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The Best Peptides For Boosting Mitochondria, Brain Health and Longevity with Dr. Daniel Stickler

The Best Peptides For Boosting Mitochondria, Brain Health and Longevity with Dr. Daniel SticklerIn this episode, I am speaking with Dr. Daniel Stickler—co-founder of The Apeiron Center for Human Potential—about the best peptides for boosting mitochondria, brain health, and longevity.

In this podcast, Dr. Stickler will cover:

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The Best Peptides For Boosting Mitochondria, Brain Health and Longevity with Dr. Daniel Stickler – Transcript

Ari Whitten:  Hey there, everyone. Welcome back to the Energy Blueprint Podcast. I’m your host, Ari Whitten, and today I have with me Dr. Daniel Stickler, who is the visionary pioneer behind the Human Potential Medicine movement, a shift away from the disease model to limitless peak performance in all aspects of life. Dr. Stickler is a physician to high-performing entrepreneurs who want to optimize their performance. He is also an author, speaker, blogger, and host of The Ironman Executive podcasts. Dr. Stickler is an expert in the use of genetics and epigenetics in clinical practice and trains healthcare clinicians from all over the world in the interpretation of genomic data for optimizing human potential. Dr. Stickler also works with each client to develop personalized human potential optimization plans based on genetics, quality of life factors, and the seven foundational aspects of health. He also serves as the Medical Director of Neurohacker Collective.

So welcome, Dr. Stickler. Such a pleasure to have you on the show.

Dr. Daniel Stickler:  Hey, Ari. Great to be here.

 

What are peptides?

Ari Whitten:  Excellent. So, I want to talk to you about, well, you have a wide range of expertise that we can talk about a whole bunch of things. But, specifically I want to talk to you about peptides and then if we have any time left over, I’d love to talk to you about some of the things I just mentioned in your bio there as far as how you use genomic data to optimize people’s health and that sort of thing. So first of all, let’s get into this topic of peptides, which I know that you have been a pioneer in, and you are an expert in. Can you give people sort of a general introduction to this topic of peptides? Like what are peptides for people that have never heard of them? People have no idea what this whole class of compounds really is.

Dr. Daniel Stickler:  Yeah, I’ve been speaking quite a bit on the peptides and surprised at the number of people who really are unaware of it. I thought that this would be a topic that a lot of people would be jumping on, especially in the medical community. Because peptides are in a class called biologics and biologics are really the new order of medicine. This is going to very quickly replace pharmaceuticals and even most nutraceuticals in that regard just because of the fact that it is so on target with what it does. So, biologics are essentially things like I guess stem cells can be classified as biologics. A lot of recombinant DNA type products are biologics. But peptides are kind of in a new area of this, but they’ve been around since, geez, probably the late ’80s, I would say.

And there’s over 7,000 of these currently in research. But they are just strings of amino acids. So just kind of like our body makes proteins, it makes it out of amino acids. When that amino acid chain is less than 50 amino acids long, they call it a peptide. It’s an arbitrary thing, but proteins are usually over 200 and polypeptides are somewhere in between there. But it’s arbitrary. It’s just a string of amino acids. So, it’s something that the body actually recognizes. To differentiate like a molecule, a pharmaceutical versus a biologic. Biologics are kind of recognized by the body and they go in and they hit a specific target in the body. That’s what they are designed to do. And there’s very little collateral affect with biologics. Versus pharmaceuticals where you get a lot of off-target hits, you get a lot of side effects from that aspect. That’s what I really love about peptides is they are highly specific. I mean this is a laser approach to precision wellness for sure.

Ari Whitten:  Interesting. So, there’s a whole bunch of different classes of these peptides. And it sounds like, with 7,000 different compounds currently in research, there’s probably a lot more than what I’m about to list off. But, you know, general classes, I know there are peptides that relate to weight loss. There’s growth hormone secretagogues, things that promote the body’s own natural production of growth hormone. There are peptides related to, you know, I know there’s one called tesamorelin related to visceral fat loss in people with HIV. It is FDA approved. And there are nootropic and brain health-related peptides. There are anti-aging peptides. There’s, what else? Healing and recovery related to peptides. So, what other classes of peptides do you think are worth mentioning there?

Dr.Daniel Stickler:  Well, there are a ton of them, like you said. I mean, with 7,000 currently known and I think there’s over a thousand in clinical trials right now. But, right now I think we have 60 that are approved by the FDA. And you’ll see them in weight loss, in soft tissue repair and gut healing and autoimmune conditions. You see them in anticancer therapies, which are really coming on strong right now. You see them in the longevity world, even in sexual function, peptides that are just blowing the other medications out of the water with their success. We have hair and skin peptides. There’s a new hair peptide that is changing the whole landscape of hair replacement for sure. This stuff is incredible and it’s just a pathway that was identified back in November. So, it is a very new one. And people are getting amazing results with hair regrowth in areas that had no follicles at all that work. So, we’re seeing quite a range of actions that can be achieved with the peptides because they are essentially leveraging the body’s own ability to do things and taking it to higher levels for sure.

 

The best peptides for longevity

Ari Whitten:  Oh, wow. Excellent. So, within that, a few specific topics I want to dig into in depth probably for this whole podcast or close to it, longevity-related peptides. I am really curious to hear your thoughts on this because I know, you know, I don’t know about the whole range of them, but certainly with one of them called Epitalon. I know that there are some mixed data and sort of controversy around mechanisms and how it’s actually working and if it works. And so, I’m very curious to hear about sort of the current state of knowledge around longevity and anti-aging related peptides.

Dr. Daniel Stickler:  Yeah, we generally, you know, it depends on what you’re trying to target with this. Now, what you’re talking about with Epitalon. Epitalon was a, it is four amino acid long. So, it is a really short little peptide. It has four amino acids, but it was isolated by Dr. Khavinson at the University of Saint Petersburg in Russia. And he did two very large-scale studies, well not very large, but they were long studies, six-year and 12 years studies on elderly patients. So, they were I think between 70 and 90 years old in this group. And they had just unbelievable outcomes with this. Now a lot of people will say, “Well, I kind of question, you know, the research because it’s almost too good to be true.” And what I know of Dr. Khavinson from people that have spoken about having worked with him and everything, he’s very meticulous with his data. The Russians are not the most ethical with studies and selection.

But they are like the Germans when it comes to the accuracy of their results and being very precise with everything. So, I’m inclined to believe it. And I have actually seen very positive results in clients that have used Epitalon in my medical practice. So, it’s one of those ones, though, you take, and most people just don’t feel anything overt when they’re taking it. And you typically run two cycles a year for about 20 days and that’s it. And you just rely on what it’s doing in the system. But it’s got, I mean, it’s got anti-tumor properties, it improves glucose utilization, it up-regulates the glutathione and antioxidants systems. There was, one aspect of the study was the telomeres and they saw between 16% and 33% increase in telomere length. And remember, this is 70 to 90-year-old people.

They had like eight times the improvement in physical performance activities and they had subjective wellbeing changes in these groups. And this is a lot of what we see with our clients. Eighty percent increase in bone density, 28% lower overall mortality in the group that was on it versus not. I mean, there’s something with this stuff that’s really creating a great outcome. And like I said, it’s a four amino acid peptide. So, for me, I’ve kind of taking it on faith that it is working. And, we do some measurements. So, we do epigenetic age markers with myDNAge and that’s going to be kind of our metric to see how this is doing, to watch the dynamic of where our epigenetic age comes out. And, I like that better than telomeres. Telomeres are just too vague and a lot of variability in the results that you get. Even with places like Life Link, which is using the… they look at the shortest percentage of telomeres, which if you’re going to get telomeres, this is the place to get it. But I really like epigenetic age because you can see very short-term improvements in what your aging is in that regard.

Ari Whitten:  Okay. Now if they’re not measuring telomeres, what specifically are they measuring there?

Dr. Daniel Stickler:  In the epigenetic age, what they did, Dr. Horvath, I think he’s out of UCLA, it’s either UCLA or Stanford, but he took a bunch of metrics that we use to assess age, like albumin levels and liver function studies and just a whole bunch of biomarkers and said, “Okay, let’s align these people up and let’s see where they are from all these biomarkers. Let’s compare that to what we see as far as the methylation patterns on DNA.” So, as we get older, we tend to change what genes are methylated so essentially turned off. And they measured this in white blood cells. And now they can look at that and they have pretty darn good accuracy with predicting what your physiologic age is relative to your chronologic age and that changes over time. So, you can actually have somebody that will reverse age essentially from an epigenetic mark standpoint. And that’s usually based on some intervention that you’ve done. And that’s what we’re using in our clinical practices as one of the metrics for aging.

Ari Whitten:  Interesting. Now is that something that you guys do in house or is that another laboratory that does that kind of testing that you send out to?

Dr. Daniel Stickler:  Yeah, actually this is available to the general public. It’s just called myDNAge and we actually have it in our store. I think it’s around a $300 test and you have to do a finger stick, send that into the lab and it takes six to eight weeks to get back. But if you go to aperion.store you can grab yourself a kit and send it in.

Ari Whitten:  Okay. Now going back to Epitalon. I know that I’ve seen some controversy around the telomere length issues, specifically some people sort of debate whether that is actually one of the mechanisms of how it works. And do you know anything about that?

Dr. Daniel Stickler:  You know, when it comes to how something works, I mean aging is a complex process. It’s not as simple as, “Oh, let’s add telomere length.” I mean, you look at Liz Parrish from BioViva. I mean she infected herself with a virus that was tagged with telomerase and she was able to reverse the age of her telomeres by 20 years. And she’s going through evaluations at Harvard to really see her metrics to see how much of an impact that had. But my guess is it’s going to have a small impact because there are so many things involved in aging, in the aging process. And I’m in the camp that believes that we are programmed to age by our genetics. Our DNA is programmed to age over time. And so, we have things that happen. So, we get cellular senescence.

So, we get these zombie cells that are taking up resources and secreting toxins that just won’t die. And we’ve got to somehow force them to die. So, you can see a whole new kind of field of senolytics coming out. And there are some pretty impressive senolytics coming onto the market that are going to have an impact. You have things like mTOR inhibitors. So, this is why a lot of people take metformin to reduce their aging. So, if we can reduce that, we can hit some aspects of aging. Some of them are actually using Rapamycin, which is an immunosuppressant that is used in kidney transplant patients. But there are two aspects of mTOR. There’s the really healthy aspect that promotes longevity. And then there’s the other aspect that causes immune suppression.

So right now, the develop person, the marketer, is looking for the way to specifically target only the one piece without getting immunosuppression. And I think there’s a couple that are getting ready to come on the market for that. So, we have that and then we have the telomere lengtheners. But there are so many mechanisms that are going to go into reverse aging. Trying to get rid of AGEs in the body, the advanced glycation end products, is another piece of the puzzle. We can’t just look at one thing and say, “This is going to make a difference.” Now, Epitalon, what’s it doing? We don’t know. I mean, that’s one of the problems with peptides is because they cannot really be patented there is a lot of difficulty in getting people to do the research on them. Pharmaceutical companies are funding most of the research.

So, they are like, “Well, we can’t patent it so there is no sense in doing it.” There’s one of the neurologic peptides called Dihexa which is amazing. We’ll talk about it. But it was developed out of the University of Washington. A pharmaceutical company kind of bought it up and they can’t, they had great results with it, but they can’t patent it. So, they are trying to figure out ways to modify it in some way that creates it as a patentable drug, even though it’s very effective the way it is. They can’t really sell it for, you know, disease model stuff where they can make money. So that’s why you don’t see a lot of research in the area of peptides. It’s just, it’s not financially rewarding for people to research it.

Ari Whitten:  Interesting. I have one more question on Epitalon and then I want to go on to maybe some other anti-aging or longevity peptides. The study you mentioned, you said it was in 70 to 80 or 70 to 90-year olds.

One of them was like 70 to 80-year olds and the other one was 80 to 90, I think. And I can’t remember if it was a six-year or the 12-year study which was the older group.

Okay. Do you think that this peptide is more suitable for use in somebody who is already, you know, up there above 70, let’s say, as opposed to, you know, somebody who is in their 30s or 40s?

Dr. Daniel Stickler:  Well, to me it is even more so indicated in that group because that’s the group that the study was actually done on. And, I mean, if you are talking about 28% lower mortality rate in the group that got it, I mean that is pretty substantial. But not only that is that the functionality of that group increased. So, it is not a matter of just delaying your death, it is actually giving you healthier years of life which is really the ultimate goal. I mean it doesn’t matter how long you live. It matters how long you can live and be functional and healthy and I think it is an ideal piece of that. I have a lot of people that are using it that are even in their early 30s just because they feel like it has that potential to really mitigate aging in the early stages.

Ari Whitten:  Yeah, I did see one, I did a Podcast with Jean-Francois Tremblay. I don’t know if you know him.

Dr. Daniel Stickler:  Yeah, out of Canada.

Ari Whitten:  I just recorded this Podcast a few days ago actually. And he was talking about a lot of positive research around Epitalon. But then he also mentioned there’s a study, I think it’s a rat study that’s currently in progress and it’s not yet published, but somehow maybe he knows the researchers or something like that. And he said the data right now doesn’t look good and that more of the rats on the Epitalon are actually dying earlier compared to the other group. I’m just curious if you also know anything about that. You know, he did say, you know, we should wait until the sort of the study completes and we have the full picture of the data, but I’m just curious if you know anything about that.

Dr. Daniel Stickler:  Yeah, I’ve heard rumors of that study and a lot of the naysayers are saying, “Well, you know, you have a human study, why not do another human study?” You have two human studies that show positive outcome. And, you know, we can use rat studies to give us, or animal studies, in general, to give us ideas of things to look at. But we’ve seen many animal studies that had a complete opposite outcome like pterostilbene. Pterostilbene was great in rat studies for lowering cholesterol and doing all these great things in the body. And then we gave it to… We looked at the human studies on all it and all of a sudden it was like jacking LDL through the roof. And even at Neurohacker, we pulled pterostilbene from the formulation because of the studies coming out that indicated problems on the human side of it.

Even in the peptide studies, there’s a weight loss peptide called AOD, advanced obesity drug, which was amazing with rats losing fat weight when they got this. And it was blowing people out of the water. I mean, that’s why they called it AOD for advanced obesity drug. And then in human trials, it had zero effect on the humans in the trials. Now I have people that tell me that they get good results with AOD or another kind of version of it is called Frag 176. And a lot of the bodybuilders swear by it. But I’ve seen maybe a 50/50 outcome with AOD. And, you know, there’s another example of a really outstanding animal trial that just didn’t translate into the human trials very well.

Ari Whitten:  Interesting. So, are there any other compounds worth mentioning as far as anti-aging or longevity peptides?

Dr. Daniel Stickler:  Well, certainly the growth hormone releasing hormones and the ghrelin hormones. They, you know, IGF 1 or growth hormone is kind of a double-edged sword when it comes to longevity. You read things about oh, people at the highest levels have the highest mortality and people with the lowest levels have the highest mortality. So, you know, you’re mixed in outcomes. The problem I think is that we’ve been measuring the wrong marker. We have been measuring IGF 1. And, I was in the anti-aging world way back in 2005 and Greg Forman was a big component of that. So, you know, all this anti-aging stuff came around for growth hormone. Then we realized that we were creating more problems than it was creating positive outcomes. So, a lot of people started stepping away from growth hormone. And now the peptides have come online with the growth hormone releasing hormones.

And what we kind of came to the realization was that that system is so complex that we had to take that complexity approach with it. Because we were looking at as, “Okay, well the hypothalamus releases growth hormone releasing hormone and then growth hormone is released and then the growth hormone circulates, goes to the liver, produces IGF 1 that goes out and causes anabolic effects in all these different cells and bone and muscle and everything.” What we neglected to pay attention to is that growth hormone releasing hormone, growth hormone, and IGF 1 all have receptors throughout the body. It’s not just in the brain area or the liver area. And even measuring serum IGF 1 levels doesn’t tell us what the local IGF 1 level is inside of the muscle. And if you have growth hormone or growth hormone releasing hormone circulating around and activating the muscle, you’re going to get the muscle producing growth hormone inside of it and IGF 1 as well.

And then IGF 1 will actually be released feedback on itself on that same cell and same like cells. So, this system is not as simple as everybody thought it was and now, we’re starting to see combinations of growth hormone-releasing hormone with the addition of ghrelin stimulators. So, ghrelin is another product of that. I think those are very potent in the anti-aging world just because it creates such antifragility in the human system. You know, it promotes good bone health, good muscle development, it reduces body fat, it has very positive effects on cholesterol and cognitive function and improves sleep qualities. So, all of these things that actually translate into very positive outcomes with it.

Ari Whitten:  Now, so, what is the current sort of state of understanding? You know, having said that there is a lot of complexity there and it’s not just as simple let’s say as maybe as was thought 20 years ago where they said, “Oh, you know, growth hormone is anti-aging. Let’s just inject lots of growth hormone.” What’s the current state of thinking as far as the use of these growth hormone secretagogues, growth hormone secretion promoting peptides that are on the market and the role that they may have in anti-aging? And one more maybe nuance that I will add to that, is it necessary that they’re thinking that this is going to extend lifespan and longevity or is it more about extending health span and having more energy and more vitality and more muscle mass and leanness and things like that throughout your life?

Dr. Daniel Stickler:  Yeah, that’s the big debate. I mean, like I said, it’s a double-edged sword. You age, and part of the aging process is a reduction in hormones. I mean it’s just that is programmed into our DNA. We lose hormones as we age. And is that necessarily a healthy aspect of aging? No. And, our bodies will lose their ability to surveil the immune system, so our immunity goes down. We are just programmed to die. I mean that is the nature of it. I think aging is a disease and we need to approach it that way. And these are aspects that promote kind of keeping the system in that resilient and anti-fragile state for sure. That said, I would not put out there that we are looking for increased longevity, but we are looking at this as increased health span for sure. There are things coming that are going to be definitely in the longevity world that are going to substantially increase lifespan, but we’ve got to also maintain the health span as well.

Ari Whitten:  Okay. Now, do you think it’s possible that playing with hormones in this sort of way where you, you know, let’s say take a 50 or 70-year-old and have them, you know, put them at the testosterone and growth hormone levels of a 20-year-old? Is that, do you think that there’s a high potential there for pro-aging, for accelerating the aging process or maybe promoting cancer or anything like that?

Dr. Daniel Stickler:  No, I think that just the opposite actually. I think we’re seeing a much better outcome. I mean we already went through that phase of, “Oh, testosterone causes prostate cancer.” And, you know, that debate went on for years and multiple lawsuits, multiple debates by different experts in the field. We have finally come to the conclusion that testosterone does not cause prostate cancer. In fact, there are some people suggesting it might actually be protective from it. What we do know, and I do a lot of work in genetics and epigenetics, is that hormones have very potent impacts on gene expressions and in a very positive way. So, you think about the human system as a biologic system. I mean, ignore the fact that you’ve got a soul or whatever it is, and we’re looking at it from some religious context or anything like that.

We are a biologic system. And when is that biologic system the most optimized for performance and what is happening in that system when that occurs? And to me, I look at it and I say, “Well, you know, the reproductive male and the reproductive female, the ones that are at the peak of the reproduction potential are really optimized for physical function, for cognitive function, for just resilience in all aspects.” And that comes about not just because of the hormones but the hormones effects on the genes themselves. And this expression change is pretty profound. I mean, even estrogen by itself. Estrogen is one of the most potent epigenetic modifiers of any of the hormones. So, we do know that the modification of gene expression is very much potentiated by the hormones. So, my feeling, and again, it’s a personal feeling, but I see people that are hormone deficient. And I see people who are optimized in hormones and I can tell you from a functional standpoint, there’s no comparison.

Ari Whitten:  As far as the people on the hormones are just superior basically in terms of mood, energy levels…

Dr. Daniel Stickler:  Absolutely. I mean, you know, it’s ironic that they call it performance enhancement like it’s a bad term. Testosterone is performance enhancement and who doesn’t want performance enhancement? I mean it’s a bad term when it comes to athletics. But why would you not want performance enhancement of your human system?

Ari Whitten: Yeah, absolutely. Yeah. So, do you think there is a pretty significant role for some of these growth hormone secretagogues as far as increasing health span?

Dr. Daniel Stickler:  I do because we’re not, you know, even with these, we’re not going to get into super-physiologic doses. That’s the great thing about peptides is they self-regulate. You can overdose all you want, and you can do, like crank it up to high levels and what happens is, you just down regulate receptors. The body knows this stuff. You know, when we were giving growth hormone, we kind of bypassed a lot of the regulatory mechanisms thinking we were doing the right thing and it just didn’t work. But with the biologics, we are getting a much better response when we are going downstream a little further and, letting the system kind of control itself. So, we enhance the system, take it to the youthful levels. But it’s, even if we tried to take it to some super-physiologic level it just, the system would resist it.

 

The best peptides for mitochondrial health

Ari Whitten:  Yeah. I want to talk about mitochondria a little bit in this context of anti-aging, longevity or promoting health span. I know there is some connection between growth hormone and mitochondria, and so there might be some connection between the secretagogues, these growth hormone secretagogues and mitochondrial function. But mitochondria have a role in this process of longevity and increased health span. Can you talk a bit about what that role is and then maybe any specific peptides, whether the growth hormone secretagogues or other peptides that may help promote increased mitochondrial function?

Dr. Daniel Stickler:  Yeah. Again, this is a double-edged sword as is everything in biology. And that’s why we have to start looking at things from a full systems-based approach and not from an isolated approach. Just to give you an example, I mean there is a lot of criticism right now that taking metformin is actually toxic to mitochondria. So, everybody’s like, “Oh, you know, we shouldn’t be taking it because it’s toxic to mitochondria.” But you can’t take these isolated microscopic views of one aspect of what’s happening. You know, pull back the microscope and look at all aspects and say, you know, “Does this input create a positive change in the system and does the negative aspects get outweighed by the positive?” You’ve got to do this with everything that we do in the human system. And don’t look at things as, “Okay, well this one is natural, this one is synthetic, whatever.” I don’t care about that.

I care about, you know, working in the system. We have an input. It doesn’t matter if it comes from a plant. It doesn’t matter if it’s made in a lab. It’s an input to the system that we’re looking at a response. And with mitochondria, it’s very much double-edged because you can really focus on things that increase mitochondrial biogenesis. And this is creating more mitochondria. And this is a great thing. You know, you turn over more mitochondria, you create more in there, you have a great metabolism, you know, you’re burning fat, all of this stuff. But you’re also creating a ton of free radicals with that. So, if you’re going to upgrade the mitochondrial biogenesis, you’ve also got to upgrade the ability of the body to mitigate those free radicals through like the glutathione system or something similar to that. So, it’s not a matter of just focusing on, “Oh, let’s give, let’s create mitochondrial biogenesis.”

It’s the same approach that Neurohacker took when they were developing a nootropic. It is great that you can turn the entire brain on with something that is a stimulant. But if you’re not supplying raw materials for that process to keep going, if you’re not increasing blood supply to the brain, and you’re talking about 20% of your metabolism and you are all of a sudden cranking it up with some stimulant. You’ve got to be able to mitigate that process in a way that you are feeding the raw materials in that it is going to need to keep running. And then you are also creating a ton of free radicals in the brain. You’re creating tons of neuroinflammation when you upgrade the brain like that. So, you have got to have ways that you enhance the body system of mitigating that problem.

Ari Whitten:  Is this a problem with stimulants specifically as far as neuroinflammation or…

Dr. Daniel Stickler:  Any of the nootropics, I mean, anything that you are looking at that is going to up-regulate performance in the brain. I mean, you really need to take a look at this and say, “Okay, if I’m going to do this, these are the consequences of it and how can I mitigate that to make the net outcome very positive for me?”

Ari Whitten:  Yeah. But just, one point I’m curious about. So, some of the natural herbs that, for example, stimulate mitochondrial biogenesis, like for example, let us say curcumin or cacao extract or you know, like EGCG from green tea or something like that. They act on the PGC-1 alpha, you know, mitochondrial biogenesis pathway. But they also act on the Nrf2 pathway to up-regulate the internal antioxidant defense system at the same time. So, isn’t that, sort of, they are increasing biogenesis, but they are also helping the cell deal with some of those free radicals, right?

Dr. Daniel Stickler:  Right. And I love curcumin from that aspect. But you are also talking about a very mild effect versus what we have available now. I mean, you know, there’s a new peptide called MOTS-c, m-o-t-s-c. And MOTS-c is profound with what it does with mitochondria. It’s actually a protein that is coded by a gene in the mitochondria. So, the mitochondrial gene will send out a messenger RNA. It will go to our own ribosomes. So, you know, mitochondria are foreign bodies in us, and this interaction is fascinating. So, the MOTS-c will code for the protein, it will go to the ribosomes. It will be transcribed. Then it goes into our nucleus and up-regulates PGC-1a and mitochondrial biogenesis in a very profound way. I mean huge. So, we’ve got that. We’ve also got metformin, which is one of the most potent, PGC-1a up regulators that we have.

So, we’ve got a bunch of them that can do this. Curcumin is kind of that mild form of it, so it’s something you can take on a daily basis and get positive results, but it’s not going to give you exceptional results in that regard. With the precision of these biologics, we can start getting into them. And there’s another one called humanin which isn’t available in the US market yet, but it is… And the MOTS-c also up-regulates Nrf2 and Nrf1 as well. But humanin is fascinating. I mean you talk about a longevity protein. People with variants of humanin have exceptional longevity and now we are quickly getting ready to release. I know it’s going to be coming from one of the pharmacies for sure in the next couple of months because I know some of the research companies have actually produced it already. But humanin is going to be a game changer for longevity, I think.

Ari Whitten:  What, can you say a bit more about… Let’s talk about humanin specifically since you seem more impressed with that one than MOTS-c. So, what are the mechanisms as far as how humanin might work?

Dr. Daniel Stickler:  You are hitting me with something that I haven’t studied enough on yet. Humanin is actually… So, the MOTS-c, they are hitting both aspects of mitochondrial biogenesis and the ability to up-regulate the mitigation of the free radical production. So, they work in combination with each other. And, now you’ve got me second guessing of which one is which, right now. I know that the mitochondrial biogenesis definitely occurs with the MOTS-c, but I think it’s more focused on really the mitochondrial biogenesis. Whereas the humanin is more along the lines of the Nrf2 pathways and the keep genes. So, I think the humanin is the one that we know for sure is associated with longevity based on genetic studies. MOTS-c is fairly new from genetic studies, but we don’t have anything that tells us anything about variants of it. But we have seen athletic performance VO2 max increases with MOTS-c that have been pretty impressive.

Ari Whitten:  Got you. Another quick digression on this mitochondrial topic. Are you familiar with compounds, I know they’re not technically peptides, but there’s a couple of compounds? One is called Cardarine, it’s GW… I forget the number.

Dr. Daniel Stickler:  501516, yeah.

Ari Whitten:  Oh, and then there is also SR9009.

Dr. Daniel Stickler:  Right.

Ari Whitten:  Do you know if those have, you know, maybe some comparable affects to MOTS-c or humanin or…?

Dr. Daniel Stickler:  Yeah, I mean GW501516 is pretty impressive with its ability to really upgrade VO2 max performance. I actually tracked my VO2 max while I was on GW501516 and I was on it for about two months and my VO2 max went up about 6 points based on my tracking with this and I could tell the performance increase with it. And I have pretty average VO2 max as it is. So, it was great for me to experience that with it. Now again, it’s a research peptide and I can’t recommend anybody to take this. The SR9009, and it’s a PPRGC1A or, yeah, PPRGC1A activator. The SR9009 is showing better results overall. But the problem is the studies are in rats that were given intraperitoneal injections and it’s a very, very short half-life. And so, a lot of people have been going with the SR9009, but I don’t see a point in it. We don’t have any evidence that SR9009 is going to be available when you take it orally and have any affects at all from that regard. So, I’m kind of standing back and waiting to see what happens with the SR9009 for sure.

Ari Whitten:  Got you. Any other topics, any other peptides worth mentioning around this topic of longevity?

Dr. Daniel Stickler:  Well, I mean all of them have some aspect of longevity associated with them. And these are really up-regulating systems in the body. I mean, just like in the brain peptides you have ones that mitigate neuroinflammation. So, you’re talking about really great longevity aspects. You’re talking about some of these will increase dendritic growth in profound ways and they are used in clinical trials for traumatic brain injury recovery, stroke recovery, people with Parkinson’s and Alzheimer’s disease. So, you know, they are not directly saying, “Okay, well this is a longevity peptide by itself.” But you know, brain health is a part of longevity and I think these peptides play a role in that regard.

How peptides can be used for improving brain health

Ari Whitten:  Do some of them have some evidence around preventing or treating neurodegenerative diseases?

Dr. Daniel Stickler:  They do. There are a lot of clinical trials going on right now with several of them. Cerebrolysin. Cerebrolysin is an extract from pig brain and it has got BDNF, GDNF, CNTF, and NGF. So, I’m giving you all these acronyms, but there is basically like brain-derived neurotrophic factor, nerve growth factor, ciliary neurotrophic factor. These are all things that create neuroprotection. They create neuro health; they reduce neuroinflammation. This one has been used in some clinical trials in Europe in degenerative brain issues as well as post recovery from a stroke and some of the traumatic brain injuries. So, it’s probably the one with the most research behind it right now. It is available by prescription from compounding pharmacies here in the US. It is not on the pharmaceutical market per se, but it can be prescribed and it’s an injection that people do for a certain period of time and see pretty profound effects with it.

Ari Whitten:  Yeah. Now you, I know there’s a couple of others. One is called Cmax and there is one called Selank. And then there’s also one you mentioned that I hadn’t heard of before, I think it’s called Dihexa or something like that.

Dr. Daniel Stickler:  Yeah. You know, Cmax, I’m getting mixed results with Cmax. I mean typically if a client is using Cmax by itself, I see about half of them say they experience something. Now if they’re taking a baseline nootropic and then they use the Cmax on top of that, I do see kind of a very positive cognitive kick for them. Selank is used mostly for anxiety and depression. So, I’ve seen really good results with Selank in people with a generalized anxiety disorder. And again, you have to use caution with this because Selank takes several days for most people to start working and they give up after, they don’t get a result after one… And it’s a nasal spray, so they tend to give up, but 60% of those people are slow responders.

So, they have to do it for a while before it really kicks in. Cmax you’re either going to notice it or you don’t. You know, it’s kind of like, putting nitrous in a car. I mean, you can really get some great productivity and improve learning and memory during the time that you’re on it. But it’s short-lived. It’s about four hours that I’ve seen that the positive results kind of kick in.

Ari Whitten:  And then there’s this other one Dihexa that you mentioned.

Dr. Daniel Stickler:  Yeah, Dihexa is fascinating. This was the one developed out of the University of Washington and this is only a six amino acid peptide. So, they’ve actually just recently come out with an oral form of it. And, what we’ve been using prior to that was a topical cream, but it can absorb, get into the system.

And now this is the fascinating part. So, we know the importance of BDNF. You know, you take some bacopa you take some holy basil you can increase BDNF in the brain. It’s always a great thing because BDNF is a kind of adaptogenic for the stress system. It’s great for learning and memory. But the big thing is it causes new dendrites to grow. So, it causes neurogenesis. Now Dihexa was found to be seven orders of magnitude stronger than BDNF in dendrite growth in the brain. Now to get your head around this, this is seven orders of magnitude. This isn’t seven times stronger. This is like 10 million times stronger than BDNF. And the animal studies on this, they showed the, you can look at the slides on the dendrite growth with it and it’s profound. So, they’re currently, looking at some clinical trials with Dihexa in the realm of neurodegenerative diseases. Even in looking at it in spinal cord injuries, looking at it in multiple sclerosis. And that’s why this company is trying to really patent this thing because it has got a great potential for it. But right now, it’s available in the form that they first discovered it in.

Ari Whitten: Got you. So, are those the main ones worth mentioning when it comes to issues related to the brain and nervous system? Any other things related to…

Dr. Daniel Stickler:  Well, you know, another one that I’ve been pretty impressed with it and it’s not really a peptide per se. It’s peptide like, but it’s RG3, which is, it’s a ginsenoside derivative. And it is a nasal spray and the company we use, the pharmacy we use, they combine it with a little NAD and a little methyl B12. But this nasal spray is really potent. I find that RG3 gives me more energy and productivity and focus than the Cmax did. So, I’ve been really impressed with the effects I have been getting with the RG3 for sure.

Ari Whitten:  Okay. A quick digression based on something you just said, the NAD+. So, this is a nasal spray. I’m curious, there seems to be some controversy around whether NAD can actually be absorbed exogenously or if it’s better to deliver nicotinamide riboside or mononucleotide or, you know…

Dr. Daniel Stickler:  Honestly, I don’t pay attention to the NAD or the B12 that is in the nasal spray. I don’t…

Ari Whitten:  It’s about ginsenosides.

Dr. Daniel Stickler:  Yeah, it is the ginsenosides. I mean, here is the profound thing. So, they looked at PPRGC1A with this RG3 and they found that when comparing it to exercise the PPRGC1A protein levels were almost equivalent to an exercise session when you did the RG3. Now, on top of that, they saw up-regulation of Nrf2 to greater levels than exercise created. They saw superoxide dismutase, as well as catalase, go up to higher levels than exercise created. Now that looks great, but then they also looked at relative messenger RNA levels of Nrf1 and TFAM, which, you know, what we’re talking about is AMPK activations and mTOR and everything like that. So, they actually saw those hit almost the same levels of exercise. So, you are talking about a nasal spray that was creating a physiologic effect from a mitochondrial DNA level of exercise.

Ari Whitten:  Interesting. And that might, you know, for people listening to this Podcast, might potentially translate into increased energy levels if you are improving mitochondrial function.

Dr. Daniel Stickler:  Yeah, absolutely.

 

The best peptides for autoimmune diseases

Ari Whitten:  Yeah, okay. So other topics within this category of peptides, autoimmunity I know is a big one. Are there any, and actually maybe this can be addressed either with or separately from cancer-related peptides. So, I’ll let you kind of decide if you want to treat those separately or together. I don’t know exactly the mechanisms of how they are working, but can you talk a bit about peptides as it relates to immune health? And actually, one more nuance to this that some people in my audience struggle with is chronic infections that can be a potential cause of severe chronic fatigue for some people. Do you know of any peptides that might play a role in helping people with chronic infections as well?

Dr. Daniel Stickler:  Yeah, we use several peptides in that regard. So, mostly dealing with people that progress to the chronic inflammatory response syndrome. So, we deal with people reaching out to us that have chronic Lyme and chronic mold issues. And we look at their genetics and a lot of people carry genetics that just doesn’t allow them to get rid of the mold toxin very well. And what’s really cool about the peptides is one of the net effects of chronic inflammatory response syndrome is severe suppression of alpha-MSH in the brain. And that cascades down to an immune system, sexual function, and libido, energy levels. So, it creates this just massive dump of just feeling terrible. And, one of the cool peptides is Melanotan-2 which people will call the Barbie drug.

Dr. Daniel Stickler:  You take it for, people take it for tanning. So, it is alpha-MSH is essentially what it is. So, it is a melanocyte stimulator and in chronic inflammatory response syndrome, it mitigates the symptoms like crazy. Amazing. I mean, a low dose of that on a daily basis has really had dramatic effects for people in utilizing that. And another one is VIP nasal spray. VIP nasal spray works really well in that regard. VIP, though, is more protective against that chronic inflammatory response progressing to an autoimmune disease because, you know, as you get down that cascade you are more prone to develop autoimmunity in that. And the VIP nasal spray while you’re healing will kind of prevent that from happening. But you have to really monitor when you’re using the VIP nasal spray because there are some side effects with that that, you know, blood pressure drops and things like that.

But one of the other ones that I’ve found, so these are mitigating symptoms so they’re not really treating anything. One of the peptides that has worked really well for treating is thymosin alpha. Thymosin alpha has had profound effects of resetting the immune system in autoimmune people, up-regulating the immune system. It is kind of cool. So, what it does is it kind of makes damaged cells or infected cells more visible to the immune system. So, a lot of the times when an infection gets into a cell like in Lyme or if you’re talking about a cancer cell or something like that, one of the things that these organisms or these processes that occur is they try to hide from the immune system. And so thymosin alpha for some reason, it resets the system so that all the markers on the surface that tell the immune system that, “Hey, you know, this cell, there’s something wrong with this cell.”

They start expressing with the thymosin alpha. So, I had, I was talking with the… I did a consult for a client the other day and this was just completely off the cuff. The guy had six years of prostate cancer and had been monitoring his PSA levels and he had gotten up to 15 and then did a course thymosin alpha and his PSA levels dropped to 2. Just from the, I don’t know if it’s from the thymosin alpha, but the correlation with the timing of that was impressive. And, you know, did it actually cause the cancer cells to be more visible to the immune system? I don’t know. But that’s one of the theories behind how that works.

Ari Whitten:  Wow. Interesting. Now would something like that potentially be detrimental for somebody with autoimmune disease where the immune system is already kind of a little too aggressive and attacking some of the person’s own body parts, let’s say, you know, Hashimoto’s where the immune system is attacking the thyroid gland?

Dr. Daniel Stickler:  Yeah. And I don’t deal a lot with too many people with autoimmunity. But I know several docs that do, and they have anecdotally told me that it really works well in those situations just because of the fact that, you know, in autoimmunity you don’t have a… It’s not like, okay, well if you improve the immune system it’s going to make it worse because they’re going to attack. In autoimmunity, you have a dysregulated immune system. And so thymosin alpha kind of resets that and gives you the balance is the theory behind what’s happening with it.

Ari Whitten:  Interesting. Any other peptides worth mentioning here as far as immune health, anticancer effects?

Dr. Daniel Stickler:  There’s a ton of them. PNC-27 for cancer. I mean I think that one is the one that really targets the p53 pathway. And then you’ve got, LL-37, which isn’t quite available yet. We’ve been waiting for it to come on and we’ve been told that it’s going to come on the market. It is really good for the immune system as well. Let’s see, we just wait. You know, we hear about these things coming onto the market and we just wait for the pharmacy to say, “Okay, we’ve got it in, we’re ready to go with it.” You know, and we try to try them out and see what kind of responses we get. But, it’s an exciting area to be in right now. Staying up to date on the peptides is hard because they change so quickly, and new data comes out almost on a daily basis with them.

 

Dr. Stickler’s favorite peptides

Ari Whitten:  Yeah. Are there any other classes or peptides that you want to mention that you think would be useful for people to know about?

Dr. Daniel Stickler:  Well, I know one of my docs from my Austin clinic is going to be on and he’s going to be talking about weight loss peptides and healing peptides. So, I’ll leave those open for him to discuss.

Ari Whitten:  Yes. Okay. Excellent. To kind of wrap up, a couple of questions. So, one, I’m curious to hear what specific peptides are your personal favorites of the ones that you’ve experimented with? What have you personally found to give you the best results? Or what are things that you continue to use because you really get benefits from them?

Dr. Daniel Stickler:  Well the growth hormone releasing hormones and usually I combine that with a ghrelin mimetic. So, I like the CJC with ipamorelin. I’ve also done courses of tesamorelin which have been pretty effective as well. Actually, I go with the CJC because I don’t have to mix it every single night. It’s just more of a convenience thing for me but tesamorelin is actually much more potent. The other one is the MOTS-c which seems to give pretty impressive results. I do like the Epitalon as something I do regularly every six months. I do a course on that. BPC-157 by far is my favorite and Dr. Bob will be talking to you more about that one. But that one is huge. I mean, talk about something that heals the gut… I mean, I do nothing for gut healing anymore. No probiotics, no supplementation aspects, nothing like that. You get them eating a healthy diet, you put them on BPC and the gut heals. It is just amazing how effective that is. And for any injuries or keeping you from getting injured, BPC is just absolutely wonderful in that regard.

Ari Whitten:  Yeah. I’m curious on that note, I know this a bit of a digression and we will probably talk more about it with Dr. Bob Harding from your institute. But have you seen Dr. William Seed’s BPC product that’s being sold as a nutritional supplement? I’m just curious if that’s legitimate or…

Dr. Daniel Stickler:  It’s not BPC-157.

Ari Whitten:  Okay. Do you know what it is exactly?

Dr. Daniel Stickler:  It’s apparently… So, BPC is produced in the stomach and it is a fairly long compound. BPC-157 is a short segment of it that is stable in the digestive tract. There are tons of studies on BPC-157, so a lot of clinical trials both in human and animal models. And there are zero studies on body protective complex or compound, can’t remember when he calls it. But, you know, it’s amazing because Seed is brilliant with peptides, but, I just, I have no confidence in that product.

Ari Whitten:  Got you. So to kind of wrap up I’m sure that there are people listening to this, probably a sizable segment of the listeners here that are probably overwhelmed with all of the mechanisms and all of this, this whole language of peptides, BPC-157 and MOTS-c and humanin, and selank and Cmax and, you know, all the rest, Dihexa and all the rest of these. If someone has, let’s say, just a desire to increase their overall level of energy and mood and wellbeing and just function and perform better, where would you say they kind of start? So right now, they are overwhelmed with this whole, you know, this whole, vast territory of all these different options. What do you think would be the highest priority to start with?

Dr. Daniel Stickler:  Get somebody who knows what they’re doing with this stuff from a complete complex system, lifestyle standpoint. People think that they are experts in their own health. I mean Dr. Google is the busiest doctor in the world right now. And the problem is you don’t know what you are getting is real. I mean, you know, I don’t do my own taxes because I know I will screw them up. People don’t need to be being in charge of their own health. They need to find somebody they trust as a coach that can give them the guidance and the inputs that they need and the objective feedback on this. But you just got to find somebody who does it. I mean, when we work with clients, I mean, we are, we don’t even put them on something unless we tell them exactly why we’re putting them on it and what we are measuring to see if it is actually doing what it’s supposed to do. You know, we have all of our clients wearing these biometric monitors. Every one of our clients has this and I creep on their stuff every month. I’m on a video call with them. I’m like, “Okay, let’s pull up your dashboard.” I look at their sleep, their stress, their resting heart rates, all the stuff so that I can see what’s actually happening in their system on a day to day basis. And any intervention we do, we have a way to measure whether it’s doing what it’s supposed to do. That’s what you need with a coach. And there’s plenty of coaches out there. I mean, we’ve trained 250 coaches worldwide in this model in our academy. And these aren’t, some are physicians, some are chiropractors, some are health coaches. So, there is a wide variety of them out there that are kind of trained in our model. But you really just need to find somebody that they can look at this from a systems standpoint and say, you know, “This is what we’re dealing with.”

Ari Whitten:  Got you. So, two things. One is if somebody wants to be trained in your model, where should they look to what, where should they sort of reach out to you? Or how can they find out more information about that?

Dr. Daniel Stickler:  That would be at Apeiron.academy and it’s a-p-e-i-r-o-n- .acadamy. I mean, we have 90 hours of online clinical training in genetics, epigenetics and systems-based approaches. And, we also have a peptide course. It’s a six-hour course just in learning peptides for clinicians out there that want to have greater knowledge in that or coaches.

Ari Whitten:  Excellent. And now if somebody also wants to work with you directly, one-on-one, or the physicians who work under you, where should they reach out to you to get in contact and find out more information

Dr. Daniel Stickler:  That would be apeironcenter.com. So a-p-e-i-r-o-n-center.com. That’s our medical center and we have offices in Austin, Asheville getting ready to open Sarasota and getting ready to open London this summer. So, a lot coming online.

Ari Whitten:  Excellent. Now, do you want to just say a quick few words about what your sort of ideal client or patient is and the kind of work that you like to do with the people you work with?

Dr. Daniel Stickler:  Yeah, I look for growth-oriented people. I mean, I turned down probably half the people that reach out to work with me just because they are stuck in the story of, I’m sick and this is my story. We don’t look at anybody as sick. We don’t have a paradigm of illness. We look at a continuum of unbalanced homeostasis optimized and enhanced. And you can enter into that process anywhere along there as long as the mindset is really growth oriented. And, you know, I am not a cheerleader. I am not a mentor. A cheerleader will basically not call you out on your shit. A mentor will teach you their path. I’m a coach and I give people that coaching guidance to get them along their own path.

Ari Whitten:  Excellent. Well, Dr. Stickler, I’ve really enjoyed this. Thank you so much for your time. And again, people can reach out to you at apeironcenter.com to work one-on-one with you.

Dr. Daniel Stickler:  Yeah. Or you can say ape-iron center. That is easier for how it is spelled, but…

Ari Whitten:  Ape-iron. Yeah. Excellent. Well, thank you so much. I’ve really, really enjoyed this, and I hope to connect with you again maybe for a future Podcast where we can talk more about genetics and epigenetics.

Dr. Daniel Stickler:  That’d be great.

Ari Whitten:  Excellent. Thanks so much.

 

The Best Peptides For Boosting Mitochondria, Brain Health, and Longevity with Dr. Daniel Stickler – Show Notes

What are peptides? (1:07)
The best peptides for longevity (6:00)
The best peptides for mitochondrial health (27:50)
How peptides can be used for improving brain health (38:00)
The best peptides for autoimmune diseases (45:04)
Dr. Stickler’s favorite peptides (51:20)

Links

If you want to work with Dr. Stickler, check out his website.

Listen to the podcast I did with Dr. Bob Harding about the best peptides for weight loss and healing
To learn more about peptides, listen to the podcast I did with JF Tremblay.

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