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Dr Deb Muth 00:03
Well, welcome back to Let’s Talk Wellness Now. I am your host, Dr. Deb. And what is the most talked-about peptides in functional medicine? aren’t actually FDA approved. Not because they don’t work, but because no one’s funded the research to prove it yet. The truth is, some of the compounds that dominate wellness forums, BPC-157, TB-500, thymosin beta-4, epitalin, occupy a fascinating space between breakthrough science and unregulated experimentation. In today’s episode, we’re stepping into that grey zone, the world of investigational peptides, to separate mechanism from marketing. I’m going to walk you through the science that actually shows and where it stops, how to evaluate claims when human data don’t yet exist, and the quality, purity, and safety red flags that you need to recognise.
Dr Deb Muth 01:06
I created it in a previous episode, so go check that one out. And why honesty is the most important prescription in peptide medicine. If you’ve ever wondered whether these research-only peptides are the frontier of healing or the next functional medicine fad, this episode is for you. So grab your cup of tea or coffee, get comfortable, and let’s talk about what it really means to use peptides that are promising but still under investigation. So we’re going to break just for a second here and have a word from our sponsor. It is because of them that we stay on the air. So thank you for this. And we will be right back. Did you know sweating can literally heal your cells? Infrared saunas don’t just relax you. They detox your body, balance hormones, and boost mitochondrial energy. I’m obsessed with my Health Tech sauna. And right now, you can save $500 with my code at healthtechhealth.com slash dr-muth-req-25.
Dr. Deb Muth 02:15
All right, guys, welcome back. Let’s dive into investigational peptides, the evidence gap. So the following peptides we’re about ready to discuss are extensively in integrative, functional, and regenerative medicine circles. They may have intriguing mechanisms and promising preclinical data. However, they lack FDA approval, and the evidence quality varies dramatically. from interesting preliminary research to essentially no human data at all. And this distinction is really critical for maintaining scientific integrity. So let’s talk about immune-modulating peptides. There’s thymus and alpha-1, and this is an international story on the thymic peptides. Thymusin alpha-1, known as TA1, is marketed internationally as zidaxin.
Dr. Deb Muth 03:16
It’s a 28-amino acid polypeptide originally isolated from thymusin fraction 5, which was extracted from bovine thymus tissue. Modern production uses synthetic peptide synthesis. The thymus gland is located behind the sternum and is the primary site for T cell maturation, and thymic peptides like TA1 play roles in human system development and regulation. Now, I love thymus peptides. I love thymus glandular products. I’ve used thymus glandular products for decades. Ground-up animal thymus gland is basically what it is. There are a couple of different supplement companies that I’ve used over the years that are amazing with this. And they do a fantastic job, and they really do help to support the immune system. So when thymus peptides came out, it was really exciting because it took the whole idea of thymus support to a new level.
Dr. Deb Muth 04:17
The mechanism actually behind the thymus in alpha-1 is complex and involves multiple aspects of immune function. At the cellular level, TA1 enhances T cell maturation and differentiation, particularly the development of helper T cells and cytotoxic T cells. It modulates T cell receptor expression and can influence the balance between Th1 cell-mediated immunity and Th2 humoral immunity responses. And it also enhances the natural killer cell activity and modulates dendritic cell function, which are critical for antigen presentation. and initiation of adaptive immune responses. And on the cytokine level, TA1 influences production of interleukin-2, IL-2, interferon gamma, IFN-γ, and interleukin-10, IL-10.
Dr. Deb Muth 05:19
These create immune modulatory rather than simple immune stimulatory effects. This is a very important distinction because TA1 appears to help balance the immune system rather than simply ramping this up, which theoretically makes it safer in conditions where immune overstimulation would be a problem, such as an autoimmune disease. Hashimoto’s, autoimmune, lupus, Sjogren’s, any of those autoimmune diseases, we don’t want to overstimulate their immune system. So you want to use a product like this that’s non-stimulating. Now, the regulatory status on TA1 is geographically variable and represents one of the challenges in discussing this peptide with patients. It is not FDA-approved in the United States. However, it is approved in several other countries for specific conditions.
Dr. Deb Muth 06:19
In Italy, it’s approved for the treatment of chronic hepatitis B and hepatitis C. In China, it’s approved for chronic hepatitis B and adjunct immune compromised patients receiving vaccinations or suffering from certain infections. It has an orphan drug designation in the United States for certain cancer indications, but its designation does not constitute approval. It simply provides regulatory incentives for further development. So the evidence base for thymosin alpha-1 is substantial in some areas but comes primarily from non-US populations and research groups, which creates challenges in evaluating quality and generalizable information. So in hepatitis B and C, multiple clinical trials, many conducted in China and Italy, have examined TA1 as an adjunct to antiviral therapy.
Dr. Deb Muth 07:21
A meta-analysis by Wu and colleagues published in the Journal of Viral Hepatitis in 2013 examined 23 randomized controlled trials, including over 2,000 patients with chronic hepatitis B. The analysis found that combining TA1 with nucleoside analogs like LAMVDUDE or an and TCAVAR improved the hepatitis antigen seroconversion rates by HBV DNA clearance compared to its nucleoside analogs alone. And the effect sizes were modest but statistically significant, with the HBE-AG seroconversion rates improving from about 24% with antivirals alone to 38% in combined therapy. Now in hepatitis C, early trials before the development of direct-acting antivirals showed that TA1 combined with interferon alpha improved sustained virological responses, and compared to interferon alpha,
Dr. Deb Muth 08:30
Furon alone, particularly in difficult-to-treat populations like those with a genotype one or a high viral load. However, the advent of highly effective direct acting antivirals that achieve SRV rates, sorry, SVR rates exceeding 95%, the role of TA1 in hepatitis C has become less clear. Now in sepsis and critical illness, more recent interest has focused on TA1 in severe cases of sepsis and septic shock. Ren and colleagues published a systematic review and meta-analysis in the Frontiers of Immunology in 2022, analyzing 18 randomized controlled trials, including 1787 patients with severe sepsis or septic shock the pooled analysis showed that ta1 administration was associated with reduced 28-day mortality relative risk at 0.70 meaning a 30 reduction in mortality compared to the standard care alone and the effect appeared
Dr. Deb Muth 09:39
most pronounced in patients with sepsis-induced immunosuppression measured by HLA-DR expression in monocytes. Now, this is amazing because going forward, we’re going to talk about something that’s commonly known as cytokine storm. Now, cytokine storm really became apparent since 2020 with the viral infection that we’re dealing with in the world today. But they were already looking at this kind of cytokine storm produced by sepsis or sepsis-induced immunosuppression. And it triggered this hyperinflammatory response called the cytokine storm. And many patients who survived the initial phase of the immune suppressed stata, characterized by a T cell exhaustion, reduced antigen presentation, and increased susceptibility to secondary infections. Thymusin alpha-1, TA1, may help restore this immune competence in this phase. However, it’s important to note that patient selection and timing are critical.
Dr. Deb Muth 10:43
Giving this immune stimulant during a hyperinflammatory phase could theoretically worsen outcomes. So you don’t want to give it to them while they’re in the flare up or the sepsis or the infection, but given to them during the immunosuppression phase afterwards might be beneficial. Now there is also some cancer immunotherapy that we see with TA1 and has been studied as an adjunct in cancer treatment with the hypothesis that it could enhance immune surveillance and response to tumors. And a comprehensive review of Garci and colleagues published in Expert Opinion on Biological Therapy in 2007 examined multiple trials in melanoma, lung cancer, hepatocellular carcinoma, and other malignancies. And the results were mixed. Some trials showed improvement in the immune parameters, increased CD4 in T-cells. improved lymphocyte proliferation responses and some actually showed trends toward improved progression free survival but overall survival benefits were inconsistent and the heterogeneity of the cancer types treatment protocols and outcome measures makes a definitive conclusion difficult as a vaccine adjunct several studies particularly from china have examined ta1 as an adjunct to enhance vaccine responses
Dr. Deb Muth 12:11
in immune-compromised populations, including the elderly, dialysis patients, and transplant recipients. The rationale is sound. These populations often mount suboptimal antibody responses to vaccines, and TA1’s immune-enhancing effects might improve protection. There are small trials. They have shown improvement in seroconversion rates of hepatitis B vaccines and influenza vaccine in these populations. And though large-scale confirmatory studies are limited, there is a possibility here. Now, on their safety profile, one of the appealing aspects of thymusin alpha-A TA1 is that it’s apparently favorable safety profile in clinical trials. There are some injection site reactions with a little redness, a mild discomfort, and most commonly reported adverse effects. is that their severe adverse events attributable to TA1 have been rare in published trials. However, comprehensive long-term safety data are limited
Dr. Deb Muth 13:13
And theoretically, concern exists that immune modulation could potentially trigger or exasperate autoimmune conditions in susceptible individuals. Though this hasn’t been clearly demonstrated in clinical trials, integrative medicine considerations for integrative practitioners concerning the thymus and alpha-1, several factors require careful thought. First, sourcing and quality control are critical concerns. Since it’s not FDA approved, TA1 available in the United States typically will come from a compounding pharmacy or an international supplier with variable quality assurance. And pharmaceutical grade product with certificates of analysis showing purity, sterility, and endotoxin testing is essential, but it is readily available from many of these companies. Second, patient selection matters immensely. TA1 should be considered in complex cases where conventional approaches have been insufficient, such as chronic viral infections not responding adequately
Dr. Deb Muth 14:21
to standard antivirals, post-viral syndromes with evidence of immune dysfunction, cancer patients with immune suppression in consultation with oncology, and it should generally be avoided in active autoimmune disease unless there’s a compelling rationale and close monitoring. Now, TA1 is not a standalone therapy. In cases of chronic viral infection, Comprehensive immune support includes addressing nutritional deficiencies, optimizing vitamin D levels to be between 50 and 80, adequate zinc, selenium, and vitamin A, optimizing gut health since 80% of our immune function is in the gut, you need to optimize gut function. Managing stress from the HPA access dysfunction, chronic cortisol elevation, suppression, and immunity, ensuring adequate sleep, immune memory consolidations during sleep, addressing any metabolic dysfunction, insulin resistance, repairs in the immune function, and the bottom line on thymus and alpha-1 is
Dr. Deb Muth 15:26
is that it represents legitimate medicine in other countries with a substantial evidence base in specific contexts, but it remains experimental in the U.S., and practitioners using it should provide comprehensive, informed consent about its regulatory status, evidence quality, and source verification. while ensuring it’s part of comprehensive protocols. It is not a magic bullet. And again, what you’re gonna hear me say quite often here is that many of these peptides should be used in conjunction with something else. They should not be used alone. And can peptides be stacked? The answer is yes, they can. So if somebody has an insulin resistance, or a metabolic dysfunction, they can tier TA1 with a GLP-1 like terzepatide or semiglutide. That is not a problem to do that. You need to just work with a practitioner that understands how to do that effectively. So let’s look at BPC-157.
Dr. Deb Muth 16:26
This is a phenomenon I love BPC-157. Let’s separate it from marketing to actual mechanism of actions here. So BPC-157 stands for Body Protection Compound 157. It is a chain of 15 amino acids that are described as a partial sequence of body protection compound, a protein found in human gastric juice. It has become one of the most hyped peptides in regenerative medicine inside the athletic performance and biohacking communities with claims ranging from healing tendons and ligaments to repairing gut lining or reversing organ damage. The challenge is separating the legitimate mechanisms of science from the marketing hype. The proposed mechanism of BPC-157 are biologically plausible and intriguing. The research suggests that it may influence several growth factor pathways, including vascular endothelial growth factor, VEGF, which promotes new blood vessel formation and has improved better supply of blood flow to injured tissues, theoretically accelerating healing.
Dr. Deb Muth 17:40
It may also affect fibrous blast growth factor, FGF, and transforming growth factor beta, TGF beta pathways. both involved in tissue repair and remodeling. And some studies actually suggest that BPC-157 modulates inflammatory cascades, potentially reducing excessive inflammation while promoting the resolution phase that allows tissue rebuilding. Now I want to talk just a few moments here about these different tests that we’re talking about tgf beta veg f for those of you who are in our mold world you are very familiar with these uh lab tests we do this to see if you have a mold exposure what’s happening to your body and it’s been very challenging to try to heal this part of the mold illness and manipulate these VEGFs and TGF betas. And so with the fact that BPC helps us modulate this inflammatory cascade, BPC can be very helpful in the world of mold or mycotoxin illness in repairing those parts of the body that have been damaged by the mycotoxins.
Dr. Deb Muth 18:48
Now there is animal research on BPC-157. It is extensive and primarily from a research group led by pre-drag, oh, I can never say these names, Cyrek at the University of Zagreb in Croatia. Published studies in animal models have shown accelerated healing in a remarkable variety of injury types. A 2011 paper by Chang and colleagues in the Journal of Applied Physiology demonstrated that BPC-157 improved therapy tendon healing in rats with Achilles tendon injuries, and the treated rats showed increased tendon outgrowth, better cell survival in the injured area, enhanced cell migration to the injury site, and improved biochemical strength of the healed tendon compared to controls. Multiple other animal studies have shown similar promising effects. Ligament tears, healing faster in rabbits, muscle damage recovering more quickly in rodent models, gastric ulcers healing in rats given experimental induced ulcerations, inflammatory bowel lesions improving in mouse models of colitis, and even bone to tendon healing showing enhancement in animal studies.
Dr. Deb Muth 20:02
The breadth of injury types showing benefit in preclinical models explains the enthusiasm of this peptide. However, this is critical. These animal studies, primarily in rodents and rabbits, animal models of injury healing don’t reliably translate to human clinical outcomes. And the doses used in these animal studies when converted to human equivalent doses vary widely. And optimal human dosing is completely unknown at this point. it is all considered experimental and perhaps most importantly there are essentially no peer-reviewed controlled clinical trials in human published in humans published in major medical journals in a 2001 review of arthroscopy and the journal of arthroscopic and related surgery specifically examined in the evidence of bpc 157 and other peptides in musculoskeletal medicine The authors concluded bluntly that BPC-157 lacks evidence from randomized controlled trials and has an unknown safety profile in humans.
Dr. Deb Muth 21:09
They emphasized that the jump from animal data to recommending peptides for humans use bypasses the fundamental requirement for Phase I safety studies, Phase II dose-finding studies, and Phase III efficacy trials that would establish whether BPC-157 actually works in humans and whether or not it’s safe. The absence of human safety data is particularly concerning given BPC-157’s proposed mechanisms. Peptides that influence growth factor signaling and angiogenesis could theoretically have off-target effects. Uncontrolled angiogenesis, for instance, is a hallmark of cancer progression. Tumors require blood vessel formation to grow beyond a certain size. And while there’s no evidence that BPC 157 promotes cancer, The complete absence of long term human safety studies means we simply don’t know. This isn’t fear mongering. It’s acknowledging uncertainty and uncertainty exists and understanding that if you’re choosing to use peptides like BPC 157, you are doing it in an experimental model.
Dr. Deb Muth 22:17
We’re experimenting with the doses that are being used. And there is potential for it to cause cancer cells in your body to grow. And you need to be aware of this and understand the risks that you’re taking when you’re using an investigational or off label use peptide. Now, quality control issues with BPC also exist. It’s not FDA approved for any indication in the US. It’s not approved in any major regulatory jurisdiction worldwide. It’s marketed as a research chemical explicitly to bypass FDA oversight. And commercial sources selling BPC-157 range from compounding pharmacies, which have some quality standards but are not FDA inspected. You can take that for what you want to believe on that one. to overseas suppliers operating with absolutely no quality assurance whatsoever. If you are choosing to use BPC-157, you have to understand who’s manufacturing it for you, where you are getting it from, how pure it is.
Dr. Deb Muth 23:26
You want to make sure that you have the certificate of analysis and that it does not contain bacterial endotoxins that can contaminate the peptide or degrade the peptide and cause other issues for you. So when you talk about peptides with patients regarding BPC-157 or if you’re listening to this and you’re already using BPC-157 or other peptides, that are quote-unquote not for human consumption, an evidence-based response acknowledges both the appeal and the limitations. And you want to talk about the animal data that’s definitely showing some progress and some potential, but we don’t know what we don’t know in humans. If people are willing to take that risk, that is up to them to do that. But using BPC right now is experimental and people need to be aware of that. Are there evidence-based alternatives for patients with tendon or ligament injuries?
Dr. Deb Muth 24:26
And there are. There’s PRP, which has been studied in multiple randomized controlled trials. for conditions like lateral epicondylitis, tennis elbow, Achilles issues, patellar issues, knee issues. However, I want to caution you on this too. So the study that was done by Cox and colleagues in muscles, ligaments, and tendons in the Journal of 2014 showed modest benefits in pain and function compared to controls. And though the effects vary by injury type, PRP preparations can be helpful. You have to understand that a lot of times when people are doing PRP injections in their office, they are not doing it exactly the same way it was done in the study. And not to mention, if you’re using your own PRP to heal a ligament or a tendon or help your arthritis and you’re 60 or 70 years old, That is not good quality protein rich plasma. It is old protein rich plasma. And you’re not going to see necessarily the same benefits that you would see if you were using placental tissue or umbilical tissue.
Dr. Deb Muth 25:33
You also want to address the nutritional deficiencies or support that’s needed for connective tissue healing. And these are collagen peptides dosed at 15 grams a day. And this has been shown in a study by Shaw and colleagues in the American Journal of Clinical Nutrition in 2017 to augment collagen synthesis when combined with intermittent loading. Vitamin C is also an essential cofactor for collagen production and stabilization of collagen structure at a dose of around 500 to 1000 milligrams a day to support this process. You also need to have good adequate intake of copper and zinc. These are cofactors in collagen. Silica is also important. This comes from horsetail extract. This provides additional support as well. So more importantly, I think remembering that rehabilitation matters as well. Doing these protocols without doing some rehab is not going to get you where you want to go.
Dr. Deb Muth 26:33
There’s a research study by Alfredson and others for Achilles tendinopathy using the control lengthening of muscle tendon units under load to promote tendon remodeling and healing. These protocols have solid evidence and cost nothing beyond professional guidance from a physical therapist. They are important for patients seeking cutting edge regenerative approaches. Stem cell therapies, growth factors, concentrates derived from patients’ own tissues like PRP. These have a lot of good endogenous materials and they have good safety profiles. BPC-157 represents the perfect example of how promising Preclinical science gets marketed far beyond the evidence and it may eventually prove to be valuable. I think it will. But right now that determination does require some human studies and hopefully with the administration that we have right now and Bobby Kennedy, we will actually start to see some of that occur. Now the next peptide I want to talk about is TB4, thymus and beta-4.
Dr. Deb Muth 27:36
This is a wound healing peptide. It is a 43 amino acid peptide that’s naturally present in virtually all human cells except red blood cells. It’s actually one of the most abundant peptides in the human body, particularly concentrated in blood platelets, wound fluid, and many tissues. It’s naturally ubiquity makes it mechanistically interesting. The body wouldn’t produce it in such abundance if it didn’t serve a function. So the primary role of TB4 involves building G-actin. It’s a form of monomeric actin. And it’s structural protein that forms the microfilaments within the cells, providing cellular structure and enabling cell movement. TB4 prevents from F-actin filaments. I’m not going to talk too much about this. It’s really critical for wound healing as cells need to migrate into the injury sites.
Dr. Deb Muth 28:37
so the cell shape changes and the cellular response to the injury. So think of this as though you tore your meniscus and the body created all this TB4 to come to that injury to try to heal that site. That’s exactly what the TB4 is doing inside the body when there’s an injury. It’s been shown in research to help produce new blood vessel formation, promote endothelial cells, It helps modulate inflammatory cytokines, potentially reducing TNF-alpha, IL-1, and possibly protecting in programmed cell death, which we call apoptosis. And some studies suggest that it is cardioprotective in its effects in animal models of myocardial infarction, so heart attack, and neuroprotective in other models for brain injury. Now, these remain to be preliminary, but they are being seen. So the regulatory status on TB4 can create some confusion.
Dr. Deb Muth 29:40
The natural TB4 molecule itself is not FDA approved as a drug. However, TB4 based drug candidates called RGN259, formerly TB4, has been in the development by regen tree for corneal injuries of the dry eye disease. And as of recent updates, this drug is completed phase three trials for its neurotrophic keratopathy, severe corneal condition. But the FDA approval is still pending. So that means that the most advanced TB4-based pharmaceuticals hasn’t yet crossed the finish line for approval. The commercial peptide market further muddies the picture with TB500, which is often described as the synthetic fragment of TB4. However, this extract’s relationship between TB500 and TB4 varies depending on the source.
Dr. Deb Muth 30:41
So some claim that TB500 is identical to TB4, but positions 1 through 4 suggest it’s a different fragment. and the quality control across suppliers is not existent. So this confusion is part of why recommending TB500 becomes problematic for practitioners and patients, often because they aren’t certain what molecule they’re actually getting. The evidence base for TB4 in humans is limited, primarily to eye research, and the studies from Sohn’s and colleagues published in journals like Vitamins and Hormones in 2016 have examined topical TB4 for corneal injuries and neurotrophic keratopathy, dry eye, and other surface diseases. Now, these studies showed some promise in promoting this, and there is, however, a topical application to the cornea that is vastly different from a systemic injection. So for systemic use in wound healing, musculoskeletal issues,
Dr. Deb Muth 31:42
cardiac protection, neuroprotection, human clinical trials. There is scarce to non-existent evidence in humans. Most of the evidence remains in animal models or cell culture studies. And a review by Flip and colleagues in the Journal of Investigational Dermatology in 2006 detailed TB4’s effects on the matrix remodeling during wound repair in animal models, showing effects on collagen disposition, granulation, tissue reformation, and wound contraction. Another review by Ho and colleagues in expert opinion on biological therapy in 2007 discussed TB4’s potential in tissue regeneration and regenerative medicine, but noted the field remained largely blank. preclinical. So this is really important again to understand that there is just not enough human data. So there is a concern with cell division and migration. This theoretically exists
Dr. Deb Muth 32:45
for the potential effects on cancer cells, which would also rely on migration and division and other intended consequences of disrupting normal cellular architecture. These aren’t proven risks, but they are unexplored questions that we need to be aware of when we’re using peptides. This can cause cancerous tissue to grow. Very similar to what we talked about with BPC-157. These are also sold as research chemicals. There is no FDA oversight. So purity, potency, contaminations all still exist for these peptides. Now from an integrative perspective, the natural presence of TB4 in wound fluid and its biological roles in healing are legitimate science. in presence does not equal therapeutic utility. The body tightly regulates where and when and how much TB4 is present through natural production and bypassing that regulation with external dosing may or may not cause us to have beneficial or introduce risk.
Dr. Deb Muth 33:49
So we need to know that this is experimental use. Those people who are seeking wound healing and tissue repair the evidence-based approach of the body’s own capacity to heal is huge definitely want to be increasing your protein intake optimizing your zinc copper vitamin c and vitamin a and then managing glucose is really important during this time as well so let’s talk about a fun topic now and that’s growth hormone secretagogues this is the anti-aging hype machine these peptides in this category are things like semoralin ipameralin cjc 1220 1295 and others and among the most aggressively marketed in anti-aging and longevity medicine they all share a common goal stimulating the pituitary gland to release more growth hormone and the appeal is understandable. GH levels decline with age, and this decline is associated with increased fat mass, decreased lean muscle, reduced bone density, and other aspects of aging.
Dr. Deb Muth 34:55
The other times we’ll see growth hormone levels decline significantly is with chronic illness, and the logic is to restore youthful GH levels and youthful physiology. Now, semirelin from an FDA approved diagnostic to compound anti-aging product. Semirelin is a 29 amino acid peptide representing the first 29 amino acids of the full 44 amino acid human growth releasing hormone, GHRH. We talked about this on another episode of the podcast. And you can go back and listen to that one a little bit if you want. This fragment contains the complete biological activity of the full GHRH molecule and it binds to GHRH receptors in the anterior pituitary and stimulates growth releasing peptides, growth hormone releasing peptides. Semirelin was previously FDA approved as diagnostic testing of growth hormone secretion, essentially, to determine if the pituitary could still respond to GHRH stimulation in patients being evaluated for growth hormone deficiency.
Dr. Deb Muth 36:06
However, the manufacturer was discontinued and there was no longer an FDA approved semirelin product on the market in the United States. What exists now is semirelin available from compounding pharmacies used off label for anti-aging, body composition, and general growth hormone optimization purposes. This represents a significant gray area. Again, compounding medications serve a very important role, but they need to meet certain recommendations and regulations, as we’ve talked about in the past. You want to make sure that your compounding pharmacy that you’re obtaining semirelin from is qualified to do that, that they are doing best practices, and that you’re getting a good product. The theoretical advantage to semirelin over direct growth hormone administration is that it preserves more of the physiological growth hormone secretion patterns. Natural GH is released in pulses, primarily during sleep, not as a continuous elevation.
Dr. Deb Muth 37:07
So semirelin stimulates the pulses rather than providing a constant super physiological growth hormone level. And that pulsatile pattern is thought to reduce some of the side effects and metabolic concerns that we have with continuous growth hormone exposure. However, the evidence supporting semirelin for anti-aging and body composition in healthy adults is minimal. Most of the data comes from studies conducted in the 1990s when the FDA approved product existed. Not that that means it’s bad. We have drugs that have been in the market for over a hundred years that are still there, that still have the research and are still being used successfully and safely today. So we don’t want to let that really make us think that this product isn’t safe. So a 2006 review from Walker in Clinical Interventions of Aging suggested that semirelin might be a better approach than direct GH for adult onset growth hormone insufficiency, but they do acknowledge that the evidence was limited.
Dr. Deb Muth 38:12
And although we don’t have any large scale trials that we can examine for semirelin’s efficacy, it is now commonly prescribed. And the optimal dosing for anti-aging purposes is still unknown. It is considered experimental and it does vary from person to person, but it is still unstudied. The effects on cancer risk, cardiovascular disease, metabolic dysfunction over long time periods are also still unknown. I would argue that the side effects or the risk factors of not having growth hormone are equally as bad as the unknowns that we have here. We’re not looking to try to get super physiological doses. We’re trying to restore youthful GH levels. Typically, we’re not trying to restore back to a 20-year-old. We’re trying to restore back maybe 10 years. That is a better way of doing this. And I think that’s important for people to understand. Now, ipamirelin is the ghrelin mimicker.
Dr. Deb Muth 39:12
Ipamirelin is a pent-up peptide, five amino acid, that acts as a growth hormone secretagogue receptor, a GHS-R agonist. It mimics the action of ghrelin, the hunger hormone, that also stimulates growth hormone release. The proposed advantage over earlier secretagogues is that ipamirelin stimulates growth hormone release without significantly affecting cortisol, prolactin, or other glucose things, which can be increased by growth hormone secretagogues. The regulatory status is clear. Ipamirelin is not FDA approved for any indication. It’s sold as a research chemical. Human evidence is thin. It’s limited to single dose studies examining how quickly it’s absorbed and metabolized with minimal data on dosing and clinical outcomes. Now there are marketing claims for ipamirelin and they are extensive.
Dr. Deb Muth 40:13
It increases lean muscle mass, it decreases body fat, it improves sleep quality, faster recovery from workouts, enhanced injury healing, better skin quality. The evidence supporting these claims in humans is not available we don’t have it these are claims that are made by the effects that we know from growth hormone so it’s not necessarily a bad thing we know what growth hormone does we know growth hormone does all of these things if ipamorelin is a precursor to that it will obviously help improve those things making that correlation of what growth hormone does So there are safety concerns that mirror the same as any other growth hormone elevating therapy. It can cause fluid retention, joint pain, carpal tunnel syndrome, insulin resistance, glucose intolerance, and theoretically, can it increase calcium? cancer risks? It can because IGF-1 promotes cell proliferation and can inhibit apoptosis in cancer cells. Now remember, your body makes IGF-1.
Dr. Deb Muth 41:15
If it’s not making enough of it, that’s a problem. If it’s making too much of it, That’s a problem. So just understand that if you are adding these things, and especially in elevated doses, you are taking a potential risk. So there is also now CJC 1295 is a modified GHRH analog of 30 amino acid peptide based on GHRH structure, but with modifications. So it includes the addition of drug affinity complex, DACC, DAC, which involves conjugation with a small albumin binding molecule, dramatically extends the peptide’s half-life from minutes to as much as potentially a week or more. And this creates sustained growth hormone elevation rather than that pulsatile release. There are actually two versions of this. There’s CJC 1295 with DAC, longer acting version, and CJC 1295 without DAC, which is essentially a shorter duration of semirelin.
Dr. Deb Muth 42:19
And so when we’re comparing products, it is… only the difference between long acting and short acting. The human evidence for CJC 1295 is limited to a single published phase one study by Techman and colleagues in the Journal of Clinical Nutrition and Metabolism in 2006. And the study involves 18 healthy young adults showed that CJC 1295 with DAC produced a sustained elevation of GH and IGF-1 lasting several days after the injection. That’s essentially the entire published human evidence of this peptide. There are no phase two studies examining optimal dose. So that is all considered experimental. And there is no phase three studies examining clinical efficacy. So the sustained GH levels created by CJC 1295 with DAC raises specific concerns because the natural GH secretion It goes up and down, up and down, up and down.
Dr. Deb Muth 43:19
And that constant elevation may have a different metabolic and cellular effect. And we just really don’t know what that’s going to be yet. So we can understand that elevated IGF-1 levels can theoretically increase cancer concerns and metabolic risks. So rather than always injecting peptides, which are very expensive… You can do other things. And there was a study by Hartman and colleagues in the Journal of Clinical Endocrinology and Metabolism in 1992 that demonstrated the 48-hour fast increased integrated growth hormone secretion five-fold through increased GH levels. Now, the problem with this is fasting for 48 hours is a challenge. And how long is it going to increase the growth hormone secretion without causing issues? Or in general, how long is it going to go up?
Dr. Deb Muth 44:19
So we have to be cautious about that as well. Sleep optimization is non-negotiable. The majority of growth hormone secretion occurs during sleep, slow wave sleep, typically the first sleep cycle, and poor sleep quality or insufficient sleep typically. can dramatically affect your growth hormone levels. And then high intensity interval training, HIIT resistance training can stimulate growth hormone as well. This was seen in a study by Godfrey and colleagues in sports medicine in 2003 and was examined in exercise-induced growth hormone responses to athletes. So we definitely see these kinds of things. So let’s talk about some longevity peptides now. These expand the telomere. So there’s epitalin and epithalamin and when these are used in anti-aging they can produce some amazing results.
Dr. Deb Muth 45:22
So epitalin is a synthetic terapeptide, just four amino acids. It was originally synthesized as a simplified version of epithalamine. a pineal gland extract containing multiple peptides. The synthetic four amino acid version was created to isolate what researchers believed might be the active anti-aging component. The mechanism produced for epitalin centers on telomere and telomerase, Telomeres are protective caps at the end of the chromosomes consisting of repetitive DNA sequencing. And every time a cell divides, telomeres shorten slightly because DNA polymers cannot fully replicate the ends of the linear chromosomes. So this progressive shortening acts as a molecular clock. After 50 or 70 divisions, the telomeres become critically short, triggering a cellular senescence.
Dr. Deb Muth 46:22
This telomere shortening is one mechanism of cellular aging and telomeres in the enzyme that can rebuild telomeres by adding these caps back onto the end of the chromosome. It’s active in stem cells, germ cells, and unfortunately in about 85 to 90% of the cancer cells. In most adult somatic cells, telomerase is inactive or present at very low levels, allowing the telomeres to shorten with division. The research on epitalin suggests it might activate this telomeres act telomeres process primarily from a research group led by Vladimir in Russia. Vladimir Kavasan in Russia. He is a huge peptide researcher or was he passed away with publications dating back to the early 2000s and a study published in bio gerontology in 2000 by Kavasan
Dr. Deb Muth 47:25
and colleagues examined the effect of epitalin on the lifespan of fruit flies, and they treated fruit flies that showed a modest increase in mean and maximum lifespan compared to its controls by approximately 10 to 15% lifespan extension in some experimental groups. And there were other studies in 2003 that examined epitalamine in a female Swiss-derived mouse. This was done by Ann Simove and colleagues. And the researchers reported that epitalin treatment was associated with increased lifespan as well. And the most cited mechanistic work comes from cell culture studies. And that is also Cavason’s group that published this research in 2003, showing increased telomeres activity in cultured somatic cells again. More recently, between 20 and 25, the series of publications have continued to explore epithelial effects on telomere dynamics in cell cultures.
Dr. Deb Muth 48:32
So there is a lot of research that’s been done. The mass majority has been done on epithelin. And most of it has been done by a single research group in Russia. There is some restrictions on some of the cell culture data that we’re seeing. And it does show that epithelin sometimes can be described as a regulating hormone. Carcadian rhythm for melatonin production, which is derived by the penile extracts. And however the evidence for this affects minimally and mechanistically unclear, the pineal gland primarily functions as melatonin secretion in that light-dark cycles. So Epithalin or epitalin is not FDA approved. It is not approved for any major regulatory jurisdiction. It is sold as a research chemical only.
Dr. Deb Muth 49:33
So you need to follow the same safety profiles that we’ve talked about in other episodes and in today’s episodes. And when we’re talking about epithalin, and we’re excited about it being an anti-aging science, we should balance this with the honesty and the evidence of the quality of that evidence. We don’t know its safety effect. We don’t know if it’s going to increase the risk of cancer. We can’t verify that. And we need to be using it in an experimental use of unknown risks only. Of course, diet, physical activity, stress management, sleep quality, all of those things are important for us to be looking at when we’re looking at these peptides. Now, I want to get into some of the brain peptides. This is the nootrophic frontier. C-Max and C-Lank, there is Russian pharmacology that’s done. C-Max and C-Lank represent an interesting case study in how different regulatory environments and research traditions
Dr. Deb Muth 50:36
create challenges in evaluating this evidence. Both peptides were developed in Russia, are approved for their specific indications and have substantial Russian language and literature supporting their use. However, the FDA approval in the United States is still not there. C-Max is a seven amino acid. It’s a synthetic analog. It is a fragment, particularly ACTH 4 through 10. It’s sometimes called the melanocortin effects because it involves the melanocortin receptors of the central nervous system. CMAX was developed by the Institute of Molecular Genetics of Russia Academy of Sciences and is approved in Russia for several indications, including acute stroke, transient ischemic attacks, cognitive disorders. It has Russian approval and is based on clinical trials primarily in Russia.
Dr. Deb Muth 51:39
It does help to increase brain-derived neurotrophic factor, BDNF, a protein critical for neuroplasticity, the brain’s ability to form new connections and adapt to the challenges. BDNF supports neuronal survival and promotes growth of these new neurons. C-Max also influences neurotransmitter systems, particularly dopamine and serotonin, and there is some research that suggests it affects on metabolism as well, and endogenous opioid peptides that involve pain reception and mood regulation. So it has some good potentials there. There is also C-Link, which is a hepatopeptide structurally similar to Tufts’ and an immune modulatory peptide. It was also developed in Russia and was approved for anxiety disorders as a neurotropic. Its effects involve anxiolytic effects, possibly through the GABAnergic system or the GABA system of the brain, and immune modulation.
Dr. Deb Muth 52:44
The Russian research is examined by C-Link for anxiety disorders. and finding reductions in anxiety without sedation. There is a dependency potential or cognitive impairment does not exist like it does with benzodiazepines with C-Link. So that is really good. And they do report attention and memory improvement using C-Link. There is a study that was done in neuroscience and behavioral psychology in 2018 that examined C-Linx effects and proposed that it exerts cytoprotective effects through BDNF pathways similar to C-Max. So both of these are Russian research-based They’re not wrong or fraudulent. It’s just that they are from Russia and we all have our concerns with Russia. However, that does not necessarily mean their research doesn’t hold quality.
Dr. Deb Muth 53:49
Neither peptide is approved by the FDA, and so you are using this off-label. The same rules apply for all of the other peptides that we’ve talked about that are produced off label. You want to do the same things that you would do with anything else. Good protein, omegas, B vitamins, acetylcarnitine, exercise, sleep, all of that still applies when we’re using these peptides. So I want to talk briefly about clinical decision and framework when we’re looking at this. First and foremost, we always want to go to FDA-approved peptides. Secondly, we would look at international approval with peptides that are established in other countries but lack FDA approval. And then preclinical evidence only or experimental peptides. These can be used, but they are not ethically recommended in the traditional medicine world.
Dr. Deb Muth 54:50
If patients use them, we need to have appropriate counseling about the evidence surrounding them, the safety, and where to find them. how to find them and how to ask for these certificates of analysis. So I think it’s really good that we were exploring all these peptides and understanding what they are. There’s a lot of controversy out there. There’s a lot of concern out there. And what we can say with confidence is that peptides are powerful biological signaling molecules. Some peptide based medications, semi-glutide, triseptide, PT 141, Lupron that are all FDA approved. can dramatically improve outcomes in patients that are obviously selected for the correct ones. There are many other peptides that we address that are integrative and longevity space in the regenerative medicine. These peptides are all experimental. That does not automatically make them wrong.
Dr. Deb Muth 55:50
It just means that we need to be honest about what we’re doing with them and we need to be cautious with the patients so that they can make a decision to be part of an experimental study. in looking at how to use these peptides. So peptides are tools like any other tools. They work best in the hands of skilled people, and they are applied to appropriate situations, integrating into comprehensive approaches that address root causes. The most powerful peptide administered to a patient with untreated inflammation, hormonal chaos, nutritional deficiencies, and disorders of sleep will disappoint. The simplest evidence-based interventions apply. to a patient whose foundational physiology has been optimized. And this is the art of the science of peptide, right? If done right, respecting both the power of these molecules and the complexity of human beings that we are privileged to serve can make a difference in their lives. So thank you for listening to this episode.
Dr. Deb Muth 56:52
I hope this was helpful. If you can know of somebody that might benefit from this, please like, share, and subscribe. It means a lot to us. And I hope you join us for our next episode of Let’s Talk Wellness Now. Welcome to Let’s Talk Wellness Now, where we bring expert insights directly to you. Please note that the views and information shared by our guests are their own and do not necessarily reflect those of Let’s Talk Wellness Now, its management, or our partners. Each affiliate, sponsor, and partner is an independent entity with its own perspectives. Today’s content is provided for informational and educational purposes only and should not be considered specific advice, whether financial, medical, or legal. While we strive to present accurate and useful information, we cannot guarantee its completeness or relevance to your unique circumstances. We encourage you to consult with a qualified professional to address your individual needs.
Dr. Deb Muth 57:54
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