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The Neuro Experience
What Are PEPTIDES & How To Use Peptides For Greater Health: Infertility, Build Muscle, & Fat Loss
00:46:42
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- [00:00]
Podcast Host
Doctor Kyle Gillette, you're a veteran. Welcome back to the Neuro Experience.
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Dr. Kyle Gillette
Thank you for having me. Again.
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Podcast Host
I'm so excited. Ever since you came on our show, you didn't have your own show and now you do and you're putting so many wonderful things out there for the world to listen. Primarily around hormones, right?
- [00:19]
Dr. Kyle Gillette
Yeah. We could talk about anything health and fitness related, but most of what we talk about is hormone related, whether it be natural hormone optimization, fertility, hrt, et cetera.
- [00:31]
Podcast Host
Well, I'm going to get straight into it. So today we're going to talk specifically instead of hormones. And you know, we did that, we did pretty much an introduction to hormones and hormonal health in the last episode, which I'll link. We're going to talk specifically today a few things about pregnancy because I, I got a lot of questions from the Neuro Experience audience and they mainly came from women. We're going to talk about that. Then we're going to spend most of the episode talking about peptides because for some reason I don't know whether it's just New York City, they seem the rage right now and I don't know so much about them and I want to know a lot about them. So we'll get into the first question, which was a question from the audience which is is there such thing as unexplained infertility?
- [01:20]
Dr. Kyle Gillette
Yeah. The answer to this is not really. If you dig deep enough, then with unlimited technology you can find a cause for all cases of infertility. However, what most people refer to is called third factor infertility. That's when there's part of the reason, if you will, is from the male, part of the reason is from the female. And you can't really, you know, I guess the way to think about this is you can't assign quote, unquote blame in a lot of factors of fertility because a lot of times someone will ask the doc, hey, you know, is it me, is it my wife or whatnot? And they're saying, well, not really either. And a lot of times, you know, instead of doing a huge workup, they do things that are both diagnostic and therapeutic. For example, try a therapy where they presume a cause of infertility. And if the, and if there is fertility, then it tells you, yes, this is the cause. And also it's therapeutic.
- [02:25]
Podcast Host
Yeah, I think. And this question obviously leads into the next one because we were talking offline and you mentioned around a lot of women who maybe can't fall pregnant. They're trying really Hard. Then they end up taking a break, they go on a holiday and then they end up falling pregnant. And this is, I think, where a lot of the confusion is around females. And I know there is a, it's a 5050 and we'll talk about that in a second. But then if that's the case, you know, people de stressing does that mean like cortisol has a lot to do with falling pregnant?
- [03:01]
Dr. Kyle Gillette
It can, most hormones have quite a bit to do with falling pregnant. And more is not necessarily better. Less is also not necessarily better. A lot of the times I see individuals who have previously been told they are unlikely to get pregnant, it's because they have a certain pathology which they've improved. So something in a lifestyle has changed. Something in regards to their hormone status. Their body fat percentage could be higher or could be lower than before. So it could be someone with hypothalamic amenorrhea that has a higher body fat than she did or different leptin receptor signaling or different cortisol signaling. Better cortisol signaling is, is a potential cause. But one of the things that I see the most is individuals who were previously doing something that drastically decreased fertility and they are no longer doing that. One example, and I've had patients like this is, you know, they, they have a history of endometriosis and they were on some orisa, which is a medication that kind of shuts down the pituitary and whether it's Orlissa or Lupron and doesn't matter if you don't know what those medications mean. Basically they just turn off the switch and you're told, oh yeah, this is not going to permanently turn off things. But the switch is not turned all the way back on as fast as you would think. Sometimes it takes years.
- [04:25]
Podcast Host
So what else could turn, what else could potentially be in the way there?
- [04:29]
Dr. Kyle Gillette
Metabolic syndrome is most common. So you know, you think about the, the insulin resistant axis or the X axis type PCOS where there's hyperinsulinemia, too much androgen signaling in the ovary, too many follicles and things like that. You tend to see a high amh. And then the opposite end of the spectrum or the continuum would be hypothalamic amenorrhea where there's no hypothalamic signaling and you're not having enough input at the ovaries.
- [05:00]
Podcast Host
Did that, that might happen in like long distance runners, for example, because I know that some of them, you know, if you're a, an athlete of some sort and you're going really hard and maybe you don't experience your menstrual cycle, not because you're on any medications each month, it's just maybe you're over exercising.
- [05:19]
Dr. Kyle Gillette
Yeah, that could be. And of course there's the female athlete triad. If people aren't familiar with that. So a lot of times you see anemia along with that and often you see low body fat percentages too. But even at the same body composition, diet matters quite a bit. In fact, this could. Hypothalamic amenorrhea is not extremely common. But if you tend to have lighter periods or a lot of times you just have a bit of spotting or they're more near every 35 days instead of every 28 to 30, then you might be more on that side of the spectrum. If you get a DEXA scan and your body fat's under 20% as a female, that should be not full alarm bells, but just little warning bells that you should be cognizant of your hypothalamic signaling. The hypothalamus, of course, is in kind of the top of the brainstem, sends signals to many endocrine organs in the body, but one of them is the pituitary to release the gonadotropins, the LH and fsh, among other things. But an interesting thing about diet is if you have really high amounts of EPA driving triglycerides down, or anything in general that drives triglycerides down, that tends to decrease leptin signaling in the hypothalamus, which may not be wanted. So occasionally I see people that are Megadosine Omegas, Omega 3s specifically, and that might make them overly leptin sensitive without enough leptin signaling. And occasionally I also see people see people that are avoiding fructose. So you can consume fructose if you're an isocaloric diet, yes, you know, it can affect leptin signaling. But if you're on this hypothalamic amenorrheic side of the spectrum, or even athletes triad side of the spectrum, a lot of doctors will tell you will eat more fat, eat more fat. That's not necessarily the case. You just think about, well, what you, what would you do that's opposite as someone who has pcos. So you eat more fructose, you consume less canola oil, because canola oil can be healthy if you get canola that's processed wrong. So it's just, I love that hyper extreme example of you have two different patients and you're telling them to do opposite things.
- [07:38]
Podcast Host
Can the likely occur if you've got high body fat percentage? Because I know you said below 20. What about if it's on the other end of the spectrum?
- [07:47]
Dr. Kyle Gillette
Yeah, usually you would be on like the, the insulin resistant X axis type pcos where you have a higher amh, you have a lot of varying follicles. You could do a, a follicle count ovaries and you have a whole bunch of them. You might get a PCOS diagnosis if you meet Rotterdam criteria or other criteria. And I would argue that is much more common, at least in the United States, than this other end of the spectrum. Although there's probably a lot of athletes listening to the podcast. So maybe among this podcast listeners it's about 50. 50.
- [08:21]
Podcast Host
Okay, well, thank you so much for clearing that up. We're going to move into peptides now. First of all, before we go into what they are and the different types of peptides, is there a reason why this is becoming such a boutique kind of accessory right now, especially in Manhattan?
- [08:41]
Dr. Kyle Gillette
Yes, it's a great question. Two main reasons. And you know, I see peptides like I do any other supplement or medication. They're usually medications, sometimes peptides or supplements like creatine and carnitine, they're both peptides. Creatine's a tripeptide. Glutathione's a tripeptide, three amino acids. Carnitine's a dipeptide, two amino acids.
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Podcast Host
Is that acetyl? L carnitine?
- [09:07]
Dr. Kyle Gillette
Acetyl L carnitine is just the dipeptide carnitine with an acetyl group attached.
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Podcast Host
So same thing then.
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Dr. Kyle Gillette
So yeah, for all intents and purposes, they're the same thing. And there's a bunch of different forms of carnitine. And, and if you're going to take really high doses of oral L carnitine, it probably does make sense to take multiple forms so that it's absorbed in the gut via multiple mechanisms. For example, instead of taking, I think there's an S adenosyl carnitine as well, a life extension. I have no connection to the brand. They have two forms of L carnitine that are very unique. So sometimes if people are taking a lot of L carnitine, most common reason for that, if they don't want to inject the L carnitine, they're trying to improve their sperm motility. A lot of people take higher doses of L carnitine. There can be other reasons too. For ovarian health, a lot of times I'll use higher doses of L carnitine. But you can combine, for example, four forms each for one gram rather than taking four grams of one form because absorption and bioavailability is the, is very difficult with carnitine.
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Podcast Host
But anyway, wait on that. I heard, I, I did hear actually a very well known fertility doctor speak about high dose L carnitine being good for ovarian health and you know, the making them, I guess, stronger if you will, or healthier. And she did mention at a dose of 4 grams a day, but she didn't mention the differences in, you know, different types. And I think that's interesting because to take 4 grams of creatine per day in capsule for me taking like, I don't know, depending on the supplement, maybe like 10, 10 pills. And that's just of the one supplement. But is it true that L carnitine increases TMAO?
- [10:53]
Dr. Kyle Gillette
Yeah, it's a great question. So the, any carnitine or choline derivative or naturally occurring carnitine in red meat can increase tmao. But TMAO is formed most often in individuals with dysbiotic gut flora, which most people don't know. And even if you've had a, you know, a Genova Comprehensive Stool analysis or a Vibrant Gut Zoomer or a GI map, there's a lot of different types of stool tests and people argue about the, you know, like the validity of them all day, but at the end of the day they are all good at what they do. But if you stool a lot or don't stool a lot, it's like testing the exhaust that comes out of your car. So it's like you're testing the residue, which tells you a whole lot about what's happening in the engine. But depending on how hard the engine runs that day and depending on how many times you run the engine that day, it's going to have a different result. So probiotics can help decrease the amount of TMAO that's converted. For individuals that have a lot of or L carnitine supplemented. I just test the tmao, I see if it's high and by the way, for those who don't know, TMAO is a potential carcinogen, it is likely a carcinogen in a high enough dose or high enough level. And I try to keep people below about 10, but I know that I know individuals who are not taking berberine or Allison or anything else that can decrease conversion to TMAO. And they have taken 4 grams of oral L carnitine and as I mentioned, choline precursors like alpha gpc, phosphatylserine, phosphatidylcholine, choline, bitartrate, they can all also lead to more tmao. And I have seen people on really high doses of both, not on probiotics, just with healthy gut microbiomes and with undetectable TMAO levels. So it's definitely possible to take a whole bunch of choline and carnitine and not have your TMAO go up. But anybody, anytime people ask me about Coq 10 or Glutathione or Omegas or TMAO or even Carnitine, I just like to check all those things because we have. The lab says to do that.
- [13:09]
Podcast Host
And interestingly, I believe if you take garlic, like raw garlic, if you cut it up, or even, like, garlic capsules, that can help lower tmao.
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Dr. Kyle Gillette
Yeah, allicin is the active ingredient in garlic, which helps decrease the conversion of choline and carnitine to tmao. So that is a great dietary intervention. It's easy to get caught up taking too many supplements.
- [13:31]
Podcast Host
But that's why I always say, get blood. I'm such a big proponent of blood testing every, like, six months. In my opinion. If you can do it twice a year, great. But really understanding your blood biomarkers before you go and supplement with, you know, grams and grams and grams of an unregulated product that you don't know is even working. So that's.
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Dr. Kyle Gillette
No, that is excellent advice. But, yeah, hopefully that rabbit trail was.
- [13:58]
Podcast Host
Sorry, guys.
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Dr. Kyle Gillette
To some degree, I know we were talking about peptides.
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Podcast Host
Okay, we'll get back into peptides. Okay. What are they?
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Dr. Kyle Gillette
Yeah, so peptides are strings of amino acids. They can be between two. So I guess carnitine would be the smallest possible peptide. There's other dipeptides and a couple hundred amino acids, usually about 100. I think that from the pharmaceutical side of things, it's now limited to something like 47amino acids. I don't remember off the top of my head, but I know that things like TB 500 are underneath that arbitrary amino acid limit. And then things like GH frag, which used to be called, or is now called AOD 9604, used to be under the arbitrary amino acid limit, and now it's not under the new arbitrary amino acid limit. So I guess if I seem a little bit jaded, it's just because whatever definition that they're trying to give peptides, the way that I see peptides, if they are peptide, like creatine or carnitine, or glutathione. I see those, they can be prescribed and they can be over the counter. And then all other peptides essentially I consider medications. And if they can be prescribed at pharmacies or compounding pharmacies, there's a whole list of FDA approved peptides. I did a newsletter for people that are on my mailing list that talked about all the currently FDA approved peptides. Insulin is one of my favorite ones people forget about. There's peptides that have been along, been around for a long time and people tend to forget about them. People are usually most excited about peptides that are just on that cusp of FDA approval. And I think a lot of the reason behind that, number one, is because GLP1s glucagon, like peptides, have excellent applicability in the right patient. They're certainly not for every man, woman and child. And then the second reason for that is there's a lot of clinics which recommend peptides or talk about peptides that make a lot of money from them. So I think that their promotion of peptides is these new things that big pharma is hiding from us. And you know, I don't think pharmaceutical companies have our best interest in heart. I think they'll also want to make money. But I think that the clinics that are kind of promoting peptides too early also want to make money. So if you're wondering why something's happening, first follow the money and then you'll probably find out why that, why that is.
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Podcast Host
Actually, I refer to these as designer peptides because what I'm seeing currently, especially in Manhattan here in New York, is this anti aging scene. And now, you know, now peptides are coming up saying, you know, we can use peptides to help with fertility, to help with skin aging, to help with hair growth. Of course every woman in Manhattan is going to run there and get the next injection. Yeah, like I would.
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Dr. Kyle Gillette
Yeah.
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Podcast Host
So I haven't yet. Because I haven't spoken to you about it.
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Dr. Kyle Gillette
Yeah. And there's a lot of applicability. So I've talked about the various medications and supplements that happen to be peptides that I've been prescribed and I've used. People know that I've used PRP for my Achilles tendinitis, for which I think it worked quite well. But I've also used BPC157. So, you know, not both. And I think that, I think that they have helped Achilles tendonitis.
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Podcast Host
Okay.
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Dr. Kyle Gillette
So things like that do help quite a bit. But the, there's several Main classes of peptides. I know, I've also Talked with Thomas DeLauer about the classes of peptides. And then I also have a peptide family tree. If people have seen the anabolic steroid family tree, making a family tree of peptides which have a bunch of different classes. But most people are interested in the growth agonist, which are very similar risks and benefits to HGH human growth hormone. And then you have your growth promoting peptides. Those are like your BPC157 which actually just upregulates angiogenesis or new blood vessel formation. And then GHK copper peptide comes from the liver growth remoting TB500 which is a chopped up version of thymosin beta 4, comes from the thymus, an organ that's usually just present in young children. You also have other thymic peptides like thymulin or thymosin alpha 1, which in my opinion are not quite there with clinical applicability and risk benefit ratio at this time, but they're awfully close. And then you have your melanocortin receptor agonist. Several of these are FDA approved set melanotide is one of them, which is called mvcri. And then brimmelanotide is another one and that's called Filisi. So those are kind of the main overarching classes.
- [19:02]
Podcast Host
One class that I am really excited to talk to you about because I believe it relates to brain health is vegf and I don't know whether that's a class. Is that a class of peptides?
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Dr. Kyle Gillette
Yeah, I usually the only one that I know that directly promotes VEGF is BPC157. There might be others. PRP also has a lot of VEGF in it. VEGF is actually technically a cytokine, but as you mentioned, it's not as pro inflammatory as most of the other cytokines. And it's not heavily skewed as far as I know towards like TH1, TH2 or TH17 immune system, like many cytokines are. But yeah, that's very likely. One of the reasons PRP works so well in areas that are not well vascularized is it improves angiogenesis. BPC157 is kind of the opposite of something like Avastin. So you think about the side effects of Avastin, which is a cancer medication, one of the WHO's essential medications and is often used in ophthalmology for cell overgrowth. So Avastin is a VEGF inhibitor. So it's literally the opposite of BPC157. So BPC157 does have some trials in Crohn's disease, so it might have other uses, but it is particularly exciting. VEGF is one of those things like you could probably make a horror movie about it. It's probably the fountain of youth, but it's also kind of like if it's systemic, then it's a shotgun based growth agonist that can grow all tissues. So it's a little bit scary as well.
- [20:44]
Podcast Host
Well, VEGF can be improved with exercise and that's how I, you know, I was relating the two because VEGF would be obviously incredible, especially as it relates to brain health and vascularization. So I think that's interesting. What about. Okay, so what are the ones that are in. You know, I'm going to be really like low key right now and just ask you, like all the things that I think about when I open up Instagram. And you know, what about the ones that like improve, like improve age and longevity? The ones that, what about skin health? What are the ones that are like, oh, you can get peptides to improve, I don't know, skin health and make you look younger. Is that a thing?
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Dr. Kyle Gillette
Yeah, the skin peptides, the ones that are actually peptides. GHK copper peptide is in a lot of prescription and over the counter creams and I do think that is helpful for skin health. GHK copper peptide is also, I forget what the patches are named life something that claim to increase endogenous GHK copper peptide production, but they also market it to very old individuals which have livers that are not, that do not have as good of synthetic potential. So you think about someone who is a geriatric population and liver is not making as good GHK cover peptide, they're probably better off just taking the peptide rather than depending on their liver to make it, if that makes sense. But I do think that one has good utility in over the counter peptide creams. If they don't say they're ghk, those are usually hexapeptides and there's a couple different types of hexapeptides. Hexa for six. And I do think that those are helpful for aesthetic purposes as well. I would call them growth promoting and regenerative, not necessarily anti aging. I know that I've done a podcast before with Alec McCarthy, a regenerative medicine PhD that has published actually kind of an insane amount of research on regenerative medicine contrasting with degenerative medicine. So usually, you know, instead of destroying the skin or doing surgery or injecting you know, exogenous fillers that are not using the body's natural processes, instead using these things like peptides or growth factors or other ways to stimulate natural fibroblast production. Proteoglycan type 1 and type 3. Collagen, elastin and more.
- [23:13]
Podcast Host
Oh, damn. That's what I need. I know that there's, like a huge rise in PRP instead of fillers now. And I know that there's this new craze with fat injections instead of getting fillers under the eyes, which I've never had any of those. But, I mean, if I was to do anything, it would. I would caution against the synthetic and go straight to the PRP or the. The fat injections. That's great. Like, take it out of my leg and just, like, put it under my eye. That would be fantastic.
- [23:40]
Dr. Kyle Gillette
Yeah. At some point, I do plan to do PRP injections under my eyes, if for no other reason, so that people stop saying that I look tired.
- [23:49]
Podcast Host
That's nice. The Internet's a really nice world. What about S a r m? Sarms?
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Dr. Kyle Gillette
So SARMs are selective androgen receptor modifiers. Not technically peptides and not steroids, but they do bind the androgen receptor. So some people are familiar with Clomid, which is clomiphen or enclomiphene, one of its diastereoisomers. Right hand, left hand, if you will. Some people are also familiar with raloxifene or tamoxifen, which is noble dex. Those are selective estrogen receptor modifiers that either block or activate estrogen receptors. SARMs will block or activate androgen receptors. And there is likely naturally occurring sarms as well. I've always postulated that cistanche. Cistanche tubulosa, I believe in Chinese traditional medicine is a naturally occurring sarm, but we just don't know which receptors it agonizes or antagonizes. Other than the pituitary. We know that it is antagonist at the pituitary, at least at the androgen receptor. But the most promising sarm, if you will, is Enobo sarm, E N O B O S A R M. And this has been renamed. It was previously called MK2866 and before that was called ostarine, that some people might realize. But this is extremely promising for something called triple negative breast cancer that's actually grown by androgens because it can activate the androgen receptor throughout the body. So it's not going to cause osteoporosis and muscle wasting in females. And it's also not going to cause unwanted hair growth or male pattern baldness like the Masterone, which is Drastanolone, or like the methenolone or any of these other androgens that we used to give females that had androgen receptor negative breast cancer. This is kind of the opposite because in general you'd think you actually want to activate the androgen receptor. And that is the case with estrogen receptor positive breast cancer. But for this rare type of breast cancer called triple negative, you actually might want less androgenic activity. So osterine is promising for that and it's also very promising for prostate cancer patients.
- [26:08]
Podcast Host
Oh, interesting.
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Dr. Kyle Gillette
Yep. In the future, perhaps it could be used for burn patients, especially burn patients who are children. But there's a lot of research ahead before it does that. But it's very interesting because it's considered and it's actually not completely non viralizing, but compared to androgens, I suppose it is non viralizing and compared to anti androgens. Cause you think about prostate cancer, you use flutamide, you use things that block the androgen receptor or block androgen production or block adrenal androgen production very strongly. And compared to that, it's not near as bad on the muscle wasting standpoint of things, and from the development of metabolic syndrome and diabetes. So for every condition, as a thought experiment, we could design the perfect sarm, and we do talk about this on the Gillette Health podcast from time to time. And we think for this condition, what is the perfect SARM for this patient?
- [27:10]
Podcast Host
Oh, wow. Exactly. So everyone's different. This is why I don't think that you should be doing this with someone who is A, unlicensed, if that's possible, and B, someone who just doesn't know really too much about what they're doing, even if they are an MD or do I think it takes a very specialized person like yourself to understand the intricacies of peptides?
- [27:32]
Dr. Kyle Gillette
Yeah, certainly. So, yeah, sarms is definitely something I'm very excited about. But they're not quite at the, they're at the point where I think they have a lot of clinical utility for patients with certain conditions, especially in clinical trials. But we're probably five to 10 years away from off label usage of these. But I do think that Anobos ARM will get its FDA approval within two to five years.
- [27:58]
Podcast Host
Everything I'm waiting for two to five years, guys. Two to five years. I feel like, you know, that's going to be a really exciting time. You mentioned earlier, I don't know what you're referring to, but you did say the fountain of youth hormone, but it wasn't dhea. And I've heard that DHEA is the fountain of youth hormone.
- [28:18]
Dr. Kyle Gillette
Yeah, vegf, which is technically a cytokine, so not clearly a hormone. But yeah, from a standpoint of function, having a lot more VEGF and angiogenesis in any area of the body from a function standpoint is definitely good. From a, you know, a tumor growth standpoint, I guess you could argue it's the opposite of the fountain of youth. Same thing for hth. There's. There's no such thing as a free lunch. There's always an upside and a downside to every intervention. But, yeah, from dhea. DHEA is what I call the pawn on the chest board of hormones. And it is a great backup hormone. So it can be converted to testosterone. It can also be converted to estradiol. In fact, after menopause, it is the sole source of estradiol. Most of it converts intracellularly throughout the body. So having plenty of DHEA around is a good backup plan. For example, if someone has a whole bunch of dhea, maybe they have nccah, which is a somewhat common condition where you just have a whole bunch of adrenal production of it, then they'll probably have less menopause symptoms and have esent estradiol and testosterone levels after menopause and have less symptoms. So I could see why people would consider it the fountain of youth. But in and of itself, it's a very weak hormone.
- [29:41]
Podcast Host
But you can get that from supplementation. I know I was, like, slightly low, like very slightly low in DHEAs. Is that the same thing?
- [29:50]
Dr. Kyle Gillette
Yeah. So DHEAs is DHEA sulfate. Most of adrenally produced DHEA has sulfate attached via sulfotransferase enzyme. And at least 80% of your DHEAs comes from your adrenals. So we always test the DHEAs. That's the lab assay that you want your doctor to check, because that is. That is what is going to tell you how your adrenals are functioning. And yes, ACTH does lead to the production of both cortisol and dheas. So really, instead of thinking about, you know, and there is utility to looking at cortisol to cortisone and other glucocorticoid ratios, but you really want to look at the ratio of DHEA s to cortisol.
- [30:35]
Podcast Host
And, and you mentioned that it's the, I guess, precursor to estradiol. But then how does that affect estrogen.
- [30:43]
Dr. Kyle Gillette
Yeah, estradiol would just be considered your most powerful estrogen. But DHEAS is not extremely estrogenic, particularly in females. So in females DHEA supplementation can lead to decreased shbg. So you want to check SHBG before and after starting. Oh, there's other things I didn't know.
- [31:06]
Podcast Host
That I'll do that.
- [31:08]
Dr. Kyle Gillette
Yeah, there's in fact Dr. Fernand Labri l A B R I E. He recently passed away. He was a well respected researcher that actually also looked at cirms. I believe it was University of Montreal or Toronto. But he had a bunch of great ideas and he frequently tried to include DHEA in a whole bunch of medications which I think is one of the reasons why it's controlled in Canada. It's actually pretty high on their equivalent of the FDA schedule. So you definitely don't want to take your, you know, DHEA and just look at it as only a supplement. It can be a medication as well. But I do think it should be over the counter in Canada. All that being said, but the point being is that it can decrease shbg. I know my friend, I've talked about, talked about this with my friend Derek who has the More plates, more dates channel. And there's a lot of women on oral contraceptives that have suppressed their androgens. You can suppress them and not just oral contraceptives. If they're just on estrogen and progesterone as hrt, you're also suppressing your androgen level. So if you just search female menopause testosterone and you look for that chart where you compare people that take estrogen versus not testosterone and free androgens especially decrease quite a bit and DHEA can be a great way, way to rectify that. So there's a, a lot of high level female athletes, college and professional athletes that are allowed not to get into that topic, allowed to take DHEA and they do so because they also are on oral contraceptive.
- [32:46]
Podcast Host
Yeah, interestingly I think maybe that's why I started taking it because I think my testosterone was slightly low and so was dhea and I thought that there would be a, I mean I'm not talking like anything like cause of concern, it was just like slightly and you know what I'm like, I'm like got to be hyper optimized. So I think that's why I started taking it probably around six months ago. Dhea. And interestingly, I don't know if you know this, there is a really tight link between DHEA and REM sleep. And my REM sleep is actually because I found a really great article on pubmed. My REM sleep has gone through the roof. It's sitting at like, 20. Well, through the roof, it's sitting at like, 29. But prior to the DHEA, it was at like 14%. And I'm like, this is. This is insane. So I investigated, and then that's how I. I saw that article.
- [33:32]
Dr. Kyle Gillette
Yeah. For a lot of females, DHEA can be particularly dopaminergic. You get that benefit, and you probably would have gotten the same benefit if you took a very low dose of testosterone as well. It's not necessarily unique to dhea. One thing that's unique to DHEA is It's also a sigma 1 receptor agonist. So it helps with parasympathetic tone. So a lot of people with ADHD or that are on stimulants for whatever reason, take it to potentiate their dose to get more bang for the buck. So that's something that DHEA is also very good at. But it. It really is a jack of all trades. And the more skewed you are, one way or another, the more DHEA will work. So DHEA works or people feel it the most if they start with a very high SHBG or if they start with a very low shbg. We usually see acne and hair loss because it can be converted to DHT very quickly.
- [34:24]
Podcast Host
Yeah.
- [34:25]
Dr. Kyle Gillette
So some females end up on something to account for that while they're on dhea, but it's a great addition. I usually have females start at 10 milligrams and males start at 25 milligrams, but a lot of females can tolerate more than that.
- [34:39]
Podcast Host
Interesting. Okay, I'm going to look at my dosage. Melanocortins. Did I say it correct?
- [34:46]
Dr. Kyle Gillette
Yeah.
- [34:48]
Podcast Host
Okay. I'm guessing that has something to do with the melanocytes and becoming darker. And is that why some people in the bodybuilding space are injecting themselves with this? Is that what it is to make themselves darker?
- [35:01]
Dr. Kyle Gillette
Yes, There's. There's actually several types of melanocortin receptors, and a lot of these medications bind two different melanocortin receptors, and one of them causes nausea and also causes lack of appetite and also causes slight hyperpigmentation of the skin so it can darken freckles. Your hair might lose some of its photo bleaching effect if a little bit of it does get lighter in the hair and the sun, the summer. And then if you have a whole bunch of it like non clinical doses, it can slightly darken the pigment of the eyes as well. But these are, these are prescribed for a few different main reasons. One of the reason is hypoactive sexual disorder, whatever that is. I always make that joke because it's obviously relative to your partner and your situation, blah, blah, blah, blah, Hyper or hypo. Hypo, hypo. One of the side effects of it is priapism or prolonged engorgement of erectile tissues in males and females. And it's actually FDA approved for females but not for males. But it can definitely be used for both. A side effect would be nausea and flushing. So the brand name of this is called Vylesi V Y L E E S I and I know that several companies are kind of studying this rimmelanotide molecule to see how they can have it be slightly longer acting or slightly less severe from like the nausea or flushing standpoint. And I do plan to have one of the PhDs for one of these companies. He's one of their field directors or medical science liaisons. I do plan to have him on the Gillette Health podcast to specifically talk about his peptide. I think it's hilarious that he refers to his medication as his peptide. But he has set melanotide, which is in Vicri, and it's indicated for different hyperphagic syndromes, e.g. genetic obesity or Barde beetle syndrome or leptin receptor deficiencies. But it is likely to get FDA approved for many more causes if they can come out with a longer acting version of the peptide. If you remember Exenatide, one of the very early GLP1s or Victoza even, you had to inject it every day and now we have the longer acting ones. And that's really when things picked up. So I think when we have the longer acting, weaker melanocortin receptor agonist, we're going to have a boom of that as well.
- [37:31]
Podcast Host
Okay, so say there's people listening and they're like, where do I even start? Do I need to start like, give me the lowdown. What should people do if they like, first of all, who should be taking peptides? Let's start there.
- [37:44]
Dr. Kyle Gillette
Yeah, the way that I phrase that question is I just kind of rephrase it because peptides like these, these are medications and there's already multiple FDA approved melanocortin receptor agonists. So I kind of phrase the same question but with a different word. Where should people start when it comes to these medications and should people be taking these medications and the way that I explain it is whatever the medication is, you can talk to your physician and you have them explain all the benefits and all the risks. That's a scale. So think about it, balancing the scale. And you want the benefits of that medication to outweigh the risks. And people say, well, my physician, she or he has no idea what any of these medications are. And I would encourage get a new physician. Yeah, just like if your lawyer has no idea about case law in accounting, then you should probably find anyone that has an idea about case law and accounting. Although some physicians are willing to learn, if you have one, that at least spends a lot of time with you and does that shared decision making process, that's what they actually teach it in med schools. So physicians should at least know, you could say, hey, I want to do shared decision making with you for this FDA approved medication called Vylisi. And if my insurance doesn't cover it, I would like to consider a high quality compounding pharmacy. So if your physician, if he or she is a decent listener, then they can go, you know, there's no shame in learning things. That's why you have cme, continuing medical education. And they can look it up and try the process of prescribing.
- [39:28]
Podcast Host
Okay. That's the first step. That's okay. If they want to go in and do it. And then what would you say would be the biggest is there? Like. Like, it's not the same as taking testosterone, really? Peptides. It's not the same as taking like injectable testosterone. Right. I think there's more like harm in doing that than taking peptides.
- [39:51]
Dr. Kyle Gillette
For most peptides, yes. So if you're thinking about short courses of something for a specific issue, you know, the melanocortin receptors, if you take a dose of brimmelanotide four times a month, then there's likely not a lot of harm. Although there is specific niche scenarios. You know, if you ask the companies that have the melanocortin receptor agonists, and I've asked both representatives of both companies, there is no concern for melanoma in their trials, but because melanoma cells do have receptors on them, theoretically they would grow your melanoma. Although again, in the clinical trials they went all the way through the FDA approval process, which for most medications, unless you pay the expedited fee or whatnot, they have like an expedited fee, which is a little sketchy to me, then it's very difficult to do that. So I think that they're relatively safe. But if you have a strong family history of melanoma. I would consider that a relative contraindication to the melanocortin receptor agonist, especially if you're going to take them very frequently. The dose makes the poison. When it comes to GHRPs, again, the relative contraindication there. Not that there isn't, you know, it is a little bit more straightforward than trt, but you'd have to go through every single organ system in the body or hrt, again, every single organ system of the body. With the GHRPs, tumor growth is the main risk, similar risk to taking growth hormone and then hyperglycemia. So in individuals that, for example, are missing their cancer screens, they really shouldn't start a GHRP or HGH. The nice thing with GHRPs is that they have the regulatory system of the body to where it is more difficult to go supraphysiologic. So there's a little bit of a speed limit. You still can. But that's why those are often preferred, although the FDA approved ones for those. Often they're used for growth hormone deficiency. They can also be used for lipodystrophy, which is an abnormal distribution of body fat just centrally and also muscle wasting. And they can also be used for things like leptin receptor deficiencies. Other rare conditions, the short courses of peptides like BPC157, TB500, because you're only using it, for example, for six weeks, then you have a limitation on the exposure which decreases your risk significantly.
- [42:25]
Podcast Host
So pretty much as long as you're doing the screening, okay, you're doing your blood tests and you're getting your peptides or anything when it comes to hormones checked by a really wonderful physician such as yourself, then you can be rest assured that you're doing the right thing. And if you're doing it for the right purpose, then that's okay too. Yeah.
- [42:46]
Dr. Kyle Gillette
Yeah. I think that's a good summary. Sometimes when I talk about things like these people are like, you know, instead of being encouraged, they're kind of discouraged. But somebody has to talk about the risks and benefits of everything. And again, if, if somebody asked me to talk about a medication, I would be equally as optimistic, but also harsh on the potential side effects because there's no such thing as a free lunch. There's always something that could potentially get you. So that's the job of the healthcare provider physician np whatever situation they're in is just thinking about what's the main risk in that patient's case and what's the main Benefit. And it's extremely important that you tell the patient both of those things.
- [43:33]
Podcast Host
I love that. So where can we find out more about you? Where's your podcast and are you taking new patients? Like, tell me everything?
- [43:42]
Dr. Kyle Gillette
Yeah, will do. Thank you for the reminder. So my main hub, I guess historically has been on Instagram, Kyle Gillette md but now at Gillette Health on all platforms as well. We have our podcast, we post on YouTube, Spotify and Apple Podcast. It's just called Gillette Health. And Our website is gillettehealth.com we do take new patients on from almost all states, but at this time our locations are just in Kansas City and Los Angeles. But we do take telemedicine patients as well. And I also post my lab panels. Even if you don't order labs from the Gillette Health website, I post all the markers in case you want to take them to your regular doctor or try to run through them through insurance or whatever. I post all the biomarkers on the Gillette Health website.
- [44:29]
Podcast Host
Oh my gosh, that's amazing. For specific conditions or just a whole round panel?
- [44:35]
Dr. Kyle Gillette
Somewhat specific conditions. So there, you know, there's a little bit more in depth for thyroid or nutrients or fertility or you know, separated between more basic and advanced panels for males and females. I believe I have one for hair loss that everyone should get before they start hair loss meds. Not it's not ideal and I'll keep working on it, but it's better than nothing.
- [44:58]
Podcast Host
Do you give reference ranges as well?
- [45:01]
Dr. Kyle Gillette
I don't give the lab printout has a reference range, but I do at this time. I do not have an optimal reference range. It's difficult to make an optimal reference range because it's different for each patient. So a lot of times I'll tell a patient what's my goal. Common questions I get is what's an optimal estradiol after menopause? It's actually really variable. Sometimes they even check free estradiols because it's if you have a high shbg, maybe you need a higher estradiol after menopause, maybe you need it to be 60 pg per mil for testosterone. For most females on HRT, that includes an androgen, you look at SHBG and the higher your SHBG, the higher you want testosterone. So to total testosterone of 100 nanograms per deciliter in a female with a high SHBG of also 100, that does not concern me whatsoever. For males in general, you want your total t between about 550 and 1000 assuming your free T is at least 12 to 15 nanograms per deciliter.
- [46:07]
Podcast Host
You heard it here. Ladies and gentlemen, Dr. Kyla Gillette. Thank you for being part of the Neuro Experience podcast.
- [46:11]
Dr. Kyle Gillette
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