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

Andrew: Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.

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Andrew: 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. These are glucagon-like peptide analogs, 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.

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.

Today's discussion is really for anybody interested in mental health, physical health, and performance. The reason I say that is that even if you aren't considering taking peptides or 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 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 therapy sits somewhere between doing nothing and supplementation and those more advanced hormone therapies. 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. 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. 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. 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.

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. 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. There's a brief and very recent update.

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. You're going to do so from one of the world's leading clinical experts. 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.

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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.

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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. 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. Now for my discussion with Dr. Craig Koniver. Dr. Craig Koniver, welcome.

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

Andrew: I'm thrilled that you're here. We are going to launch ourselves into the space that is called peptides. It's an interesting space-

Craig: For sure.

Andrew: -because I think most people probably don't know what a peptide is. They should feel no guilt or shame about that. I'm sure you'll tell us. 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. I find it particularly interesting because 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. If anything, we can be sure that in the years to come, peptides are going to be increasingly popular.

Craig: Totally agree.

Andrew: There's, of course, the incredibly popular peptide of GLP-1 agonists.

Craig: For sure. Taking over.

Andrew: To drop into this and make sure everyone's on the same page, what is a peptide?

Craig: Just from a very elementary level, peptides are just chains of amino acids. Amino acids, all naturally occurring molecules. We call it a peptide if it's 40 amino acids or less. We 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. We probably, therapeutically, are using close to 250 over the years, which is obviously tiny compared to that. To your point, this is blossoming. We've been using peptides for about eight years, a long time, but still very early in our understanding of how best to use peptides and how clinically we're going to get the most out of them, so it's exciting.

Andrew: Maybe just to orient ourselves, we should talk about GLP-1 first. Not because it's necessarily the category of peptides that I think people would want to consider for themselves, but because most people have probably heard of Semaglutide and Mounjaro and things like that.

Craig: Sure.

Andrew: How long ago was it that humans started injecting GLP-1 agonists in order to lose weight?

Craig: I think the weight loss aspect has only been a couple of years. It's been tremendous how it's accelerated to literally becoming the number one prescribed in America. Semaglutide, Ozempic, was approved longer than that for type 2 diabetics, helping with glucose control and helping with glucose utilization. What they found as a side effect was that these people were losing weight. Then that word caught on. What's interesting, and I don't think most people understand, is most of the medicines prescribed, particularly in America, are prescribed off-label. Meaning they've never, ever been approved for what they're used.

Andrew: Is that right?

Craig: Yes, the vast majority are never approved. As a physician, I'm allowed to prescribe any drug for any reason I want, as long as it's been approved for something. As long as we're safe. We don't want to be cavalier about this and renegade and do all these things that are out of bounds, but that is the truth. Semaglutide is a great example being used for helping type 2 diabetics lower their blood sugar, and then it got to, "Well, now let's help diabetics lose weight, because diabetics struggle with weight, the insulin resistance." Then it became, "Well, even if you're not a diabetic, could you benefit from losing weight?" Heck yes.

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. Then it spread. It did eventually get FDA approval specifically for weight loss, but at first, no, it's been just for type 2 diabetics to help with glucose utilization. We've been using primarily tirzepatide, which is like Semaglutide version 2.0, mostly for the past two years, have learned a tremendous amount, and my opinion's actually changed from working with people.

Andrew: What is your opinion? My understanding is that there's two camps on this, it seems. At least two camps. One camp seems really bullish on this. They seem very excited about this drug. The other camp seems to point to the fact that one may be creating a drug dependency. That it's very expensive. They point to the also potency of lifestyle factors like exercise and caloric restriction, eating mostly non-processed foods, et cetera, as a "better alternative." I'm not necessarily saying that. I think they both have their place. To me, it seems very contextual, but as a clinician, I'm curious what you think.

Craig: Yes, I agree. Both have their place. My philosophy is I want everyone to have access to things that are number one safe, that propel them to look, feel, and perform their best. If that means, if it was just about, if I can exercise my way out of this, eat my way out of this, meaning lose weight, change my body composition, why do we have an epidemic of so many people who struggle with that? Because it's really hard. We don't totally understand it. The processed food thing's a massive problem. I know that's come to light recently with people pushing for us to take a look at food companies and the quality of our food, which is amazing.

If people aren't interested in doing better for themselves, and this 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. This goes against the grain of conventional medicine, which is, if you want to train for the race, you have to 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, and losing weight is a struggle. 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 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." She is there. That is what it's about. For people, if you can help them achieve their goal first, then they're going to be motivated. The light bulb turns on, they're going to be like, "Wow, I want more of this." That's the aha moment that I love helping people with.

At first, I was like, "Oh, we got to be really cautious with this." Same thinking, like, "I don't want people to lose too much weight. This is a problem. Are they going to be dependent, unlike the notion that you have to take something the rest of your life?" I'm not saying it has to be the rest of their life, but when something works, and as far as I can tell, is very safe, I think it's worth discussing. I like people having those options at least.

Andrew: Yes, it sounds like, from the story you just told us, that it's not just about an aesthetic change that motivates people to lean into other aspects of their health and life when they lose some weight.

Craig: Totally.

Andrew: That it's also just that the sheer literal weight. Also, that adipose tissue, fat tissue, produces a lot of hormones that-

Craig: It does.

Andrew: -we know impact the brain and 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. I think now, thanks to Chris Palmer, and actually at Stanford, there's also a program in metabolic psychiatry, we're starting to see, or understand and appreciate, the link between adipose tissue and brain health, or lack of brain health in most cases.

Craig: Sure.

Andrew: In the case of GLP-1, people have criticized it, saying that a fair percentage of the weight that's lost is lean body mass, muscle loss, but it seems to me that can be remedied pretty easily if people just do some resistance training.

Craig: I think part of that, yes, resistance training. The other thing I would say is from what we've seen is when people are using the conventional dosages, they're losing weight too quickly. What we do is we get both Semaglutide, mostly tirzepatide, compounded, and that allows us to use basically micro-dosages and start very low in terms of dosage and go slowly with people. What we found is, as long as people are losing two pounds or less a week, they're not losing the muscle mass.

We certainly encourage adequate protein intake, resistance training, but that micro-dosing has been a game changer, literally a game changer, because then people don't feel like-- I've seen it where when we started, people were losing 15 pounds in three weeks.

Andrew: Goodness.

Craig: Then they're excited, but then they're not because 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. We've seen this called Ozempic face. We don't like the way that looks, and that fat takes a while to come back. If we just go slowly with this and we can really dial it in and nuance it, that has had a tremendous impact. Now, beyond the weight loss, we're seeing cognitive benefits. We're seeing inflammation benefits. 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: Is that a direct effect of 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 inflammation?

Craig: Great question or I could say, is it the positive thoughts that come from looking at yourself in the mirror and feeling good, which transcends to you 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. I think that's going to be hard to dissect, but it's real. I have a patient, she's 50. She has Hashimoto's thyroiditis, meaning she attacks her thyroid. She doesn't make enough thyroid hormones, so she takes thyroid hormone. One of the challenges with that is they make a lot of thyroid antibodies, this antibody called thyroid peroxidase antibody.

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. It's a challenge to get that number down. It's certainly a challenge for me. We traditionally use probiotics, a lot of things to help bolster the immune system. Now we're starting to use the GLP-1s, and we're seeing those antibody levels come down. I don't have a great way of explaining it, but there's something going on that's very positive.

Andrew: Very interesting. I suppose moving from most widely known, peptides are still fairly unknown to most people, even the concept, but that's why you're here. You're changing that right now. 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, and that's BPC-157, Body Protection Compound-157, which, to my understanding, there are a lot of animal data, very few, if any, clinical studies on humans.

Craig: Agreed.

Andrew: A lot of people now taking BPC in various forms. What are some known uses for BPC? Let's just say within your clinic.

Craig: Sure.

Andrew: Then we'll get around to the fact that BPC has, let's hope temporarily, been taken off market and what some of the alternatives are. What is BPC? What instances or people have you found it useful for?

Craig: So many. I think with BPC, for me, the most utilized peptide that we've used. We'd like to use BPC almost with every patient. It is very anti-inflammatory. Just from a very general perspective most people walking around who are adults, they're stiff, they're sore as they get older. They work out. We work with 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. BPC, I 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. We've learned that we start with the dose based upon these, like you said, animal studies, which is conservative, make sure it's safe. Then we've seen over time that we can get to higher and higher dosages and have even more of an impact. I think, for people understanding using BPC, we started with a dose of 500 micrograms a day. We got up to 5,000 micrograms a day.

We'd like a protocol of five days on, two days off. That's been very helpful for a variety of things from post-viral with the pandemic, had a lot of success with BPC, to, again, you name it. 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 going to benefit.

It's going to help improve the inflammatory status, but also help with recovery. It doesn't seem to be one of these agents that's going to be detrimental. We were talking earlier, Rob and I, for the starter, they found that people are working out hard taking antioxidants, that there seems to be a negative consequence to that because you don't allow the body to repair itself. I don't think that's happening with BPC.

Andrew: That's interesting because my understanding is also that part of the specific and general adaptation of exercise is triggered by inflammation. 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 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 that leads to the hypertrophy and strength training is an inflammation response that triggers the compensation or the hyper-compensation.

It's interesting you're saying that BPC-- By the way, I must say this because then 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. Back to the topic at hand, forgive me. This can set off a complicated storm of sorts if I'm not ultra-clear about the details. BPC-157 strongly anti-inflammatory. My understanding is it also may upregulate growth hormone receptors.

Craig: It does. It works well if you're-- we'll get into taking a growth hormone-releasing peptide. It pairs very well with that because 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. If you combine it with BPC, which upregulates the growth hormone receptor, you make the process of growth hormone binding more efficient. You get more out of it, then you can use less of the growth hormone-releasing peptide with the same result.

Andrew: Got it. BPC-157 comes in many different forms, or it used to when it was FDA-not-disallowed.

Craig: Sure.

Andrew: I could imagine how the oral forms would allow for a just general anti-inflammatory response. It's a gut peptide. We don't have to worry about it being destroyed by the gut. Most peptides that go into the gut are broken down.

Craig: Correct.

Andrew: This peptide, when it's naturally occurring, occurs in the gut.

Craig: That's right.

Andrew: It survives in the gut. If somebody is taking BPC-157 orally through a capsule or tablet form, my guess is that has a general anti-inflammation response.

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

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

Craig: I've certainly observed that clinically. Interestingly, I've observed a better clinical response when people inject it, even for gastrointestinal-related things. I think injecting. 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. I know a lot of people are like, "I'm never injecting."

Andrew: Now this is less painful than a Texas mosquito bite.

Craig: [chuckles] There you go. Super easy. Once you do it once or twice, it's really easy. We walk people how to do that. Interestingly, we started thinking, "Okay, if you've got something going on in your gut, you should take oral PPC because it's going to target it right then." I found if we're injecting, it actually works better than the oral. Then it came up, "Well, what if I've got an elbow injury? Should I inject it in my elbow?" We found, actually, don't. It's going to work systemically. You can inject it in your abdomen or your rear end. You're still going to get benefit in your elbow, but now you're going to get benefit in all your joints, all over your body systemically.

Andrew: How do you think that's working? My understanding is BPC-157 can initiate fibroblast migration. Some of the cells that make up the various connective tissues that when injured or sore, other things can make us injured or sore, of course, but when injured or sore that those need repair. It always was perplexing to me why one could put BPC-157 in such a small volume under the skin, just a few centimeters off the belly button, and it would somehow seek out the injury site in an elbow or an Achilles.

There are all these wild anecdotal tales of lore of, let's just say, there was this Olympic athlete, not this last Olympics, but the previous summer Olympics, that had a torn Achilles who came back a few weeks later and medaled, took podium, that is, and people were talking about BPC-157. Who knows? That's just chatter and fog, as they say.

Craig: Sure.

Andrew: Wild, the idea that you could just inject something systemically, put 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: It's interesting. Not to get off topic, but we've seen it with stem cells. They've taken stem cells, they've tagged them radiographically so you can see them. The study I read, which I can find for you, someone had a broken wrist, and they gave them intravenous stem cells. 24 hours later, when they visualized radiographically, those stem cells had aggregated at the site of the fracture. There's a lot about our bodies obviously we don't know.

Andrew: Sure.

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

Andrew: If one has ever gone into the hospital for a surgery and got a cold saline infusion, you realize how quickly it hits your toes. They're putting it into your elbow.

Craig: It's almost instantaneous.

Andrew: Yes, within a few seconds. It also makes one appreciate how we're all generally a little bit dehydrated. When you start getting a real proper saline infusion, all of a sudden you feel yourself come to life in a way that, "Oh, this is what it feels like to have just the right amount of salt in my bloodstream."

Craig: Exactly. Going back to BPC, where I think it shines, is in these ligaments and tendons. I think this is where most of these injuries happen, is where muscle is connecting to the bone. People 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. I think that's where BPC shines. That's certainly where it's been studied in animal studies. I know that because we can inject it directly into tendons, which is unlike steroids. We would never inject steroids into a tendon. You damage the tendon.

BPC, we mix with things like PRP, PRF, which is platelet-rich fiber, and a little bit different than PRP, and you'll get healing within days. It's awesome.

Andrew: Wild.

Craig: It's super safe, and it's amazing for people.

Andrew: BPC is definitely shorthand for BPC-157. That is certainly in widespread use. I have been concerned just personally about gray market sources that contain contaminants and the fact that many people are obtaining BPC-157 not from a physician, not from a compounded pharmacy, but just "on the internet."

Craig: Sure.

Andrew: You're a physician. I'm guessing that until the recent ban by the FDA, you were able to prescribe clean BPC as it were. What's the story with BPC now? Maybe we could talk about gray market--

Craig: Sure. I think it's a great question.

Andrew: -versus prescribed, and made at a compounding pharmacy versus a pharmaceutical company pharmaceutical. Then, of course, there's black market, but let's just leave that out.

Craig: Sure.

Andrew: There are people that are going to tell you, "Hey, this is BPC," and sell it to you. That's obviously bad and dangerous.

Craig: We see that with the anabolic steroids. Anabolic steroids are in the black market. There's one anabolic steroid, which is nandrolone, which is Deca, which can be officially prescribed. You can combine it with testosterone, all in the up and up, totally above table. The rest things, like trenbolone, others, you can't get them from a physician. In fact, very hard to get them from a reputable website in the United States.

Andrew: As long as we're here, my understanding is Deca-Durabolin and testosterone cypionate can be prescribed or testosterone enanthate, things like that, by physicians. That's because it's been FDA-approved for the treatment of various things, hypergonadal syndrome, testosterone replacement therapy in both men and women, et cetera. Those categories of testosterone-like compounds, cypionate, enanthate, et cetera, and Deca-Durabolin, which is basically like-- Is it similar to DHT?

Craig: A little bit, yes. The generic name is nandrolone. It has the flavor of helping with joints. I think it works synergistically with things like testosterone, whether it's testosterone cypionate or enanthate. I like it particularly for people who've been on testosterone, men who've been on testosterone replacement for a long time, which is many men. They tend to get less out of testosterone. It becomes less potent like anything. If you use something for a long time, you're going to get less out of it over time. Anything you expose yourself to continually doesn't work as well.

To make this really real, I had a patient who was in the Marines and served at Secret Service for several White Houses, and he had a lot of osteoporosis, osteopenia, and bone loss. This is where I learned about using something like nandrolone because we combine nandrolone with testosterone. It changed his life. This guy is in his 80s, who has had to use a cane, who came back to life, who started becoming super mobile and working out again. Synergistically, I think it works really well, not to get too far off topic.

Andrew: No, it's interesting. I think another brief editorial for me, if I may, 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, even early 40s, think that they need to look to synthetic testosterone in order to look a certain way, perform a certain way in the gym, libido, et cetera.

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 are taking good care to sleep well, eat well, take care. I realize 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, where there are things that can help move the needle in the right direction, pun intended. Here with synthetic testosterone and Deca, there's a real concern about loss of fertility.

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

Andrew: Goodness. Not goodness, meaning badness. That does not seem like a good idea.

Craig: It's still very common.

Andrew: Goodness gracious.

Craig: Still very common. One in particular, this is probably 10 years ago, came to see me. He's 25. He got married. To your point, he said, "I'm ready to have kids. I have zero sperm left." That's a real thing. 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, crush it, wake up the next morning, was not sore, crush it again, and just kept going, and 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 was a little bit wiser, mature, and he was like, "Oh, my goodness. Now there's a repercussion for this." I've seen that time and time again. The repercussion is big. You're not making any sperm, or the sperm quality is super poor. Now, what do you do? Now you got to come off the testosterone. You got to rebuild your system, which we can do. We can use things like clomiphene and clomiphene hCG, lots of different agents to help in that regard, even certain peptides.

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, and they're getting it from websites, and they're getting it from people saying, "Oh, just try this peptide." I've had lots of people talking about the websites or whatever, not to name any names, who have had anaphylactic reactions to research-type peptides, which are not for human consumption. I'm not saying that there's bad companies or whatever. You just got to be careful. You got to be selective, at least.

Andrew: Right. What brought us onto the conversation about testosterone was this black-market issue. There's also what I would call this dark gray market issue, which is that there are a number of companies that will sell. all sorts of things, but peptides in particular, and listed on their website, it'll say, "Not for human or animal consumption, for research purposes only."

Craig: Correct. Right.

Andrew: One of the major issues is that the potency and cleanliness, so to speak, purity of those compounds is not established. Many of them have LPS, lipopolysaccharide, in them, which is inflammatory. Earlier, before we started recording, you mentioned that you have heard of or interacted with not your patients, but people who have come to you saying that they had really serious, life-threatening-

Craig: For sure.

Andrew: -consequences for using these black market, certainly, but dark gray market peptides.

Craig: Yes. To tell the story further, is back in October of 2023, the FDA put many peptides, BPC, and we can name them out, on what's called a Category 2 list, meaning they are no longer allowed to be compounded. Now, 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: The compounding pharmacies are distinct from these other black and dark gray sources in that they actually can establish purity. They are designed to be injected into humans.

Craig: They have a totally different standard. 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 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 because they're inspected all the time. It's a big deal to them. They want to do it right with purity, with processing, and making sure that anything they make, especially a sterile compound, which is going to be anything injected, eye drops, things you inject in yourself, whether it's IV, sub-Q, or intramuscular, they're considered sterile.

They have to then be tested by an outside lab to make sure of purity, make sure that there's no endotoxins, things like that. It's highly regulated, and it's a big deal for them. It's a big deal for the physicians who prescribe with them, which I appreciate because 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 one plus one doesn't equal two now. It equals four. That, to me, is a huge advantage.

Just like we were talking about the GLP-1, Semaglutide, and tirzepatide, we get those compounded so that we have a-- the compounding pharmacy we're using now, we're making a unique combination of tirzepatide and Sermorelin, which will address some of this muscle loss that people are getting. We can combine them.

Andrew: Sermorelin to stimulate growth hormone release, offset some of the muscle loss from tirzepatide.

Craig: Exactly. Yes.

Andrew: Yes.

Craig: You can do things like that with a compounding pharmacy. Again, just to make sure people understand, compounding pharmacies are highly regulated, highly regulated. Again, there's always going to be bad apples, but 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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Is it fair to say that if one is interested in exploring the use of peptides for what you refer to as performance medicine, mental, physical health, and performance falls underneath that, to essentially only put peptides into their body, maybe even on their body surface, that they're obtaining from a physician who's obtained the peptides from a compounding pharmacy.

Craig: Yes, and who's developing a relationship? 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." 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 walk that walk and help people in that regard. If someone's out there on the internet doing it themselves, they're walking in on their own. Not to make it like everything bad is going to happen, but when you have the help of someone who has experience, that goes a long way, I think, particularly with something like this.

Andrew: I agree. It worries me very much that people are buying BPC from dark gray market or black market sources. Anything that says on it, "Not for animal or human use, for research purposes only," you can pretty much guarantee the endotoxin, that lipopolysaccharide, at least has not been removed. That can 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 an inflammatory response over time. Then you don't know where the tipping point is, and then somebody can have a really terrible reaction.

Craig: Then, taking a step further, getting away from just peptides, but 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. They called me up and they said, "Oh, I'm having terrible headaches, terrible headaches for days." They came in. Their blood pressure was through the roof. 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 differently?" "Yes. This doctor recommended I take this weight loss compound."

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 clean up the mess, and not that there's always mess, but this is what we enjoy doing. As a physician, we've seen the darkest of dark. We're able to help people when things don't go perfectly planned. I think that's a big deal, particularly when there's lots of these tools and they're exciting tools and they're great tools.

Fortunate for me, I've been in this space longer than most that I've just a large repertoire of experience of observing people and working with people, and seeing, "We've got to tweak this. We've got to nuance this," or sometimes, "We don't ever want to use this again. This is not for most people."

Andrew: Given that BPC-157 has been effectively removed from the legitimate market, what are people's alternatives, again working with the caveat that people should work with a physician? Where can physicians get something similar enough to BPC-157?

Craig: There's a new compound, newer, a peptide called the short for PDA, Pentadeca Arginate. It's basically the same molecular structure as BPC, except they've swapped out an acetate for arginate.

Andrew: One amino acid-

Craig: Correct.

Andrew: -substitution.

Craig: One amino acid substitution. We're using that and having really good results. 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. I think I surmise that this is how it's going to be with all of these peptides, because again, peptides are just chains of amino acids. Certainly, a lot of people smarter than me trying to figure out how do we then create other types of amino acid combinations, i.e., peptides that do similar actions to BPC, to thymosin alpha, to Ipamorelin, to TB-500, on and on and on.

I'm hopeful in that regard. Also, 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 because they've been using peptides and they're concerned that, oh my goodness, the FDA came in and changed the game. It's been a huge setback for all of us.

Andrew: I definitely want to circle back as to what the motivation was by the FDA for doing that at some point. In the meantime, however, I think there's a lot of interest in BPC-157, a lot of use of BPC-157. The sources of BPC-157 are now drying up. That's why I'm personally concerned that people are going to start going to the dark gray market and black market. I'm excited about the Pentadeca Arginate. Let's put that on people's ear map, brain map. Pentadeca Arginate may be a good physician-prescribed substitution for people that can benefit from BPC-157.

Craig: A good starting dose, so 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. We'll see how that goes. We probably can use larger dosages. That's conservative, but that's a good starting point for people.

Andrew: Thus far, you haven't mentioned any side effects of BPC-157 or Pentadeca Arginate. That's remarkable.

Craig: It's been tremendous. We were using BPC intravenously as well. Patients would come in and, "Oh, tweaked my knee, tore my ACL, tore my meniscus," whatever. You can give them BPC essentially as a bolus intravenously. My goodness, that made a difference. Now, using something intravenously from the pharmacokinetic standpoint, it's not going to last in the system very much. It's more of a spark. Whereas if you use an agent subcutaneously, you're going to get more of a long-lasting-- Again, not terribly long-lasting with peptides, but longer than using something intravenously.

The sweet spot was certainly using both. We could use something as a spark to initiate that anti-inflammatory cascade, then follow up with the subcutaneous dose.

Andrew: Even though earlier we were talking a little bit about some hormone replacement therapies, before that, off a microphone, you mentioned that you prefer peptides to direct hormone manipulations in most cases. I think while peptides can be hormones, there are things like oxytocin, is sometimes called a peptide hormone. In general, when people think about hormone therapies, they're thinking testosterone, estrogen, pregnanolone, thyroid, et cetera.

It sounds to me like much of your practice is built up around the notion that there are things that one can use, peptides, to push and pull on these various systems without getting into them directly. My understanding is the advantage of that is you don't get the negative feedback. You don't get the shutting down of natural production.

Craig: Yes. Testosterone is a great example because, like we were saying, I don't ever want to manipulate hormones. Growth hormone is another example. I don't ever want to manipulate that, meaning 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 going to 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.

Peptide, same thing. I don't want to manipulate the hormones. I want to just stick within the highways or the swim lanes for how they should operate, and then take advantage of that. That's been a safe way to do it, as opposed to, and I've seen it, talking about another peptide, which is Ipamorelin, a growth hormone-releasing peptide. Ipamorelin, you inject under the skin, travels up to the posterior pituitary in the brain, which is responsible for putting out growth hormone.

That growth hormone then leaves pituitary, enters the bloodstream, travels to the liver, or we make insulin-like growth factor I, which then enters the circulation as very anabolic, meaning growth, healing, mending. As we get older, we make less growth hormone. As we get older, we wear down. Obviously, we get degenerative conditions. Part of that, I don't know what part, for everyone, it's a little bit different, is because of our hormonal decline.

When you can give something like Ipomerelin, and we can talk about others, you're actually helping not only push out a little bit of growth hormone for people, but you are directing when you push it out. 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 largest pulse of growth hormone during the 24-hour period.

Andrew: Is that right? I've long wondered whether or not 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.

Craig: That may be true.

Andrew: That feels true to me. Then again, feels true is often misleading, but feels true to me. It makes perfect sense if the largest pulse in growth hormone is occurring in a couple of hours before midnight.

Craig: Yes, that's how I learned it. I agree with you. It feels true to me as well. Taking advantage then of injecting something like Ipomerelin at bedtime, then you're going to within a few minutes. With ipomerelin, it's interesting because people will get a little flushing, tingling at times. What I've seen, the point I'm making is there are some physicians and some pharmacies, which the dosage of ipamorelin, and most of these growth hormone-related peptides, should be 100 micrograms. That's the max dose to bind the receptor.

What I've seen is, with ipamorelin, rare, but some people do get anaphylaxis, and it's happened. I think that happens when people are pushing it and giving more than they should. I've heard of that. They're giving 200, 300, 400 micrograms at a time, which is a big dose. What they're getting is the patient is like, "Oh my gosh, I feel this amazing flushing. It must be working." Then you could spiral into, "Oh my goodness, I don't feel so good." Your circulation system collapsing.

Andrew: Yes, using side effects as an indicator of whether or not something's working just seems like a terrible idea. [chuckles]

Craig: It's very common.

Andrew: I tend to be very conservative about these things. By the way, I've tried various peptides for short periods of time because I like to experiment very safely. Some things, like sermorelin, and we'll talk about other growth hormones, secretagogues, for me, for whatever reason, gave me great sleep but only in the first part of the night. It nuked my rapid eye movement sleep in the second half of the night. It spiked my prostate-specific antigen. It was a very consistent effect.

Craig: Oh, wow.

Andrew: I came off it. It went back down, and it went back on. It went back up. I just found I couldn't take it. It didn't take me very long to figure that out. I know that there are some people who love sermorelin and don't see any of the same issues. It seems like it can be very individual.

Craig: I agree with that. I agree with that. That's why I think it's, again, helpful to work with a physician who has experience, who can kind of, I think of these peptides as having flavors, particularly the growth hormone-releasing peptides. Ipamorelin, very clean. As long as you stay within 100 micrograms or less, people are going to lean out a little bit, sleep a little bit better. There's no real side effects.

Andrew: They take it pre-sleep.

Craig: Pre-sleep at bedtime.

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

Craig: Yes, or 45 minutes, technically. Yes, that's right. They're saying growth hormone-releasing peptide 6, GHRP-6, which is also going to bind. I think of ipamorelin being the most specific for the growth hormone receptor but the weakest. When you inject it, you will get growth hormone to come out, and only growth hormone, but it's not going to 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 going to have your adrenals put out cortisol. Now you're going to get a hunger response, right?

Andrew: Maybe even have trouble sleeping if you're getting it.

Craig: You may have trouble sleeping, but where that's beneficial for is, if you're looking to put on mass or get strong, GHRP-6 is your go-to. You will increase your appetite. If you're smart, you'll eat a lot more protein. The building of muscle is not necessarily complicated. It's resistance training, sufficient protein, which is where I think most people fall off, and then having some anabolic hormone in the background, like growth hormone or testosterone or both, helps that process.

That's where GHRP-6 can shine. Within weeks, people will get big and strong, increase their bench press, whatever. Stuff flat out works, but you got to know how to use it and understand the flavors. The point I'm making is these different peptides have different flavors, and to your point, there's individual responses, that can be a good thing.

Andrew: I think for most of our audience, the interest in growth hormone secretagogues probably relates to the better sleep and the overall feelings of vitality, and probably most people are seeking to not spike their appetite or put on muscle, really.

Craig: No, I agree.

Andrew: These days, we're hearing more and more from people, both men and women, who want to be strong without being big, and they prefer to be lean as opposed to not lean, which I think is a great goal. Frankly, that's my goal at this stage of life. I just turned 49 yesterday, and I really--

Craig: Happy birthday.

Andrew: Oh, thank you. Thank you. Yes. Thanks for coming out to the birthday-

Craig: That was a lot of fun.

Andrew: -mini bash the other day. It was a lot of fun. Yes, 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 up a lot of space, and I think most people fall into that category.

Craig: I agree.

Andrew: If GHRP-6 can spike appetite, which, for a subset of people, might be useful, but probably most people will want to avoid it. Ipamorelin, I've always been calling it ipamorelin, but ipamorelin at a 100 micrograms dosage or less per night sounds like it's an interesting tool. What are some of the other growth hormone secretagogues? I should just brief. I'll take the liberty of defining it. These are peptides that stimulate the release of your own endogenous growth hormone. This is not taking growth hormone.

Craig: Yes. Two other main ones that we use one would be tesamorelin, which is similar to sermorelin, and that it also is going to work on the growth hormone-releasing hormone aspect a little bit higher up in the chain of how these hormones are released. Both sermorelin and tesamorelin, 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, which is going to work on the GHRH, which allows the peptide and then the growth hormone to stay in your system a little bit longer.

Andrew: The growth hormone-releasing hormone?

Craig: Correct.

Andrew: Yes, but we can almost set aside CJC now because CJC-1295--

Craig: That's on the same list as being the same.

Andrew: The FDA just came in, and let's just say, one acronym took out another.

Craig: There you go.

Andrew: The FDA took out CJC.

Craig: That's right, and BPC.

Andrew: Yes, and BPC. People are probably getting a little dizzy with these acronyms, but I think we're doing a good job of guiding people along. Sermorelin and tesamorelin are similar enough?

Craig: Similar in that regard. Again, talking about flavors, Tesamorelin works on visceral fat reductions, so fat around the organs.

Andrew: It's been FDA-approved for that purpose.

Craig: Yes, with HIV patients, having this lipodystrophy, which is abnormal accumulation of fat, in particular, visceral fat around organs. Tesamorelin works well for that. My observation from using it with lots and lots of people, it seems to work better in females than males.

Andrew: Or does it lead to this feeling of enhanced sleep as well?

Craig: Yes, so I think any of the growth hormone-releasing peptides, anytime you're going to make growth hormone more active in your world, that's how I think about it, better sleep, better skin tone, texture. You're more resilient. I think growth hormone is a resiliency hormone. Durability. 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, and that's how I think about where growth hormone can shine. Not that you got to go all the way to growth hormone, but these peptides can be a really nice push.

Andrew: This is taken before sleep, no food within 45 minutes-

Craig: Correct.

Andrew: -of the injection.

Craig: Then the magic and what we do is, when we first started about eight years ago, we'd use one peptide at a time. Then what we learned is let's combine these peptides. Let's stack peptides, and that's how we do it.

Andrew: At lower dosages?

Craig: Sometimes lower dosages. For example, we had a great combination, BPC, ipamorelin, and tesamorelin all together, taken at bedtime, and you're going to get subcutaneous fat reduction from the ipamorelin, visceral fat reduction from the tesamorelin, upregulation of the growth hormone receptor from the BPC. It was a wonderful peptide. We 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 that's where I think that's where we enjoy it, is stacking these peptides together. It's not, again, just one peptide at a time, but able to do it. That's why, again, working with a compounding pharmacy, we can put these together. You're only doing one shot a day. You may be doing three to seven peptides, but it's still one shot.

Andrew: Got it. If one is combining tesamorelin or sermorelin, ipamorelin and, well, not BPC anymore, but Pentadeca Arginate instead, because you can't get BPC-157 compounded, is that done every night, fve days a week? Three days a week? What's the rationale of this five days on, two days off?

Craig: Yes. Five days on, two days off I came up with it because of how we would dose growth hormone. The traditional growth hormone dosing cycle would be five days on, two days off, taken at bedtime. That's where it came up. Then I, personally, with patients and myself, I like to take breaks. Even with supplements, I won't take them on the weekends. Again, anything you expose yourself to on a regular basis is going to 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. Change it up. We have to throw on the crazy switch every now and then. Change it up, and so then you're going to make it more potent for you. I do the same thing with supplements so that-- it just resonates with me, with people to take a break from stuff.

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Before we started recording, you mentioned that you're actually not a huge fan of taking massive amounts of supplements. That you are a big fan of taking CoQ10.

Craig: Yes.

Andrew: Coenzyme Q10, 200 milligrams per day in the morning. I also take CoQ10. I think I started taking it for "general mitochondrial health." I don't know that I thought very carefully about exactly what I was trying to accomplish with it. What is the rationale of taking CoQ10?

Craig: If I can break it down and try to keep it simple, people are familiar with the mitochondria. It's the battery of the cell, these little organelles inside each cell, and they're responsible for doing many things, but primarily making ATP chemical energy. How do we make energy? Well, there's three main ways the body uses it or makes it. First is glycolysis. We take glucose, which is a six-carbon molecule. We break it in half to make two pyruvates.

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. We're then making these intermediate products, one of those intermediate products. The main one is something called NADH. That NADH is then shuttled to the mitochondrial membrane. This is the magic where we make the most ATP. There's five different hubs or we call cytochromes.

This is how I think about it, because I just like to simplify. Cytochrome 1 is where we use NAD. What the different hubs are doing is we're exchanging electrons for protons. That's 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. Cytochrome 1 is NAD, cytochrome 2 is riboflavin, vitamin B2, and succinic acid. Cytochrome 3 is CoQ10, vitamin K2. Cytochrome 4 is methylene blue, which we can talk about. Then cytochrome 5 are things like magnesium, vitamin A, and copper. If you're thinking about mitochondrial health, if you include any or better, all of those, you're going to maximize how your mitochondria can work and make energy. It's the strongest way to do it. It's , again, not necessarily the complicated.

When I think of CoQ10, and again, we use a lot of NAD, which we can talk about, where I think most people, the traffic congestion happens on cytochrome 1. When we give people or upregulate their NAD production, it's essentially we're allowing for more electron flow at cytochrome 1, which has a downstream effect on the other cytochromes, so the traffic jam opens up. Now you can move electrons to exchange for protons and make way more ATP.

That's not true for everyone. Some people, it could be at cytochrome 3 with CoQ10. It could be at cytochrome 2. A lot of people at cytochrome 4, which is again we call it cytochrome C oxidase, which is where methylene blue binds, but that's just a simplistic view. People, we run into traffic jams. This electron flow gets stuck. We're just trying to open up the traffic jam.

Andrew: 200 milligrams a day of coenzyme Q10 can facilitate some of that.

Craig: Correct. Cytochrome 3 for sure. CoQ10 has been studied, very safe, up to 2,400 milligrams a day. No harmful effects. Sometimes I'll take more. Like I was telling you earlier, it's been dramatic for me with migraine, headaches and basically reducing them to zero.

Andrew: As people are hearing this, they're probably thinking, "Okay, this is what I call anec data or whatever." I don't have to remind people that you're a board-certified physician. I think that 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.

I don't think I've ever heard that stated out loud. It's wild. The idea that people would take something that wasn't shown in a clinical trial to be effective for purpose A, that it gets approved for purpose A, but then can be prescribed by doctors for purpose B, C, D, or E. You're not telling me this is commonplace. You're telling me this is the majority of prescription drugs.

Craig: It makes sense if you think about it. If you took an antibiotic, an antibiotic is going to be very specific what it gets approved for in terms of working against a specific bacteria. Then, through clinical use and just experience, we learned 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. Would that make sense?

Andrew: Does that ever cycle back to the clinical trials? Or no, it just becomes physician understanding and lower? Like, "Hey, I've got patients that they get on azithromycin and their acne clears up." By the way, I'm not saying that, folks. I'm not a physician, but for instance.

Craig: Exactly what happened with semaglutide and Ozempic. Approved for helping glucose utilization or lowering blood glucose in patients with Type II diabetes. They found, through use only, people were losing weight. Now it's become a blockbuster. We see it with things like repurposing drugs for cancer. There's a lot of that going on, a lot of the repurposing.

Doxycycline is a very common one that's used in cancer therapies, I think, by sophisticated oncologists. I don't treat cancer, but by sophisticated oncologist to use things like doxycycline, metformin, and mebendazole, which is an anti-parasitic drug, to help with cancer. That's amazing.

Andrew: So interesting. It is amazing. I think also I'm reminded that medicine, as beautiful field as it is, I have tremendous respect for it, of course, is a field of fairly siloed training. I love the idea that now, thanks to public education efforts like this one 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, and this is not editorial, this is a real observation, pharmaceutical companies are very interested in the other uses of already approved drugs.

Craig: Sure.

Andrew: The research and development process for a drug, the safety evaluation, is incredibly expensive. 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 off-label use and understanding of these compounds and then essentially marketing them for these other purposes? Or I guess with Ozempic, that's exactly what happened.

Craig: That's what happened with Ozempic. Again, I write prescriptions. I think there's a time and place. I think it's challenging for me, though. I think, for a lot of physicians, it's become challenging operating in a paradigm where we talk about chronic disease, which is essentially failing. We all know this statistically. We're not making huge dents in heart disease, cancer, autoimmune disease, or neurodegenerative. We're not at all, but we're spending exorbitant amounts of money.

This is something that I had to learn over time. I don't know how I got into it, but when I started my practice back in 2006, it was a traditional family medicine practice, but I started using these nutritional IVs. This is before hangover IVs. This is before it was popular. This is 20 years ago. What I learned was that these nutritional IVs help people feel better quickly.

I developed this model for my patients, which I think is a better model, which is I want to help people feel better first, like we were talking about earlier in this podcast. If I can get people to feel better-- what we learned through COVID, and honestly, what I want to say to you, Andrew, which is really true, 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. People lost that trust of what do I do? This is a scary time. I don't know what's going on.

You guys come along, you in particular, providing this very stable, vetted information that people can trust and have a starting point be like, this is what I want to do. One of the gifts of COVID was it put our health on the forefront of most people's mind and life. What you're doing is tremendous work. I can tell you personally--

Andrew: Thank you.

Craig: No, literally, like as a physician, it's such an honor to be here and to talk to you because every day my patients come to me and said, "I heard this on the Huberman Lab podcast. What do you think of it? I am not joking. 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 I'll tie this back in, is physicians are hard to trust. It's this paternalistic model, and that's how I was trained, which is, you're going to do this because I'm going to tell you to do it.

I remember being in medical school, which was in the '90s, and I can't remember the exact specifics of the study, but they did a study where they collected the trash outside of physicians' offices, found that greater than 30% of prescriptions written that day were thrown away. Greater than 30%. I remember learning that, and I was like, "What is going on?

Andrew: By the patients?

Craig: Correct. You came to the doctor because you wanted a prescription, right? No, you came to the doctor because you weren't feeling good. You came to the doctor because you wanted to be listened to. You came to the doctor because you wanted to be validated. Most of the time, and this still happens today, the vast majority of doctors will just write you a prescription, or they'll write you two prescriptions. That's not what most people want. Sometimes it is, and I do it, and sometimes it is. There are so many other tools that we can use.

When I help people feel better, first, why I've been successful, and I work with 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. That trust is really important. I take that really seriously. You know what I mean? Tying it back in is, we've lost a lot of that with the pandemic. It's actually come to the forefront. That's why I want to help people feel better first.

The traditional model of medicine is just get a diagnosis, write a prescription. If that prescription doesn't work, write another prescription. Yes, there's a time and place for that, but there's also a time and place for just helping people-- it only works when people value themselves enough. Like we were talking, I can tie this back to weight loss. 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 emotionally eating. You know what I mean? To do the right things that they--

Actually, it's going to 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. Tremendous gift.

Andrew: Thank you for the kind words. The birth of the podcast did take place during the pandemic, and in large part because I saw everybody getting very anxious. Their circadian rhythms disrupted. Those were focuses of my laboratory. Frankly, when I was a postdoc and graduate student, but especially as I got a little older in my years, I couldn't believe that-- I was reading these papers about how important morning sunlight is and all these things.

Then my colleagues were all getting sick and dying around me or getting what we call the tenured look, where they show up, start their job, and five years later, they look like they've aged 25 years. I realized that I wanted to avoid that. I've always just enjoyed learning and sharing science and health tools. Thank you for the kind words. I've certainly been both astonished and positively amazed in the ways that the pandemic and the post-pandemic years-- I like to think we're in the post-pandemic years.

Craig: I do too.

Andrew: I think we can safely say that. Now, how they've drawn people's attention to this idea that they need to take agency into their own healthcare. No one, no pill, potion, injection, et cetera, can replace good behaviors. Pills, potions, and injections can potentially augment those good behaviors and get people going down the right path, which is what we're talking about today. It's really a personal responsibility.

Craig: For sure.

Andrew: No one can give us a calmer mind. No one can give us a healthier body. No one can do that. It's interesting that some of the wealthiest people in the world, the new thing isn't for people to boast about their yachts or their properties. It's about their health. It's about their vitality, their longevity, because that's the thing that, 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 body and mind.

Craig: It doesn't. What I've learned, and I've had to learn this over time, and I think the wisdom is-- and this is why it's even more challenging, because I think people go on social media, and they listen to podcasts and they listen to influencers, and a lot of the messages is additive. If you're not doing a high-intensity workout every day and then doing sauna for X amount of time and then cold plunge and all this kind of dieting, you're not doing it well.

I know that stress of that is cumulative to people. What I've learned, and I have a really good friend, probably the most affluent, successful, but also the most generous and smartest person I know, who lives on the Big Island, and he says to me, which is worth repeating here, I look for every opportunity to surrender. It is that surrender to people who you can trust to guide you. You don't have to be the quarterback of everything. That takes off the pressure.

I think finding, it's not always about adding, it's actually creating space for us to just be in that flow. I know you've talked about this a lot, that active rest place where it's not about being super focused, and it's not about just going to sleep, but almost the best parts of our day is when we're in that flow state where things just click. To me, helping people with those types of times and figuring that out is the most valuable. I don't think people talk about that enough. I appreciate that you do a lot.

Andrew: I appreciate that you're bringing up this notion that just stacking more and more behaviors, you got to crush a workout and do sauna, that is not the message. Sometimes we get teased, and there's some good comedy that takes on me that make me chuckle now and again about that, but that's not that the approach.

Craig: I know it's not.

Andrew: These are tools that people can-- It's a buffet. I think most everyone agrees that sleep is key.

Craig: For sure.

Andrew: Most everyone agrees that exercise is key, nutrition is key, great social connection is key. I want to make sure that we circle back to this, when it comes to the peptides, it seems that one of your approaches, if I may, is to raise the tide so that the boat can get out to sea. We were talking about these growth hormone secretagogues. We covered GHRP-6, which is the one that stimulates the appetite. That's probably going to be a niche case condition that people would want to use that. Ipamorelin, tesamorelin, and sermorelin, I get a lot of questions about, is it MK-677?

Craig: Yes.

Andrew: What in the world is MK-677? It sounds like a weapon.

Craig: It does. I think of it just like GHRP-6, however, it's absorbed well orally, so it's basically the same. I see it working this very similarly.

Andrew: To GHRP-6?

Craig: Yes.

Andrew: It stimulates appetite?

Craig: It does.

Andrew: It can stimulate cortisol, prolactin?

Craig: Yes.

Andrew: It sounds like a not good situation for most people.

Craig: Not for most people, although-- let me give you an example where-- I have a client, very successful guy, and he's been on testosterone. He's doing all the things. He's in his early 60s. He's working out well. He eats well, super well, all these things. He can't put on muscle mass well. Actually, as people get older, that does become an issue for a lot of people is maintaining healthy muscle mass. MK-677, before it was taken off, the compound list by the FDA, it's another one that was included.

Andrew: Another acronym, take it out by the FDA acronym?

Craig: Yes. You can take it orally, which again removes the stigma or burden of having to do a shot, and you will increase your appetite. That actually is a very useful agent metabolically for people as they get older. I know this, my kind of approach with this, both personally and professionally, is I try everything I can. I remember MK-677, I took at bedtime, and it was an hour later, I was in a dead sleep. I woke up, and I had to go eat.

Andrew: It sounds like puberty.

Craig: It was. I was like, "What is going on? I didn't totally understand. I was like, "What? Oh, I took that cap-- Oh my gosh, I should never have taken it right before bed." I had to go up and eat, and destroyed my sleep that night. I learned, and I'll always learn, and I'm grateful for it, but don't take that one at bedtime. It absolutely will stimulate your appetite.

Andrew: Which are the growth hormone secretagogues that your more typical patients, who don't want to stimulate appetite, both male and female patients prefer? What are you compounding for them?

Craig: A tesamorelin, I don't see any appetite stimulation from that. Hexarelin, we haven't talked about that. I don't really see--

Andrew: Tell us about Hexarelin.

Craig: Hexarelin, I think it is more, again, if we talk about the flavor of these peptides, is how I look at it in my head, is more of the energy, endurance, growth hormone-releasing peptides. I like it for people to use it in the morning. They get a nice burst of energy. They feel it's a clean energy. It's not a caffeinated energy or jittery or anything like that, and it's good for more endurance-type. Athletics are working out. People in that field of competition or whatever, I think hexarelin's a great choice.

Andrew: Does not spike appetite?

Craig: I have not seen that.

Andrew: This is taken first thing in the morning, you get an additional growth hormone release?

Craig: Yes, you do in the early mornings when you're waking up.

Andrew: You used to compound it with CJC-1295 to get the other pathways involved that can help, but now CJC has been taken out-

Craig: Correct.

Andrew: -by the FDA.

Craig: Right, but hexarelin still exists. That can be compounded.

Andrew: What's the dosage on hexarelin that you typically prescribe?

Craig: A 100 micrograms. It's the same as these other, like ipamorelin, GHRP-6, a 100 micrograms. The two that are different would be tesamorelin, ideal dose 2 milligrams per dose, which is 2,000 micrograms, so quite different. Then sermorelin has actually a very broad dosing range anywhere from 200 micrograms. I've used it up to 3,000 micrograms-

Andrew: Whoa.

Craig: -depending on your goals.

Andrew: We were talking about coenzyme Q10 and the Kreb cycle, and I forgot to close the hatch on supplements more broadly. Again, it doesn't sound like you're a big fan of taking lots of pills and capsules. I think some people will take that as a relief. I think a lot of people get tired of taking a lot of pills. Some people don't like to do that. What are some of the other things that you do take besides coenzyme Q10? Earlier we were talking about methylated vitamins of different types.

Craig: Methylated B vitamins.

Andrew: This is becoming increasingly popular. We're starting to hear more about methylation and methylated compounds. Could you educate us on methylated B vitamins?

Craig: Yes. I think people are familiar with it. Some people are talking on podcasts about the MTHFR SNP.

Andrew: We've not talked about that in this podcast, so it'd be nice to.

Craig: Sure. A SNP is a single-nucleotide polymorphism, meaning that genetically things don't flow as easily. Again, that's an oversimplification. You could be homozygous for that, meaning you have both genes influencing you more. You could be heterozygous, meaning it's just one gene, meaning--

Andrew: One copy from one parent or homozygous, copy from each parent.

Craig: Yes. You say it way better than I did. What that means is and where we see that reflected, homocysteine is a marker we use, a lab marker we use. It's an emerging marker for looking at one's cardiovascular risk profile. If one's got an elevated homocysteine, and elevated by some labs is going to be greater than seven by most labs greater than nine, means you're at an increased risk. What that is I don't remember, but you're in increased risk of having a cardiovascular event, which would mean a heart attack or stroke.

We want to lower that number. The best way to lower that number is taking ample methylated B vitamins. Methylated means you're adding a methyl group. Methyl B12, methylfolate, trimethylglycine, methionine. These are all methylation donors, which just metabolically and, through your detoxification pathways in your liver is going to help you lower that homocysteine.

I'm sure it's more complicated than that, but most people-- if you're going to take a B vitamin, take a methylated B vitamin because then you overcome-- again, we've done a lot of MTHFR testing. I don't think it's as profound as some people make it out to be like it's going to change their life. I've never seen that. Can it help you? Sure, but you're going to overcome it by taking sufficient methylated B vitamins anyway.

Andrew: Again, those methylated B vitamins are methylated B12--

Craig: B12, folate. There's a methylated B6 and then trimethylglycine. TMG is a good compound. Methionine is a good methyl donors, amino acid.

Andrew: Are these taken in the morning or in the afternoon?

Craig: I like taking them in the morning. Although, I think, for people to play around with it, because I've certainly seen it, people get that 3:00 PM kind of slumber as opposed to reaching for the coffee or the donut, take some more methylated B vitamins and see what happens.

Andrew: Or just the coffee. No, sorry. You're not supposed to drink caffeine too late in the day. Lately, what I find-- I don't know if this is wrong to bring up on this podcast, but I can't help myself. I love yerba mate in the morning and afternoon. Coffee in the morning now makes me feel nauseous. I don't know-

Craig: Wow.

Andrew: -if I'm pregnant or something, but it makes me feel-

Craig: Probably not pregnant.

Andrew: -nauseous pregnant. I love the taste of coffee in the afternoon. This is like a midlife thing. I don't know what it is. Now in the afternoon, around 1:00 or 2:00 PM, even just the smallest amount of coffee, it's like the most delicious thing I've ever tasted.

Craig: I love coffee.

Andrew: It can mess with your sleep too late in the day, but that's a perfect segue to talk about sleep.

Craig: Sure.

Andrew: One thing that I know you've done a lot of work on and with are these peptides that can improve sleep, not just by virtue of enhancing growth hormone release but-- I'll just be very direct. For the last, gosh, four to six months, I've had the opportunity to try Pinealon and injectable Pinealon combined with glycine. Goodness gracious, in the positive sense of the goodness gracious, you're from the South so I don't know where people have it, never before have I found something that can improve the amount of rapid eye movement sleep that I get. Besides rapid eye movement, sleep deprivation. Sleep deprivation, the next night, you'll get a compensatory effect. That's not the way to increase your REM sleep, folks.

There are a lot of things like high-intensity exercise that improve my slow-wave deep sleep. Cold plunge early in the day improves slow-wave deep sleep. There have been a few other things. With Pinealon-- by the way, I'm not doing this every night. I do this occasionally. I ran a little experiment, and I track my sleep using the sleep tracker that's in Eight Sleep. It's doubling the amount of rapid eye movement sleep that I'm getting, doubling, from an hour to two hours or from an hour and 30 minutes.

Craig: Tremendous.

Andrew: Nearly three hours. I posted a picture of a sleep score with some rapid eye movement sleep. It's not something I typically do. Even the most competitive of biohackers, Brian Johnson was like, "Oh, nice sleep score." Now, he touts a sleep score that's perfect every night for every night. I'm poking at Brian because we like to poke back and forth. We're friendly with one another.

The point being that Pinealon is a remarkable way to increase rapid eye movement sleep. I have very little knowledge about it, except that my understanding is that it might stimulate some regeneration or stimulation of the pinealocytes of the pineal.

Craig: That's exactly it. You've nailed it. I remember when you messaged me after starting it, you were like, "This is amazing."

Andrew: It's amazing.

Craig: Yes, you were saying it's amazing.

Andrew: It's amazing. I hope the FDA doesn't nuke it as a consequence of this conversation.

Craig: It's still available. Yes, yes.

[laughter]

Craig: I hope so too. Your response is what we see with our other patients, who are loving-- I think that combination with glycine, I'm a big fan of glycine, and injecting it seems to work really well. Back to your question about Pinealon. It's one of the smallest peptides, but I think it's one of the most profound. We used to combine it with Epitalon, the Russian peptide that was used for circadian rhythm.

Andrew: For my understanding, Epitalon also, it's involved in DNA repair-

Craig: It is.

Andrew: -and has been explored in animal studies for trying to offset vision loss in some retinal degenerative conditions.

Craig: Yes. Again, put on the do-not-compound list with all the others.

Andrew: Oh, that's a shame.

Craig: That's gone. Pinealon stays and remains. Your response to it and experience with it has been very commonplace for working with patients and seeing that. I think there's a circadian rhythm aspect with it as well and helping with melatonin production. Obviously, that comes from the pineal gland. I'm postulating. I think there's more to the pineal gland than we understand.

Andrew: Yes, it makes things other than melatonin. That's for sure.

Craig: Yes. I think it's elusive, but I think there's something to it. I say that, having used a lot of Pinealon with people over the years and having very similar responses, which is awesome. Everyone knows, like you said, when you sleep better, your entire day is better. When you sleep better, your life is better, exponentially better.

Andrew: I think of the millions of people that suffer from lack of rapid eye movement sleep, the lack of neuroplasticity that can be the consequence of that, the lack of healthy removal of emotional labels on previous day memories, that is the consequence of REM deprivation. The enormous impact on depression rates, the enormous impact on-- pretty much every mental health issue is made worse by lack of REM sleep.

I say or I raise this conversation about Pinealon with a little bit of trepidation because I do worry that, on the one hand, people will see it as a miracle drug. That's not what we're talking about. It has this effect, but at the same time, I'll just say that there's another drug that was released recently.

This is an FDA-approved drug in the category of sleep drugs called the DORAs. It works a little differently. It doesn't push on the sleepiness system, so to speak. It suppresses the wakefulness system.

The idea is that it's supposed to increase REM sleep. It goes by name Quviviq and things like that. I tried it. It was a total disaster for me. I fell asleep, woke up three hours later, couldn't fall back asleep. I tried it. It was lower dosage. It's extremely expensive as well. I'm going to piss off whoever makes Quviviq. I forget who makes it. It was a complete disaster for me.

Pinealon has been incredible. Here's what's really interesting about it to me, is that it seems to improve my sleep on the nights when I don't take it, which makes total sense if it indeed is providing some regeneration of the pineal sites that make melatonin and other--

Craig: That makes sense to me.

Andrew: Here we're talking about something that one could potentially pulse with now and again-

Craig: Sure.

Andrew: -and get improvement in sleep every night.

Craig: Yes.

Andrew: Wild.

Craig: I think it's worth noting that you also take care of your health on many other aspects, and that's probably why you were sensitive to it, but it worked really well for you. Some other people, it's going to take longer, if they're having to work on their diet and having to work on their exercise and having to work on their thought patterns. We don't talk about that enough, having positive thoughts. Yes, it's so safe. I never ever have seen a side effect or negative side effect from Pinealon. Your response has been uniform. People don't always get there as quickly, but people get there with their sleep.

Andrew: Love it. You compound it with glycine?

Craig: Yes.

Andrew: What's the rationale there?

Craig: I really like glycine as an inhibitory neurotransmitter. It's calming to the nervous system. Over the years, I tend to start with that when people are having trouble settling down at night. Not that it's going to sedate people, but just transitioning from being active 8:00 PM, 9:00 PM, wanting to settle down. Glycine in pretty large dosages, at least most people think they are, starting with 3,000 or 5,000 milligrams orally kind of tones down the nervous system.

People relax a little bit, and then they tend to sleep better from it. Then you can dial it up. I've used very large dosages for it. The other advantage of glycine is it works on phase 2 liver detoxification, which is amino acid conjugation. You're helping your liver work better. In a world where we're being exposed with all these toxic things from glyphosate to heavy metals, we all need to do some sort of liver mitigation strategies. Glycine is one of the best.

Andrew: Wow. Interesting. We haven't done an episode of this podcast yet on heavy metals, but I'm very interested in this because many people write to me asking about metal toxicity and about mold toxicity.

Craig: Molds become super big. Big. It's very prevalent, and it seems the more we talk about it-- We've seen it for years and years and years. It makes sense. If you think about the amount of airplanes flying above us every day, pouring down heavy metals. It's massive. It's in the air, it's in the water, it's in the soil. You talk about glyphosate or Roundup, same exact thing, so many chemicals, and it's challenging for us as humans.

The way I break it down, not to get too far off topic, is we're water soluble organisms living in a fat soluble world. It's the job of our liver essentially to take the fat-soluble stuff, make it water soluble so we can excrete it. That takes place in the liver in two phases. Phase 1, we're using the P450 enzyme. It's like taking the trash, putting the trash in the trash can, putting it on the side of the road.

You have phase 2, amino acid conjugation. The trash truck comes and picks up the trash. Very few things in nature induce phase 2 independent of phase 1, meaning most of us have trash piled up on the side of our road. Those things are the polyphenols, so things like the blues, the reds, the pigments. That's why it's important to eat a wide variety of colors in your diet. Matcha tea has a very strong inducing effect on phase 2 liver activity.

Andrew: Is that right?

Craig: Yes.

Andrew: I need to develop a taste for matcha. I feel like it's kind of grainy.

Craig: It is and it's bitter, but bitter things tend to be, again, helping that phase 2. Glutathione helps phase 2. We do a lot of that intravenously. Then glycine is a wonderful agent for inducing phase 2, independent of phase 1. The trouble is, I don't think people realize, most pharmaceuticals induce a P450 enzyme. A misconception is, well, if I'm just inducing one, I'm good.

If you induce one, you induce them all. If you take any pharmaceutical, you're inducing your entire P450 system. You're speeding it up, meaning you're putting more trash out on the side of the road. If you look at the amount of things we're being exposed to outside of pharmaceuticals, it's mounting. It's crazy.

Andrew: When you say on the side of the road, you mean in the liver?

Craig: That's what I'm saying. I'm just using that as a metaphor.

Andrew: Yes. You're talking about building up of debris, cellular debris with it, or metabolic debris within your body.

Craig: Right. The trash, again, very oversimplification, you need to speed up phase 2 to get the trash trucks come to pick up the trash so that you can then take that compound and excrete it in your stool and your urine, your sweat, your breath. That's the only way it works. It's not complicated per se, but I think there's a lot of misconceptions about it.

Andrew: When people take a peptide, that's injectable pineal and glycine, they're getting glycine, obviously. Let's say somebody doesn't have access to you for whatever reason. There's a barrier to getting ahold of those peptides. Can people take glycine orally?

Craig: They can. Glycine's absorbed well orally. It has a really sweet taste. It's actually the smallest amino acid. A huge fan of it, we've been using it a long time. You can take big dosages of it such as--

Andrew: Very sick.

Craig: Again, my starting dose is usually 3 to 5 grams at bedtime.

Andrew: Wow.

Craig: The way I do this, recommend it is, try that for a few nights in a row. You're not noticing a thing? Double the dose. Go to 10 grams, literally. Most people at 10 grams of glycine will notice it. Again, it's not going to necessarily make you drowsy. You're not going to be sedated, but your nervous system's going to be toned down a little bit and help you fall asleep a little bit better. Then while you sleep, where a lot of this detoxification process starts working, you're going to be more efficient in how your liver works. Everything ties together.

Andrew: I'm still a big fan of things like magnesium 3 and 8, apigenin, which is a chamomile derivative. I'll try glycine. I think a few years back I was using a little bit of glycine, but it was more like 1,000 milligrams, but now that it's in the injectable peptide, the Pinealon, I don't take it. Is there an oral form of Pinealon that works?

Craig: There is these bioregulator peptides, which were developed by this Russian scientist, last name Corvinson, I think. Done a lot of research, actually. There's published research about it. I think Pinealon is one of the ones that they say will survive the stomach acid and get through the gut and be absorbed. I think that's true. We've always used it as injectable. I tend to like injectable things for the bio-availability. To your point, I think people can. Those are going to be harder and harder to find, actually. It's probably easier to find an injectable Pinealon than an oral one.

Andrew: Yes. As we're talking about this, I'm realizing, unfortunately, just the way the internet works, that people are going to start, likely as a consequence of this conversation, will start selling Pinealon, but you need to know that you're actually getting Pinealon. It's very-

Craig: Like anything.

Andrew: -easy for somebody to just pop something up on-

Craig: Totally.

Andrew: -Amazon and sell it.

Craig: Totally.

Andrew: Maybe they just throw some melatonine in there and call it Pinealon. There's a lot of BS stuff out there.

Craig: Tons.

Andrew: This is why the compounding pharmacy component and working with a physician is so key.

Craig: Yes, and researching, making sure that what you're taking is legit. A lot of illegitimacy out there.

Andrew: Do you think that pharmaceutical companies are going to move into these other peptides? Certainly, ipamorelin for the reduction in visceral body fat, that's an FDA-approved drug, so is sermorelin, FDA-approved drug. The GLP-1 agonist, FDA-approved drug. The FDA is unlikely to pull those. They're a blockbuster, especially with GLP-1. They're making, not even a small fortune, but a large fortune.

Craig: Big money. The concerning part about the GLP-1, to me, is what we're starting to see, they've been able to be compounded because there was a shortage. The way it works with the compounding pharmacy is, because those are brand-named drugs, and they are not patented for the peptide, they're patented for the delivery system, which is the pen, which most people don't realize. They've been able to be compounded, and then way more affordable because they're compounded.

There is rumors that the pharmaceutical companies now have supply back, they'll come back, and they will remove the ability to allow these peptides to be compounded, which means we'll have to stick to traditional dosages and people lose access, because they're going to be way more expensive. They are, if insurance doesn't cover it, $1,500 a month for most people.

Andrew: Wow.

Craig: Very expensive.

Andrew: That's a lot more.

Craig: Yes.

Andrew: For a lot of people, that's rent and more.

Craig: I'm hopeful that doesn't happen, but that's in the works. That's in the works, and that would be a huge shame. Again, I'm not a pessimist by any means, I'm a perpetual optimist. We'll just make sure that it stays this way. Again, if it does happen, we'll get creative and go other routes as well.

Andrew: Earlier you mentioned stem cell therapies. Those are not FDA-approved in this country.

Craig: They are actually.

Andrew: Oh, sorry, my mistake.

Craig: I think that using the term stem cell is a problem. If we use the term autologous cell, which would be PRP, it's basically the same thing.

Andrew: Platelet-rich plasma.

Craig: Right.

Andrew: They take your blood, they spin it down, they take the platelets [crosstalk]

Craig: Right. The ruling, as I understand it, as long as you're taking a cell from you, and you give it back within four hours, then that is allowed under the FDA guidelines.

Andrew: Interesting. There was this clinic in Florida a few years ago, was touting stem cell therapies for macular degeneration. Injected some stem cells into these patients' eyes, and they went blind really quickly. They were not blind prior to the injections. That, to my understanding, caused a severe setback to the whole-

Craig: Sure.

Andrew: -field. I'm old enough to remember when gene therapy was set back by about 10 years because a patient received gene therapy, which is now pretty common for certain diseases, and the patient died. It's unclear exactly why they died, but that delayed the field of gene therapy by at least a decade. This country is very conservative when it comes to the approval of new therapeutics.

Craig: Sure. I think, like anything, there's going to be people who get too aggressive amount of it. I've heard of doctors injecting stem cells into people's discs, and then they get discitis and infection, and that can just spiral very quickly. I think you've got to be reasonable in what you're trying to accomplish. I'm excited about stem cells and exosome therapy and PRP and PRF and using them as biologics, because I think there's a lot to learn. I think we only know very little from what we've seen from working with our patients. It's been tremendous from a rejuvenation standpoint. As long as, I think, it's taking from your own and then giving back your own within how the FDA outlines it, I think that's a great way to do it.

Andrew: Well, certainly you have the clinical data to back those statements. Thymosin alpha-1, what is this peptide? Maybe before we discuss it, did the FDA nuke Thymosin alpha-1?

Craig: They sure did.

Andrew: Whoa, okay, they're coming through with a howitzer and taking out all these peptides. Okay. Well then, let's keep this relatively brief. What was Thymosin alpha-1 being used for previously?

Craig: I think it was, from my observation, the best peptide for immune modulation. We would use it if you had an overactive immune system like autoimmune disease. By definition, if someone has an autoimmune disease, their immune system is attacking their own self. That's classically lupus, rheumatoid arthritis, things like that, celiac disease, type 1 diabetes. Those are all autoimmune diseases. We could use Thymosin alpha-1, and we tone down the immune response.

We'd also use it a lot in post-COVID, where you have an abnormal immune response or the immune system hasn't caught back up, and you can dial it up using Thymosin alpha-1 in a very safe way. We use it a lot with long COVID, and we were using 5,000 micrograms a day, sometimes intravenously, getting great results, very safe, had no issues with it. Unfortunately, it's off the table.

Andrew: I hear a lot of complaints about brain fog with long COVID and brain fog generally. Cerebrolysin is a very interesting compound. My understanding is that cerebrolysin is available in Europe more broadly than it is in the US. Is it [crosstalk]-

Craig: It's available here.

Andrew: -to the FDA, or is it taken out?

Craig: No, it's still available.

Andrew: All right. Cerebrolysin made the cut.

Craig: Yes, it made the cut.

Andrew: We'll see what happens after this podcast. [laughs]

Craig: That's right. We've used a lot of cerebrolysin. We actually have a clinic that's open in London. We actually did use it. We've used it a lot more over there than over here.

Andrew: You have a US clinic and a UK clinic?

Craig: We have one based in London and one in Charleston, yes. I think cerebrolysin has been used for decades in the setting of post-stroke, post-traumatic brain injury. The trouble with it, again, I've observed with people, they get cerebrolysin, we're talking about IV, you can also use it sub-Q, they will have a day or two where they feel really down and out. Their mood shifts to like this dark place.

Andrew: Scary?

Craig: Yes, and they come out of it. Most people don't like that feeling, and so we stopped using it mostly for that reason.

Andrew: My understanding is that cerebrolysin is kind of a cocktail of brain-derived neurotrophic factor, ciliary neurotrophic factor, some other things. It's not one thing.

Craig: Right. I think collectively, it increases BDNF levels. There was dihexa too. I don't know if you're familiar with dihexa. That's another one that was removed by the FDA. Supposedly, the most potent way to increase brain-derived neurotrophic factor, kind of the juice the neurons live in, again, oversimplification. That's gone, but I think cerebrolysin did the same thing.

Andrew: Interesting. As long as we're talking about maintaining or boosting cognitive function, here's one I've never tried, but you and I have talked a little bit about. It's still seen as a renegade, but it's becoming more commonplace, and that's methylene blue. I always make the joke that I used to use methylene blue to clean my fish tanks, because I'm a big fish tank aficionado. At least I was when I was a kid. Right now, I have a tank, but it's empty. No pun intended. What is methylene blue, and what are people using it for? Does it turn your tongue blue?

Craig: It does, for sure.

Andrew: Is that permanently?

Craig: Not permanently. It's actually the first pharmaceutical ever prescribed in this country in the late 1800s, was methylene blue.

Andrew: Goodness. It sounds like really renegade, but it's--

Craig: It's not.

Andrew: Got it.

Craig: Yes, but it's gained favor in the last five years. That's certainly when we learned about it. Particularly, I learned about it through this doctor who was telling me, with COVID patients, he was getting immediate, within a day of stopping of COVID symptoms, from using methylene blue. That's what piqued my interest. I was like, "Wow, that's incredible." Then he went on to say that then COVID tests were turning negative within a matter of two days, which was unheard of.

Andrew: I've seen that with something else, but I'll get back to that.

Craig: That's when I was like, "Oh, this is-" It started to be talked about, and learned about it. Methylene blue, when we talk about the mitochondria, using that mitochondrial membrane binds to cytochrome C oxidase. I think of it, traditionally, it's used when people have carbon monoxide poisoning. They'll still use it. You go in the emergency room, you have carbon monoxide poisoning, it'll give you methylene blue, and it helps your red blood cells displace the carbon monoxide and put oxygen there. It's an oxygenator. That's how I think of it.

Andrew: Is it used as a performance-enhancing drug in endurance sports? Because this sounds like the kind of thing that cyclists would really want to use.

Craig: For sure.

Andrew: Check with your local governing body. There's always a question I get. People are like, or they hear something on a podcast, and they go, "Can I take it, or am I going to get disqualified?" I always say, "I have no idea if you'll get disqualified."

Craig: I don't believe it's on the water list.

Andrew: We'll just look for the people with the blue tongues. Easy test.

Craig: Methylene blue, very well absorbed, very well orally. I think of it like NAD, the molecule NAD, because it works on the cytochromes. Different than NAD, though, because if you're taking NAD by itself, not absorbed orally well at all. That's one of the trouble with it. Methylene blue is, and actually, you can take way bigger dosages orally than intravenously. We've given it intravenously a lot, but we're limited in using it intravenously just because it'll start to cause some spasm of the vein. The arm starts hurting if you're giving too much methylene blue, either too much or too quickly. We can give it orally. You can get a capsule of it. That's how we, our pharmacy--

Andrew: What dosages?

Craig: I think a good dose is no more than 10 milligrams.

Andrew: 10 milligrams?

Craig: Yes.

Andrew: Taken when?

Craig: In the morning. It's a cognitive stimulant for sure. I've had more people over the last five years, because we make methylene blue, we combine it with some other agents, a little bit of caffeine, some B vitamins, and people say, "This is the best thing for my brain function, recall memory."

Andrew: Kind of "Nootropic." A term I don't really like, because there aren't circuit for being smart, they're circuit for task switching.

Craig: I get it.

Andrew: It's 10 milligrams of methylene blue combined and you've got some other things in the cocktail version you make. Taking in the morning on an empty stomach?

Craig: Yes. You could take it with food though. Again, it's going to be well absorbed. Interesting to people, I need to say, it will turn your urine green or blue.

Andrew: For how long?

Craig: About 24 hours, depending.

Andrew: It's kind of fun.

Craig: Yes. Well, and a good caveat is if it doesn't, and I've had patients, then that's interesting to me as a clinician because it means that your mitochondria is not working well. The way I see this is you should get spillover. You shouldn't use it all and if you're not, there's something wrong there that you're using all of it, and you're getting no spillover back into your bloodstream which gets filtered into your bladder, your urine, which you urinate out. That's happened with a couple of patients. It's like, "Oh wow, you had no green or blue urine. There's a problem with your mitochondria."

Andrew: It's putting more oxygen onto the blood cells?

Craig: Correct, like your hemoglobin is able to pick up more oxygen. That's exactly right. Then there's a mild MAOI inhibitor.

Andrew: Monoamine oxidase inhibitor.

Craig: Yes, which will allow things like serotonin to work a little bit longer in that synaptic cleft. You've expounded way better than I can about serotonin and dopamine and how those work, but there is a cognitive enhancement from it for sure. It's very real. We have a lot of people using it and love it. It also seems to be an antiviral. You get this, again, that's probably through the mitochondria, making your mitochondria more efficient.

Andrew: It's a prescription drug.

Craig: It's a prescription drug, but there's now, and I don't totally understand it, there's now strictly over-the-counter nutraceutical supplement options that are methylene blue. For sure, anyone can go online and buy it. For sure.

Andrew: Trust me, now there are going to a be a few.

Craig: You talked about turning your mouth blue. If you take a liquid form, and we'll do that sometimes in the office when we're doing other treatments, we'll give a big dose of methylene blue to help fuel, quickly make a lot of ATP, which we want to do with some different IV treatments we do. We'll give sometimes up to 50 milligrams at a time. Their gums, teeth, lips are blue for about an hour or two.

Andrew: How often can people take methylene blue?

Craig: Again, you could take it every day. I think it's a little bit longer acting. I don't take it every day. I take it about three times a week. I think it's about right. I do have people who need it more for whatever they're dealing with. I do think as a nutrient, if we're going to call it that, it's a lot of it. It's an insurance policy for your mitochondria.

Andrew: Earlier, you mentioned a patient, or maybe it was patients, plural, that experienced a more rapid transition out of a COVID infection or maybe more recovery from long COVID symptoms, et cetera. It reminded me of the second time I got COVID, far less intense than the first time. The second time I got COVID, I had an amazing experience where my COVID test was very strong band.

It was very clear. I had COVID. There was no question about it. I didn't feel good. I was fatigued. Wasn't super severe. I would put it on a six out of 10 on the malaise level. No fever. I stayed in bed and stayed away from people, this sort of thing. I did an NAD infusion. I, of course, told them I had COVID. They came over, they gave me an NAD infusion. Correlation is not causation, but I think it was 750 milligram NAD infusion over the course of about 45 minutes.

I had the usual feelings that one gets when you get an NAD infusion, of you feel like an elephant is stepping on your legs. Your chest got the cramps, so you feel. Then, when that stops, you feel much better than you go into the thing. The band was absent the next day. My symptoms were, I don't want to say gone. I went from a five, six out of 10, as I mentioned, to a two out of 10.

Within another 48 hours, I was good to go and better. Now, this is correlation, not causation. I don't know what was going on. It could have been the saline bag, right? It could have been any number of things. The shift from a dark band to no band was so dramatic that I took another test after the no band, and then, of course, the next day, and the next day, this kind of thing. It's interesting.

I don't know what it means, but one wonders whether or not it's just a global way of combating inflammation. Every time I think about a systemic effect, and the reason I raise this is that I don't want to give the impression that I think that NAD is specifically in the pathway that was targeted, but that my brain and body were inflamed. Clearly, I had an infection, so you could have a flu, you could have a cold, you're inflamed. What are your thoughts on that anecdote? Again, it's just anecdote, but what are your clinical reflections?

Craig: We've seen it so many times. For the longest time, and so we've been using NAD longer than most. I'm fortunate that I was given the original NAD infusion protocol, which came from Mexico. It's a long story. I don't want to bore you, but that dosage of 750 milligrams is actually what we came up with in my office. That's what most people adopted just because we've used it more than probably anyone else on the planet.

Huge fan of NAD, very biased, but that's only because I've seen it work over and over and over in inexplicable scenarios just like you're describing, where it's not just you go from A to B, but you're going to A to Z very quickly. I used to use the word transformational, talking about it. Not just going from a sick state to a well state, but in most people, going from a well state to a super well state really quickly.

It's super impressive. There's a lot more to NAD than we understand, right? Because just very empirically, giving someone this coenzyme, this vitamin B3 derivative, how is it dramatically changing symptomatically how someone feels? It does. I've seen it with thousands upon thousands of people, certainly in the setting of COVID, certainly in other bio infections, you name it. I have been more impressed with the work of NAD than probably any other agent we've ever used.

Andrew: Amazing. I take sublingual NMN each day. It makes my hair grow ridiculously fast. I've done the control experiment. I'm a scientist. I know how to do control experiments. It's still just N of one. It's just me. It makes my nails grow really fast. It makes my hair grow fast. That's the major consequence. By the way, I want to be clear, I don't have any stake in any company that sells NAD or NAD infusion, so I'm just reporting what I'm reporting.

Craig: I think it's great.

Andrew: Somebody who's quite expert in the NAD pathway, Charles Brenner, who I believe has a relationship to a company that makes NR supplements-

Craig: I think that's right.

Andrew: -encouraged me to try NR. I took these NR supplements. This is what? It's NAD minus a phosphate group, is my understanding. Those I took orally. I couldn't tell if I got the same or different effect because I was taking them together. I didn't continue to take them because, compared to NMN, it was very expensive. I just stopped taking it. That's why I use sublingual NMN. In brief discussions with Charles, and how we are forging online, it seems that there is some human clinical literature showing that NR can reduce inflammation. Is that right?

Craig: Yes, for sure.

Andrew: Okay. Less data that NMN can reduce inflammation, at least lack of human studies. It's still murky, foggy territory with respect to the research and clinical--

Craig: The biochemistry. Yes, what does the biochemistry do? The way I think about it, again, because we pioneered the infusions, the NAD drips, which for me, transformational, just observing lots of people who I never saw the same thing with NMN and NR. You're not having these transformational experiences within a week. I tell the story a lot, is I had a patient, he was diagnosed with a chronic Epstein-Barr virus, which is rare, but it does exist. He was depressed and on disability just because he couldn't almost get out of bed.

Andrew: This is mono?

Craig: It was reactivation of Epstein-Barr. Yes. Very fatigued and depressed, and literally on disability, couldn't work. I said, "Before we do anything, the way I operate, I want to get you feeling better first before we start to tackle some of the bigger things." We did the loading dose of NAD, which we came up with five treatments in 10 days. Came back to my office, his wife was there, she was crying. She goes, "Within a week, my husband is back."

Andrew: Wow.

Craig: I've seen that so many times with NAD. I can't explain it. If I just stick to the biochemistry, it doesn't make sense. Oh, you're increasing the NAD, NEH ratio, fueling the mitochondria, which are all over the body, thousands per cell. There's something that we just told-- there's got to be outside the mitochondrial effect of NAD that's not well understood.

Andrew: In the backdrop of our conversation today, there've been a number of themes, but one of the themes that seems to keep coming up is that there are a lot of things about medicine that we don't understand.

Craig: Totally.

Andrew: Yet there are tools that seem to work for certain people extremely well. A few years ago, I went to a meeting. This is a foundation meeting, a foundation I was a part of, where you get to see talks from really the best of the best laboratories. They only show unpublished data. I don't know if this paper's published yet, but at the time, they were showing that they took people that were diagnosed with major depression.

They started doing a bunch of metabolomics on them. Now, this sounds pretty standard for social media. It's actually pretty heretical. Not a lot of places have done this right. A couple thousand patients, blood draws, they're trying to figure out, they ask a simple question, are there any specific vitamin deficiencies that are associated with depression? As I recall, they identified a few different types of vitamin deficiencies. It's not like one vitamin, it's not always methylated B6 or something like that.

Excuse me, it's not always B6 or B12. They found these clusters of patients that had major depression that were deficient in particular B vitamin. They supplemented back the B vitamin, and lo and behold, those patients showed remission of their depression. One could conveniently conclude, oh, well, all depression is a B vitamin deficiency, but of course that's not true. More likely depression, like fever, is just a broad description of symptoms. What was so exciting about this talk, to me anyway, was that people were starting to look at nutritional deficiencies as a potential source of mental illness, which now has a bit more traction, but at the time was like, "Whoa, what are we really saying here?

I thought all of depression was a serotonin deficiency," this kind of thing. When you talk about NAD having these transformative effects, and the fact that NAD can raise the tide on a number of different biological processes, to me, it makes perfect sense. It might've kicked off some mitochondrial pathway or some cellar pathway that then fills in a blank that's desperately needed. Is that one way that we can conceptualize this?

Craig: That makes total sense to me. I like how you've described it.

Andrew: How often do you encourage your already healthy patients to do NAD infusions? What are the dosages? I should mention the NAD infusions for most people are a little bit costly.

Craig: They are costly.

Andrew: They're like anywhere from $500 to $1,000.

Craig: Or more in Los Angeles.

Andrew: More if you're in Los Angeles. Assuming someone has the means.

Craig: Here's what we found. Again, just found it by treating a lot of people and learning is we do a loading dose for most people. We found the sweet spot to be 750 milligrams.

Andrew: Intravenous?

Craig: Intravenous.

Andrew: Venous, excuse me.

Craig: When they were doing NAD in the '90s, and they were doing it for substance abuse, so alcohol, pain medicine, morphine.

Andrew: They used it for that?

Craig: That's where it came from, actually. It was in the '90s. People traveling to Mexico for NAD infusions. That protocol was 10 straight days of intravenous NAD. The doses was 3,000 milligrams.

Andrew: 3,000 milligrams?

Craig: Yes, and that's why it took 6 to 8 to 10 hours per infusion. You could not get through it.

Andrew: Putting 500 milligrams in over the course of 45 minutes is going to be-

Craig: Uncomfortable.

Andrew: -very uncomfortable. Many people take an anti-nausea med.

Craig: I'll say about that. There was a gentleman in the States in 2006 who lived in Louisiana. He had a pain medicine addiction. Went to Mexico, got the NAD protocol, changed his life. He then licensed the use of the only injectable NAD product, which was from a South African company at the time, brought it to the United States, opened a clinic in Atlanta. All he did was addiction. I got to know him because I'm Charleston, not too far involved in IV work.

He was not a physician. I don't remember the time, but he came to me and said, "Hey, I need some help, because I'm getting a lot of questions about this NAD stuff." He handed me the original protocol. I'm super grateful and fortunate, but what I realized is, no one has time to spend 6 to 8 to 10 hours in someone's office. They may do that once, but they're not doing it more than once.

We started trialing different dosages, 250, 500, 750, 1,000 on up, and I just found collectively by watching people and how it did, 750 milligrams is the sweet spot. Meaning, they'd get the benefits, which we can talk about, but then they could get through it in an hour or two hours. That was meaningful. Then we found that we don't need 10 straight days. It's too much. That just is crazy.

We found that five treatments in 10 days, again, afforded people the ability to have great benefits, which were uniform, probably 95% of people who do a loading disk will come back and tell you their brain is getting bigger. They're feeling more creative. They have a elevated mood. They can sleep less, but have more energy. Colors look brighter. Languaging is easier. This is all very real. I think it affects the nervous system first, just because of the concentration of the mitochondria for every single neuron in the body.

The physical components, meaning recovery, and helping with physical exercise, those come, but I think they come later. We settled on 750 milligrams. We settled on the loading dose. Then what I noticed is that people were coming back between three and four weeks saying, "Hey, I don't feel as good as I did after I did that loading dose." We started doing a once-a-month maintenance dose, and that is what we still recommend to do today.

Some people do less and some people do more. I have some people who do it once a week. Plenty of people do it once a month, and then some people do it quarterly, some people do it whenever they can. On average, once a month seems to work really well for people. Then during the pandemic, and realizing this is growing, because again, we train practices in the medicine that we practice, we trained 300, 350 practices and give them playbook, so to speak, people weren't coming to the office as much with COVID, so we started doing it subcutaneously.

Actually, that's worked out really well. We'll do 100 milligrams subcutaneously, again, five days on, take two days off. You get a little bit of that stomach cramping from the 100 milligram injection. Like you said, can't really be absorbed well orally. Not going to really work, so you're going to have to inject it or infuse it. Agreed, there is a price point here. It's going to cost money, but like most things, to me, if I had to pick one thing for people, engaging in NAD would be it.

Andrew: Really?

Craig: Yes, I would.

Andrew: Of all the things we've discussed?

Craig: Of all the things, I've just been so impressed over the years. Now, peptides are amazing. Not to knock peptides. There's so many peptides, and I will get there, because you take this peptide for the nervous system, and this peptide for the immune system. Collectively, one agent, one thing, it's NAD has been the most impactful, from where I sit working with patients.

Andrew: That's a significant statement. 100 milligrams injected subcutaneously?

Craig: Yes.

Andrew: You get a little bit of stomach cramping?

Craig: Yes.

Andrew: As compared to the 500 milligrams to 750 or 1,000 milligrams-

Craig: IV.

Andrew: -that one brings in IV?

Craig: Yes.

Andrew: The fastest I've ever dripped it in was, I think, 40 minutes.

Craig: I can tell you the record.

Andrew: What's the record?

Craig: 3 minutes and 26 seconds.

Andrew: Is that you?

Craig: No, no, no. Never.

Andrew: For 500 milligrams?

Craig: 750 milligrams, two separate people did it. 500 CCs of saline, 3 minutes and 26 seconds.

Andrew: Wow.

Craig: It's insane.

Andrew: Yes. I don't recommend it.

Craig: No, no, we wouldn't allow it to happen. It's too much. You've got to have a lot of experience with NAD.

Andrew: Yes. I found that, because you have to sit there for a while, you could think, "Well, if you organize the plumbing correctly, that you could type or something," but you feel-

Craig: It's hard.

Andrew: -garbage enough-

Craig: It's hard.

Andrew: -during the infusion that you get irritable. It's actually a very interesting window into empathy for people who have pain.

Craig: Totally.

Andrew: When you're in this whole-body systemic pain and discomfort and you getting that saliva, I'm sensing it now, I have a distinct memory of this, for people that get seasick, you think about being on a boat and walking back and forth get a little nauseous, someone would walk in the room and you're like, "God, why are they walking like that?" It's your sense of pain. I normally don't have that response to people. I'm not a moody person in general. Then when you remove the infusion, you feel great. All of a sudden, people seem delightful, the irritating person. It's a very interesting experiment in social empathy.

Craig: It is. This is just what I postulate, is that a lot of people are challenged because a lot of people are numb to the world they live in. They don't feel things. When you do NAD, there is nothing like that experience and that feeling. You are going to just psychologically say, "Something is changing inside of me. It's something powerful because when I receive it, it's a lot." To your point, what we do is, we have an IB room where you have eight chairs and we make it social. When you're talking to people and learning about their experiencing it, there's actually a lot of healing that occurs just from that community.

Andrew: That bonding experiment.

Craig: It is.

Andrew: For people that can't afford the infusions, the injections would be the next best bet. If they can't afford those, would it be the sublingual NMN or NR?

Craig: I think so. I think the NMN I would choose over NR.

Andrew: Going from most expensive to least expensive, most expensive would be-

Craig: IV.

Andrew: -IV. Then it would be subcutaneous, then it would be NR, and then it would be sublingual NMN?

Craig: Yes, that's about right. You could do NAD topically. It's a little bit wild card doing it topically. You could do it under your patch.

Andrew: The antipyretic patches. Those give me a really terrible--

Craig: The problem is the patch.

Andrew: I get this itchy thing.

Craig: It's the patch. It's the adhesive. It's too strong and lots of people get irritated. Their skin gets irritated. I think the NAD gets in well, but the patch itself is a hindrance, obstacle.

Andrew: For those that are listening to this and they may recall, I did an episode of this podcast with Dr. Peter Attia, where we talked about NAD and NMN and NR. That was mainly focused on the research literature. You're not going to find much.

Craig: You won't.

Andrew: What we're talking about here is clinical experience.

Craig: It is. Full disclosure, I'm a clinician through and through, so my experience is observing people.

Andrew: You're interested in what works.

Craig: I'm confident about it because I've done a lot of it. I've seen a lot of how peptides work because we've done a lot of it. NAD, because we've overseen, again, a lot of NAD here and in London all over, and the providers we work with. We get a lot of feedback about what works and what doesn't work.

Andrew: Speaking of clinicians and science and all of this, there are a couple other peptides that have received FDA approval that are commonly in use. Things like PT-141, which is in this melanocyte hormone pathway that's used. One of its FDA-approved uses is, I think the brand name is Vyleesi, for female hypo-libido. It stimulates libido in women. It's also used to stimulate libido in men. Is that right?

Craig: Can be. It's a neurogenic mechanism for erectile dysfunction.

Andrew: It's not just related to blood flow?

Craig: Actually, it's not. PT-141, a fragment or derivative of the peptide melanotan, which stimulates alpha-melanocyte-stimulating hormone, which is becoming more in play in the environment I operate in just because of mold toxicity. We think of mold toxicity being a biotin and hitting-- MSH being the general, in terms of a lot of these hormonal pathways, actually. Melanotan can strip bolster by putting out more melanocyte-stimulating hormone. It seems to bolster immune response. I think there's an element with energy too. The downside of melanotan is it stimulates melanocytes, so you're going to get this tanning. It's like an orange-looking tanning.

Andrew: From the inside out?

Craig: Yes, you see it. You recognize it. PT-141, what they found is, in rats, I think it was, female rats were copulating more when they got this compound. They were like, "Oh, cool. Let's try it in humans." It's led to that. Our trouble with it is a very small or narrow therapeutic window. If you give too much, you're going to get nauseous pretty quickly. Some people, particularly women, don't like that tanning look. It's not a very--

Andrew: It can look very unnatural.

Craig: Unnatural is the word.

Andrew: The medial pituitary, which at least my understanding is the origin of these peptides that we're talking about now, is super interesting. You mentioned the nausea. These peptides hit multiple pathways When we had Dr. Zachary Knight from University of California, San Francisco on to talk about GLP-1 in a lot of detail, he mentioned that some of the nausea associated with ozempic and Mounjaro and things like that relates to the fact that there are receptors for these things, not just in one hypothalamic structure, but also in area postrema and areas of the brain that are these "primitive" areas that are associated with generating nausea when you need to rid yourself of a poison that-

Craig: Makes sense.

Andrew: -nature conveniently engineered us with neurons that, when they detect chemical changes in the blood, make us vomit.

Craig: Yes. To touch on that is what we found is if we start with, again, a micro-dose and go slowly with the GLP-1s, the nausea is virtually unheard of. Not saying it doesn't occur, but it's super rare if you just take your time with it. I think the people that have the most problems is they're shotgunning the dose essentially. You're overwhelming your system.

Andrew: I have two more questions. The first one is a bit of a controversial one. Today, we've talked about a lot of peptides that you've observed incredible clinical utility for. We also talked about a lot of peptides that the FDA has banned, basically, to be blunt. We've also talked about peptides that at one point, not too long ago, were considered part of a niche culture like fitness or bodybuilding culture that are now approaching what will probably be trillion-dollar industries over the next 10 years, things like GLP-1 agonists.

Any listener with their neurons firing will put two and two together and say, "Okay, what's the deal?" Obviously, the FDA, I like to believe, has a genuine interest in our safety. They don't want us taking things that are dangerous for us. At the same time, there seems to be a clawing back of what's out there and then a handing off to pharmaceutical companies to put out compounds for which there are tremendous profit margins.

Craig: Correct.

Andrew: The profit margins on these are insane.

Craig: We can't comprehend it.

Andrew: We can't comprehend it. MK-677, I crossed out, right? The FDA grabbed that one. Thymosin alpha-1, crossed out. A bunch of other things that have been-- BPC-157, clawed back. How should we frame this in our mind? In other words, do you think that the FDA has genuine good intentions of trying to protect the general public, and that's why they're doing this, or is this a plan to make that appear to be the case so that these can then be sold at a very, very high profit margin? Perhaps it could be both, right? It's not an either or. I want to be very clear, I work at a major medical school, but I'll speak freely anyway, as would my colleagues. I like to think that these governing bodies have some people there, at least, with very good intentions.

Craig: Sure.

Andrew: I don't think it's a bunch of bad people writhing their hands together with getting kickbacks on pharma. I don't believe that. In fact, I know that not to be the case. What's really going on here? Because this is weird. There's this huge class of compounds we call peptides that clearly have immensely beneficial uses in the right dosage, in the right hands, with the right physicians. They're being clawed back. Why?

Craig: It's confusing. I think it's probably both. I would say that, unfortunately, a lot of times when the government acts, they overreach. I do think they probably have good intentions. I think there's probably sound reasons to want to have oversight of things that seemingly is the Wild, Wild West. There's truth to that, because peptides came on the scene, and people started using them. They're recommended here and there.

People could get them from, still can, research companies. There's not a lot of corralling, of understanding, well, what is going on? I'm sure there's an element to, "Hey, let's understand this better." On that side, I think they went too far, because I think if you really look at data or if you were really interested in that, there's ways to understand how things work without removing them from the marketplace.

The other side of me is like, just like we're talking about, Ozempic and Mounjaro, semiglutide and trizepatide, are blockbuster drugs. If you're a pharmaceutical company and you see that there's 15 to 20 other peptides which are really working and really working, because again, we've just seen the clinical response over and over and over, it's not a large leap to think, "Hey, if we're a pharmaceutical company, what if we turn that peptide, which was available to the commoner, for lack of a better term, into a drug?"

Andrew: Oh, like Vyleesi. That was done for melanocyte-stimulating hormone pathways.

Craig: Yes. I'm sure, I think it's both. That's why I go back to-- We have to operate within certain boundaries. That's great. We have to understand these boundaries. I say this sincerely, when we're talking about healthcare, when we're talking about people's health, we're not even close to talking about the truth for most things. We're not talking about why people get chronic disease. We're not talking about how our food is really over-processed, and the availability of high-quality nutrients and what that means.

We're not talking about all the toxicities. We just look at roundup, glyphosate, and its interference with so many pathways in the body, and people say, Monsanto and whoever runs that now saying it's so safe, and it's just not true. I think it's in line with, and what I support is, unfortunately and fortunately, as an individual, you have to be your own best advocate. You can't rely on someone to say, particularly the government, that you have permission or not permission to do this.

If you think it's best for people to do their own research, seek out reliable information. Start here. You guys vet so much stuff, very safe place for people to be like, "This is where I want to start." Then life is, you learn by exploring and seeing what works for you. It's like you start with a recipe to cook. Some people like it saltier. Some people like it spicier. You got to see what works best for you, and that's why I seek out other people, people like myself, other physicians, other people who have experience saying, "Hey, we'll help you guide you in this." That's where the magic happens.

To be honest, we're not being truthful in many levels when we talk about health. We spend so much money for what? We're not making a dent in chronic disease. We're not making an impact. We're not helping people lead better lives. Medicine is great for life and death things. It really is. In August of 2020, I had terrible abdominal pain. I just come back from visiting our friends in Hawaii. I tried to treat myself unsuccessfully.

Eventually, it was on Labor Day. I had so much pain. The next day, I called my friend who's a radiologist and said I needed to do a CAT scan. I did the CAT scan. He called me on the way back to the office. I had a blood clot in the vein going to my liver that had completely cut off. I almost died. It was really serious. I had to be hospitalized. I'm on blood thinners now. I am forever grateful for pharmaceuticals, saved my life.

Those same medicines aren't probably going to help me lead my best life. It's challenging. Having been educated in a very formal conventional medical system, which is dominated by the pharmaceutical industry, is a problem. We go back to the Flexner Report, which is like 1917, 1915 or something, where they studied medical education and basically said, "If you're a medical school and you're not promoting pharmaceuticals and in line, and we're going to kick out alternative remedies and modalities like chiropractic and acupuncture and nutrition. They don't count anymore."

That's where we are. The only thing that matters, and we see it as a society, we're deemed healthy by the pills we take. If we're going to be really honest, those pills aren't making us healthy, and by and large, they're not even making us well anymore. You know what I mean? I think it's time, and it's wonderful to have this form to be able to talk about, this is why I support so many other people talking about it, we need to make a change in that we need to start being honest about what we're doing.

Our health is not going to be coming from doctors saying, taking this pill or that potion. It's not. Not at this stage. It's more likely that people are going to feel healthy from seeing their trainer in their gym. This is why these things go to the gray market or black market. These people actually get results. It's just sad but true. To answer your question, I think it's both. I think the pharmaceutical companies are greedy.

I think they like making money. I think they also like helping people. They want to help people, but it comes with a big cost. The government's there to corral that, but like most things, the government does that go too far. I think we need to be honest about those discussions, and it's not threatening and it's not harmful. Just to be saying, "Hey, how do we make this better and how do we even agree to disagree?" Let's just start there.

Andrew: I really appreciate your take. I, too, rely on prescription drugs now and again. I don't know, maybe I'll lose some following for saying this, but I've had some situations where it made sense to take an antibiotic after surgery or something. I'm not anti-antibiotics. I also don't eat them like M&Ms. Everything you said, I generally agree with. I don't have the clinical expertise or the nuance to really understand these governing bodies. That's one of the reasons why I'm asking today, and I really appreciate you shedding light on this. I think you're clearly a truth teller. You're telling us your truth, from the clinical perspective, but it's clear you also have a broad optics here, and we appreciate that.

Craig: Sure.

Andrew: This podcast has always been about bringing in diverse outlooks on the same things. It's been wonderful today to be able to explore peptides, NAD, and this issues of FDA approval and FDA removal, as the case may be. You said something earlier a couple of times, that I'd like to finish up on. You talked about positive thoughts. You're a physician?

Craig: Yes.

Andrew: Not a psychologist?

Craig: No.

Andrew: But you're a physician, and you're in the business of making people feel better. It's clear to me that, among your many talents, you have great powers of observation. What is this thing about positive thoughts? There are a lot of immunological data out there showing that stress makes us sick. If we stress too long, repeatedly for too long. Stress in the short period is actually good for us, right?

Craig: Yes.

Andrew: There are some data showing that positive thoughts can enhance immune system function, et cetera. The data are pretty cool. Clinically, however, what's your observation about mindset and health?

Craig: I think we're just scratching the surface, and I think it is the most profound way to effect your life. There's a couple things I'll say about it. One, no good has ever come from a negative thought. Nothing ever good has come from a negative thought. Because all of us have a choice about every decision we make, to me, it's always best to slant that decision in a positive frame. Now, it doesn't mean you're fake about it. People really suffer. It is a very stressful time right now. Maybe the most stressful time in human history. There's no need to gloss over it and saying life is peaches and cream, because it's not for a lot of people.

What I know just personally and professional, is that when you start pivoting towards positivity, you get more positivity. All of us, every single human, has that opportunity to do that. Some people, it's way harder choices. They are dealt a much more challenging and difficult hand, lots of people. If we think about it, we didn't get to choose our eye color. We didn't get to choose our family. We didn't get to choose where we were born or how we were brought up, but we do get to choose how we respond to those things. What I've learned is, there's never enough positive I can exude.

There's never enough positivity I can be around, ever in my life. It is just the most amazing thing, and it can never be taken from you. When we talk about success, and longevity, and health span, to me, positivity has to be a part of that, because the mindset of positivity will override almost everything, literally. I can't tell you how that happens on a biochemical or a physiologic basis, but I know it to be a truth. I know it in the core of my being, that the more positive I am, the more I can influence other people, and plant seeds, and help people be more positive. That is something that I cherish, and just love, and is not talked about enough.

Especially as a physician, we're talking about the science, and, "Oh, this study," and putting people on this medicine, but really, the value, and I made this decision back in 2010, because I had my own practice, and I decided to stop taking insurance. It wasn't a money thing. It wasn't like, "Oh." It was because I was no longer valuable taking 5 to 7 minutes with each person and seeing 40 patients a day. For me, I felt like I'm not fulfilling my purpose here when I'm just writing prescriptions. That my purpose will be fulfilled if I can really have conversations where I get to know people.

Peptides and NAD tie into that because they are gateways to build trust with me, so that I can actually help you, an individual, learn how to be more positive, and to slant yourself and have that posture. Because, ultimately, all of us need the energy and want the energy to find out purpose. Once you find that purpose, oh my goodness, life gets magical, because we're all unique. We all have a different DNA structure. God gave us that. To be unique, to shine our light, to contribute, to help others. Most people don't know about that because they're in pain, or they're tired or whatever, they're suffering. If we can help walk people through that, and help them heal that, that's going to get really good. That's just what I enjoy doing.

Andrew: Beautifully said.

Craig: Thank you.

Andrew: So grateful to you for doing that within your clinical practice, for making that decision a few years back, to shift over to being aligned with your purpose, and the way that you've now expended your practice to public education. We'll provide links to your practice and to your public education-

Craig: Thank you.

Andrew: -efforts, and for coming here to do this significant public education effort about peptides and other compounds and regulatory bodies, and also just the field of medicine. Also just, I think so often we hear from scientists or from physicians, and we forget the human component. What's so beautiful about what you do and the way you do it, is that your humanity really comes through.

Craig: Oh, I appreciate that.

Andrew: It really does.

Craig: I appreciate that.

Andrew: I can tell you really care. I know our listeners and viewers can tell as well.

Craig: Thank you.

Andrew: As this field evolves and advances, please come back and talk to us again.

Craig: I'd love to.

Andrew: Meanwhile, again, we'll provide links so that people can find you, and some of the resources that back up what we've discussed today. Craig, Dr. Koniver, thank you ever so much.

Craig: Well, thank you, Andrew. No, it's really, I'm so honored to be here. I respect and love the work you're doing and the light you're shining, and you're helping so many. You have such a wide audience that trusts you. It's amazing. Like I said, I see it every day with people coming to me and bouncing what you do and saying, "Hey, is this good for me?" That is amazing. I love that. That's how we get better. We help support each other. I just appreciate what you're doing. Being here is truly an honor, really a big deal for me. Thank you.

Andrew: Thank you. I'll take that in and write back at you. Come back again.

Craig: I appreciate it.

Andrew: I appreciate you. Thank you. Thank you for joining me for today's discussion with Dr. Craig Koniver. To learn more about his work and his clinic, as well as to find links to some of the things discussed in today's episode, please see the show note captions. If you'd like to learn more about peptides, including some of the ones that we discussed today, but also some additional ones, please see the link to the solo episode that I did about peptide therapies in the captions. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel.

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