The Power of Peptide Therapies

dugdeep

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The following is for informational purposes and should not be construed as medical advice, nor a replacement for your doctor, nor should it be taken as encouragement. Nor should this be viewed as a definitive guide. Adults are responsible for their own actions, forum posts are not responsible for anything. As with everything, DO YOUR OWN RESEARCH.

It seems like peptide therapy is getting more and more popular lately, so I thought we should have a forum thread about it so we can share what we've learned and anyone with personal experience with them can report what happened. I've been doing a deep dive on using injectable peptides for health and I've been pretty blown away by what I've found. I'm leery of over-hyping health protocols, so I hesitate to say it, but I do think these things are potentially a game-changer for multiple health issues.

I feel like peptides kind of have the reputation for being the sole domain of bodybuilders, fitness influencers and biohackers, but they're really so much more than that. Yes, there are a lot that do body recomposition, skin rejuvenation, hair regrowth, etc., but I think their potential for truly deep healing means dismissing them as vanity supplements really misses the mark.

So far my own experience has been limited to a GLP-1 peptide called Retatrutide, which is touted as a weight loss peptide but is actually more like a healer of broken metabolisms. I plan on doing a few posts on specific peptides and I'll detail more on the details of GLP-1s in a later post. I've also just started taking a mitochondrial peptide called MOTS-C, but it's too early to give much of a report on it.

First off, what are peptides? The dictionary definition: Peptides are short chains of amino acids linked together by peptide bonds, which are the fundamental building blocks of proteins in the body. They typically consist of between two and 50 amino acids, although some definitions extend the upper limit to 100 amino acids. Peptides are distinct from proteins, which are longer chains of amino acids, often forming complex three-dimensional structures. The distinction between peptides and proteins can be somewhat arbitrary and context-dependent.

Peptides that are taken exogenously are generally ones the body uses as extracellular signaling molecules, hormones and neurotransmitters and can regulate processes like metabolism, tissue regeneration and immune response. Lots of biologically active substrates we already know about and supplement with are actually peptides, like insulin, glutathione, ghrelin, oxytocin, vasopressin, etc.

By taking a peptide, you're inserting a signal into the body; a signal it already has the potential to send itself. Therefore, every effect a peptide is able to have on the body is something the body already has the potential to do. By introducing a signal, rather than just triggering one biological effect, it often sets in motion a whole cascade of effects.

As such, very few peptides are 'one-trick poneys'. They tend to activate entire pathways that have multiple downstream effects, not targeting specific reactions like many drugs or nutrients do (not all). This is why you tend to see the list of benefits for a peptide be wide-ranging and sometimes seemingly unrelated. The signals one is sending with peptide therapies are like telling the body to activate an overall state rather than small tweaks to downstream reactions.

And while individual peptides can have multiple benefits, people often take more than one. In many cases there are synergistic effects between multiple peptides that go above and beyond what the individual peptides can do. People call this as 'stacking' peptides, or refer to 'peptide stacks'.

Pros of Peptide Therapies:
* From what I can tell, they're very effective and deliver on their promises; the caveat here being that I only have limited personal experience with one peptide (and starting a second). But there are lots of anecdotal reports out there, some of which are coming from practitioners who have worked with thousands of clients collectively. Some things undoubtedly get over-hyped (as with all health protocols), and individual results are obviously going to be varied. But as a general rule, peptides seem to do what they're supposed to do.

* Peptides are like sets of instructions for processes our bodies are generally not using or are using in a limited way (reasons for this aren't really known, but looking at our current environment will probably yield some theories, not even getting into the esoteric nature of our reality). They're not pharmaceuticals which tend to strong-arm outcomes through force by blunting, breaking or circumventing pathways, often leading to side effects (NOTE: I'm not saying pharmaceuticals are bad, this is just to highlight how peptides are different). They're also not like vitamins, minerals or nutraceuticals which tend to flood the body with substrates to encourage particular outcomes (in some cases they work by other mechanisms, of course). I think of peptides as working at a higher order within the system, like managing rather than micromanaging.

*There is quite a bit of research out there. Some of these peptides have been studied for decades, while others are relatively new, and the research will reflect that.

* To speak generally, there's a very good safety profile for the majority of peptides. Side effects are usually minimal, in some cases non-existent. But obviously each case varies and needs to be researched!

Cons of Peptide Therapies:
* The major stumbling block is access: peptides are either expensive or difficult to get. Getting peptides through resellers in the West is generally safe as long as they're testing them (and they should be willing to provide test results) but even this is not entirely without risk, obviously. This option is expensive, however, as mark-ups can be astronomical. Alternatively, to get them cheap means getting them through the Chinese grey-market which requires a lot of know-how: you're usually dealing in crypto, which has its own steep learning curve (although it is possible to find sellers that will take WISE transfers or in rare cases even Paypal); you may find yourself navigating Discord servers, Telegram and Whatsapp channels and somewhat dodgy steroid and peptide forums; and on top of all this, the space is littered with scammers. It's high risk and not for the feint-of-heart. It's not impossible but requires some determination.

* While there are small number oral peptides, most require sub-cutaneous self-injection. This isn't too difficult to learn to do and the pain is really quite minimal, but it will no doubt pose a major stumbling block for some people. It also requires equipment and hygiene procedures for safety.

* The injectable peptides come as powders in vials which need to be reconstituted with bacteriostatic water (water with a tiny amount of benzoic acid to sterilize). There's a bit of a learning curve here, but it's nothing too complicated. I thought I should mention it though, because it is more involved than just popping a pill.

* Misinfo - finding good reliable information on peptides is challenging. The peptide space is loaded with 'influencers' who all just tend to parrot each other, so the wrong information can spread fast. I've been following a few people on YouTube who are experienced (practitioners working directly with patients) and/or who cite research studies. Bodybuilder channels can have a lot of great info, going into autistic-level detail on mechanisms of action, but one has to keep in mind that many of them are coming at it from the goal of strength and physical appearance and not necessarily overall health. (As an aside, I think we owe a lot to the bodybuilder community since they fearlessly experiment on themselves with new supplements, compounds, medications, therapies, etc. If you hear about a "new" supplement, chances are you can find bodybuilders who have been using it for years and can tell you the ins and outs of it). Fortunately, as I said, there are a lot of studies out there and answers can often be a Pubmed search away.

That wraps up the general introduction. I'll do a few posts on specific peptides or groups of peptides soon. But if anyone has anything to add or experiences with peptides, this seems like a good place to post them!
 
I have been following this space for a while now, and I have dabbled in a peptide a while ago (unsuccessfully). But the major issue here in Australia is access - whether you get it legally with a prescription to import from abroad, or from the grey market, it’s a pain!

I had a batch confiscated by customs despite having a valid prescription, because I didn’t get their letter asking me to prove this was legal early enough, so they just destroyed the shipment. I had an insurance from the seller, so he sent a second batch through for free. I asked the seller to add a copy of the prescription to the shipment, which the seller refused to do (for whatever reason). The next batch went through, but required a constant stream of emails to and from customs, so in the end I got the product, but I thought I would need a miraculous effect to make that worth doing on a recurring basis.

So for me, at the moment - despite being able to get a prescription if I wanted - it’s in the “too hard” department, as I would need to repeat the process every three months or so, as there are limits to how much peptides I can import at anyone hit.

Unfortunately …
 
I think Hunter and Jay could bring some informations here, they have their own brand if I remember correctly. So with the research they've already done on this topic, they could give us books to read, and other food for though.

I also found recently this database on supplement / Peptide which work with AI, you can give it a try, it's well done even if we need to ponderate depending of what source is taken directly from this database OpenHealth - Daily Medical Insights & AI-Powered Health Research
 
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Some days I say to myself, "thanks to the Divine Cosmic Mind for peptides!". Will love to contribute and share too. And I think it's a good time to do a Wave recap on peptides:


...internal chemicals, the neuropeptides and their receptors, are the actual biological underpinnings of our awareness, manifesting themselves as our emotions, beliefs, and expectations, and profoundly influencing how we respond to and experience our world. (Pert 1999, 9)
My favorite category of ligands by far, and the largest, constituting perhaps 95 percent of them all, are the peptides. … Like receptors, peptides are made up of strings of amino acids …

[Peptides are tiny pieces of protein and the word protein is derived from proteios, which means primary. Proteins are recognized as the fundamental materials for life. A peptide consists of a string of amino acids joined together like beads on a string. The bond that holds the amino acids together is made up of carbon and nitrogen. This bond is so strong that it takes hours, and in some cases, days of boiling in strong acid to break it apart! When there are approximately 100 or more amino acids in such a protein, it is called a polypeptide. After it reaches 200 amino acids, it is then known as a protein. (p. 64)]
… If the cell is the engine that drives all life, then the receptors are the buttons on the control panel of that engine, and a specific peptide (or other kind of ligand) is the finger that pushes that button and gets things started. (Pert 1999, 24, 25)
The peptides (remember, this word is related to the number 5, and there are 3 basic types of chemical messengers, so we are actually looking at one part of the 3-5 code here) can act like neurotransmitters, diffusing across the synaptic cleft, but their primary function seems to be to move through extra-cellular space, flowing with the blood and cerebrospinal fluid, traveling great distances in the body, and stimulating complex and fundamental changes in the cells when they lock onto the receptors.
Although the structure of peptides is simple, their effects are complex. This is why they are subcategorized as hormones, neurotransmitters, neuromodulators, growth factors, gut peptides, interleukins, cytokines, chemikines, and growth-inhibiting factors. But, in the end, they are all doing a single thing – conveying information to the body cells. They are a cell phone system composed of protein, or prime substances. Light, if you will.
Just as neuropeptides flow among the cells of the body, causing all the receptors to vibrate in response to information, so does knowledge act on our consciousness the way the strings of a resting violin will vibrate when another violin is played. Knowledge produces resonance among different people who are unique, but unified in their diversity. With knowledge we can truly feel what others feel – not just assume that they feel what we feel. The oneness of life is based on the simple fact that with knowledge, we are all vibrating together.

Knowledge protects.
 
This little book is an excellent introduction:


It's Kent Holtorf, MD "Mold Illness and the Holtorf Updated Peptide Protocol for the Rapid Treatment of CIRS)"

Here is a summarizing table of the various possibilities:

Screenshot 2025-10-25 at 13-16-23 Mold Illness and Peptide Protocol for CIRS by Kent Holtorf 5...png

Notice that we have a discouraging disclaimer on Methylene Blue. And there's Sayer Ji's summary on it as well.

Big heads up on LL-37, which triggered a localized reaction in me and a friend:

UptoDate
Cathelicidins are a family of AMPs [antimicrobial peptides] widely distributed in nature. The human cathelicidin LL-37 is released from both neutrophils and epithelial cells. It exhibits a broad range of antimicrobial activities [116,118,133], neutralizes LPS, and plays a role in wound healing, angiogenesis, and clearance of dead cells. LL-37 is induced by vitamin D [134-136]. In both keratinocytes and macrophages, stimulation of TLR2 results in the induction of the cytochrome P450 enzyme that converts vitamin D to its active form, which in turn induces the expression of LL-37. In this way, vitamin D can influence microbicidal defenses of both skin and circulating phagocytic cells [137]. This may explain, at least in part, why certain human infections (eg, tuberculosis) are more prevalent among populations with inadequate plasma levels of vitamin D, including those with more deeply pigmented skin [137]. (See "Vitamin D and extraskeletal health", section on 'Immune system'.)
So far, so good.
In vitro studies show that human LL-37 stimulates dendritic cells to express increased endocytic capacity, modified phagocytic receptor function, upregulation of costimulatory molecules, enhanced secretion of T helper type 1 (Th1) inducing cytokines, and enhanced Th1 responses [522].

●The beta-defensins and LL-37 are chemoattractive for mast cells and can induce their degranulation [523,524]. Mediators in mast cell granules can affect adaptive immunity by modifying dendritic cell function [525].
LL-37 – LL-37 is proposed to contribute to skin inflammation through activation of the NLRP3 inflammasome
Mast cellsMast cells are a source of cathelicidin and can be activated to produce inflammatory mediators and proteases in response to the active LL-37 form of cathelicidin [16]. Mast cell activation also contributes to the production of mediators that result in angiogenesis and fibrosis [15].

I have mast cell activation syndrome (MCAS) within the context of a congenital conjunctive tissue disorder, my mast cells degranulate because the surrounding conjunctive environment is abnormally "loose". And my friend has asthma and allergy issues. Our reactions to LL-37 took about 2 weeks to resolve. It was mostly localized urticaria-like nodules on the site of injection. Knowledge protects!

There's a lot of research in all currently used peptides, let's see what we can learn.
 
Thank you for your post @dugdeep I got not so far in the topic yet, but it really is so hard to decide which information is right or wrong, it is a jungle :-D And every time I start to search or read I have those "Ozempic-faces" in my mind and my brain shuts down :-D
It makes total sense to me though, that the body gets information through peptides. How can I find out the ones which are helping for certain conditions, because all peptide practitioners are recommending tests before using the peptides? Or are you thinking of a condition you have and then just search for that condition and the peptides recommended? And sometimes you think you have this or that condition because of whatever, but maybe it has another rootcause than you think. I am so hestiant :-D What could be the worst thing happening if its not the right peptide for you? And would one have to take it forever or just until the body "gets" the information and changes what needs to be changed? Sorry for so many questions :whistle:

To get the peptides wouldn´t be the problem in Germany (they are expensive though :nuts: )

Some days I say to myself, "thanks to the Divine Cosmic Mind for peptides!". Will love to contribute and share too. And I think it's a good time to do a Wave recap on peptides:
Thank you Gaby for the recap :-) Interesting! Waiting for these days :halo: have to find the courage first
 
Thank you for your post @dugdeep I got not so far in the topic yet, but it really is so hard to decide which information is right or wrong, it is a jungle :-D And every time I start to search or read I have those "Ozempic-faces" in my mind and my brain shuts down :-D
I'm working on a post about GLP-1s like Ozempic, but just to note here: Ozempic, generic name Semaglutide , is a first generation GLP-1 agonist and they're now on the third generation. It's still popular mostly because it's easy to get and people don't know about the newer versions, but truthfully, it's kind of obsolete (speaking generally here, there may be some instances where it's useful). The reason people get "Ozempic face" or "Ozempic butt" is because they're not using them correctly: they require an intelligent approach that includes dietary and lifestyle factors, otherwise you're just starving yourself. To preserve muscle mass you need to be doing resistance training and getting adequate protein in the diet. The problem is that some dodgy Hollywood doctors are handing out Ozempic like candy and not enforcing the lifestyle changes with their patients. Combine that with rampant body dysmorphia and you get Hollywood starlets treating peptides like "anorexia made easy" and looking like concentration camp victims. The same could be said for bone loss that's being reported - bones need proper nutrition and exercise to keep them strong. The newer generation of GLP-1 agonist largely mitigates this problem, but it still requires the peptide is accompanied by the proper lifestyle factors, particularly nutrition and exercise.

It makes total sense to me though, that the body gets information through peptides. How can I find out the ones which are helping for certain conditions, because all peptide practitioners are recommending tests before using the peptides? Or are you thinking of a condition you have and then just search for that condition and the peptides recommended? And sometimes you think you have this or that condition because of whatever, but maybe it has another rootcause than you think. I am so hestiant :-D What could be the worst thing happening if its not the right peptide for you? And would one have to take it forever or just until the body "gets" the information and changes what needs to be changed? Sorry for so many questions :whistle:
This thread shouldn't be looked at as an "everyone should do peptides!" rallying call because not everyone should do them. This isn't a passive approach to health like trying a new supplement - it requires a lot of diligence. (I'm not suggesting you're approaching it this way, this is just general advice).

That said, if I were interested but starting from zero, I would start with establishing what my health goals are. Then I'd get an idea of what peptides are out there and see if anything matches those goals. This thread will probably be a good resource at some point, but in the meantime you could try reading Jay Campbell's book "The Ultimate Therapeutic Peptides Guide for Optimized Living" (I think he offers it free if you sign up for his email list) or the book Gaby posted above, or read some general articles or watch some YouTube videos. Once you've found something that resonates, dig into the research so you know exactly what you're getting into. Read studies, check out testimonials, see what people are advising before you take the plunge.

To get the peptides wouldn´t be the problem in Germany (they are expensive though :nuts: )
Yeah, that's an issue...
 
I'm working on a post about GLP-1s like Ozempic, but just to note here: Ozempic, generic name Semaglutide , is a first generation GLP-1 agonist and they're now on the third generation. It's still popular mostly because it's easy to get and people don't know about the newer versions, but truthfully, it's kind of obsolete (speaking generally here, there may be some instances where it's useful). The reason people get "Ozempic face" or "Ozempic butt" is because they're not using them correctly: they require an intelligent approach that includes dietary and lifestyle factors, otherwise you're just starving yourself. To preserve muscle mass you need to be doing resistance training and getting adequate protein in the diet. The problem is that some dodgy Hollywood doctors are handing out Ozempic like candy and not enforcing the lifestyle changes with their patients. Combine that with rampant body dysmorphia and you get Hollywood starlets treating peptides like "anorexia made easy" and looking like concentration camp victims. The same could be said for bone loss that's being reported - bones need proper nutrition and exercise to keep them strong. The newer generation of GLP-1 agonist largely mitigates this problem, but it still requires the peptide is accompanied by the proper lifestyle factors, particularly nutrition and exercise.


This thread shouldn't be looked at as an "everyone should do peptides!" rallying call because not everyone should do them. This isn't a passive approach to health like trying a new supplement - it requires a lot of diligence. (I'm not suggesting you're approaching it this way, this is just general advice).

That said, if I were interested but starting from zero, I would start with establishing what my health goals are. Then I'd get an idea of what peptides are out there and see if anything matches those goals. This thread will probably be a good resource at some point, but in the meantime you could try reading Jay Campbell's book "The Ultimate Therapeutic Peptides Guide for Optimized Living" (I think he offers it free if you sign up for his email list) or the book Gaby posted above, or read some general articles or watch some YouTube videos. Once you've found something that resonates, dig into the research so you know exactly what you're getting into. Read studies, check out testimonials, see what people are advising before you take the plunge.


Yeah, that's an issue...
I have a question, more out of curiosity than anything. When using peptides, is it the case that once you stop, you lose the benefits? Or are the benefits largely maintainable through lifestyle choices? Not sure if you know!

I’ve watched some of Jay Campbell’s videos on YouTube, and the impression I got was:
  • It all sounds very complicated.
  • It’s very expensive, like orders of magnitude more costly per month than regular supplements.
From my limited understanding, the decision to use peptides really comes down to one’s goals. When it comes to optimising physical and mental performance, it seems that unless you have a profession requiring you to be at “peak end” performance (and those individuals often have access to resources that most people don’t e.g. think professional athletes), the goal for most of us normies is simply to feel healthy enough to function well day to day, and to set ourselves up for long-term health.

I’ve been more thinking about these questions from a philosophical perspective as there’s a strong cultural trend toward striving for “peak end” physical and mental performance — but what this means is never clearly defined. The effect, I think, is that it creates an ever-shifting goalpost: something to chase but never fully attain. This raises an interesting question, at least for me, at what point should someone stop chasing the end point?

The best answer I can come up with is that the “end point” isn’t a fixed point, but rather the habits and practices that help one achieve an optimal physical and mental state to meet the demands of daily life, without compromising future health. Naturally, these habits evolve as life and the body change, so the practices in turn must evolve too.

Within that perspective, perhaps peptides make sense.
 
GLP-1 Peptides
As stated in the thread intro post, this should not be treated as a definitive guide. This information represents a summary of what I've gathered on these peptides. Because I'm not an expert in biology or biochemistry, there are no doubt some mistakes here, and corrections are welcome.

GLP-1 agonists are one of the most popular classes of peptide currently being used because they offer fast and effective weight loss. They were originally developed as treatments for type 2 diabetes, later for atherosclerotic cardiovascular disease and obesity, for which they are quite effective. They also reduce food intake and weight significantly which is what has lead to their recent rise in popularity. Some GLP-1 agonists have been approved for the treatment of metabolic syndrome in the absence of diabetes and are in development for treatment of non-alcoholic fatty liver disease, polycystic ovarian syndrome and even some addictions. GLP stands for glucagon-like peptide which is a naturally occurring peptide in the body which is released by the gut after eating. The mechanism of action of GLP-1 peptides is to act on the glucagon-like peptide-1 receptors.

GLP-1 works by acting on receptors in the beta cells in the pancreas and neurons in the brain. This leads to a slowing of gastric emptying making you feel full faster and for longer, an inhibition of the release of glucagon thereby stopping the release of carbohydrate from the liver and inhibiting gluconeogenesis (synthesis of new glucose), and stimulating insulin production thereby improving glucose homeostasis (increasing blood sugar clearance). It emphasizes 'glucose-dependent insulin secretion' meaning that the body only releases insulin when blood sugar is elevated, contributing to postprandial (post-meal) glucose control. It also increases insulin sensitivity meaning less insulin is needed to accomplish the job, directly addressing a modern metabolic plague: insulin resistance. This leads to less overall insulin release and less insulin hanging out in the bloodstream for no good reason which can lead to hypoglycemic episodes as well as all the damage associated with hyperinsulinemia (DNA damage, impaired neuronal function, senescent cell states, among other issues). It basically gets rid of wild insulin spikes and replaces it with a with a precise glucose management system.

GLP-1s have come in 3 different generations:
1st Generation: Semaglutide also known under the branded names Ozempic, Rybelsus and Wegovy
2nd Generation: Tirzepatide also know under the branded names Mounjaro and Zepbound
3rd Generation: Retatrutide

Semaglutide
The first generation of GLP-1s, Semaglutide, is just a GLP-1 agonist, with the above listed effects.

Tirzepatide
Tirzepatide was the second generation GLP-1 peptide, which added a second agonist to the mix: GIP (glucose-dependent insulinotropic polypeptide, aka gastric inhibitory polypeptide). This really elevated the peptide from an appetite suppressant to a very promising metabolic reconditioner. It's a bit confusing since GIP generally promotes fat storage rather than burning, but in combination with GLP-1, the synergy of the two leads to metabolic enhancement, improving insulin sensitivity, supporting healthy fat distribution, and amplifying the central and peripheral effects of GLP-1. The dual agonist peptide:
  • Directs proper fat distribution by enhancing lipid buffering and preventing ectopic fat. It improves the capacity of subcutaneous white adipose tissue to safely store lipids after meals, preventing harmful "spillover" of fats into liver, muscle, and other organs for storage (ectopic fat deposition) thereby reducing lipotoxicity and improving insulin sensitivity. It also keeps the fat from being stored in visceral fat leading to a safer form of fat distribution (visceral fat releases inflammatory molecules directly into the bloodstream and is a risk factor for multiple disease states including heart disease, type II diabetes, hypertension, Crohn's, ankylosing spondylitis, insulin resistance, impaired organ function and even some cancers). This metabolic stabilization reduces insulin resistance and inflammation, creating a more favorable environment for fat mobilization.
  • Central appetite suppression: In pharmacological doses, GIP crosses the blood-brain barrier and acts on hypothalamic neurons to stimulate satiety, complementing GLP-1's appetite suppressing effects.
  • GIP’s optimizing of adipose tissue effects appear to "permit" or enhance the actions of GLP-1 by improving metabolic flexibility (being able to efficiently switch between glucose and fatty acid burning for energy, this switching being something impaired in obesity, metabolic syndrome and type 2 diabetes).
  • Dual agonists significantly raise adiponectin levels — a hormone linked to improved insulin sensitivity and fatty acid oxidation, and glucose uptake in the muscle and liver, further promoting a metabolically healthy adipose phenotype where tissues respond better to insulin and utilize fuels more efficiently.
Retatrutide
The third generation GLP-1 peptide was a real game-changer: Retatrutide. As you probably guessed, they added a third agonist to the mix: glucagon receptor agonist. The addition of this agonist enhances energy expenditure and fat oxidation. It increases thermogenesis (heat production) and lypolysis (fat breakdown), and reduces lipogenesis (new fat creation).

Glucagon tells the liver to stop storing glucose and fat and start burning it for energy. It increases energy expenditure (boosting metabolic rate) and promotes hepatic lipid oxidation, so the liver burns its fat stores for fuel (decreased fatty liver, anyone?). It also activates a gene called PGC-1α, a master regulator of mitochondrial biogenesis, increasing the number of mitochondria in the cells for more energy production. (PGC-1α also plays a key role in regulating energy homeostasis, cellular respiration, fatty acid oxidation, and circadian rhythm). Normally, insulin goes up when you eat, glucagon goes down (they're antagonistic). Glucagon works with glucose homeostasis and rises when in a fasted state to release stored energy. It preferentially looks for the highest density energy source (fat and ketones). So by stimulating glucagon receptors constantly (as someone on Reta would be doing), the body preferentially burns stored fat even when not in a fasted state. It's a constant low-grade action of fat-burning. The overall effect is to raise Basal Metabolic Rate (BMR), despite being in a caloric deficit, and that increased energy expenditure is coming from stored fat, for the most part sparing the muscle.

There have been a few human studies on Reta, but the major Phase-2 trial that is often cited (Jastreboff et al.) showed participants in the highest dose category lost 24% of their body weight over the course of 48 weeks. A substudy (Sanyal et al.) looking at liver steatosis (fatty liver) found "significant reductions in liver fat content at all doses. At the two highest doses, 80% or more of participants achieved ≥70% relative reduction in liver fat and more than 85% achieved resolution of steatosis, defined as <5% total liver fat content." Another study looking at HbA1c in type 2 diabetics found reductions in glycated hemoglobin (HbA1c) levels: "At 24 weeks, least-squares mean changes from baseline in HbA1c with retatrutide were –0.43% for the 0.5 mg group, –1.39% for the 4 mg escalation group, –1.30% for the 4 mg group, –1.99% for the 8 mg slow escalation group, –1.88% for the 8 mg fast escalation group, and –2.02% for the 12 mg escalation group, versus –0.01% for the placebo group and –1.41% for the 1.5 mg dulaglutide group." (Note: dulaglutide is a GLP-1 single receptor agonist like Semaglutide). [quotes taken from Retatrutide—A Game Changer in Obesity Pharmacotherapy, see references]

A recent study (Coskun et al.) looked at body composition on subjects on different doses by doing before and after DXA scans and found some muscle-loss in a dose dependent fashion (the higher the dose the more muscle loss). But the researchers concluded that even the highest amount of muscle loss was not outside the normal range for people undergoing rapid weight-loss. It's hard to know if any of the participants were doing any resistance training or what their diets were like (anecdotal reports by Retatrutide users say they can fairly easily mitigate any muscle loss through engaging in resistance training and keeping protein consumption high).

Interestingly, as the next generations of GLP-1s superseded the previous, the amount of appetite suppression has actually decreased (possibly due to the fact that the percentage of GLP-1 in any given dose is decreased compared to precursors). Some report barely being able to eat on Semaglutide, whereas on Retatrutide it's generally reported that you still want to eat at mealtimes, you just want less. Although people still call Reta an appetite suppressant, this effect is fairly minor and unlikely to be the primary mechanism of action, in my opinion. It seems more appropriate to call it a metabolic optimization peptide, or something along those lines. Similarly, the gatrointestinal side effects seem to be less severe with Reta as opposed to the previous iterations, although they're not entirely absent and individual experiences will vary.

My Experience
My own experience with Reta is that I have lost about 9kg in 10 weeks. The beginning was a bit rocky in trying to figure out the right dose (everyone is different when it comes to dosage and it has nothing to do with body weight or other factors you can predict) and also the right dosing strategy (I have now forgone the 'microdosing' advice many influencers promote and am doing the once weekly dosing, as it's done in the studies. My experience has improved substantially since making this change). I had reflux in the beginning, but was able to mitigate it using betaine HCl. A number of people report nausea, which I haven't experienced, but if I ever do overeat it's very uncomfortable. I still struggle with constipation due to the slowed down gastric motility but I am using different things to mitigate it.

As a person who has struggled with weight all my life, with nothing ever putting much of a dent in it, Retatrutide really seems like a godsend. It's not just a vanity thing (although I'm not above that, LOL) but an overall health thing. I've had issues with fatty liver in the past and we all know how carrying extra fat is associate with multiple disease risks. I was also diagnosed with severe sleep apnea earlier this year and have been sleeping with a CPAP machine since (obesity is directly implicated sleep apnea).

That said, it's still early days. Changing over to a weekly dosing strategy has meant kind of starting from scratch in figuring out the right dose, so I'm still titrating up, assessing and titrating up again. I anticipate reaching a stable dose at one point, but I'm happy with the progress so far. Since starting Retatrutide, the Apnea-Hypopnea Index (AHI) scores on my CPAP machine are consistently lower on a nightly basis, meaning I'm having fewer apnea events over the course of the night and undoubtedly sleeping better. The scores I'm getting at this point are consistent with someone who doesn't need to be treated (fewer than 5 events per hour, which is considered normal). I've also noticed improvements in my tolerance of exercise, getting less "gassed" during high-intensity exercise; although there's still room for improvement on this front.

So I'm optimistically continuing the experiment.

Studies
 
I have a question, more out of curiosity than anything. When using peptides, is it the case that once you stop, you lose the benefits? Or are the benefits largely maintainable through lifestyle choices? Not sure if you know!

I’ve watched some of Jay Campbell’s videos on YouTube, and the impression I got was:
  • It all sounds very complicated.
  • It’s very expensive, like orders of magnitude more costly per month than regular supplements.
From my limited understanding, the decision to use peptides really comes down to one’s goals. When it comes to optimising physical and mental performance, it seems that unless you have a profession requiring you to be at “peak end” performance (and those individuals often have access to resources that most people don’t e.g. think professional athletes), the goal for most of us normies is simply to feel healthy enough to function well day to day, and to set ourselves up for long-term health.

I’ve been more thinking about these questions from a philosophical perspective as there’s a strong cultural trend toward striving for “peak end” physical and mental performance — but what this means is never clearly defined. The effect, I think, is that it creates an ever-shifting goalpost: something to chase but never fully attain. This raises an interesting question, at least for me, at what point should someone stop chasing the end point?

The best answer I can come up with is that the “end point” isn’t a fixed point, but rather the habits and practices that help one achieve an optimal physical and mental state to meet the demands of daily life, without compromising future health. Naturally, these habits evolve as life and the body change, so the practices in turn must evolve too.

Within that perspective, perhaps peptides make sense.
Rich people's problems that simply don't matter to people of my class (middle class with debts).:-D
 

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