it's safe, and then we've seen over time that we can get to higher and higher dosages and have even more of an impact, you know? And I think, so for people understanding using BPC, we started with a dose of like 500 micrograms a day. We got up to 5,000 micrograms a day, you know? Uh, and we'd like a protocol five days on, two days off, and that's been very helpful for a variety of things from post-viral, you know, with the pandemic, had a lot of success with BPC too. Again, you name it, h- honestly almost everyone I could think of, particularly as people are engaging more fitness related lives, they're working out more, I would argue that anyone who's working out on a regular basis, BPC is gonna benefit. It's gonna help, you know, improve the inflammatory status, but also help with recovery, and it doesn't seem to be one of these agents that's gonna be detrimental like we've, we were talking earlier, Rob and I, before this started, like, you know, they found that people who are working out hard taking antioxidants, that there seems to be a negative consequence to that because you don't allow the body to kind of repair itself. I don't think that's happening with BPC.

Andrew Huberman 21:41 That's interesting because my understanding is also that, um, part of the specific and general adaptation of exercise is triggered by inflammation.

Craig Koniver 21:50 Yeah.

Andrew Huberman 21:50 This is why indeed it is true that doing ice bath or really cold water immersion, cold shower seems fine, but cold water immersion in the, you know, four to eight hours after resistance training can limit some of the hypertrophy and strength gains from resistance training because what you're inducing when you actually go into the gym-

Craig Koniver 22:08 Yeah.

Andrew Huberman 22:08 ... is the, that leads to the hypertrophy and strength training is an inflammation response-

Craig Koniver 22:12 Right.

Andrew Huberman 22:12 ... that triggers the compensation-

Craig Koniver 22:14 Right.

Andrew Huberman 22:14 ... or, um, or the hypercompensation. So, um, it's interesting you're saying that BPC... And by the way, I must say this because then, uh, forgive the editorial, but that is not to say that cold plunges and cold immersion is bad, it's just in the hours following resistance training specifically for hypertrophy and strength training, if those are your goals, probably best to do it outside of that window. Other times, it has some tremendous benefits. Be safe, but there. Okay. Back to the topic at hand.

Craig Koniver 22:42 Yeah.

Andrew Huberman 22:42 Forgive me, but-

Craig Koniver 22:42 No. Yeah.

Andrew Huberman 22:42 ... this can set, it can set off a complicated-

Craig Koniver 22:46 Sure, sure.

Andrew Huberman 22:46 ... um, storm of sorts if I'm not-

Craig Koniver 22:48 I hear you.

Andrew Huberman 22:48 ... if I'm not ultra clear about the details. Um, BPC-157 strongly anti-inflammatory.

Craig Koniver 22:53 Yes.

Andrew Huberman 22:54 My understanding is it also may upregulate growth hormone receptors.

Craig Koniver 22:57 It does, right.

Andrew Huberman 22:58 Mm-hmm.

Craig Koniver 22:58 And so it works well if you're, you know, we'll get into taking a growth hormone releasing peptide, it pairs very well with that, 'cause then you're working both sides of the equation, meaning if you're using a growth hormone releasing peptide like sermorelin or ipamorelin, GHRP-6, whatever, you're helping your pituitary put out more growth hormone. Well, if you combine it with BPC which upregulates the growth hormone receptor, you make the process of growth hormone binding more efficient, so you get more out of it. Then you can use less of the growth hormone releasing peptide with the same result.

Andrew Huberman 23:27 Got it.

Craig Koniver 23:27 Yeah.

Andrew Huberman 23:28 BPC-157, um, comes in many different forms-

Craig Koniver 23:31 Mm-hmm.

Andrew Huberman 23:32 ... or it used to when it was allow- uh, when it was FDA, uh, not disallowed, um-

Craig Koniver 23:36 Sure.

Andrew Huberman 23:37 ... so I could imagine how the oral forms-

Craig Koniver 23:40 Mm-hmm.

Andrew Huberman 23:40 ... would allow for a just general, um, anti-inflammatory response.

Craig Koniver 23:45 Mm-hmm.

Andrew Huberman 23:45 It's a gut peptide-

Craig Koniver 23:46 Mm-hmm.

Andrew Huberman 23:46 ... so we don't have to worry about it being destroyed by the gut. Most peptides that go into the gut are broken down and so on-

Craig Koniver 23:51 Correct.

Andrew Huberman 23:52 ... but this peptide, when it's naturally occurring, occurs in the gut-

Craig Koniver 23:56 That's right.

Andrew Huberman 23:56 ... so it survives in the gut.

Craig Koniver 23:57 Right.

Andrew Huberman 23:57 So if somebody is taking BPC-157 orally through a capsule or tablet form-

Craig Koniver 24:02 Right.

Andrew Huberman 24:03 ... um, my guess is that has a general anti-inflammation response.

Craig Koniver 24:08 I think it can. What we've observed is more limited to the gut, so people with any sort of, you know, gastrointestinal issue, whether that's inflammatory bowel disease like Crohn's or ulcerative colitis, you know, irritable bowel, you name it, leaky gut, I think oral BPC is more effective there. Mm-hmm.

Andrew Huberman 24:23 Has it been shown to be effective for those conditions or have you observed that clinically?

Craig Koniver 24:27 I'v- I've certainly-

Andrew Huberman 24:28 Okay.

Craig Koniver 24:28 ... observed that clinically. But interestingly, I've observed a better clinical response when people inject it.... even for gastrointestinal-related things. So, I think injecting, and then, so people injecting sub-q, which is right under the skin. We use the tiniest of needles, like an insulin needle, 30 or 31 gauge. We're talking super small.

Andrew Huberman 24:45 Mm-hmm.

Craig Koniver 24:46 Um, and so, I know a lot of people are like, "I'm never injecting one of these."

Andrew Huberman 24:48 Yeah. This is less painful than a, um, than a Texas mosquito bite.

Craig Koniver 24:51 (laughs) There you go.

Andrew Huberman 24:52 Yeah.

Craig Koniver 24:52 Super easy. Once you do it once or twice, it's really easy. And we-

Andrew Huberman 24:54 Mm-hmm.

Craig Koniver 24:54 ... we walk people how to do, how to do that. But, uh, interestingly, I, we started thinking, "Okay, if you've got something going on in your gut, you should take oral BPC 'cause it's gonna target it right then." And I found, you know, if we're injecting, it actually works better than the oral. And, uh, and then it came up, "Well, what if I've got an elbow injury? Should I inject it in my elbow?" And we found, actually, don't. It's gonna work systemically.

Andrew Huberman 25:13 Mm-hmm.

Craig Koniver 25:13 You can inject it in your abdomen or your rear end. You're still gonna get benefit in your elbow, but now you're gonna get benefit in all your joints.

Andrew Huberman 25:20 Hm.

Craig Koniver 25:20 All over your body, systemically.

Andrew Huberman 25:22 How do you think that's working? And my understanding is BPC-157 can initiate fibroblast migration. Some of the cells that make up the, the various connective tissues that, um, when injured or sore, other things can make us injured or sore, of course, but when injured or sore, that they, those need repair.

Craig Koniver 25:38 Yeah.

Andrew Huberman 25:39 Um, so it always was, um, perplexing to me why one could put BPC-157 in such a small volume under the skin.

Craig Koniver 25:46 Right.

Andrew Huberman 25:46 You know, just a few, uh, centimeters off the belly button, and it would somehow, um, seek out the, the injury site in an elbow or an Achilles. And there are all these wild anecdotal tales of, you know, lore of, let's just say, uh, there was this Olympic athlete, not this last Olympics, but the previous Summer Olympics-

Craig Koniver 26:05 Right.

Andrew Huberman 26:05 ... that had a torn Achilles who came back a few weeks later.

Craig Koniver 26:08 Mm-hmm.

Andrew Huberman 26:08 And everyone was, and medaled. People were talking about, you know, took podium, um, uh...

Craig Koniver 26:13 Mm-hmm.

Andrew Huberman 26:13 That is, and people were talking about BPC-157. There was kind of this-

Craig Koniver 26:16 Mm-hmm.

Andrew Huberman 26:16 ... you know, and who knows? That's just, uh, chatter-

Craig Koniver 26:19 Sure.

Andrew Huberman 26:19 ... and fog, as they say.

Craig Koniver 26:21 Sure.

Andrew Huberman 26:21 But, um, kinda wild, the idea that you could just inject something systemically, put it into the systemic circulation, into the bloodstream, and it would ferret out the location in which the injury took place and initiate a recovery response.

Craig Koniver 26:34 It is interesting, but we've seen it with, uh, not to get off-topic, but we've seen it with, with stem cells.

Andrew Huberman 26:38 Mm-hmm.

Craig Koniver 26:38 So, they've taken stem cells. They've tagged them radiographically so you can see them, um, and the study I read, which I can find for you, someone had a, a wrist, broken wrist, and they gave them intravenous stem cells, and 24 hours later, when they visualized radiographically, those stem cells had aggregated at the site of the fracture. So, there's a lot, you know, about our bodies-

Andrew Huberman 27:03 Mm-hmm.

Craig Koniver 27:03 ... obviously we don't know.

Andrew Huberman 27:04 Sure.

Craig Koniver 27:05 Uh, there's a kind of innate human, like, design and intelligence, which I believe in. Um, I see it 'cause we, we've done a lot of IV therapy over the years. And you, you know, it's interesting, when you give some- something intravenously, you're getting it in the bloodstream, and you can feel some of these different compounds, we were just talking about vitamins, working within seconds. And it shows you how quickly things circulate. People don't understand, like, how quickly we move our circulation. It's massively fast.

Andrew Huberman 27:34 Uh, if one has ever gone into the hospital for a surgery and, and got a s- a cold saline infusion-

Craig Koniver 27:39 Yeah.

Andrew Huberman 27:40 ... you realize how quickly it hits your, your toes. You know, they're putting it in-

Craig Koniver 27:43 It's-

Andrew Huberman 27:43 ... at your elbow.

Craig Koniver 27:43 It's almost instantaneous.

Andrew Huberman 27:44 Yeah, within a few seconds. It also, uh, makes one appreciate how we're all, uh, generally a little bit dehydrated. When you start getting a real, proper saline infusion-

Craig Koniver 27:52 Totally.

Andrew Huberman 27:52 ... all of a sudden you feel yourself come to life in a way that, "Oh-"

Craig Koniver 27:54 Right.

Andrew Huberman 27:54 "... this is what it feels like to have just the right amount of salt in my bloodstream." Yeah.

Craig Koniver 27:58 Exactly. So, go- so going back to BPC, where I think it shines is in these ligaments and tendons, right? I think this is where most of these injuries happen is where muscle is connecting to the bone, um, you know, and there's, you know, people, you know, grow their muscle, but we don't stretch the tendons and ligaments well, and that's where we get pull, sometimes strain and sprain and tearing, and I think that's where BPC shine. That's certainly where it's been studied in animal studies, and I know that because we can inject it directly into tendons, which is unlike steroids. We would never inject steroids into a tendon. You'd damage the tendon.

Andrew Huberman 28:29 Mm-hmm.

Craig Koniver 28:29 BPC we mix with things like PRP, PRF, which is platelet-rich fibrin. A little bit different than PRP. And you'll get healing within days. Like, it's awesome.

Andrew Huberman 28:38 Wild.

Craig Koniver 28:39 Super safe, uh, and it's amazing for people.

Andrew Huberman 28:42 BPC

Andrew Huberman 28:43 is definitely, uh, shorthand for BPC-157, that is, is certainly in widespread use. I have been concerned, just personally-

Craig Koniver 28:52 Yeah.

Andrew Huberman 28:52 ... about, um, gray market sources-

Craig Koniver 28:55 Yep.

Andrew Huberman 28:55 ... that, um, contain contaminants and the fact that, um, many people are obtaining BPC-157 not from a physician, not from a compounded pharmacy-

Craig Koniver 29:04 Right.

Andrew Huberman 29:04 ... but just kind of on, quote-unquote, "On the internet."

Craig Koniver 29:07 Sure.

Andrew Huberman 29:07 Uh, you're a physician. Um, I'm guessing that until the recent ban by the FDA, you were able to prescribe clean BPC as it were.

Craig Koniver 29:17 Yeah, there was-

Andrew Huberman 29:17 Um, what's the story with BPC now? And maybe we could talk about gray market-

Craig Koniver 29:21 Sure.

Andrew Huberman 29:21 ... versus, um-

Craig Koniver 29:22 I think it's a great question.

Andrew Huberman 29:23 ... you know, versus prescribed and made at a compounding pharmacy versus a pharmaceutical company, uh, pharmaceutical. So, um-

Craig Koniver 29:31 Yeah.

Andrew Huberman 29:31 ... and then, of course, there's black market, but let's just leave that out. Um-

Craig Koniver 29:34 Sure.

Andrew Huberman 29:34 ... you know, there are people that are gonna tell it, you know, tell you, "Hey, this is BPC," and sell it to you. That's obviously bad and dangerous, so.

Craig Koniver 29:40 Well, we see that with the anabolic steroids, right?

Andrew Huberman 29:42 Right.

Craig Koniver 29:42 Like, so anabolic steroids are on the black market. You can't really... I mean, there's one anabolic steroid which is nandrolone, which is Deca, which can be officially prescribed. We use it. You can combine it with testosterone all in the up and up, totally above table. The rest, things like Trenbolone, others, you, you can't get them from a physician. In fact, you, very hard to get them from a reputable website in the United States.

Andrew Huberman 30:05 So, as long as we're, we're here, my understanding is Deca, Durabolin, and, uh, testosterone cypionate are, can be prescribed, or testosterone enanthate, things like that-

Craig Koniver 30:13 Different esters.

Andrew Huberman 30:14 ... by, by physicians. That's-

Craig Koniver 30:14 Correct.

Andrew Huberman 30:15 That's because it's been FDA approved for the treatment of various things. Hypocretinial syndromes-

Craig Koniver 30:19 Correct.

Andrew Huberman 30:20 ... uh, testosterone replacement therapy in both men and women-

Craig Koniver 30:22 Correct.

Andrew Huberman 30:23 ... et cetera. So, th- tho- those categories of testosterone, um, like compounds-

Craig Koniver 30:28 Right.

Andrew Huberman 30:29 ... um, cypionate, enanthate, et cetera, and-... Deca Durabolin, which is basically like, is it similar to DHT? Is it, uh, go a-

Craig Koniver 30:38 A little bit.

Andrew Huberman 30:38 Mm-hmm.

Craig Koniver 30:39 Yeah, I mean, it's, uh, the, the generic name is Nandrolone.

Andrew Huberman 30:42 Mm-hmm.

Craig Koniver 30:42 Yeah. I mean, it has the flavor of helping with joints.

Andrew Huberman 30:46 Mm-hmm.

Craig Koniver 30:46 I think, uh, it works synergistically with things like testosterone, different, you know, whether it's testosterone cypionate enanthate. Um, and, and I like it for people who, particularly people who have been on testosterone, men who've been on testosterone replacement for a long time, which is many men. Um, they tend to get less out of testosterone, it becomes less potent, like anything, right? If you use something for a long time, you're gonna get less out of it over time. Anything you expose yourself to continually doesn't work as well. Um, and so, you know, like to, to make this really real, I had a patient who was a, uh, in the, uh, Marines and served as Secret Service for several, uh, White Houses. And he had a lot of, you know, osteoporosis, osteopenia, you know, bone loss. And, you know, this is where I learned about using something like Nandrolone, 'cause we combined Nandrolone with testosterone. It changed his life. You know, this guy in his 80s who was, uh, had to use a cane who came back to life, who started, you know, becoming super mobile and working out again. And synergistically, I think it works really well. Not to get too far off topic, but-

Andrew Huberman 31:46 Mm-hmm. No, it's interesting, and I think, uh, another short of brief editorial from me if, if I may. Um, you mentioned this patient was in their 80s. I think nowadays, unfortunately, a lot of younger males in particular, guys in their, gosh, even teens, but 20s and 30s-

Craig Koniver 32:02 Yeah.

Andrew Huberman 32:02 ... even early 40s, think that they need to look to, um, synthetic testosterones-

Craig Koniver 32:07 Mm-hmm.

Andrew Huberman 32:07 ... in order to, uh, look a certain way, um, perform a certain way-

Craig Koniver 32:12 Mm-hmm.

Andrew Huberman 32:12 ... um, in the gym, libido, et cetera. And I, I'll go on record again and again and again saying that it's absolutely not necessary for most people of those ages, provided that they, um, are taking good care to sleep well, eat well, take care. Now, but I, I realize-

Craig Koniver 32:28 Yeah.

Andrew Huberman 32:28 ... that there are a growing number of use cases where people, for whatever reason, aren't able to recover from exercise, they're struggling. This is a little bit like the Ozempic conversation, right? Where th- there are things that can help move the needle in the right direction, uh, pun intended. Um, but here with testosterones, synthe- synthetic testosterones and Deca, there's a real concern about loss of fertility.

Craig Koniver 32:50 Totally.

Andrew Huberman 32:50 Right?

Craig Koniver 32:51 I, I think it brings up a larger point, which is, and obviously I'm biased, but I think it's super helpful for people to have a physician help them in this course.

Andrew Huberman 32:59 Mm-hmm.

Craig Koniver 33:00 Particularly with testosterone. It is just known that people get it from their trainers, their bros from the gym, right, who are saying, "Oh, you gotta use this." I mean, I have so many patients who are started using testosterone in their late teens, early 20s.

Andrew Huberman 33:12 Goodness.

Craig Koniver 33:12 Yeah.

Andrew Huberman 33:12 That's it. I mean, not goodness, meaning badness. That does not seem like a good idea.

Craig Koniver 33:16 And it's still very common, like it's still-

Andrew Huberman 33:17 Goodness gracious.

Craig Koniver 33:18 Still very common. And, you know, one in particular, this is probably 10 years ago, came to see me. He's 25, he got married. And to your point, he said, "I'm ready to have kids. I have zero sperm left." Right? And that's a real thing. And so he had been using, and I would say abusing both testosterone and growth hormone for years. Now, what he told me was, and I get it, he was Superman. He could wake up, do a hard workout, you know, crush it. Wake up the next morning, was not sore, crush it again. And just kept going, kept going. He was super fit, super happy in that regard, in how he looked, how he felt, how he performed. Then he got to a point where he's a little bit wiser and mature, and he was like, "Oh, my goodness. Now, there's a repercussion for this." And I've seen that time and time again. And the repercussion is big. You're not making any sperm or the sperm quality is super poor. Now what do you do? Well, now you gotta come off the testosterone. You gotta rebuild your system, which we can do, you know? We can use things like Clomiphene, Enclomiphene, HCG, lots of different agents to help in that regard, even certain peptides. But I think it brings up a large point, even getting into peptides, which is having a physician who's knowledgeable, to me, is super helpful. The challenge for people is they don't know where to get the right information, right? And they're getting it from websites, they're getting it from people saying, "Oh, just try this peptide." And I've had lots of people talking about the, you know, websites or whatever, not to name any names, who have had anaphylactic reactions to research type peptides, which are not for human consumption. And I'm not saying that they're bad companies or whatever, you just gotta be careful.

Andrew Huberman 34:45 Yeah. Well-

Craig Koniver 34:46 You gotta be selective, at least.

Andrew Huberman 34:47 Right. Well,

Andrew Huberman 34:48 what brought us onto the, uh, conversation about testosterone was this black market issue.

Craig Koniver 34:52 Yeah.

Andrew Huberman 34:52 There's also what I would call this, um, dark, dark gray market issue, which is that there are a number of companies that will sell all sorts of things, but peptides in particular-

Craig Koniver 35:02 Sure.

Andrew Huberman 35:02 ... and listed on their website, it'll say, "Not for human or animal consumption-"

Craig Koniver 35:06 Correct.

Andrew Huberman 35:06 "... for research purposes only."

Craig Koniver 35:08 Right.

Andrew Huberman 35:08 And one of the major issues is that the, um, potency and cleanliness, so to speak-

Craig Koniver 35:15 Mm-hmm.

Andrew Huberman 35:15 ... of, uh, purity-

Craig Koniver 35:16 Yes.

Andrew Huberman 35:17 ... of those, um, compounds is not established-

Craig Koniver 35:20 Right.

Andrew Huberman 35:20 Um, and many of them have LPS, lipopolysaccharide in them, which is inflammatory. And earlier, before we started recording, you mentioned, um, that you have s- heard of or interacted with, not your patients, but people who have come to you saying that they had, l- like, really serious, l- life-threatening, um-

Craig Koniver 35:37 For sure.

Andrew Huberman 35:38 ... consequences for using these black market certainly, but, um, dark gray market-

Craig Koniver 35:42 Yes.

Andrew Huberman 35:43 ... uh, peptides.

Craig Koniver 35:44 Yeah. And so to, to tell the stor- story further is back in October of 2023, the FDA, uh, put many peptides, BPC, and we can name them out, on what's called a category two list, meaning they are no longer allowed to be compounded, right? Now, that, that excludes then research companies who are not under the purview of the FDA. But these compounding pharmacies, it's been a huge blow, because they've been told they cannot use these agents.

Andrew Huberman 36:10 And the compounding pharmacies-

Craig Koniver 36:11 Yeah.

Andrew Huberman 36:12 ... are distinct from these other, um, black and dark gray, um, sources, um, in that they actually can establish purity, they are designed to be injected into humans.

Craig Koniver 36:22 And they have a totally different standard, right? So they, and I think it's confusing for people when they hear compounding pharmacy, they thought fringe. They're not fringe. They're FDA regulated, they're Board of Pharmacy regulated in every state. They are monitored, they are inspected all the time. I've worked with compounding pharmacies my whole career, which is going on tw- you know, close to 25 years now. Just like anything, there's some amazing compounding pharmacies and there's some not so amazing compounding pharmacies which cut corners. The ones we work with don't cut any corners, and I know that 'cause they're inspected o-... all the time, right? And it's a big deal to them and they wanna do it right with purity, with processing and making sure that anything they make, especially a sterile compound, which is gonna be anything injected, you know, eye drops, things you inject in yourself, whether it's IV, subQ or intramuscular, they're st- co- considered sterile. Um, they have to then be tested by an outside lab to make sure purity, make sure that there's no endotoxins, things like that. It's, it's highly regulated and it's a big deal for them and it's a big deal for the physicians who, you know, prescribe with them. Which I appreciate, because w- the advantage of a compounding pharmacy is we can tweak the dosage. We don't have to use a standard set dosage. We can combine things synergistically to get, you know, one plus one doesn't equal two now, it equals four.

Andrew Huberman 37:34 Mm-hmm.

Craig Koniver 37:35 And that, to me, is a huge advantage. Just like we were talking about with the GLP-1, semaglutide and tirzepatide, we get those compounded so that... You know, we have a, a... The compounding pharmacy we're using now, we're making a unique combination of tirzepatide and sermorelin, right? Which will address some of this muscle loss that people are getting. So we can combine that.

Andrew Huberman 37:54 So sermorelin to stim- to stimulate growth hormone release, offset some of the muscle loss from-

Craig Koniver 37:58 Exactly.

Andrew Huberman 37:58 ... tirza- tirzepatide?

Craig Koniver 38:00 Yeah.

Andrew Huberman 38:00 Yeah.

Craig Koniver 38:00 And, and so you can do things like that with a compounding pharmacy. But again, just to make sure people understand, compounding pharmacies are highly regulated, highly regulated. Um, again, there's always gonna be bad apples, but, uh, you know, physicians who know how to work with compounding pharmacies I think provide access to things that these conventional, both pharmaceuticals and conventional pharmacies can't.

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Andrew Huberman 39:51 is it fair to say that if one is interested in exploring the use of peptides for what you refer to as performance medicine-

Craig Koniver 39:57 Yep.

Andrew Huberman 39:57 ... um, mental, physical health and performance-

Craig Koniver 40:00 Yes.

Andrew Huberman 40:00 ... um, falls underneath that, to essentially only put peptides into their body, uh, maybe even on their body surface-

Craig Koniver 40:11 Sure.

Andrew Huberman 40:11 ... that they're obtaining from a physician who's obtained the peptides from a compounding pharmacy?

Craig Koniver 40:15 Yeah, a- and who's developing a relationship. So we, for any peptide that we use, we meet with the patient. We make sure they're a good fit. We make sure that there's no contraindications. We also can recommend and specifically dial it up or down, whatever it is, come up with, "This is what we think you should use based upon your life experience, the medicines you're taking or not taking, the conditions you're treating or not treating," right? I think that's really important. Again, I'm biased being a physician. My whole goal is to get to know patients. That's why I'm here, is to kind of walk that walk and help people in that regard. And, you know, if someone's out there on the internet doing it themselves, they're, they're walking in, you know, kind of, you know, on their own.

Andrew Huberman 40:55 Mm-hmm.

Craig Koniver 40:55 And so, you know, not to make it like everything bad is gonna happen, but when you're, when you have the help of someone who has experience, that goes a long way, I think particularly with something like this.

Andrew Huberman 41:04 Yeah, I agree. And, um, and it worries me very much that people are buying PPC from, um, gray mar- dark gray market-

Craig Koniver 41:11 (laughs)

Andrew Huberman 41:11 ... or, uh, uh, black market sources.

Craig Koniver 41:14 Yeah.

Andrew Huberman 41:14 I mean, anything that says on it, "Not for animal or human use. For research purposes only," y- you can pretty much guarantee the endotoxin, the lipopolysaccharide at least has not been removed. And that could be really problematic, especially since my understanding is that it can be cumulative over time. It's not that one injection causes somebody to go into anaphylactic shock, it's that some of this LPS can build up a, an inflammatory response-

Craig Koniver 41:37 Sure.

Andrew Huberman 41:37 ... over time, and then you don't know where the tipping point is. And then somebody can have a really terrible reaction.

Craig Koniver 41:42 Well, and then taking it a step further, n- n- you know, getting away from just peptides, but any... I remember this was, I don't know, 15 years ago, someone was taking advice from a very famous doctor on TV about taking an oral compound to lose weight. And they called me up and they said, "Ugh, I'm having terrible headaches, terrible headaches for days." They came in, their blood pressure was through the roof, you know, like I don't remember the specific numbers, but let's just say 220 over 140, and normally it's 120 over 80. "Well, did you take anything different?" "Yeah, this doctor recommended I take this weight loss compound," right? So the problem is people have access to all this information, but if they're not under the guidance of a doctor to help clean up the mess and we cleaning up the mess, and not that there's always mess, but this is what we enjoy doing. You know, as, as a physician, like, we've seen the darkest of dark, you know, we're able to help people when things don't go perfectly planned. And, uh, I think that's a big deal, you know, particularly when there's lots of these tools and they're exciting tools and they're great tools. And, um, fortunate for me, I've been in this space longer than most, that I've just, you know, built up a large repertoire of experience, of observing people and working with people and seeing, we gotta tweak this, we gotta nuance this. Or sometimes we don't ever wanna use this again.

Andrew Huberman 42:56 Mm-hmm.

Craig Koniver 42:57 You know, this is not for most people.

Andrew Huberman 42:59 So,

Andrew Huberman 43:00 given that BPC-157 has been effectively removed from the, um, legitimate market-

Craig Koniver 43:06 Yep.

Andrew Huberman 43:07 ... uh, what are people's alternatives? Again, uh, working with the, the, uh, caveat that, um, people should work with a physician-

Craig Koniver 43:16 Yeah.

Andrew Huberman 43:16 ... um, where can physicians get something similar enough to BPC-157?

Craig Koniver 43:20 So, there's a new compound, newer, a peptide called, uh, the... shortened for PDA, Penta-DCA arginate. It's basically the same molecular structure as BPC, except they've swapped out an acetate for arginate.

Andrew Huberman 43:34 One amino acid-

Craig Koniver 43:35 Correct.

Andrew Huberman 43:35 ... substitution.

Craig Koniver 43:36 One amino acid substitution. Um, and so we're using that and having really good results. Um, I... certainly, it's early in the game of using PDA, but it seems very close to BPC in the clinical responses we're getting from our patients who are reporting back decrease in inflammation, all these wonderful things that we used to see with BPC. So, and I- and I think, uh, I surmise that this is going... how it's gonna be with all of these peptides, right? Because, again, peptides are just chains of amino acids, you know, certainly a lot of people smarter than me trying to figure out how do we then create other types of amino acid combinations, you know, i.e. peptides, that do d- similar actions to BPC, to thymosin alpha, to ipamorelin, to TB 500, on and on and on. So I'm hopeful in that regard.

Andrew Huberman 44:23 Mm-hmm.

Craig Koniver 44:24 Um, and I- and I also... you know, some of my patients work at the very highest level of the US government. They are well aware of this and who have assured me they're going to look at this, that this is serious, you know, because they're- they've been using peptides and they're concerned that, oh, my goodness, the FDA came in and changed the game. Very... it's been a huge setback for all of us.

Andrew Huberman 44:44 I definitely want to circle back as to what the motivation was by the FDA for doing that, um-

Craig Koniver 44:50 Yeah. I mean-

Andrew Huberman 44:50 ... at, at some point.

Craig Koniver 44:51 Yeah.

Andrew Huberman 44:51 I think, um, in the meantime, however, I think, um, there's a lot of interest in BPC-157, a lot of use of BPC-105-57. The sources of BPC-157 are now drying up.

Craig Koniver 45:03 Yep.

Andrew Huberman 45:03 And that's why I'm personally concerned that people are gonna start going to the dark gray market and black market. I'm excited about the, uh, Penta-DCA arginate.

Craig Koniver 45:13 Yes.

Andrew Huberman 45:13 Um, so let's put that on people's, um, ear map, um-

Craig Koniver 45:16 Yeah.

Andrew Huberman 45:17 ... brain map. Penta-DCA arginate may be a, a good, uh, physician-prescribed substitution for-

Craig Koniver 45:23 Yeah.

Andrew Huberman 45:23 ... people that can benefit from BPC-157.

Craig Koniver 45:24 A- and a good starting dose of, to make it really clear for people and helpful, 250 micrograms to 500 micrograms. We're using 500 micrograms injected daily. Again, we like Monday through Friday, take the weekends off. That's a good dosing schedule.

Andrew Huberman 45:36 Mm-hmm.

Craig Koniver 45:37 We'll, we'll see how that goes. We probably can use larger dosages. That's conservative.

Andrew Huberman 45:41 Mm-hmm.

Craig Koniver 45:42 Um, but that's a good starting point for people.

Andrew Huberman 45:44 And thus far, you haven't mentioned any side effects of BPC-157-

Craig Koniver 45:48 Mm-mm.

Andrew Huberman 45:48 ... or Penta-DCA arginate.

Craig Koniver 45:49 Mm-mm.

Andrew Huberman 45:50 It's... that's kind of remarkable. Uh-

Craig Koniver 45:51 It's been tremendous. Yeah. And we were using BPC intravenously as well. You know, patients would come in and, you know, "Oh, tweaked my knee, tore my ACL, tore my, you know, meniscus," whatever. Um, you can give them BPC essentially as a bolus intravenously. My goodness, that made a difference. Now that... using something intravenously from the pharmacokinetic standpoint, it's not gonna last in the system very much. It's more of a spark.

Andrew Huberman 46:16 Mm-hmm.

Craig Koniver 46:16 Whereas if you use an agent subcutaneously, you're gonna get more of a long-lasting... you know, again, not terribly long lasting with peptides, but longer than using something intravenously. Kind of the sweet spot was certainly using both.

Andrew Huberman 46:28 Mm-hmm.

Craig Koniver 46:28 You could use something as a spark to initiate that anti- inflammatory cascade, then follow up with the subcutaneous dose. Yeah.

Andrew Huberman 46:34 And

Andrew Huberman 46:35 even though earlier we were talking a little bit about, um, some hormone replacement therapies-

Craig Koniver 46:40 Yeah.

Andrew Huberman 46:41 ... um, before that, off microphone, um, you mentioned that you prefer peptides to direct hormone manipulations in most cases. So I think, um, while peptides can be hormones, there are things like, uh-

Craig Koniver 46:53 Sure.

Andrew Huberman 46:53 ... um, uh, oxytocin is sometimes called a peptide hormone.

Craig Koniver 46:57 Sure.

Andrew Huberman 46:57 Um-

Craig Koniver 46:58 Insulin.

Andrew Huberman 46:58 ... in general, when people think about hormone therapies-

Craig Koniver 47:00 Yeah.

Andrew Huberman 47:00 ... they're thinking testosterone, estrogen, pregnenolone, uh, you know, thyroid-

Craig Koniver 47:05 Thyroid.

Andrew Huberman 47:05 ... et cetera. It, it sounds to me like much of your practice is built up around the, the notion that there are things that one can use, peptides, to kind of, um, push and pull on these various systems-

Craig Koniver 47:17 Mm-hmm.

Andrew Huberman 47:17 ... without getting into them directly. My understanding is the advantage of that is you don't get the negative feedback. You don't gain the-

Craig Koniver 47:22 I agree.

Andrew Huberman 47:22 ... shutting down of natural production.

Craig Koniver 47:24 Yeah. You know, and testosterone's a great example. Um, because, like we were saying, I don't ever want to manipulate hormones. You know, growth hormone's another example. I don't ever want to manipulate that. Meaning, you know, providing it to people more than they would get in nature. This is why I actually don't... a little bit off topic, like when people use testosterone pellets or any sort of pellet therapy, because you're exposing people to a concentration of hormones we would never, ever see in nature. I would prefer people inject it, where you're gonna get some variation in dose on a day-to-day basis, which, we're humans, so we do get some day-to-day variation, or topically or under the tongue or something. Um, peptides, same thing. I don't want to manipulate the hormones, right? I want to just stick within kind of the, the highways or the lanes, swim lanes for how they should operate and, and then take advantage of that. And that's been a safe way to do it, as opposed to... and I've seen it, you know, talking about another peptide, which is ipamorelin, a growth hormone-releasing peptide. Uh, ipamorelin, you inject under the skin, travels up to the pituitary, the posterior pituitary in the brain, which is responsible for putting out growth hormone. That growth hormone then leaves the pituitary, enters the bloodstream, travels to the liver, where we make insulin-like growth factor one, which then enters the circulation as very anabolic, meaning growth, healing, mending. You know, as we get older, we make less growth hormone. As we get older, we wear down, obviously, we get, you know, degenerative conditions. Part of that, uh, I don't know what part, for everyone it's a little bit different, is because of our hormonal decline.

Andrew Huberman 48:53 Mm-hmm.

Craig Koniver 48:53 And so when you can give something like ipamorelin, and we can talk about others, you're actually helping not only push out a little bit of growth hormone for people, but you're directing when you push it out, right? We, we think that's why it's important for people to be asleep by 10:00 PM, between 10:00 PM and 2:00 AM, because we think that's the big, largest pulse of growth hormone during the 24-hour period.

Andrew Huberman 49:12 Is that right? Uh, so, I've, um, long wondered whether or not the, um...... the tale I was told when I was growing up, which is that every hour before midnight is worth two hours of sleep post-midnight. Um...

Craig Koniver 49:23 Does that ring true?

Andrew Huberman 49:23 That feels true to me.

Craig Koniver 49:24 Yeah, yeah.

Andrew Huberman 49:24 Um, then again, feels true is, is often misleading, but feels true to me. Um, but it makes perfect sense if the, the largest pulse in growth hormone is occurring in the, in the couple of hours before midnight.

Craig Koniver 49:35 Yeah. I mean, that's, that's how I learned it.

Andrew Huberman 49:37 Mm-hmm.

Craig Koniver 49:37 Um, I agree with you, it feels true to me as well.

Andrew Huberman 49:39 Mm-hmm.

Craig Koniver 49:40 Um, but taking advantage then of, you know, injecting something like ipamorelin at bedtime, then you're gonna, you know, within a few minutes... And with ipamorelin, it's interesting, 'cause people will get a little flushing, tingling at times.

Andrew Huberman 49:52 Hmm.

Craig Koniver 49:53 Um, and what I've seen, what the point I'm making is, uh, there are some physicians and some pharmacies which, you know, the, the dosage of ipamorelin and most of these growth hormone-releasing peptides should be 100 micrograms. That's the max dose, uh, for, to bind the receptor. And, you know, what I've seen is, with ipamorelin, rare, but some people do get anaphylaxis. And it's happened, and I think that happens when people are pushing it and giving more than they should.

Andrew Huberman 50:19 Mm-hmm.

Craig Koniver 50:19 And I've heard of that, and they're giving 200, 300, 400 micrograms at a time, which is a big dose. Now, what they're getting is the client, the patient's like, "Oh, my gosh, I feel this amazing flushing, it must be working." But then you could spiral into, "Oh, my goodness, I don't feel g- so good," and your, you know, circulation system collapsing. So...

Andrew Huberman 50:36 Yeah, using side effects as a, as a, uh, indicator of whether or not-

Craig Koniver 50:39 (laughs)

Andrew Huberman 50:39 ... something's working just seems like a terrible (laughs) idea. But, um...

Craig Koniver 50:43 But it's very common.

Andrew Huberman 50:45 And again, I, I, you know?

Craig Koniver 50:45 Yeah.

Andrew Huberman 50:46 Um, I tend to be very conservative about these things. And by the way, um, I've tried various peptides for short periods of time-

Craig Koniver 50:52 Yeah.

Andrew Huberman 50:52 ... 'cause I like to experiment, um, very safely. Um, and some things like sermorelin, and we'll talk about other-

Craig Koniver 50:58 Yeah.

Andrew Huberman 50:58 ... growth hormone secretagogues, uh, for me, uh, for whatever reason, you know, gave me great sleep, but only in the first part of the night. It nuked my rapid-

Craig Koniver 51:07 Mm-hmm.

Andrew Huberman 51:07 ... eye movement sleep in the second half of the night.

Craig Koniver 51:09 Mm-hmm.

Andrew Huberman 51:10 It, um, spiked my prostate-specific antigen, it was a very-

Craig Koniver 51:13 Oh, wow.

Andrew Huberman 51:13 ... consistent effect. I came off it and it went back down. I then went back on it, it went back up. And so I just found I couldn't take it.

Craig Koniver 51:18 Yeah.

Andrew Huberman 51:18 And it didn't take me very long to figure that out, but I know that there are some people who love sermorelin and don't see any of the same issues. So, it seems like it can be very individual.

Craig Koniver 51:27 I agree with that.

Andrew Huberman 51:28 Yeah, yeah.

Craig Koniver 51:28 I agree with that, and that's why I think it's, again, helpful to work with a physician who has experience, who can kinda ... You know, I think of these peptides as having flavors, particularly the growth hormone-releasing peptides. Ipamorelin, very clean. You know, as long as you stay within 100 micrograms or less, people are gonna lean out a little bit, sleep a little bit better. There's no, never real side effects. It's really-

Andrew Huberman 51:47 They take it pre-sleep?

Craig Koniver 51:49 Pre-sleep at bedtime.

Andrew Huberman 51:50 Without carbohydrates ingested in the previous two hours, correct?

Craig Koniver 51:53 Yeah, or 45 minutes-

Andrew Huberman 51:54 Yeah.

Craig Koniver 51:54 ... technically. Yeah, but that's right. And then they're saying like growth hormone-releasing peptide 6, GHRP-6, which is also going to bind. So, I think of ipamorelin being the most specific for the growth hormone receptor, but the weakest. So, when you inject it, you will get growth hormone to come out, and only growth hormone, but it's not gonna be a big burst of growth hormone. You inject GHRP-6, now you may bind some prolactin. Now you may bind some ACTH, which is gonna have your adrenals put out cortisol. Now you're gonna get a hunger response, right?

Andrew Huberman 52:21 And maybe even have trouble sleeping if you're getting-

Craig Koniver 52:23 May, may have trouble sleeping.

Andrew Huberman 52:24 Yeah.

Craig Koniver 52:24 But whereas th- where that's beneficial for is if you're looking to put on mass or get strong, GHRP-6 is your go-to, right? Because you will increase your appetite. And if you're smart, you'll eat a lot more protein. You, you know, and, and the building of muscle is not necessarily complicated, right? It's resistance training, sufficient protein, which is where I think most people fall off. And then having some anabolic kind of hormone in the background, like growth hormone or testosterone or both helps that process. That's where GHRP-6 can shine. I mean, within weeks, people will get big and strong, increase their bench press, whatever. Stuff flat-out works, but you gotta know how to use it, and, and understand the flavors. So, the point I'm making is, these different peptides have different flavors.

Andrew Huberman 53:05 Mm-hmm.

Craig Koniver 53:05 And to your point, there's individual responses. That's, that can be a good thing.

Andrew Huberman 53:09 I think for most of our audience, um, the interest in growth hormone secretagogues probably relates to the better sleep and the overall feelings of vitality.

Craig Koniver 53:17 Yep.

Andrew Huberman 53:17 And probably, uh, most people are seeking to n- not spike their appetite-

Craig Koniver 53:22 (laughs)

Andrew Huberman 53:22 ... or put on muscle, really.

Craig Koniver 53:23 No, I agree.

Andrew Huberman 53:23 These days, we're hearing, uh, more and more from people, both men and women, who want to be strong without being big-

Craig Koniver 53:29 Yeah.

Andrew Huberman 53:30 ... and they prefer to be lean as opposed to not lean-

Craig Koniver 53:32 Sure.

Andrew Huberman 53:32 ... which I think is a great goal.

Craig Koniver 53:34 I-

Andrew Huberman 53:34 Frankly, tha- that's my goal at this stage of life. I just turned 49 yesterday, and I, I really-

Craig Koniver 53:38 Happy birthday.

Andrew Huberman 53:38 Oh, thank you, thank you.

Craig Koniver 53:40 (laughs)

Andrew Huberman 53:40 Yeah, thanks for coming out to the, to the birthday, uh-

Craig Koniver 53:42 Oh, yeah. That was a lot of fun.

Andrew Huberman 53:43 ... mini bash the other day.

Craig Koniver 53:44 Yeah.

Andrew Huberman 53:44 It was a lot of fun. Um, you know, I, I, yeah, I want to be strong and capable. I also want to be able to run and have cardiovascular fitness, but I don't want to be large. I don't want to take up a lot of space. I'm not interested in taking-

Craig Koniver 53:56 Yeah.

Andrew Huberman 53:56 ... up a lot of space. Um, and I think most people fall into that category.

Craig Koniver 54:00 I agree.

Andrew Huberman 54:01 So if GHRP-6 can spike appetite, which for a subset of people might be useful, um, but probably most people will want to avoid it-

Craig Koniver 54:09 I agree.

Andrew Huberman 54:09 ... ipamorelin ... I've always been calling it ipamorelin, but ipamorelin at 100 micrograms, um, dosage or less per night sounds like it's an interesting

Andrew Huberman 54:17 tool. What are some of the other growth hormone secretagogues? And I should just brief ... I'll, I'll take the liberty of defining it. These are peptides that stimulate the release of your own endogenous growth hormone.

Craig Koniver 54:27 Correct.

Andrew Huberman 54:27 This is not taking growth hormone.

Craig Koniver 54:29 Right.

Andrew Huberman 54:29 Yeah.

Craig Koniver 54:30 Yeah. Um, two other main ones that we use, one would be tesamorelin.

Andrew Huberman 54:34 Mm-hmm.

Craig Koniver 54:35 Uh, which is s- similar into semorelin in that it also is going to work on the growth hormone-releasing hormone aspect, a little bit higher up in the, you know, chain of how these hormones are released. So, both semorelin and tesamorelin, um, you, you don't necessarily need to add anything else to it. Classically, with ipamorelin, hexarelin GHRP-6, we would add this other compound, CJC-1295-

Andrew Huberman 55:00 Mm-hmm.

Craig Koniver 55:00 ... which is gonna work on the GHRH, which allows the peptide and then the growth hormone to stay in your system a little bit longer.

Andrew Huberman 55:06 The growth hormone-releasing hormone, so-

Craig Koniver 55:08 Correct.

Andrew Huberman 55:09 Yeah. But, we can almost set aside CJC now, because CJC-1295-

Craig Koniver 55:13 That's on the same list as BPC.

Andrew Huberman 55:13 The FDA just came in and, uh-

Craig Koniver 55:15 It's now on.

Andrew Huberman 55:15 ... one a- let's just say one acronym took out another.

Craig Koniver 55:17 There you go.

Andrew Huberman 55:18 The FDA took out CJC. Okay.

Craig Koniver 55:20 (laughs) That's right. And BPC, yes.

Andrew Huberman 55:21 And BPC.

Craig Koniver 55:22 Yeah.

Andrew Huberman 55:22 Um, people are probably getting a little dizzy with these acronyms. But I think we're, uh, we're, uh, doing a good job of guiding-

Craig Koniver 55:27 Yeah.

Andrew Huberman 55:27 ... people, uh, uh, along. So, sermorelin, um, and tesamorelin-

Craig Koniver 55:33 Yeah.

Andrew Huberman 55:33 ... are similar enough.

Craig Koniver 55:34 Similar in that regard.

Andrew Huberman 55:35 Yeah, okay.

Craig Koniver 55:35 Tesamorelin, again, talking about flavors, tesamorelin works on visceral fat reduction, so fat around the organs.

Andrew Huberman 55:41 And it's been FDA approved for that purpose?

Craig Koniver 55:43 Yeah, with HIV patients having this lipodystrophy, which is, you know-... y- you know, abnormal accumulation of fat, in particular visceral fat around organs. So tesamorelin works well for that. My observation from using it for lots and lots of people w- seems to work better in females than males.

Andrew Huberman 55:59 Or does it get, lead to this, um, feeling of, uh, enhanced sleep as well?

Craig Koniver 56:03 Yeah, so I think any of the growth hormone-releasing peptides, anytime you're gonna make growth hormone more active in your world, that's how I think about it, better sleep, better skin tone, texture, right? You're more resilient. I think growth hormone is a resiliency hormone-

Andrew Huberman 56:15 Mm-hmm.

Craig Koniver 56:16 ... durability. You know, people find that, "Oh, I do a hard workout, but it takes me days to recover. I sprain my ankle, it takes me a week to recover. I cut my skin, it takes me forever to heal." They've got a durability issue.

Andrew Huberman 56:26 Mm-hmm.

Craig Koniver 56:26 And that's how I think about where growth hormone can shine, not that you gotta go all the way to growth hormone, but these peptides can be a really nice push.

Andrew Huberman 56:33 And this is taken before sleep, no food within 45 minutes-

Craig Koniver 56:36 Correct.

Andrew Huberman 56:36 ... of the in- of the injection?

Craig Koniver 56:38 And then w- and then the, kinda the magic in what we do is, you know, when we first started about eight years ago, we'd use one peptide at a time, and then what we learned is, let's combine these peptides, let's stack peptides, and that's how we do it. We-

Andrew Huberman 56:49 At lower dosages?

Craig Koniver 56:50 Sometimes lower dosages.

Andrew Huberman 56:52 Mm-hmm.

Craig Koniver 56:52 Um, but for example, we had a, a great combination, BPC, ipamorelin, and tesamorelin all together-

Andrew Huberman 56:59 Mm-hmm.

Craig Koniver 56:59 ... um, taken at bedtime, and you're gonna get subcutaneous fat reduction from the ipamorelin, visceral fat reduction from the tesamorelin, upregulation of the growth hormone receptor from the BPC.

Andrew Huberman 57:09 Mm-hmm.

Craig Koniver 57:10 It was a wonderful peptide. We, we kinda labeled it as a fat loss peptide, but people would put on lean muscle mass, they'd sleep better, their skin would be better, they'd be more durable, their thought process would be better. Awesome stuff. And th- and that's where I think the, that's where we enjoy it is stacking these peptides together.

Andrew Huberman 57:24 Mm-hmm.

Craig Koniver 57:25 So it's not, again, just one peptide at a time, but able to do it, and that's why, again, working with a compounding pharmacy, we can put these together so you're only doing one shot a day. You may be doing three to seven peptides, but it's still one shot.

Andrew Huberman 57:36 Got it. And, um, if one is combining, uh, tesamorelin or sermorelin, uh, ipo- ipamorelin and, well, not BPC anymore, but pentadeca-

Craig Koniver 57:48 Yep.

Andrew Huberman 57:48 ... uh, arginate instead, 'cause you can't get BPC 157 compounded, um, is that done every night, five days a week?

Craig Koniver 57:56 Mm-hmm.

Andrew Huberman 57:56 Three days a week? What's the rationale of this five days on, two days off?

Craig Koniver 57:59 Yes, fi- five days on, two days off, I came up with because of how we would dose growth hormone. So the traditional growth hormone dosing cycle would be five days on, two days off, taken at bedtime.

Andrew Huberman 58:10 Hm.

Craig Koniver 58:11 Yeah. And that's where it came up, and then I, I personally with patients and myself, I like to take breaks. So even with supplements, I won't take 'em on the weekends. Right? Because I think you, we, you know, a- again, anything you expose yourself to on a regular basis is gonna decrease the potency. We see that with exercise, we see that with food. If you're eating the same food every day, it seems to become less valuable for you.

Andrew Huberman 58:31 Mm-hmm.

Craig Koniver 58:31 Right? Like, change it up. Like, we, we have to, you know, throw in the crazy switch every now and then. But change it up and so then you're gonna make it more potent for you. I do the same thing with supplements just so that, you know, just resonates with me with people to take a break from stuff.

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Andrew Huberman 1:01:54 we started recording, uh, you mentioned that you're actually not a huge fan of taking massive amounts of supplements.

Craig Koniver 1:02:00 Mm-mm.

Andrew Huberman 1:02:00 That you are a big fan of taking CoQ10.

Craig Koniver 1:02:03 Yes.

Andrew Huberman 1:02:03 Coenzyme Q10.

Craig Koniver 1:02:04 Yeah.

Andrew Huberman 1:02:04 200 milligrams per day in the morning.

Craig Koniver 1:02:06 Mm-hmm.

Andrew Huberman 1:02:07 I also take CoQ10. Um, I think (laughs) I started taking it for, uh, quote-unquote, "general mitochondrial health."

Craig Koniver 1:02:13 Yeah.

Andrew Huberman 1:02:13 I don't know that I thought very carefully about exactly what I was trying to accomplish with it.

Craig Koniver 1:02:17 Yeah.

Andrew Huberman 1:02:17 Um, but what, what is the rationale of taking CoQ10?

Craig Koniver 1:02:21 So if I can break it down, try to keep it simple. If we... People are familiar with the mitochondria, it's the battery of the cell, these little organelles inside each cell, um, and they're responsible for, you know, doing many things, but primarily making ATP, chemical energy. And so, how do we make energy? Well, there's three main ways the body uses it, right, or makes it. First is glycolysis. We take glucose, which is a six carbon molecule. We break it in half to make two pyruvates, right? That, when we do that, we make a little bit of ATP. That pyruvate then is converted to something called acetyl-CoA. We run that through the Krebs cycle, where we're also making ATP, but we're, then we're making these intermediate products. One of those intermediate products, and the main one, is something called NADH. That NADH is then shuttled to the mitochondrial membrane for, uh, you know... This is the magic where we make the most ATP, and there's five different hubs, or we call cytochromes, right? And this is how I think about it, 'cause I just like to simplify. Cytochrome I is where we use NAD. And, um, what the s- what the different hubs are doing is we're exchanging electrons for protons, and that's a, kind of an electrical process. We're exchanging electrons for protons, going down an assembly line to eventually turn this wheel, the ATPase wheel, to make ATP. The way I understand it is, the five different hubs, different nutrients hit them. So cytochrome one is NAD. Cytochrome two is riboflavin, vitamin B2 and succinic acid. Cytochrome three is CoQ10, vitamin K2. Cytochrome four is methylene blue, which we can talk about. And then cytochrome five are things like magnesium, vitamin A, and copper. So if you're thinking about mitochondrial health, if you include any, or better, all of those, you're gonna maximize how your mitochondria can work and make energy. It's the strongest way to do it, and it's, again, not necessarily that complicated. So when I think of CoQ10, and again, we'd use a lot of NAD, which we can talk about, where I think most people, the, the traffic congestion happens on cytochrome one, right? And so when we give people or upregulate their NAD production, it's essentially, we're allowing for more electron flow at cytochrome one, which has a downstream effect on the other cytochromes, so the traffic jam opens up, and now you can move electrons to exchange for protons and make way more ATP. And if you're... And, but that's not true for everyone. And so some people, it could be at cytochrome three with CoQ10. It could be at cytochrome two. A lot of people at cytochrome four, which is, again, cytochrome... We call it cytochrome c oxidase. This is where methylene blue binds, but that's just a simplistic view. We just... People, we run into traffic jams, right?

Andrew Huberman 1:04:52 Mm-hmm.

Craig Koniver 1:04:52 These electron flow gets stuck. We're just trying to open up the traffic jam.

Andrew Huberman 1:04:56 So 200 milligrams a day of coenzyme Q10 can be, um, can facilitate some of that-

Craig Koniver 1:05:01 For cytochrome three, for sure.

Andrew Huberman 1:05:03 ... flow through. Yeah.

Craig Koniver 1:05:03 S- And CoQ10 has been studied, very safe up to 2,400 milligrams a day.

Andrew Huberman 1:05:06 Oh.

Craig Koniver 1:05:07 No harmful... Yep.

Andrew Huberman 1:05:07 Yeah.

Craig Koniver 1:05:08 No harmful effects. Sometimes I'll take more. Uh, like I was telling you earlier, it's been dramatic for me with migraine headaches and, you know, basically reducing them to zero.

Andrew Huberman 1:05:16 Uh, you know, as people are hearing this, they're probably thinking, "Okay, well, these are just, you know, this is what I call anecdata or whatever." I, I, you know, I don't have to remind people that you're a, a board-certified physician. I think that what was, w- what's still ringing in the back of my mind this entire conversation, even though I'm paying very careful attention, is that most of the drugs that are prescribed in this country are off-label.

Craig Koniver 1:05:35 (laughs) Yeah.

Andrew Huberman 1:05:35 I think that just, like, I, I don't think I've ever heard that stated out loud.

Craig Koniver 1:05:38 Mm-hmm. Yeah.

Andrew Huberman 1:05:39 It's wild.

Craig Koniver 1:05:40 Yeah, yeah.

Andrew Huberman 1:05:41 Right? So the idea that people would take something that wasn't, um, shown in a, uh, clinical trial to be effective for purpose A, um, that they would... But it gets ap- that it gets approved for purpose A-

Craig Koniver 1:05:52 Yeah.

Andrew Huberman 1:05:52 ... but then can be prescribed by doctors for purpose B, C, D, or E.

Craig Koniver 1:05:56 Right.

Andrew Huberman 1:05:57 I mean, you're not telling me this is commonplace. You're telling me this is the majority of-

Craig Koniver 1:06:01 The majority.

Andrew Huberman 1:06:01 ... prescription drugs.

Craig Koniver 1:06:02 Uh, but it makes sense if you think about it, right? So if you took an antibiotic, right? Like if we can just... An antibiotic's gonna be very specific what it gets approved for in terms of, like, working against a specific bacteria.

Andrew Huberman 1:06:12 Mm-hmm.

Craig Koniver 1:06:12 But then through clinical use and just experience, you know, we learn that, oh, I can use doxycycline or a Z-Pak azithromycin or whatever it is for a variety of bacterial infections that extend well beyond just what it's approved for. Well, that makes sense.

Andrew Huberman 1:06:27 And, and does that ever cycle back to the, uh, clinical trials or-

Craig Koniver 1:06:31 Mm-mm.

Andrew Huberman 1:06:31 ... or no? This just becomes physician understanding and lore. Like, "Hey, yeah, you know, I've got patients that-"

Craig Koniver 1:06:36 Yes.

Andrew Huberman 1:06:36 "... you know, they get on, on azithromycin and their, uh, their acne clears up." By the way, I'm not saying that, folks. I'm not a physician, but, um, but for instance.

Craig Koniver 1:06:43 E- exactly what happened with semaglutide and Ozempic, right?

Andrew Huberman 1:06:47 Hm.

Craig Koniver 1:06:47 Approved for helping glucose utilization or lowering, you know, blood glucose in patients with type 2 diabetes, and they found, through use only, people were losing weight.

Andrew Huberman 1:06:57 Mm-hmm. So-

Craig Koniver 1:06:57 And now it's become blockbuster and it's... And we see it with, you know, things like, you know, repurposing drugs for cancer, right?

Andrew Huberman 1:07:04 Mm-hmm.

Craig Koniver 1:07:04 There's, there's a, there's a lot of that going on, a lot of the repurposing. So, you know, doxycycline is a very common one that's used in cancer therapies-

Andrew Huberman 1:07:12 Mm-hmm.

Craig Koniver 1:07:12 ... I think by sophisticated oncologists. I don't treat cancer, but by sophisticated oncologists who use things like doxycycline, metformin, mebendazole, which is an antiparasitic drug, right? Um, to help with cancer, so that's amazing.

Andrew Huberman 1:07:25 So interesting. It is amazing. I think also, um, you know, I'm, I'm reminded that, um, you know, medicine, as beautiful a, uh, field as it is-

Craig Koniver 1:07:37 Yeah.

Andrew Huberman 1:07:37 ... I have tremendous respect for it, um, of course, uh, is a field of, of fairly siloed training.

Craig Koniver 1:07:44 Mm-hmm.

Andrew Huberman 1:07:45 Um, and I love the idea that now, thanks to public education efforts like this one, um, that you're providing us, that physicians learn from each other in a much broader way and can potentially hear about what drugs can be useful for this or that. The other thing, um, and this is not editorial, this is, uh, this is a real, uh, uh, observation-Pharmaceutical companies are very interested in the other uses of already approved drugs.

Craig Koniver 1:08:09 Sure.

Andrew Huberman 1:08:10 The research and development process for a drug, the safety, uh, evaluation is incredibly expensive. So they want nothing more than to take a drug that's already been approved for one purpose and to take that already safety approved drug and find other uses. How are they not circling back to the, uh, off-label, uh, use and understanding of these compounds and, um, and then, uh, essentially marketing them for these other purposes? Or I guess with Ozempic, that's exactly what happened.

Craig Koniver 1:08:39 That's what happened with Ozempic. I mean, it's again, I, I write prescriptions. I'm, I think there's a time and place. I think it's challenging for me though, right? And I think for a lot of physicians, it's become challenging operating in a paradigm. Um, when we talk about chronic disease, which is essentially failing, I mean, and we all know this statistically, we're not making huge dents in heart disease, cancer, autoimmune disease, neurodegenerative disease. We're not at all. But we're spending exorbitant amounts of money, right? Um, and this is, you know, something that I had to learn over time and, and I don't know how I got into it, but when I started my practice back in 2006, I started, it was a traditional family medicine practice, but I started using these nutritional IVs and bef- this is before hangover IVs. This is before it was popular. This is, you know, 20 years ago. And what I learned was that these nutritional IVs help people feel better quickly. And I developed this model for my patients, which I think is a better model, which is I wanna help people feel better first, like we were talking about earlier in this podcast 'cause if I can get people to feel better, what, what we learned through COVID, and honestly, what I wanna say to you, Andrew, which is really true, w- w- your podcast and what you do has been so successful at a time during the pandemic when people lost so much trust in people like me, right? People lost that trust of, "What do I do? You know, my hou- this is a scary time. I don't know what's going on." And you guys come along, you, in particular, providing this very stable, vetted information that people can trust and have a starting point and be like, "This is what I wanna do." Because health, one of the gifts of COVID, was it put our health on the forefront of most people's mind and life. And, and so what you're doing is tremendous work. And I can tell you personally-

Andrew Huberman 1:10:28 Thank you.

Craig Koniver 1:10:28 ... no, literally, like as a physician, I am just, it's, uh, it's such an honor to be here and to, to talk to you because every day, every day my patients come to me and said, "I heard this on, uh, the Huberman Lab Podcast. What do you think of it?" And, and I am not joking, and I love that. I think it is awesome because people, one, taking their health seriously, but two, they have a stable resource that they can trust. The problem with physicians, and, and I'll tie this back in, is physicians are hard to trust, right? And it's this paternalistic model, which is, and that's how I, I was trained, which is, "You know, you're gonna do this 'cause I'm gonna tell you to do it," right? And I remember being in medical school, which was in the '90s, and I can't remember the exact specifics of the study, but they would go, they did a study where they collect- collected the trash outside of physicians' offices, found that greater than 30% of prescriptions written that day were thrown away. Greater than 30%.

Andrew Huberman 1:11:27 Wow.

Craig Koniver 1:11:29 And what, and I remember learning that and I was like, "What is going on?"

Andrew Huberman 1:11:32 By the patients?

Craig Koniver 1:11:33 Correct.

Andrew Huberman 1:11:33 (laughs) Yeah.

Craig Koniver 1:11:34 Like, you came to the doctor because you wanted a prescription, right? No. You came to the doctor 'cause you weren't feeling good. You came to the doctor 'cause you wanted to be listened to. You came to the doctor 'cause you wanted to be validated. And most of the time, and this still happens to today, the vast majority of doctors will just write you a prescription or they'll write you two prescriptions. And that's not what most people want. Sometimes it is, and I do it, and sometimes it is. But there are so many other tools that we can use. And so when I help people feel better first, what I, why I've been successful, and I work with, you know, the, the, the peak, you know, people on this planet, whether they're athletes, the best athletes, celebrities, the royal family, you name it, I'm so privileged. It's because they trust me, and that trust is really important. I take that really seriously. You know what I mean? And so, you know, tying it back in is we've lost a lot of that with the pandemic. It's actually come to the forefront. And so that's why I wanna help people feel better first. You know, the traditional model of medicine is just get a diagnosis, write a prescription. If that prescription doesn't work, write another prescription. And so yes, there, there's a time and place for that, but there's also a time and place for just helping people w- i- it only works when people value themselves enough. Like, we were talk- I can tie this back to weight loss, right? Why do people have such trouble losing weight? I would argue that most people don't value themselves enough to actually care enough to make the hard disciplinary choices in their life to get away from emotional eating. You know what I mean? To do the right things that they actually, it's gonna be a struggle to get the right food for themselves, get away from processed foods, to be disciplined to go to the gym on a regular basis. They don't have the right people that they trust. This is where you've been such a gift.

Andrew Huberman 1:13:19 Hm. Mm-hmm.

Craig Koniver 1:13:20 Tremendous gift.

Andrew Huberman 1:13:21 Well, thank you for the kind words. I mean, the, the, um, the birth of the podcast did take place during the pandemic and, um, in large part because, uh, I saw, uh, everybody getting very anxious, their circadian rhythms disrupted-

Craig Koniver 1:13:34 Yeah.

Andrew Huberman 1:13:35 ... and, um, those were focuses of my laboratory and, and frankly, when I was a postdoc and graduate student, but especially as I got a little older, uh, in my years, um, I couldn't believe that, you know, I was reading these papers about how important, uh, morning sunlight is and all these things, but then my colleagues were all getting sick and dying around me-

Craig Koniver 1:13:52 Yeah.

Andrew Huberman 1:13:52 ... or getting what we call the tenured look-

Craig Koniver 1:13:54 Yeah.

Andrew Huberman 1:13:54 ... where they show up, you know, start their job and five years later, they look like they've aged 25 years.

Craig Koniver 1:13:59 Yeah.

Andrew Huberman 1:13:59 And I realized that I, I wanted to avoid that. So I've always just, uh, enjoyed learning and sharing, uh, science and health tools. And, uh, so thank you for the, the kind words. I've,

Andrew Huberman 1:14:09 I've certainly, um...... been, um, e- kind of both astonished and positively amazed in the ways that the pandemic and the post-pandemic years, I- I like to think we're in the post-pandemic years.

Craig Koniver 1:14:22 I do too.

Andrew Huberman 1:14:22 I- I think we can safely say that-

Craig Koniver 1:14:24 Yeah, yeah.

Andrew Huberman 1:14:24 ... now. Um, how they've drawn people's attention to this idea that they need to take agency into their own healthcare.

Craig Koniver 1:14:31 Yeah.

Andrew Huberman 1:14:31 That- that no o- no one, no pill, potion, injection, et cetera, can replace good behaviors. Um, pills, potions-

Craig Koniver 1:14:38 Correct.

Andrew Huberman 1:14:38 ... and injections, uh, can potentially augment those good behaviors, um, and get people going down the right path, which is what we're talking about today, but that it's a- it's really a personal responsibility. I mean, n- no-

Craig Koniver 1:14:49 For sure.

Andrew Huberman 1:14:49 ... no one can give us a calmer mind, no one can give us a healthier body. (laughs) Um, no- no one can do that, right? You can inh- it's interesting that some of the wealthiest people in the world, um, th- the new thing isn't for people to boast about their- their yachts or their properties, it's about, uh, their health.

Craig Koniver 1:15:05 Sure.

Andrew Huberman 1:15:05 It's about their vitality, their longevity, because that's the thing that, uh, I suppose in some sense money can start to buy, but it doesn't require a ton of funds to take great care of one's- one's