As a diabetic, you’re in a situation where your body is struggling to add kindling to its own furnace. You’re taking in food, which is then broken down into its molecular composites (lipids, sugars, proteins), but is not being efficiently or even correctly appropriated to support your body’s functioning. This is why the unmanaged progression of diabetes mellitus can eventually lead to the deterioration of entire bodily systems (cardiovascular, nervous) and result in major complications like kidney failure, nerve damage, and stroke.

When your doctor prescribes you a GLP-1 like Ozempic (semaglutide), you’re being given a peptide — a complex chain of amino acids — that will function similarly to natural hormones released in the gut directly after we eat. The GLP-1’s effect on the system is fourfold: 1) it triggers the release of insulin from the pancreas so that the recently eaten food can be transformed into cellular energy; 2) it signals for the inhibition of glucagon, which is a blood sugar-raising hormone that counter-regulates the effects of insulin when blood sugar drops too low; 3) it slows stomach emptying, to keep you feeling fuller longer; 4) it sends satiety signals to the Hypothalamic-Pituitary-Adrenal (HPA) axis of your brain, which reduce cravings — aka “food noise.”

The GLP-1 will facilitate bio-regulatory changes in your system that have well known positive effects for diabetics. The peptide will support your pancreas in the manufacture of insulin, which will result in regulated blood sugar, efficient glucose absorption, and vastly reduced risk of cardiovascular or nervous system failure, as well as other complications of diabetes mellitus. Because you are feeling fuller and sated for longer, you will eat less and crave fewer high-sugar and high-fat foods: this will lead to weight loss, which has been demonstrated to improve the prognosis for diabetes patients across the board.

This may sound all well and good — and if you’ve been prescribed a GLP-1 for diabetes, you’re certainly allowed to feel that way — but it’s extremely important that you avoid falling into the trap our diet-forward culture has laid when it comes to just about any weight loss protocol.

We at Peptide Partners believe in the responsible, safe, and scientifically sound application of peptide-based health and longevity protocols.

For the diabetic and pre-diabetic — and really for anyone interested in peptide-based treatments for weight loss — this means the following: you cannot treat GLP-1 therapy like a crash diet.

If you want to inject GLP-1s with the goal of suppressing your appetite and losing as much weight as possible as quickly as possible, you certainly can — but that will not be conducive to managing your diabetes. Nor is it what any medical doctor with a competent grasp of the delicate relationships among the endocrine, digestive, cardiovascular, and nervous systems would recommend.

Diabetes is an autoimmune disease, which is a type of disease that results from the body attacking its own healthy tissue, thus impairing its own function. This means that there is no foreign pathogen the body is trying to purge: the disease is simply the result of an overactive immune system. The diabetic body’s autoimmune response happens to be an impairment of pancreatic function.

So, how to mitigate a faulty immune response? The answer does not lie in weight loss alone. Instead of taking the GLP-1 and then starving the body of nutrients — i.e. conveniently forgetting to eat — consider what you could eat that will keep you fuller and more energized for longer.

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Think about it: if the semaglutide is increasing the glucose absorption from your bloodstream and sending simultaneous messages to your HPA axis to reduce hunger cues — that would be the “food noise” — then it’s up to you to eat mindfully enough so that you don’t experience a dip in blood sugar, otherwise known as hypoglycemia. Why is this important? If the amount of sugar in your blood gets too low, counter-regulatory hormone glucagon will take effect. That means the inhibition of insulin (something your body already struggles to produce), the powerful signal of hunger cue hormones like ghrelin to summon more food into your system, and the consequent buildup of more blood glucose.

Perhaps you’ve had the experience of trying to regulate your blood sugar and swinging from hyperglycemia to hypoglycemia in the span of a single day. This is not conducive to the long-term treatment of diabetes, and that’s probably easy to recognize when you’re looking at your blood sugar reading or your glucose pump and feeling exhausted by these challenging fluctuations in your body’s chemistry.

But that’s just the thing: successful management of diabetes is all about reducing fluctuations in your blood sugar. This means that no matter what, you need to eat. And maybe now that the GLP-1 has helped reduce your cravings and allowed you to feel sated for longer, those dietary choices will look different. No more skipping breakfast only to correct the resultant blood sugar drop with a high-sugar snack in the early afternoon. Instead, what about eating oatmeal with fruit and yogurt for breakfast, followed by a turkey sandwich on rye and seaweed salad for lunch? What about ensuring that you meet your ideal caloric intake for the day — 1,600 to 2,400 calories for women; 2,000 to 3,000 for men — but by eating food that actually helps the GLP-1 help your body instead of sending your system into a state of starvation for which it will eventually overcorrect?

This is why it’s important to recognize GLP-1s as valuable tools to help you make positive lifestyle changes instead of cure-all silver bullets. Recall that many of the complex amino chains we now know as consumer peptides also occur naturally in the body. The body wants to eat, and it should. All these interventions are designed to help the body’s long-term functioning by mimicking or facilitating chemical reactions, not derailing them.

Sometimes you actually do need to listen to the food noise.

Can you think of any part of a COA more enthusiastically discussed than the test results for a given peptide’s purity?

Take a look at online forum chatter about a suspicious lab or a bunk batch. You’d think these comments were written by a ‘roided-out James Joyce or an Ozempic-faced Virginia Woolf:

COA’s got peaks all over the place, man, basically sprinkled with homeopathic fairy dust. Endotoxin city, bought it at TrashTier so yeah got what I paid for. Batch is bunk, straight-up garbage peptides, COA’s copypasta from last year lmao how did u miss this. Bathtub brew. Back-alley synthesis. Play stupid games, win stupid prizes. COA says 99%, your body says copium. It’s like endotoxin soup. It’s like endotoxin chowder, man who knows what’s floating in there. Random mystery powder, amino acid daisy chain, no way that’s legit, terrible separation on the HPLC…

I could go on, but I’m sure you get the point. When it comes to assessing the quality of a given batch of research peptides, purity is the foremost criterion on the COA, the one that everyone pays attention to – and arguably, the one that inspires the most fear among a given lab’s clientele.

To be clear, these fears aren’t exactly unfounded. If that deconstituted powder in the vial is going to have any sort of experimental contact with a biologic system (or systems), it’s certainly worth knowing that the powder is the same thing that its label purports it to be. But as with so much online discourse, the real truth lies in the nuance.

We’ve reported this before here at Peptide Partners Corner: a high purity rating on a given batch of peptides isn’t everything. It’s crucial to understand that popular purity screenings like High-Performance Liquid Chromatography (HPLC) and mass spectrometry are fundamentally incapable of screening for endotoxins:

Chapter 85 of the United States Pharmacopeia (USP 85) specifies the mandatory testing protocol for bacterial endotoxins in pharmacological substances, none of which are HPLC and mass spectrometry. So the wordy, dissatisfied research chem customers are altogether wrong to think that a given sketchy lab’s falsified COA could meaningfully reflect the presence of endotoxins in their peptides. (Though they wouldn’t be wrong to infer that a lab producing impure peptides would more than likely lag behind on its sanitation and endotoxin screening as well.)

So what are purity tests actually measuring? If you’re a loyal reader of our Substack, you’ll probably remember this article that broke down the parts of a viable COA. Put simply, your average purity test runs a chemical ID on a given batch of peptides to determine the mass amount of the substance matching that ID.

Let’s say that I’m a vendor, and I tell you I’m going to sell you a 3ml vial of retatrutide with an alleged potency of 20mg/ml. Perhaps you’re suspicious of me, so you decide to send it off to a lab for independent testing. The lab runs a test on my retatrutide that confirms your fears: though the vial appears full when reconstituted, there’s only 30mg-worth of material in it that matches the chemical ID for retatrutide. The rest is just unknown filler. This means not only that my retatrutide’s potency is just 10mg/ml as opposed to the 20mg/ml I claimed, but that it’s mixed with substances of unknown origin. In other words: it’s weak and impure, but we don’t know exactly what’s making it that way unless we add more chemical ID determinants to our test.

More on the necessity of independent verification:

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So what’s the science behind HPLC and mass spectrometry? There’s a whole lot of pressurization, ionization, high-tech measurement of molecular speed, and in some cases, high-tech measurement of molecular UV absorption. But unpacking the chemistry of these processes is the remit of lab scientists. What we’re concerned with here is understanding why consumers so afraid of purchasing bunk or impure peptides continue to swallow misinformation and overlook questionable COAs while continuing to purchase bunk and impure peptides in daunting quantities.

(Amino) Chain of Fools

The rapidly expanding peptidesphere contains very few players with solid backgrounds in analytical chemistry. Thousands of words of this very Substack have been dedicated to elucidating how someone like the gym bro influencer with the “triple stack” of retatrutide can exert the sort of social pressure that inadvertently derails legitimate scientific progress.

Now, let’s go ahead and consider that very example step by step. Say a well-known gymfluencer with an illustrious bodybuilding career and a massive fan base receives what amounts to a sponsorship deal from a notoriously untrustworthy vendor looking to launder its reputation by purchasing social media legitimacy.1 The resulting chain of events is predictable, but no less invidious:

• The influencer tells his 2 million followers to buy large amounts of untested retatrutide from a vendor that recycles shoddy COAs but is happy to pay influencers handsome commissions.

• The influencer’s followers buy the influencer’s Clinically Proven™ TripleStackReta in droves, inject it, and become ill from bacterial endotoxins that the vendor never bothered to test for.

• ERs across the country are flooded with young men experiencing flu-like symptoms from the endotoxins in the TripleStackReta. A few unlucky customers have severe inflammatory responses that necessitate hospitalization, and these make the news.

• The news stories travel from local outlets to major networks and ultimately gain purchase on social media. A headline like COULD THE PEPTIDE BOOM BE THE NEXT PUBLIC HEALTH CRISIS? appears in the New York Times.

• RFK Jr. gives a cryptic press conference decrying the FDA for “suppressing peptide research” while announcing that he (and, of course, the FDA) will be going after the “exploiters of human need” currently furnishing the grey market with untested research chemicals.

• The outcome: several vendors spanning the range of integrity from dubious to trustworthy get slapped on the wrist or raided by the FDA; scientific grant money for peptide research gets slashed, with pro forma austerity reasoning cited; corporate monopolies on certain compounds tighten (e.g. semaglutide/Ozempic and tirzepatide/Zepbound); longevity-enhancing experimental peptide protocols continue to be enjoyed by the ultra-rich and no one else.

As you can see, impulse-purchasing “research-use only” peptides from a vendor without the faintest understanding of what real scientific research is can have a profoundly negative impact on the actual work being done in the fields of chemistry and biogerontology to understand the powerful healing properties of peptides and make them safe and accessible to people who might stand to benefit from them.

It doesn’t matter if the gymfluencer has millions of followers, if he’s best friends with Andrew Huberman or can bench 280. If he’s promoting bunk peptides through a bad vendor, he’s forestalling scientific progress. And you’re doing the same if you buy them from him.

Recognizing Trustworthiness

How to know who to trust in the peptide world? It’s one thing to search for vendors – or even journalists and commentators – who demonstrate a modicum of interest in the actual science behind peptides (as opposed to their cosmetic benefits). But nowadays even scientific expertise can be convincingly faked (hello ChatGPT).

So where to find the real experts? Take a look in the margins: the quote-tweets and restacks correcting the lazy, garbled half-truths of would-be science writers.

Here we see an analytical chemist correcting the half-truths of a member of the peptide world’s online commentariat.2 What appears at first glance to be an intelligent article about endotoxin measurement in peptide samples is in fact riddled with inaccuracies.

“All of these [allegedly invalid] results can be valid, acceptable, actionable, and generated using validated quantitative methods,” the TrustPointe chemist writes, and goes on to offer a helpful breakdown of the detection and quantification of endotoxins in samples using endotoxin units (EU).

Had I simply taken the prior tweet at face value without bothering to read the chemist’s quote-retweet, I would never have learned about Limit of Quantification and Limit of Detection, valuable principles in understanding how analytic chemists screen for endotoxins, and how those screenings translate to the quantitative results I encounter on my peptides’ COA.

Continuing to use X like an ad hoc STEM research library, I may decide to learn a bit more about the vendors TrustPointe is working with. Take a look at the below from our very own Peptide Partners:

This fact-checking chemist does a comprehensive metals test for a vendor that’s willing to prioritize safety in a commercial space where “speed” is the watchword and convenience is prioritized at all costs. And furthermore, this vendor is willing to go the extra mile and pay two separate labs for heavy metal and endotoxin screenings that deliver a picture of a given peptide batch far fuller than “here’s the mass amount of peptide X in your vial, enjoy.”

This isn’t just immaculate quantitative analysis, as any member of Gen Z would say. It’s also real, bankable trustworthiness, the kind that makes a vendor’s name among its competitors. Prioritization of safety, compliance with regulatory guidance and oversight, and a rigorous understanding of the scientific backbone of the COA all make for a healthy peptide practice.

Hold research chemical vendors to the same standard you’d hold the research scientists who design those compounds. Because at the end of the day, the human body is a highly reactive organism deserving of more care than mega-profiteers are willing to provide it. None of us needs an advanced degree in chemistry to recognize that.

Picture this: you are a family practice physician performing a routine health exam for a patient. Let’s say you’ve known this patient for something like twenty years, serving as the primary care doctor for both her and her husband. When they’ve required specialized care, you’ve referred both of them both out to specialists within your professional networks. Their children’s pediatrician is a colleague of yours who works in the same building.

Suffice to say, you know this patient well. Even have an easygoing rapport with her. You also know that she has a history of disordered eating. She has a DSM diagnosis of anorexia nervosa, for which she received once as an adolescent and again in her early thirties. These flare-ups were both occasioned by periods of high stress (going to college in the first case, and giving birth to her first child in the second) and accompanied by worsening symptoms of Generalized Anxiety Disorder and Major Depressive Disorder. Fortunately, your patient was able to navigate these difficult periods with the help of a psychotherapist and psychiatrist. Now she’s in her early forties, and her anorexia appears to be in complete remission, along with her other psychiatric symptoms.

But when this patient enters your office, you know something’s amiss. Her expression bears the hallmarks of her old generalized anxiety: her eyes dart, and she has trouble holding eye contact with you. Most tellingly, you notice a significant decrease in body mass. The weigh in confirms it: she’s lost twenty-five pounds since you last saw her six months ago.

Given the patient’s history of disordered eating and other psychiatric comorbidities, you become concerned that she’s experiencing a resurgence of behavioral health issues, possibly related to a new stress in your life. And sure enough, it comes up in conversation as the two of you review her recent health history. There’s been a death in her extended family, a high-stress event that resulted in feelings of despondency, fear, and inadequacy. As a result, she’d gained weight in excess of what constitutes a healthy BMI — a development that has only redoubled her behavioral health symptoms, and reintroduced the possibility of “control” via food restriction.

“Things were feeling hard, and I knew I didn’t want to fall back into my old restriction patterns,” she tells you. “I knew I needed to make a real change. And then I saw an ad online.”

The ad she saw was for a local med spa, offering “revolutionary fat-burning protocols.” The protocol? Non-FDA approved retatrutide, injected at 2mg/weekly over the course of six weeks. Your patient was initially thrilled with her weight loss progress, but now she’s worried: she couldn’t afford the $100/week injections indefinitely, and doesn’t want to finagle herself a prescription from a compounding pharmacy online. She’s wondering if you’d be willing to resume this protocol with her?

“It’s really changed my life,” she says hopefully.

As this patient’s long-term provider, you are now presented with a choice:

1. Find a way to move forward with this peptide-based weight-loss protocol (albeit in a way that’s better suited to your patient’s needs and approved by the FDA and her insurance)

2. Deny your patient’s requests on the grounds that she obtained the retatrutide from a medical spa, and that it could interfere with the treatment plan for her behavioral health.

Both options have their benefits and risks. The first choice allows you to maintain the patient’s trust by listening to her (“It’s really changed my life”) and offering her personalized care that will be safer and more scientifically rigorous than the injections she was receiving at the med spa. The patient has always struggled with her weight — a major contributing factor to the emergence of her adolescent anorexia — and has at a few points in her recovery exhibited bloodwork that indicated pre-diabetes. Given that certain peptides like semaglutide and tirzepatide have proven to be incredibly effective in the realm of weight management for Type II diabetes, there’s a compelling case to be made for a continuation of this protocol. Provided her insurance approves of the treatment, you might have found a way to regulate her health and curtail a major trigger of her eating disorder.

The second choice feels riskier in that you’re jeopardizing your patient’s trust by appearing to dismiss her testimony. But it has the major clinical advantage of slowing down the process to gather more information before initiating an intervention that may or may not be necessary: i.e. doing no harm, a central tenet of your Hippocratic oath. You may say, “I’m not going to prescribe you this today, because I want to get more information from you,” and then interview the patient about the protocol. She may have benefited from an initial burst of weight loss, but what else has she been doing to sustain her physical and mental health? Has she experienced any other symptoms from the retatrutide, physical or mental? Because you have a long history with her, you might even dip into that well of accumulated trust and let her know that you noticed she seemed anxious when she walked into her appointment with you.

These choices are difficult ones, and the answers are never completely clear. As a clinician, you are contending with an oversaturated alternative health marketplace, the limitations of both your practice and your patients’ insurance, and the very real time limitations of your patients’ appointments. Given the way our healthcare system is structured, it can feel more like you’re providing revolving-door consumer service than the personalized medical treatment you trained for. Even so, finding ways to provide your patients with that well-considered, personalized treatment — wherever you can, and however you can — should always be the goal.

In this upcoming series on peptides in clinical settings, we’ll discuss the realities of being a medical provider during the peptide boom and how to balance exciting advancements in longevity research with your clinical responsibilities and your patients’ needs. In the coming weeks, you’ll hear from actual patients who’ve benefited from peptide therapies as well as those who haven’t. And if you’d like to comment with your own thoughts on peptide therapeutics in a clinical setting, we’d love to hear what you have to say!

Peptides are here to stay in the medical field, and that’s not at all a bad thing. But as with any scientific advancement in the healthcare realm, we have to ensure that persuasion doesn’t outstrip the science. Ask yourself: What does the medical research need? What do medical patients need? And proceed from there.

Further reading:

For as long as we frail little mortals have walked the Earth, we’ve been wondering how to extend our fleeting lease on life. Life – with its known quantities, its predictable realities, its measurable data – has always felt safer than death, which represents not only the erasure of all that, but a total vanquishing of the self to boot!

Efforts to extend the human lifespan began long before biohacking, health optimization, or the very concept of the scientific method. In the 1200 BCE Epic of Gilgamesh, King Gilgamesh himself undertakes a massive journey in search of the secret of eternal life. In Daoist China, herbal teas, breathwork, and a study of the body’s alchemical makeup – now popularly referred to as “Chinese Medicine” – were employed with the intention of extending patients’ lifespans.

Stories of a Fountain of Youth with restorative waters cropped up in the writings of Herodotus and Christian patriarch Prester John. Spanish conquistador Juan Ponce de León traveled to North America in search of the fountain, which was rumored to be located in a mythical land called “Bimini.” From ancient Mesopotamia to the pre-modern Islamic world to medieval Europe, an immortality-granting “elixir of life” was sought by clerics, caliphs, and alchemists.

In the 18th century, the Enlightenment released a tidal wave of rationalism across Europe that would eventually result in the dawning of the scientific age. Mythic journeys and alchemical elixirs were replaced with a focus on public health. French chemist Louis Pasteur (among others) popularized the idea of germ theory, that foreign pathogens cause illness and health is the state of being pathogen-free. In the 19th century, major cities like London, Paris, and New York underwent massive improvements to their water purification and sanitation systems. Vaccines and antibiotics were introduced.

All of these efforts served to increase life expectancy dramatically, but did nothing to solve one of the greatest bugbears of the human experience: aging. The lifespan could be extended, but the body’s wellness and vitality could not.

Perhaps you’re wondering: How do peptides figure into all this? Rest assured, there’s more in store for you here than a mildly interesting history lesson.

If your interest in complex amino chain health protocols could be traced back to a single medical phenomenon, it would be the development of the field of gerontology.

Commonly understood as the study of aging, gerontology first emerged in 1935, when Clive McCay and his colleagues at Cornell University first discovered that caloric restriction in mice could extend their lifespan by as much as 30-40 percent. McCay et al.’s findings would be underscored some thirty years later by anatomist Leonard Hayflick, who discovered that there’s a maximum number of times a normal human cell population can divide in a culture before it stops altogether, leading to cellular senescence. The discovery of this maximum number – referred to as the “Hayflick limit” – would go on to revolutionize the study of aging and the field of gerontology with it.

In the mid-1950s, the American gerontologist Denham Harman advanced the free radical theory of aging. Harman’s theory stipulates that the human body ages because of something called “oxidative damage,” caused by free radicals that impair the functioning of DNA, lipids, and proteins. In other words, oxidative stress basically looks like the slow degradation of a cell over time, strain followed by the steady impossibility of recovery.

For those of you familiar with how Human Growth Hormone stimulates protein synthesis, which then contributes to cell repair, this will no doubt ring a bell. Now we’ve arrived at one of the foremost building blocks of the broader longevity movement: reverse-aging the already-senesced.

Ponce de León never found that elusive Fountain of Youth – his sixteenth century expedition landed in what we now call Florida. And while the search for an immortality-granting elixir of life remained on permanent hiatus, the field of gerontology underwent a major commercial boom during the second half of the twentieth century.

Hormone therapies emerged to mitigate the effects of menopause in women and adrenopause in men. Endocrinologist-cum-gerontologist Harry Benjamin found a way to expand his hormone replacement therapy (HRT) practice to include a demographic that was itself rapidly expanding, even in the mid-twentieth century: male-to-female transsexuals. By prescribing these patients the estrogen typically prescribed to natal females in menopause, Benjamin induced a cosmetic change in sex. One of his transsexual patients reported him musing: “If we cannot alter the conviction to fit the body, should we not, in certain circumstances, alter the body to fit the conviction?”

Benjamin’s legacy would amount to reshaping gerontology as a field concerned not just with the science of senescence, but with its aesthetics. As the twentieth century sprinted to a close, American athletes and bodybuilders embraced the performance-enhancing effects of testosterone and HGH. The health-conscious sought antioxidant supplements like vitamin E and resveratrol to reduce oxidative stress. The American Academy of Anti-Aging Medicine was founded in 1992, much to the chagrin of a broader gerontologic community who dismissed its leadership as uncredentialed and its methods as “quackery.”

In the new millennium, gerontology would undergo a set of revolutionizing advancements. First, the discovery of the mTOR (or mechanistic target of rapamycin) pathway, a “master regulator” enzyme that controls major cellular processes like growth, motility, proliferation, survival, transcription, and protein synthesis. Then, the discovery of another enzyme family called sirtuins, which work with coenzyme NAD+ to regulate cellular health, metabolism, and stress resistance. Discoveries like these were enough to cause leading scientists to characterize aging as a “disease” that can be medically treated like any other.

Maybe you had a moment of recognition when you read the word “enzyme.” If you’re as into peptide science as we are at Peptide Partners, then you’ll recognize enzymes as a specific category of protein that facilitate necessary biochemical reactions like digestion, metabolism, and DNA replication. When such reactions happen with frequency and efficiency, the human body is often felt and observed to be “well” or vital.

As we know, all peptides are proteins (i.e. linked chains of amino acids), but not all proteins are peptides. Peptides are conventionally understood to be shorter chains of amino acids, typically 50 or less1, that lack the larger and less stable 3D structures of bigger proteins. Enzymes are quite large, ranging in length from 62 amino acids to over 2,500. They help maintain the health and structure of peptides, which in turn act directly on the systems of the body.

Recall the longevity scientists who determined that caloric restriction could increase the lifespans of mice in the 1930s. GLP-1 agonists like semaglutide and tirzepatide mimic the GLP-1 blood sugar hormone to improve blood sugar control and reduce appetite; this is precisely why they are so effective in the treatment of type 2 diabetes, which is pancreatic insulin resistance often resulting from excessive caloric intake.

And then there are peptides like BPC-157 and Thymosin Beta-4, both of which aid in tissue repair, anti-inflammation, and blood vessel growth. Whether organic or synthesized, both facilitate cellular recovery in ways that would appear to reverse-senesce the cell, and thus enhance longevity in the body.

But before we get too far ahead of ourselves, let’s return to the earlier days of gerontology and anti-aging science. Recall how Harry Benjamin introduced HRT to a new population – one ostensibly more concerned with the cosmetic effects of anti-aging endocrinology (and thus their psychological benefits) than longevity alone.

As it turns out, it’s pretty hard to separate the desire to live longer from the desire to look as if we’re living longer. It’s all too human, after all: even if it doesn’t have a genotype, wellness certainly has a phenotype, and our evolutionary instinct is forever driving us towards the appearance of physical fitness.

Perfectly understandable, but it still begs the question: when does an investment in cosmetic “fitness” overtake or potentially jeopardize an investment in real, biological health? Harry Benjamin’s case is an excellent example: HRT is an endocrine health longevity treatment for a woman receiving estrogen and a psychological health longevity treatment for a man receiving estrogen, with the reasoning that the cosmetic changes will effect better psychological health, and thus a longer lifespan, in the gender-distressed patient.

But what about the long-term consequences of taking estrogen and testosterone? Or, for that matter, getting a deep plane facelift, injecting HGH bought at the gym, or taking high doses of melanotan? These interventions are bound to yield physical changes, which could result in positive psychological changes – but do these boosts in mood come at the expense of bona fide bodily longevity?

Take Bryan Johnson, the tech centimillionaire whose mission to “not die” is as inscrutable as his methods. Johnson is striving for immortality – or something close to it – through a $2 million per year health protocol that includes everything from nightly infrared therapy to electromagnetically stimulating the muscles of his abdominal floor to blood transfusions and experimental stem cell treatments. Johnson suffered a dangerous allergic reaction to fat injections in his face (undertaken to “restore lost volume”), and a series of infections due to the immunosuppressive effects of his experimental rapamycin protocol. While some of his interventions could very well prove beneficial to experimental gerontology and the longevity movement more broadly, missteps like these suggest that Johnson’s mission may be just as motivated by fear and vanity as by a desire to explore new frontiers in anti-aging science.

For those of us who value empirical data and legitimate advancements in medical research, longevity is an uneven field. How to separate the quacks from the scientists? The life-sustaining interventions from the cosmetic ones? When does the life-sustaining become cosmetic – and vice versa?

As with many questions in the realm of bioethics, there are no clear answers. Only one thing remains for certain: scientific research can do as much for your peptides as your peptides can do for you. Research chemicals are powerful, but they’re not cure-alls. Looksmaxxing is, regrettably, not the same as lifemaxxing.

The Curious Case of the L-Carnitine in the COA

Did you know that when it comes to strength-building, biohacking, and body optimization, peptides as we know them today were not the first of their kind?

There was a world that predated the gray-market peptide world as we know it today: the world of bodybuilding. You can call it what you’d like – the meathead scene, endurance and performance enhancement, getting shredded at the gym – but you’d be describing a Venn diagram with a wide surface area of overlap. Male athletes have historically taken substances such as testosterone, dianabol, and Human Growth Hormone (HGH) in order to build their physiques, increase their endurance, and heal faster after injuries. This is a practice that more or less began in the 50s, intensified during the Cold War (staying competitive with the USSR became an imperative for American athletes), and was met with a good deal of fear and moral panic from the 70s-90s only to intensify once again at the turn of the century.

However you might feel about the phenomenon of “doping” in athletics – whether by professional athletes or non-professional ones – there’s no contesting its prevalence, nor its influence on popular culture. What began in the gym scene, discussed on encrypted forums and purchased through illegal back channels, seems to have “jumped the walls” of the gym and become so widespread that it’s now scrawled across countless affiliate pages on social media, talked about on the news, discussed among members of the scientific research community, and touted on podcasts. Body optimization isn’t just for bodybuilders anymore: as we’ve seen countless times before, average Americans will show an active interest in cutting-edge health treatments, regardless of their price point – or their seeming outlandishness.

Luckily for average Americans, the medical industrial complex is more than willing to step right up and meet that interest. As I’ve recently reported here at Peptide Partners Corner, a series of powerful biological, medical, and sociocultural forces have joined hands to make it more possible than ever to directly purchase heretofore inaccessible healthcare treatments and have them delivered to your doorstep.

Peptide Partners Corner

Telehealth, Ease of Access, and the Medical Consumer Boom

This is part two of a multi-part investigative series. Read part one here…

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3 months ago · 7 likes · Peptide Reporter

The biological? None other than the global pandemic that shut the entire world down and called for a large-scale overhaul of our country’s rapidly deteriorating healthcare system. In order to accommodate the CDC’s shelter in place guidelines, medical practitioners had to embrace telehealth on a scale we’d never seen before. This was great news for the disabled, the low-income, and those whose physical access to healthcare was otherwise impeded by bureaucracy or geographic remoteness. It was also great news for profiteers who saw the pandemic as a chance to expand their clientele: If I can’t physically examine you for this experimental treatment but I can get your verbal consent over Zoom, then I can book you for it anyway and charge $1,999 – sound good?

The medical? Even with stop-and-go funding and FDA strictures, research science still tends to move quicker than the healthcare system can accommodate it. The result: studies will surface indicating the radical benefits of treatments that are either not FDA-approved or not widely available. People with stubborn health problems will get wind of these studies and become set on trying them; soon enough, demand will far outstrip supply, and the prescribing doctor will be supplanted by the alternative health practitioner, the med spa nurse, the compounding pharmacy.

The sociocultural? It’s a biohacker’s world, and we’re either along for the ride or opting out – a move that’s beginning to look more and more like opting out of society altogether. Rapid advancements in the medical research, wellness, and longevity spaces mean that we no longer have to settle for a definition of health that means little more than “the absence of disease.” Now, consistent with the original definition of wellness as a state of holistic health or “vitality,” we have the tools to focus on optimizing our health instead of just maintaining it. The positive side of this looks like scientific findings and lifestyle changes joining forces to deliver more and more people a much higher quality of life. The negative side looks like countless people striving and striving for perfection, putting their bodies – and pocketbooks – through the ringer only to find that they’re perpetually one “magic treatment” away from finding their silver bullet.

Which brings us back to peptides and the bodybuilding community. It doesn’t take a rocket scientist to see that strength and endurance training is all about optimization. How many reps can I manage in an hour? How much can I shorten my recovery time? How can I maximize the amount I’m lifting while minimizing the likelihood of injury? Any pro athlete is no doubt accustomed to treating their body like a Turing machine, inputting the right “stack” of rest, training, and nutrition in hopes of maximizing output; the bodybuilder is doing the same thing, except instead of training at an elite facility in the Swiss Alps with a team of coaches, he’s driving his Mitsubishi to the gym, blasting his lats, and then reading online forums about nutritional supplements and recovery times.

Though average by an Olympian’s standards, the bodybuilder still strives for excellence, and he talks to his friends at the gym about it, who talk to their friends about it, who talk to their girlfriends about it, and so on. Standards for physical fitness and physical beauty are swapped or equated. Health becomes nothing but vitality, and vitality becomes a moral imperative.

Having said all this, I’ve now set the scene for the story of erstwhile online peptide retailer Amino Asylum and one of the most notorious COA-related scandals of recent years. Depending on who you are – customer, Redditor, lab technician, federal agent – the story is either infuriating, tragic, exasperating, or routine. It’s also a story without a neat resolution, as the only player in possession of all the details – Amino Asylum founder Austin Carpenter – passed away in 2024 at the age of 32. It’s also a story, like the broader narrative of peptide use in the U.S., that began in the gym only to end someplace else entirely.

Inside the Asylum

Amino Asylum emerged on bodybuilding and biohacking scenes around 2018, just barely predating the beginning of the global pandemic. It was an online vendor selling peptides, Selective Androgen Receptor Modulators (SARMs), and various other injectable wellness and longevity supplements within the RUO – or “research use only” – commercial framework.

The founder, Austin Carpenter, was a millennial man whose professional credentials belonged more to the world of sports medicine and kinesiology than that of tech and bio-optimization. He was a 2017 graduate of James Madison University, where he earned a B.S. in Kinesiology and Exercise Science. He worked for a time as a personal trainer and security guard before founding Amino Asylum, making his shift into the peptide scene that much less surprising: if you’re already spending your time helping individual clients optimize their strength and endurance, why not set up shop and cast your net wider?

As it turned out, Carpenter was in the right place at the right time. With some customer service savvy, a reputation for trustworthiness, and a dash of business acumen, he was able to effectively scale Amino Asylum during the peptide boom of 2021-2023. The Asylum became a go-to peptide vendor for the fitness and bodybuilding communities. And then, thanks to the modern miracles of Reddit and Discord, Carpenter’s business achieved breakthrough status.

As more and more Americans assessed the ravages of the pandemic, the slow-moving stutters of governmental bureaucracy, and the ever-widening wealth gap, interest in alternative treatments exploded. And as ours is a culture that prizes innovation and experimentation, not to mention being hyper-connected and communicative all of the time, people were as keen to get their health information from bodybuilders and high-performance athletes as from a primary care physician. Add to this heady brew the fact that the primary care physician was just as likely supplementing their health information with findings from the exercise/kinesiology space, and you’re off to the races.

It was a good time to be Mr. Carpenter; indeed, it was a good time to be one of Mr. Carpenter’s customers. Unfortunately, this heyday would also be short-lived.

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The Fall

I have no doubt there are those of you reading this who will recall that Amino Asylum was recently shut down by the FDA. For some loyal customers, this may have come as a shock. But for many others, the writing had been on the wall for a long time.

When Amino Asylum burst onto the scene, the company paid lip service to FDA strictures on its website – “research use only” – while presenting itself quite differently on social media. Flashy posts about muscle building, libido improvement and fat loss. Affiliates crowing about the same. Whatever expertise Carpenter might have brought to the table in terms of kinesiology and health science was veritably invisible. And forget about research science, FDA guidance and oversight, or the critical symbiosis between advancements in healthcare and raising public consciousness with regards to wellness and longevity. What does empirical science matter when your customer base is growing exponentially?

Amino Asylum was making sales hand over fist, but doing so with the internet equivalent of several LOSE WEIGHT NOW! billboards. And worst of all, the company’s credibility had begun to slip.

A 2024 review of the company on the website MuscleandBrawn noted that a recent Janoshik COA on the Amino Asylum website showed no verification code at the bottom, no client information at the top, and no Amino Asylum watermark. “It is possible that Amino Asylum removed the code, client name, and watermark,” the reviewer speculated, “but it doesn’t really look all that good.”

Indeed it didn’t. If you’ve been following my reportage here, you may recognize these alterations as hallmarks of a recycled or falsified COA.

Suspicion was aroused on Reddit, enough for a handful of customers to send vials of injectable L-Carnitine sold by Amino Asylum off to be tested by reliable third-party laboratories. The results were damning. “Each vial had half the amount of mass it was being sold at,” a source close to the online peptide scene told me. “So their 600mg/ml vials were actually 300 mg/ml.” This is the bodybuilding supplement equivalent of charging customers $8k for a Brazilian Rosewood dining room table that’s actually made out of $10 plywood from Menards.

Trust was lost, and the peptide community descended into an uproar. It seemed only a matter of time before the FDA raid that would confirm what even the most loyal customers had begun to fear: in a rush to meet consumer demand, Amino Asylum had long ago ceased to be a safe, transparent, and well-monitored operation. They’d been operating so far out of the remit of nutra- and pharmaceutical regulations for so long that their business had become legally dubious, placing their consumer base in serious jeopardy.

Though the business has since attempted to revive itself under the name Soma Chems, the damage appears to have been done: speculation about scamming abounds in the very same online communities that once uplifted Amino Asylum. And to confound matters further, Austin Carpenter has passed away. He was just 32, most likely in the prime of his life. The cause of his death was not made public, and it’s unclear whether it was in any way linked to the issues at Amino Asylum.

With Carpenter died the chance for a more nuanced look at the goings-on in his business. How did the rapid scaling of Amino Asylum impact his health? What about his own peptide usage: was it regulated and medically/scientifically sound, or unregulated, impulsive, experimental?

There is one question that can be answered without qualification: What can the Amino Asylum scandal teach us? Here, we need look no further than Peptide Partners’ founder for an answer: Never trust a supplier that doesn’t submit to third-party testing. Never trust a certification that cannot be independently verified.

Put another way: there’s no business opportunity or silver-bullet cure that’s worth jeopardizing the money and health you already have.

What Is Wellness?

Odds are if you’re reading this, you have at least a glancing notion of the concept of wellness.

Maybe you’ve heard the term tossed around by Instagram beauty influencers claiming that a combination of ayurvedic yoga, “facial balancing” surgeries, and yogurt enemas are the key to a happy marriage and everlasting gender euphoria. Or maybe you’ve listened to a podcast hosted by a weightlifting neuroscientist who claims that true wellness is achieved by sitting in a hyperbaric oxygen chamber and abstaining from all forms of pornography and seed oils.

Or maybe you, like me, are a child of the ‘90s and recall that noxious Presidential Fitness Test and the near-omnipresence of diet food and aerobics brands. Back then, the idea of “wellness” felt almost like a religious imperative we all had to follow at risk of being labeled either deviant or noncompliant. It wasn’t just about maintaining a certain Body Mass Index, or being able to run a mile without getting winded, or eating the correct combination of protein, grains, and produce – though these things were without question all part of it. Wellness was about achieving a holistic state of health (mind, body, and to a lesser and lesser extent, spirit) and then optimizing that state.

For a little context, here is the Global Wellness Institute’s definition of the term: Wellness is the active pursuit of activities, choices, and lifestyles that lead to a state of holistic health.

A simple and accurate enough definition, but consider the fact that one must always be making choices over the course of a lifetime, weighing pluses and minuses, optimizing outcomes. This has resulted in the widespread feeling that, no matter what we were doing to be well, we could always be doing more. There were, unshockingly, always more vitamins and supplements to buy, more workouts to do, more experimental treatments to try, higher standards of health and beauty to achieve. It was a treadmill – pun intended! – that proved immensely challenging to get off, even after we realized it was powered more by corporate lobbies, Big Pharma, and various government agencies than by a genuine or nuanced interest in public health. It’s precisely the same empty striving that’s landed us where we are today: a populace that, in the words of Health and Human Services Secretary RFK Jr., is “hooked” on prescription drugs, “over-medicalized,” and in the midst of a “chronic disease epidemic.”

You may be wondering: But how did optimizing our health for decades land us here? To understand that, we’ll need to travel back to the 19th century to understand the emergence of “wellness” as a concept.

John Harvey Kellogg and Progressivism’s Christian Influence

Those of us who recognize John Harvey Kellogg’s name most closely associate it with the Kellogg’s cereal brand, which began more or less in 1896, when John Harvey was issued U.S. Patent No. 558,393 for “Flaked Cereals and Process of Preparing Same.”

For still fewer of us, mention of the health-conscious physician-turned-entrepreneur conjures some association with his Seventh Day Adventist religious background. But for those who do remember this about Kellogg, the association tends to be quite strong. I’ve been told many times, and in no uncertain terms, that Kellogg’s Cereal is a “religious project” and that the brand’s signature corn flakes were intended to play some role in preventing the consumer from sexual excitation. (How exactly this is supposed to work my interlocutors have never managed to explain.)

But truth be told, the characterization of Kellogg’s project as “religious” isn’t altogether wrong. Kellogg was part of a social movement spanning roughly 1890-1929 known as the Progressive Era, a time when thinkers and innovators were contending with the social issues that had arisen as a result of the Industrial Revolution and finding promising linkages between the health of the individual and the health of the collective. This was the era of trust-busting and Upton Sinclair’s The Jungle – the novel that would eventually lead to the founding of the FDA – first-wave feminist Elizabeth Cady Stanton and women’s suffrage, efforts to preserve the environment by naturalists like John Muir, and the prohibition of alcohol.

Much of this era’s activism had its basis in human rights advocacy: from trust-busting to reforming slums and eliminating poverty to containing industrialization and political corruption. But what we denizens of the twenty-first century often forget is that such advocacy wasn’t considered at odds with Christianity: in fact, it was inspired by it. Early feminist Jane Addams – founder of the Hull House in Chicago – counted Calvinist-turned-spiritualist Thomas Carlyle and noted Christian anarchist Leo Tolstoy among her biggest intellectual influences. Upton Sinclair saw Jesus Christ as a proto-socialist figure and advocated for a “socialist Christianity” capable of protecting the poor.

And John Harvey Kellogg saw the Bible and science not only as irreconcilable but as fundamentally intertwined. “I can not stop the heart’s beating, or make it beat faster or slower by commanding it by my will,” he wrote in 1901:

But there is a will that controls the heart. It is the divine will that causes it to beat, and in the beating of that heart that you can feel, as you put your hand upon the breast, or as you put your finger against the pulse, an evidence of the divine presence that we have within us, that God is within, that there is an intelligence, a power, a will within, that is commanding the functions of our bodies and controlling them.

Whether or not you’re a person of faith, it’s hard not to see Kellogg’s view as an elegant one: there is a breath of life that animates the body, something that extends beyond our own freewill and connects us to the cosmos. This is a view that has been espoused just as readily by Sufi mystics, Buddhists, and Kabbalists alike.

But Kellogg was a Seventh Day Adventist during a time when good works and social progress were linked up with popular Christian doctrine. There was faith in its lyricism, and then there were rules to follow. As chief medical officer of the Adventist-owned Battle Creek Sanitarium, Kellogg followed Adventist prescriptions for health: patients were to maintain a vegetarian diet, abstain from tobacco and alcohol, and follow a moderate-to-rigorous regimen of exercise. Adventists believed that a bland diet reduced the need for the sort of “carnal stimulation” frowned upon by Protestantism – hence the corn flakes (and aforementioned rumors about them).

There is no doubt that Kellogg was a pioneer in the realm of medical science. He understood the importance of photo- and physiotherapies, and was leagues ahead of his time in theorizing about the linkages between the gut biome and our physical and mental health. But his concept of good health – aka “wellbeing” or “wellness” – was tightly bound up with Adventist moral righteousness. One was “well” if and only if she was living a morally unimpeachable life, which meant not just turning the other cheek and abstaining from vices like alcohol and tobacco but following church-sanctioned imperatives to get and stay healthy.

Halbert L. Dunn and High-Level Wellness

Kellogg had a natural successor in biostatistician Halbert L. Dunn, whose work for the Mayo Clinic would eventually garner him the unofficial title of “father” of the wellness movement.

Born in 1897 during the height of American Progressivism, Dunn would no doubt have been influenced by popular Christian concepts of good public works and private virtue. After working as an attending physician at various hospitals in New York and Minnesota, Dunn was hired by Mayo in 1929 to derive a system for coding medical statistics. This led to a twenty-five-year career as Chief of the National Office of Vital Statistics, where Dunn would apply his biostatistical findings to develop concepts of public health, wellness, and vitality.

Dunn saw health not simply as the absence of disease, but as the holistic vitality, aliveness, and engagement of a human subject. “[Wellness] is not a relatively flat, uninteresting area of ‘un-sickness,’” Dunn wrote, “but is rather a fascinating and ever-changing panorama of life.” He saw humans as “bio-psycho-social beings” existing along a continuum of severe disease to peak wellness. At our most well, we experience vitality – i.e. excitement, energy, enthusiasm – and the maintenance of this condition will depend upon the intersection of many physical, psychological, and social factors. According to Dunn, whether an individual is “vital” or flourishing might depend on whether the course of her life is animated by purpose-driven or goal-directed behaviors, whether she reports a sense of freedom in her personal and social lives, and whether she has a prior history of disease.

This conceptual framework revolutionized a pathology-centric medical model that defined health as the absence of illness. Dunn’s ideas spread like wildfire, in no small part due to the fact that Abraham Maslow introduced his famous Hierarchy of Needs in 1943, directly in the middle of Dunn’s tenure at the National Office of Vital Statistics.

The modern concept of wellness as self-actualization – and self-optimization as a perpetual striving-towards-wellness – wasn’t so much established as re-established by Dunn’s work. Like his forebears, Dunn’s definition of holistic wellness would align closely with Christian concepts of virtue. In a 1966 paper called “Mental Health and the Concept of High-Level Wellness,” Dunn reported that “consumerism and materialism” stood athwart the growth of empathy and altruism that engender high-level wellness. Giving of oneself – and in a Christlike fashion – could actually improve one’s health.

Wellness in the 21st Century

Perhaps it doesn’t surprise you that wellness as we understand it in America today has its roots in Christian virtue ethics: we’re a country founded by Protestants, after all!

But you might be surprised by how these same concepts continue to permeate healthcare today. From the food pyramids – original and revised – to the premiums we place on exercise, endurance, and restraint, to our concept of certain foods, goals, and lifestyles as “good” or “bad,” ours is a healthcare system that bears the indelible stamp of Kellogg and his coevals.

And to be clear, this isn’t a categorically bad thing. Empathy and altruism have much to recommend them, as do regular movement and a vegetarian diet. It’s when these things become not just valuable guidelines but moral imperatives – and those who fail to follow them ostracized outcasts, the slovenly damned – that the pursuit of high-level wellness can become fanatical, its pursuers dogmatic. If you’re wondering how dehumanizing practices like human trafficking and eugenics could have gained any sort of ideological popularity in the United States, look no further than the false dichotomy between the “ill” – i.e. the dispensable, the subhuman – and the “well.”

But how does any of this apply to innovations in healthcare like research peptides? As usual, it’s not the science behind the peptides or their remarkable curative properties that link them back to the centuries-old concept of wellness – it’s the public’s attitude towards them.

Stay tuned to learn more about smart peptide protocols, bodily optimization, and high-level wellness in subsequent columns!

What Is a COA Really Measuring?

The market for research peptides is indeed a strange ecosystem. It’s a place where one slick looking internet storefront may represent a regulation-compliant supplier working in conjunction with a legitimate compounding pharmacy, whereas another near-identical one was just tossed up by a dude operating out of his bedroom in Nanjing. This market’s goods are obscure molecules with names that sound like discontinued Pokémon evolutions, and its consumers range from scientific researchers to bodybuilders who’d like to inject some complex amino chains after chugging a creatine shake.

It’s also a space rife with skepticism. There are everyday consumers grappling with a variety of health issues who’ve stumbled into the research chemical space out of skepticism towards their doctors – allopaths, osteopaths, naturopaths etc. – and the various big-money industries that seem to back them. There are scientists who’ve been watching in quiet horror as research funding has run dry.

Log onto any online forum dedicated to the discussion of peptides and you’ll find an environment florid with paranoia. People are worrying about the FDA, about the public’s waning faith in the scientific method, about doctors and their ability to treat anything beyond symptoms, about influencers and their “stacks,” about Discord channels and shady WhatsApp group buys. The list goes on.

In such an ecosystem, there are few reliable signposts of truth. Jumpy consumers feeling spurned by mainstream medicine want something else, but don’t know who to trust. Empirical data can be easily faked, as can authority; one may assume she’s speaking with an “expert” about her peptide protocol only to discover she’s been DMing an AI. Suffice to say, it’s wild out there, and a bit disheartening. If you’re reading this, you almost certainly have a sense of just how disheartening it can be.

If I were to ask how you distinguish a trustworthy peptide supplier from a scammer, what would your answer be? Something about demonstrated scientific knowledge? A personal touch instead of faceless automation? Honesty? Integrity? (Once again, the list goes on.)

“I would be most likely to trust a supplier who prioritizes research integrity and consumer safety over profits,” you might say. “Someone who’d be willing to get their peptides tested by a third-party laboratory for safety and purity.”

And you wouldn’t be wrong. To quote the founder of Peptide Partners himself: Never trust a supplier that doesn’t submit to third-party testing. Never trust a certification that cannot be independently verified.

It takes a lot of humility for anyone in the rapidly expanding peptide space to pursue safety over profits – even when that means dumping hundreds of thousands of dollar’s-worth in inventory that didn’t meet quality standards.

Take a look at this compelling drama in three acts:

A batch of tirzepatide failed an endotoxin screening. Since endotoxins are extraordinarily dangerous to consumers, the company has elected to dump the batch and try again, sacrificing something in the neighborhood of $20,000 in the process. A sizable loss, and one rarely stomached in the rapid-growth peptide ecosystem. The comments reflect this:

(SatsScholar has a valuable point – more on that later.)

Next, the company tweets a Certificate of Analysis from TrustPointe Analytics, a chemical quality control lab specializing in peptides and other wellness products: “They nailed purity and assay. We would consider this good.”

This new batch of tirzepatide is without question a better performing one:

Here, I see just about every box checked: scientific knowledge, personal touch, honesty, and integrity. And, to paraphrase a certain transcendentalist poet known for his own eccentric wellness habits: so much depends on the COA.

So much indeed! It’s the gatekeeper, the dealbreaker, the guarantor of truth about your peptides. But what is it measuring, really?

How the COA Works

A Certificate of Analysis is essentially a laboratory report attached to a specific batch of a compound. Its purpose is to document the results of tests that verify the identity, composition, and quality of that batch.

These tests are conducted via a variety of testing methods – e.g. mass spectrometry, gravimetric analysis, High-Performance Liquid Chromatography – designed to analyze chemical attributes such as weight, purity, and sterility.

Provided the tests go off without a hitch, the COA should inform you of three things:

1. Identification (Whether the substance in the vial actually is what it claims to be)

2. Net Content (How much of the substance is present in the vial versus non-peptide contaminants like endotoxins, heavy metals, etc.)

3. Net Purity (The identities of any other non-peptide substances in the vial)

Identification

The first and most fundamental anyone will want to know of the peptides they’ve just ordered: Is the thing in the vial what the label says it is?

This test is usually performed through mass spectrometry, which measures the molecular weight of the compound. Every peptide has a characteristic molecular mass determined by its amino acid sequence.

By measuring a certain peptide’s molecular mass, the Mass Spectrometer confirms its identity. For example, if the expected mass of a given peptide is 1570 daltons (a unit of molecular mass) and the Mass Spectrometer confirms 1570 daltons, that’s strong evidence that the peptide exists in the vial.

It’s important to remember that the mass spectrometry measurement is not a conclusive positive ID – other measurements must be taken as well – but it’s still a critical part of any chemical analysis.

Net Content

The next question is quantitative: How much material is actually in the vial?

Manufacturers label peptide vials with nominal quantities—5 mg, 10 mg, and so on—but those numbers are targets rather than guarantees. Net content testing determines the actual mass present in the sample through either gravimetric analysis or quantitative chromatography.

If a vial labeled 10 mg tirzepatide actually contains 8.9 mg tirzepatide, that discrepancy matters enormously. Any researcher calculating doses or concentrations from the label alone will unknowingly start their experiment with incorrect numbers. When examining a COA for net content, ensure the report explicitly states the mg per vial found, not just the purity percentage.

Net content measurements name the difference between empirical precision and guesswork.

Net Purity

Purity refers to the percentage of the material in the sample that corresponds to the intended peptide rather than synthesis byproducts, fragments, or contaminants. Purity tests are typically conducted using a method called high-performance liquid chromatography (HPLC). On a COA, it’s usually displayed as a percentage. For research purposes, you’d generally want to see net purity in excess of 98% or 99%.

Purity is also the COA metric that’s most frequently bandied about. A “high-purity” peptide sample is automatically understood to be a high-quality sample. But closer examination proves this to be a facile line of thinking:

Peptide Partners Corner

The Hidden Danger in High-Purity Peptides: Why Endotoxin Testing Is Non-Negotiable

The Purity Paradox That’s Putting Lives at Risk…

Read more

9 months ago · 13 likes · Peptide Partners

A COA that reports 99% purity in a given peptide batch is claiming that the peptide accounts for 99% of the measured material. Reassuring, certainly, but here’s what the purity test doesn’t tell us:

• Whether the remaining 1% of material is completely harmless

• The chemical identities of any potential impurities

• That the assay has measured everything present

Like net content and chemical ID tests, purity results are most meaningful when taken into account with other data.

Additional Quality Tests

Any third-party lab that’s serious about its chemical analyses – and by extension the lives of the individuals interacting with those chemicals – will also be sure to test for the following in any given batch of peptides:

• Heavy metals

• Endotoxins

• Sterility

• Residual solvents

These tests matter because synthesis and purification processes can introduce contaminants that can adversely affect research outcomes or biological systems. Suppliers who advertise “full panel testing” typically mean that the peptide on offer has been evaluated across several of these categories in addition to net content and net purity.

Which leads to an important point – one little discussed among the hungry-for-results gray market crowd: Not all COAs are created equal. Some contain extensive analytical data, while others contain a few numbers and a logo from a lab run by a far-flung Redditor.

Conformity Testing

Conformity testing functions as a replication check. Really, it’s the sort of simple due diligence that ought to be routine.

Instead of testing a single vial from a batch of freshly obtained Chinese peptides, the supplier chooses instead to test multiple vials from that batch. The vials are sent to a third-party lab and tested independently; the results are then compared to determine whether they align.

If the batch is consistent, the measurements across samples should fall within a very small window of variance. If not, this could indicate an uneven batch: one whose quality varies from vial to vial.

Recall the screenshots above: a high-integrity, trustworthy supplier would dump a batch that failed conformity testing – or any of the tests I’ve described – even if it meant sacrificing profits. Such a move would be anathema to a corporate machine that could care less about the human lives it’s trammeling. But for those of us in the wellness and longevity space who actually care about using science to help people get healthy, poisoning your consumer base pretty much defeats the whole point.

Strong and Weak COAs

Let’s return to SatsScholar’s comment on the Peptide Partners post about the bad batch of tirzepatide: “Nice man. Most would just ship it out. Or worse. Claim a different batch number to obscure purity.”

What does SatsScholar mean? Here, he’s referring to how easily COAs can be falsified to serve a shady supplier’s purposes. One can conveniently neglect to conformity-test a batch of peptides, or simply recycle a COA for a dubious batch and nonchalantly look the other way. And this doesn’t even begin to touch the discrepancies among labs: does Janoshik measure up to TrustPointe? Chromate to MZ Biolabs?

Without getting into the finer points of chemical assays and lab etiquette, I want to briefly outline the differences between a good – i.e. trustworthy, robust – COA and a not-so-good one.

A robust COA typically contains the following:

• Batch or lot number tied to the tested product

• Testing date

• Lab name and accreditation

• Analytical methods used

• Raw analytical data (chromatograms or spectra)

• Quantitative test results
  
  

Above, we see many of the indications of a robust COA. Lab name in the upper left corner, testing date in the upper right. A listing of the analytical methods used (RP-HPLC with UV detection) and the raw data in the form of a chromatogram, along with the quantitative results.

Such transparency matters because analytical chemistry is a process with traceable steps. Therefore a trustworthy report ought to show its work.

By contrast, a weaker COA might look like this:

No raw analytical data, no real sense of the testing methods, not even a number or QR code to verify the test online. With little tethering this COA to a specific batch of retatrutide, it becomes eminently recyclable. One can imagine the shady group buy organizer terrorizing his customers with such a document, using a little Dunning-Kruger effect arrogance:

Purity: 99% PASS

Such a limp summary of an unknown chemical instills little confidence in the consumer. Imagine a health inspection report that reads: “Food: Probably fine.” You might think twice before eating at that restaurant.

In such cases the COA’s work is less analytical than theatrical. It signals legitimacy without doing the hard work of demonstrating it. Beware the supplier who would show you a report like this. You’re better off – i.e. safer – ordering your amino chains elsewhere.

More on COAs and illusions of trust:

A COA Is Not a Medical Doctor

There’s no contesting the fact that Americans have entered a collective phase of taking our health into our own hands.

This means different things for different people, of course. For the tech founder, it may mean sourcing peptides – among other compounds – from overseas vendors biohacking herself into a state of mental and physical wellbeing (with the venture capitalist and market analyst both close on her heels). For the podcast bro, it may mean sauna reps, cold plunges, and avoiding seed oils. For the MAHA mom, it may mean scouring the house for hidden microplastics and taking up farming so her children only have to drink raw milk. For transhumanists like boomer biotech CEO Martine Rothblatt, it may mean contesting the very notion of a “natural” or “given” body altogether.

But at its base, the popular trend towards healthcare reclamation – aka “sovereign health” or “optimization” in tech and finance spaces – means something fairly simple for a vast cross-section of Americans: we are the experts on our own bodies, and thus in charge of our own treatment. Healthcare has shifted away from the patients-consulting-experts model and towards a patient-as-expert model. That this has coordinated with the rise of peptide-based health protocols should surprise no one: these chains of amino acids are currently the most visible in a series of innovations that combine the powers of scientific empiricism

And now we’ve arrived in the rapidly expanding wellness economy, where healthcare isn’t administered to us after a long and bureaucratic wait. Instead, it’s purchased by us after a process of self-directed research and vetting. By the time we arrive in the virtual doctor’s office – or, as the case may be, at the direct-to-consumer website, the WhatsApp-coordinated group buy – we believe ourselves informed enough about our treatment in order to consent to it. If we couldn’t trust bona fide medical doctors to overcome their confirmation bias – or worse, their loyalties to drug companies – in order to tell us what we actually need to know about our treatments, then why should we pretend that true medical expertise can be sought anywhere outside the realm of our own research? What do the “experts” have, in other words, that we don’t?

The answer is somewhat sobering. It’s not necessarily about a lack of applicable scientific data – though these, too, can be suppressed, as reminds us in this excellent essay. The problem is with the consumer experience itself.

Maybe you’ve purchased a used car before, or at the very least walked through a Costco and had the experience of being pitched to about an in-home security system or some sleek looking patio furniture. There’s already been buy-in from you on some level – you need a car, or you’ve come to the Costco to stock up before a party – and the salesperson in your presence is now charged with closing the deal. Their job becomes to persuade you; your job (ideally) becomes to navigate around their persuasion and towards real information – and thus the product(s) best for you. It’s a challenging dance. I know few who’ve mastered it, myself not included.

Now, consider this fact: with the rise of medical consumerism, the medical “expert” has now effectively shifted into the role of medical salesperson.

While Americans have certainly been right to call the healthcare system on its fairly obvious pursuit of profit, this doesn’t mean that healthcare professionals or pharmaceutical reps scurried off with their tails between their legs, or dutifully changed their ways. If anything, the direct-to-consumer healthcare model seems to be encouraging clinicians to lean into it.

Peptide Partners Corner

Telehealth, Ease of Access, and the Medical Consumer Boom

This is part two of a multi-part investigative series. Read part one here…

Read more

3 months ago · 6 likes · Peptide Reporter

We’d all like to pretend we enter every sales situation armed with enough information to render ourselves invulnerable, that we’d be able to keep our cool under pressure and resist coercion at all odds. But what if the situation feels like a life-and-death one for us, and the salesperson standing in front of us effectively becomes the gatekeeper of our health? And what if, given the profundity of our distrust, we’re not even interfacing with a doctor or pharmaceutical representative, both of whom are beneficiaries of some degree of regulatory oversight? What if our research has taken us to a Reddit forum and then to a Discord server and then to the Shopify storefront of some dude in China who just wants our money?

“There is a massive assumption out there that if a company has a website, a shopping cart, and a label on the vial, [there’s] some quality standard being met,” writes peptide industry veteran . “Some regulatory body making sure the product is what it says it is. There isn’t.”

Mars warns that while there are plenty of trustworthy and scientifically-minded research peptide vendors out there, the demand for peptides has grown so exponentially that the market has become bloated with scammers. He goes on:

“The people buying [these peptides] have no idea how much risk they’re actually taking on. They see a COA that says 99% purity and they think the product is fully vetted. It’s not. That COA tested the peptide chain. That’s it. It doesn’t tell you about the manufacturing process, the facility conditions, or what else might be in that vial besides the peptide itself…Nobody thinks about that because nobody explains it.”

Mars is referring to the Certificate of Analysis (COA), usually issued by independent chemical testing laboratories like Janoshik or Finnrick, that ascertains the purity and safety of a batch of peptides. Good independent analysis of peptides requires a given vendor to submit their product to a rigorous battery of tests applied frequently, the processes of which I’ll be delving into in this series.

For now, I’m hoping you’ll see the parallel Mars is drawing: in a medical consumerist paradigm where the salesperson has replaced the expert and the patient has already made up her mind, the COA becomes the basis of a sales strategy. And in cases where a given vendor is honest – e.g. is actually testing and verifying their peptides in the interest of consumer safety, has a demonstrated interest in scientific advancements and healthcare applications, isn’t pretending to be anything more medically high-faluting than a vendor with a loyal customer base – the COA is a legitimate method of building trust.

But what about when this isn’t the case? Could the shady vendor potentially weaponize a fabricated COA against unsuspecting consumers? The answer is most likely yes — but how?

The Falsified COA

Let’s begin with the most obvious example of bad actor chicanery: the falsified COA.

If you spend any time in peptide-adjacent corners of the internet, you’ll start to notice a peculiar aesthetic uniformity. Crisp PDFs. Lab logos. Lot numbers. HPLC chromatograms with satisfying peaks. Percentages carried out to two decimal places. A signature at the bottom, often difficult to decipher but suggestive of someone in a white coat somewhere far away. It feels scientific. Like something that’s been submitted for regulatory oversight. Most importantly, it feels real.

And this is precisely the point. A falsified COA doesn’t need to be elaborate. In its laziest form, it can just be a Photoshopped version of another vendor’s certificate, with the batch number and company name swapped out. In more sophisticated iterations, it may involve fabricating an entire report format that mimics a reputable lab’s template—Janoshik, for example, or any number of European or Asian analytical testing companies whose branding is publicly available online. Critically, the average consumer has no way of knowing the difference.

Here’s the uncomfortable truth: unless you personally contact the lab listed on the COA and verify that the batch number corresponds to a real submission from that vendor, you are taking the document at face value. You are trusting the PDF because it looks official. You are lulled into trust by a precise-looking set of numbers. But, alas, precision is not the same thing as truth.

This is where the gray market intersects with something much older than peptides: the psychology of trust. We are primed to defer to documents. Stamps, seals, signatures, logos—they’re the cultural artifacts of authority. They soothe the part of us that knows we can’t personally replicate high-performance liquid chromatography in our kitchens. They allow us to believe that someone else has done the due diligence.

And in some cases, someone has. But in others, the COA is functioning less as a scientific record than as a psychological prop. A sort of doctor-without-the-doctor.

Let’s imagine our used car salesman again. He opens the hood and gestures vaguely at the engine. He hands you a maintenance report. He tells you the vehicle was owned by a little old lady who only drove it to church. You do not have the tools to independently verify any of this. What you have is a charming story with narrative coherence.

And in this case, the falsified COA provides narrative coherence. It tells you that this batch was tested and it passed. It is 99% pure, “completely safe.” What it doesn’t tell you is whether the vial in your hand bears any relationship to the batch in the PDF. Nor does it tell you whether the test was ever performed. Nor whether the peptide was synthesized in a facility with proper contamination controls, or in a warehouse where quality assurance is a rumor.

And because peptides are frequently purchased for research purposes in legal gray zones, the recourse available to consumers is limited. If you ingest something impure, mislabeled, or contaminated, you may not have a regulatory body to complain to. You may not have a formal paper trail.

The falsified COA, in other words, weaponizes the very mechanism meant to safeguard consumers. It leverages our desire for transparency against us. It allows a vendor to build unearned trust quickly, cheaply, and at scale. And in a market exploding with demand, unearned trust converts to revenue. Confoundingly, we find ourselves face-to-face with the medical charlatan again — just now in PDF form.

The Carry-Over COA

If the falsified COA is a blunt instrument, the carry-over COA is a subtler cudgel.

Here’s how it works: A vendor submits a single batch of a peptide—let’s say BPC-157 or Semaglutide—to an independent lab. The results come back clean. 99% purity. No detectable heavy metals. Chromatogram looks like the textbook picture of Grade-A Product.

Now, that PDF has become a powerful asset. Instead of testing each subsequent batch, the vendor can just continue to attach that same COA—sometimes with the original date intact, sometimes with a quietly updated one—to future inventory. The batch number on the website may change, s will the lot printed on the vial. But curiously – conveniently – the COA remains the same.

Peptide synthesis is not a static process. Raw materials vary, as do manufacturing partners and shipping conditions. Even reputable labs can produce inconsistent outputs depending on scale, oversight, and economic pressure. A peptide that tested at 99% purity six months ago tells you very little about the peptide sitting in your mailbox today—unless it’s been tested again.

Imagine trying to scale your business to meet the unrivaled market demand for peptides. To submit each batch to be independently tested and verified safe is absolutely the right thing to do. Given the potential harms posted by heavy metals and endotoxins, the stakes are quite literally life and death: these compounds are about to cross paths with human beings, whether in a lab setting, a clinical setting, or otherwise. But then submitting each batch to be tested is expensive. It eats into margins and requires a good deal of logistical coordination and time. And of course there’s always the possibility that any given batch will turn up contaminated, and you’ll have to do the right thing and throw it out – money down the drain, and all in the name of safety!

In a booming market where customers are often more concerned with price and speed than documentation minutiae, the incentive to cut this corner is obvious and probably quite appealing to the bad-acting vendor who’d rather not concern themselves with the ethics of what they’re doing, nor the gravity of imperiling customers’ health for their personal profit. And because most consumers desperate for a product that they feel will revolutionize their lives are unlikely to scrutinize a given COA for dates or batch alignment, the practice can persist frictionlessly.

If you happen to have a COA on hand, look closely at it. You may notice at least one of the following:

• The test date predates the supposed manufacturing date of your peptides’ batch.

• The lot number on the COA does not match the lot number on your vial.

• The report is labeled “sample provided by client,” with no indication of chain-of-custody controls.

These are not necessarily signs of fraud. But they are at the very least signs of slippage.

The carry-over COA exploits the temporal lag between testing and consumption. It relies on the consumer’s assumption that testing is routine rather than occasional. It banks on the fact that few people understand what “per-batch testing” actually entails, or why it matters. In pharmaceutical manufacturing – a realm which exists under some form of regulatory oversight – each batch of a drug undergoes rigorous quality control before release. Deviations are documented. Failures trigger investigations. There is an infrastructure of accountability.

In the gray peptide market, that infrastructure is largely absent. So when a vendor reuses an old COA, they’re not exactly inventing data. What they’re doing is allowing past good behavior to stand in for present verification.

Sadly, the human heart doesn’t care about past good behavior! It cares about sustained good behavior. So does the human cardiovascular system – especially when it comes to bacterial endotoxins.

A batch of peptides contaminated with endotoxins, residual solvents, or mis-sequenced amino acids will jeopardize the body regardless of what it says on a PDF. The carry-over COA is dangerous precisely because it maintains the illusion of ethical behavior. After all, the peptide once tested clean. If pressed, the vendor may say he has no reason to believe his supplier to be inconsistent. He may even opine that repeated batch testing is redundant.

But without regulatory oversight or any demonstrable commitment scientific rigor, repeated batch testing is all we’ve got.

Why all of this matters

Perhaps you feel inclined to shrug at this point, throw the DIY self-optimizer to the wolves. Caveat emptor, right? Buyer beware. If you’re ordering research peptides from the Discord server of peppypepper99, a guy you met on some shady corner of WhatsApp, what did you expect?

But this is a callous framing of the situation that manages to dodge the point altogether. Medical consumerism is here to stay. There is a reason this is happening, and a good one. The collective movement toward self-directed care – otherwise known as sovereign health, biohacking, optimization, etc.—isn’t an inherently foolish one. As we’ve seen, it’s a rational response to a healthcare system that has long degraded into disrepair. Americans are tired of “expert-driven” healthcare that’s opaque, paternalistic, profit-driven, exclusive, and profoundly slow. As always, we want agency and access. When viewed from this wide angle, even the desires of gym bros sitting in hyperbaric oxygen chambers come into highly relatable focus: they, too, just want to heal and survive.

And of course, there’s always the chance that the experimental big swings pay off. (If they didn’t, you wouldn’t be reading this newsletter!) Sometimes self-directed research produces meaningful improvements in chronic pain, metabolic dysfunction, mood disorders, recovery timelines. The problem arises when agency outruns information, and empirical science becomes more inconvenience than guidepost.

Put another way: sovereignty without complete transparency is theater. We imagine we’ve taken control of our health only to find ourselves right back at square one, staring into the face of yet another profit-seeking pseudo-medical juggernaut.

If you’re going to assume the role of medical decision-maker in your own life, you need data that is at least as rigorous as the data you would demand from a clinician. You need to know not just that a peptide can work in theory, but that the vial in your hand contains what it purports to contain. Otherwise – and this is crucial to understand – your care is not self-directed. You are the non-consensual experimental group in a study that doesn’t exist, and never will.

The falsified COA and the carry-over COA both undermine the foundational premise of sovereign health: that we are choosing a certain product in full cognizance of what we’re getting.

When a vendor fabricates a certificate, they aren’t just committing a petty act of fraud. They are stripping consumers of the ability to consent meaningfully. When a vendor reuses an old COA, they are asking you to trust continuity where there may be none.

You’ll learn a bit more about what informed consent means as you read this series, but suffice to say it’s far more than a bureaucratic hoop to be dodged by some dude with a Shopify storefront. It’s one of the foremost ethical principles of medicine. It’s what we sense is being sacrificed when a doctor begins pitching us on a hot new pharmaceutical drug he’s essentially being paid to push as opposed to honestly assessing our best treatment protocol. And without access to the lab conditions required to ascertain the best possible treatment protocols, we average Americans risk having our pursuit of better health hijacked by a variety of self-interested charlatans, both with and without medical degrees.

Of course this doesn’t mean that the road to self-directed care need be forever obstructed by grifters, nor that our only viable option is to retrace our steps back in the direction of a traditional healthcare model we’ve long since come to distrust. What it means is that our capacity for discernment must evolve alongside our tools for self-optimization.

This is a process that can begin simply enough at the consumer level. For instance: a self-optimizer considering a peptide purchase might do well to ask for batch-specific COAs. She ought to check dates and verify lot numbers, contact labs whenever possible. Educate herself on which tests were run and which were not. Recognize that a purity percentage does not equal sterility, and sterility does not equal safety under all conditions. In other words, she can exercise her right as a consumer to demand the information that actually undergirds her autonomy.

The promise of sovereign health is not that we no longer need experts. It is that we become literate enough in the systems around us to recognize when expertise is genuine and when it’s being simulated. To this end, a COA can either be a trust-building bridge between vendor and consumer, or a means of disambiguating an investment in science from an investment in sales.

The difference between the two hinges not just upon the integrity of the vendor, but upon the vigilance – and exercised discernment – of the consumer. Which means that it’s time for all of us to get better acquainted with the science behind our self-directed care.

Next week in Part 2: we’ll dive deeper into what COAs are actually testing, and informed consent in self-directed healthcare.

This is the final installment of a three-part series. Read part one, part two, and part three.

Part 4: 2024 RAADFest and Healthcare Skepticism

In 2024, the Revolution Against Aging and Death Festival – commonly known as RAADFest – was held in Las Vegas. The high-stakes wagers of Sin City proved a fitting ambience for the rather unsettling gamble Dr. Kent Holtorf saw fit to take in the festival’s convention hall, which had been converted into a RAADClinic offering attendees the chance to sample bleeding-edge longevity treatments on the spot. Holtorf’s offering? Peptide injections administered directly at his booth. According to a ProPublica report, two women who’d received these injections left the festival fighting for their lives.

The women, ages 38 and 51, had both described feeling as if their tongues were swelling upon leaving Holtorf’s booth. Both were taken by ambulance to the hospital. One was already intubated upon arrival, and the other couldn’t open her eyes or communicate with doctors. Fortunately, both women recovered. According to the Lifespan Research Institute, the Las Vegas Police Department reported that “up to seven people sought treatment after receiving the peptide injections at Holtorf’s booth,” though RAADFest sponsor Coalition for Radical Life Extension reported that “the Southern Nevada Health District…[confirmed] only the two severe cases.”

Holtorf told ProPublica he was “so freaked out,” because none of the women’s symptoms “made any sense.”

“Of course, I want to get to the bottom of it,” he said. “But almost assuredly it will come out that it was not the peptides.”

Holtorf’s view was at least partially corroborated by Dr. Amy Gutman, a Florida emergency room doctor who was also in attendance at RAADFest. Gutman felt the women’s symptoms were consistent with an allergic reaction, a rare occurrence with peptide injections. More likely, it was whatever secondary agent the peptides had been compounded with that caused these women to become ill.

The incident was paradigmatic of the kind of worst case scenario that dogs the nascent field of longevity science. Arkadi Mazin sums it up well in his report for the Lifespan Research Institute:

“What happened at RAADFest highlighted some well-known problems and contradictions in the longevity field…There is a sense of urgency that pushes some people to offer and others to try therapies that have not been rigorously tested for safety and/or efficacy. Many rightfully lament the increasingly lengthy and expensive regulatory process, which is not properly suited for rejuvenating therapies. There is a growing push to extend the ‘right to try’ to all patients and all reasonably safe therapies, and to accelerate clinical trials by relaxing certain regulations and transitioning towards cost-effective methods, such as human organoid and in silico models.”

These issues will be familiar to anyone with even a passing interest in longevity science. The long and demanding regulatory process that seems to grow lengthier and more bureaucratic with each passing year. Rising public skepticism toward a federal agency that appears to be withholding – and in some cases has actually withheld – lifesaving treatments from average Americans while one percenters like tech entrepreneur Bryan Johnson appear to be gleefully purchasing longer lives. Consumer urgency and even indignation arising from the idea that lifespan extension may not be an option within one’s lifespan: not because the scientific method is a slow and precise process that cannot be hurried along with market demands, but because science is something being “kept” from the average person by greedy elites. Direct-to-consumer telehealth company Hims & Hers articulated this view plainly in their “Rich People Live Longer” Super Bowl ad:

Within its first twenty seconds, the ad evokes ultra-wealthy pop culture mainstays with whom most any American will be familiar. There’s a Kris Kardashian-like woman getting a deep-plane facelift straight out of A Clockwork Orange. There’s a Jeff Bezos-type popping a bottle of champagne as he prepares to board a rocket to another planet. There’s a trim, pasty-looking man stationary-biking while wearing an oxygen mask and lying in what looks like an infrared tanning bed that is a clear recreation of Bryan Johnson’s multimillion-dollar longevity protocol. I’m sure I’m speaking for many of us when I say that it’s not a challenge to roll one’s eyes at these images: indeed, we hardly need to see the average Americans doing so in the Hims & Hers Superbowl spot to know precisely the feeling the telehealth company would like to remind us of. Or, to rephrase it in marketing terms, how they’d like us to feel in that moment.

Which brings us back to a truth that will feel uncomfortable for longevity enthusiasts, biohackers, and FDA skeptics alike: just because self-interest has been known to rear its head at the federal level, that doesn’t magically absent it from the private sector.

While it is in fact true that vast wealth can afford someone access to legal loopholes and extra-regulatory treatments, it’s also true that not all of these treatments have the data to prove their efficacy, or even their safety. (This is why Bryan Johnson is more of a human test subject than a clinical patient, trying out radical new longevity therapies on an experimental group of one, with a control group of zero. Try turning that into a meaningful data set!)

As I’ve written before, this sort of wellness-optimization comes with a great deal of risk. Some optimizers feel they’ve been apprised of this risk, and accept what they’re getting themselves into. But in many cases, what they’re getting themselves into is a null data set – a complete unknown.

This situation is especially true for those of us who want to optimize our health, but lack the vast resources of biohacking tech entrepreneurs to do so. Maybe we’ve grown skeptical of regulatory agencies like the FDA – perhaps rightfully so, given the lengthy and bloated-with-expense regulatory process, and the agency’s affiliation with corporate interests and notorious characters like “pharma bro” Martin Shkreli. So we decide to seek affordable, extra-regulatory outlets for our longevity medicine from specialists who claim to have our back. But this is where we abandon nuance at our own risk, because Dr. Kent Holtorf is one such specialist. And he’s just one of scores of private physicians, direct-to-consumer pharmaceutical companies, and cash-pay healthcare sites in the business of making dubious claims.

Mazin expounds on the threats of snake oil salesmanship to longevity science:

“A legitimate concern exists that the longevity movement might be overshadowed, compromised, and ultimately impeded by the murky wave of overblown claims, unfounded promises, unproven therapies, and flat-out ‘snake oil’ cures.”

This calls to mind extraordinary false advertising claims, like that of Brooklyn-based entrepreneur Andrew Martin Sinclair, who claimed that his $60, 16-ounce bottles of Earth Tea could cure COVID. Or the widespread use of “magnetic healing bracelets” to improve circulation and reduce joint pain: studies have found limited benefits, though their effect seems to be more placebo than anything. And then there’s Holtorf himself, whose website’s scientifically unfounded claims about peptide therapies that “may even support prevention and treatment of COVID-19” and colloidal silver, which “may ease symptoms and encourage the resolution of COVID-19,” landed him a warning letter from the Federal Trade Commission. Both Sinclair and Holtorf have received warning letters from the FDA, though Holtorf’s are no longer listed in the agency’s database as of this writing.

One doesn’t want to die suddenly in the process of trying to live forever, and there’s nothing quite like snake oil salesmanship to invoke the specter of fatal malpractice. At this point you might be thinking, “How can I realistically expect to tell which regulators and healthcare providers have my back, and which don’t?”

It’s a simple question with a deceptively simple answer: you just need to look where the science is.

Reader, are you feeling distrustful of the federal government, multibillion-dollar pharmaceutical corporations, and medical consumerism? Want to take control of your health without becoming ensnared by bureaucratic red tape or the machinations of the pharmaceutical-industrial complex? Then let’s dive deeper into a couple commonly held beliefs about all these things, and see what holds up:

1. The FDA is an ideologically captured federal agency that withholds valuable medical treatments in pursuit of profit.

Verdict: Yes…and no.

This is a tricky one, and requires a bit of nuance to tease out – perhaps that’s why I’ve chosen to start with it. As some of you have pointed out in my subscriber chat – and I’ve pointed out myself in previous installments of this series – FDA approval cannot be reasonably regarded as the be-all end-all of safe clinical treatment. For instance: I will often drink a cup of mullein tea for a sore throat, and brew a mixture of ginger and dandelion root to drink when I have a stomach ache. These are generations-old family remedies, and as far as I’m concerned, they’re quite effective ones. They’re also not FDA-approved, nor are they clinically indicated for the illnesses I take them for. Thinking bigger: vast swaths of the healthcare and wellness industries (naturopathic health, cutting-edge longevity science, diet interventions) are not FDA-approved. It would be unreasonable to expect an individual consumer to go his or her whole life consuming only FDA-approved goods – indeed, I imagine you’d be hard-pressed to find anyone living their life this way, whether by accident or design.

The entanglement-with-Big-Pharma point is well taken here, too. Peptides – in particular GLP-1s – are not the only popular medications whose patents and manufacture are siloed at pharmaceutical giants like Eli Lilly, Pfizer, Moderna and Novo Nordisk because of lengthy clinical trials and FDA approval. The case has also been the same for both COVID vaccines, as well as for certain non-generic diabetes medications – the list goes on,

And while all that may be true, here’s something else that’s true as well: the FDA is an ideologically heterogeneous institution that continues to count a number of well-trained and scientifically minded personnel on its staff. And it’s these food and pharmaceutical scientists who can credibly debunk snake oil cures like Earth Tea, or issue a consumer warning when the Holtorf Medical Group claims it can cure your COVID with an injection of colloidal silver. These warnings are not nothing – neither are any of the warnings in this database. Even a cursory scan will reveal that they were issued in the interest of preserving consumer safety. (And yes, Novo Nordisk and Eli Lilly got slapped with warning letters, too – both for false advertising and misbranding.)

Next, you may recall the constant refrain we hear emerging from the longevity sphere: Interest in longevity treatments moves faster than our ability to generate meaningful data about these treatments. We may hear rumors that the drug rapamycin works to decelerate aging, or that stem cell injections could keep us from experiencing brain fog; we may even see the ultra-wealthy seeking these treatments out, and giving interviews about their untold benefits to legacy media outlets. But are these treatments actually effective, or could we be witnessing placebo effects from afar? (Or in extreme cases like Kanye West’s, what appears to be bona fide medical malpractice.) Will these treatments ever be available to the general public? And how can their safety and effectiveness across a diverse consumer base be ensured?

The answers to these questions will lie for better or worse with a regulatory body that has the resources to conduct scientifically rigorous randomized controlled trials – a regulatory body like the FDA. It’s the FDA – not a direct-to-consumer pharmaceutical company, not a centimillionaire, not a group buy organizer on Facebook, and not the influencer who’s excited to share her “pepper stack to stay petite and youthful” – that can recruit a large cross-section of average Americans to participate in a multi-phase study that will generate actual scientific data about a given medical treatment. Data that can then be used to make the treatment available to wider varieties of medical patients – and covered by their insurance no less! Data that could someday grant you access to your favorite peptides for cheap or even for free, and with no worries about purity, potency or quality control.

There’s the not-so-easily-summarized truth about the FDA for you, reader.

2. If a healthcare provider is an “outsider” who rejects the systems that have jeopardized my health, I can trust them.

Verdict: Not always.

While it’s certainly true that there are all variety of doctors – allopathic, osteopathic, naturopathic, etc. – who’ve challenged prevailing medical trends and reinvested themselves in actually helping their patients heal, I’m going to be realistic, reader: “I’m a maverick doctor” is also a highly convincing sales pitch.

Not all mavericks are scammers, but you’ll be hard pressed to find a scammer who doesn’t bill themselves as some form of maverick. Sometimes, this means you get hit with a story of personal triumph over tragedy: Dr. X lost his mother to Y heritable disease and nearly lost his own life to it as well; after experimenting with Radical New Treatment, he was able to pull himself out of his tailspin. And now you can be pulled out of a tailspin of your own, all for the low, low price of $2,999* (*paid in full in advance of treatment; not covered by any form of insurance).

Sometimes, the doctor will have a general sense of an effective protocol – weekly semaglutide coupled with a certain number of lifestyle changes – but will attempt to cash in on market trends by applying that protocol sloppily and indiscriminately across his entire patient population. Are you a 65 year old man with a history of emphysema and heart disease? Are you a 23 year old woman with a known history of disordered eating? Are you a 43 year old distance runner coming off a recent knee surgery? Try weekly semaglutide, a low carb diet, and high-intensity cardio three times a week!

Here as always, it’s up to you as the consumer to exercise discernment. Maybe you’ll recall Jordan, the trans man from the second installment of this series [LINK]: his desperation for a testosterone prescription landed him in a prescribing dynamic with a medical professional who was not well-equipped to handle his concerns about the medication, and who applied a protocol that was mentally and physically strenuous for him. This doesn’t mean that Jordan should not have sought a testosterone prescription at all. What it means is that he needed a doctor committed to working with him instead of hurriedly selling him a product.

As is the case with anything you choose to put in your body – whether that be a philly cheesesteak or a vial of reconstituted proteins – your discernment is what matters most. That discernment can (and probably should) be informed by judicious research and the guidance of a trusted expert. But you’re the one who decides what to research and how, and which experts are actually trustworthy. It’s a delicate balance for us to maintain, that of openness and skepticism. But when it comes to our health and wellbeing, it’s more than worth it.

Suffice to say you won’t see me getting any on-the-spot peptide injections at a convention expo anytime soon.

This is Part 3 of a four-part series. Read Part One and Part Two.

Part 3: The Med Spa to Gray Market Pipeline

It’s not difficult to imagine the transition from medical consumer to gray market buyer. You may very well know such a patient.

Let’s trace this patient’s steps and their consequences. First, she paid for a telehealth appointment or med spa consult seeking a prescription for a weight-loss peptide she’s seen advertised online and has already researched extensively. Maybe it’s tirzepatide or retatrutide. Tirzepatide was only recently FDA approved, and is manufactured by Eli Lilly and prescribed under the brand name Zepbound to adults who have type 2 diabetes or who have been deemed clinically obese. Retatrutide, another GLP-1 agonist, is still in phase three clinical trials for FDA approval.

But the telehealth provider or med spa have ways of obtaining these compounds that don’t require clinical diagnoses or explicit breaches of the law. They use compounding pharmacies like Hallandale or Red Rock, which must be licensed by their respective states’ Boards of Pharmacy, remain compliant with state pharmacy laws, and are subject to random inspections to ensure compliance. Pharmaceuticals manufactured on-site have USP Monographs, or an index from the United States Pharmacopeia-National Foundry (USP-NF) that identifies the APIs (active pharmaceutical ingredients) in a given drug substance, as well as its purity, dosage forms, and excipients (i.e. inactive substances that serve as vehicles for active ones). If these pharmacies ship to customers out of state, they must be compliant with the United States Postal Service’s standards for shipping pharmaceutical drugs, as well as the pharmaceutical laws in the destination states. While the pharmacies’ operations are subject to state regulations – and thereby to some degree of guidance and oversight from the FDA – the pharmaceuticals themselves are not compounded in FDA-approved form. Some formulations may feature vitamin B12, sometimes described as an “additional supplement” added to help patients deal with nausea or low energy – it also allows the peptide to qualify as a distinct chemical formulation, which helps the compounding pharmacy avoid any legal action from deep-coffered pharmaceutical mega-giant Eli Lilly.

Back to our patient in question: let’s say she gets her peptide prescription, starts the protocol, and sees impressive results. She’s losing weight, regaining energy, and noticing a diminishment in food noise like she’s never before experienced in her life. She feels – as many have – as if this peptide has brought her back from a sort of waking nightmare of ill health into a life well lived. And it was so easy! To quote tech CEO and lifestyle entrepreneur Cate Hall, “much better lives are not only possible, but astonishingly close at hand.”

But then, our patient is hit with the prices. She’ll have to pay $300 per med spa visit, which certainly adds up if she wants to keep up with her weekly peptide protocol. If she got her peptides through Hers, she would be paying $199/month for a six-month prescription (which translates to $1,194 before taxes, paid upfront and in full). Being neither clinically obese nor type 2 diabetic, she doesn’t qualify for brand-name prescriptions of Wegovy, Zepbound or Mounjaro, all of which would be covered by her insurance. As costs stack up, our patient realizes her options are becoming increasingly limited.

So, she takes to the internet. First to Reddit, and then to messaging sites like Discord or Telegram. Where to get affordable peptides to continue her protocol? Can she maintain her newfound health without having access to a lavish lifestyle?

She’s sent links by other searchers. She finds sites on her own. Semaglutides and human growth hormone boosters for such low prices she’s a little stunned. Research use only, these sites advertise. Not for human use. She researches and researches and researches. Her options are many, and unregulated. But as federal and state regulations continue to fall away, she’s not all that worried. “The entire diet and supplement industries aren’t FDA-approved, and it’s not as if those compounds haven’t helped people,” she reminds herself. And she’s right. Depending on who you are, you may or may not raise your eyebrows at the “cures” of the Make America Healthy Again movement like raw milk and seed oil. But what about something as innocuous as an herbal tea for insomnia? Or a sprig of peppermint for indigestion? These things have helped people for centuries, and they’re neither FDA approved nor indicated for clinical use.

Our patient is justified in her skepticism – at least to a degree. So she finds a Research Use Only site that sells drugs on the cheap from a compounding pharmacy that happens to be located in her state. No legal or insurance loopholes to jump through. And now shipping is so much easier. Perfect!

Within days, her peptides arrive. But the bottles look dubious. A shiny wrapper boasting that the product she’s ordered is “99% pure,” “high potency” and “research-grade,” with a Certificate of Authentication (COA) from a “trusted third-party lab.” The peptides need to be reconstituted from powder to injectable liquid using something called bacteriostatic water. They can last 56 days once reconstituted, and one year in powdered form.

The patient may be feeling a little wary. If so, she wouldn’t be alone. Like Jordan in last week’s installment of this series, she’s navigating the uneasy medical consumerist territory circumscribed by urgency, scarcity, and desire. There’s a peptide that she knows could help her but has long been financially and bureaucratically out of her reach. And now here it is in its gray market form, with a wrapper that looks like it belongs on a Mars Bar from the ‘90s and a COA whose authenticity she can’t corroborate. Influencers on TikTok are telling her that reconstitution is “super easy,” but what she’s seeing in these videos looks like a lab-grade chemical process being conducted in residential kitchens without the slightest concern for sterilization or the challenges of long-term storage.

According to Verge reporter Victoria Song, there’s a lot of nuance missing from the gray market peptide world – starting with what consumers don’t know about how these drugs are being compounded. While not the same as FDA-approved brand name manufacturers like Novo Nordisk or Eli Lilly, compounding pharmacies are still state-regulated and, Song writes, often “godsends” for patients who fall outside tightly circumscribed clinical boundaries, like individuals who aren’t diabetic but are nevertheless struggling to lose weight due to hormonal conditions.

“Compounding pharmacies aren’t the same as the gray market,” Song cautions. “The gray market consists of any wholesaler, distributor, or manufacturer that sells outside of authorized distribution networks.” This is an admittedly large umbrella, including everyone from distributors who genuinely strive to ensure the safety and efficacy of their products via rigorous third-party testing to Chinese pharmaceutical manufacturers who may or may not have been previously implicated in DEA probes. The problem: there’s not yet a reliable way for the average consumer to tell the difference.

The reality of our current state of affairs is that the medical consumer to gray market pipeline is going to persist as long as demand for peptides exceeds limited – and, in view of many, bureaucratically and/or financially gatekept – supply. The idealist might wish for the overnight institution of a socialized healthcare system capable of offering compassionate, personalized healthcare to every American citizen regardless of resources. The realist will acknowledge the rosiness of this vision and then offer a more workable solution for the situation we’re in: individual vendors need to take responsibility for creating market conditions that reward safety protocol and scientific rigor. In other words: sloppiness and callousness need to become unprofitable.

Consumers can participate in this by choosing to order their peptides from vendors who are thoroughgoing and scientific when it comes to ascertaining the safety and efficacy of their peptides. But how to find these vendors and weed out the insincere ones? One need only screen a given vendor for an investment in scientific nuance – and while you’re at it, maybe input the vendor’s name in this FDA warning letter database.

In September of last year, the FDA announced “sweeping reforms to rein in misleading direct-to-consumer pharmaceutical advertisements.” In the ensuing months, the regulatory agency sent thousands of letters warning pharmaceutical companies to remove misleading ads, and approximately 100 cease and desist letters.

“Pharmaceutical ads hooked this country on prescription drugs,” Health and Human Services Secretary RFK Jr. was quoted as saying in the agency’s September 9th press release. “We will shut down that pipeline of deception and require drug companies to disclose all safety facts in their advertising. Only radical transparency will break the cycle of over-medicalization that drives America’s chronic disease epidemic.”

Though RFK Jr. is a sometime-FDA antagonist and controversial figure on both sides of the aisle, the above statement is rooted in the truth. In the free market economy in which our healthcare system currently exists, the entire medical consumerist enterprise hinges upon the successful persuasion of the medical consumer. If I have a health problem (or, in some of the more nakedly manipulative cases, if I can be convinced I have a health problem), then pharmaceutical companies have a vested interest in selling me on their drugs as the best possible solution. This is the same for healthcare professionals who are not technically employees of the pharmaceutical company, but who are nevertheless on the payroll in the form of consulting fees, speaking fees, research grants, meals, and other gifts. If I walk into the practice of a certain Dr. X who’s currently benefiting from a million-dollar Eli Lilly research grant, it’s safe to say that whatever Dr. X prescribes me is more likely than not going to align with the financial interests of Eli Lilly.

This might help to explain why many of the FDA warnings issued last year were for the “unlawful sale of unapproved and misbranded drugs to United States consumers,” frequently over the internet.

“A drug is misbranded if its labeling is false or misleading in any particular,” reads one warning letter to an online vendor that alleges to work with licensed compounding pharmacies. “A compounded drug is misbranded if its advertising or promotion is false or misleading in any particular.”

The letter goes on to cite the issue: the vendor has labeled its compounded tirzepatide and semaglutide products as having the “same active ingredients” as name-brand drugs like Zepbound, Mounjaro, Wegovy, and Ozempic.

“Compounded drug products are not FDA-approved,” the letter goes on. “Your claims imply that your products are the same as an FDA-approved product when they are not. As a result, these claims are misleading, and your products are misbranded.”

We see this verbiage over and over again, in letter after letter: the vendors advertise their compounded products as having the “same active ingredients” as FDA-approved medications, or yielding “clinically proven results” when there is no clinic to speak of. Most of these letters were sent roughly 4-5 months ago, so I revisited the sites of the affected vendors and telehealth providers to see how they’d addressed the FDA’s concerns. In most every case, wordings had been changed: one site now only mentions the FDA in conjunction with its FDA-approved prescriptions for hair loss treatments, while another has scrubbed the phrase “clinically proven” from all of its digital copy. If name-brand medications like Wegovy or Mounjaro come up at all, it’s as points of comparison to show consumers how much money they’re saving by ordering custom-compounded semaglutide or tirzepatide from the vendor in question. Put simply: the words seem to have changed while the actions haven’t.

Such subterfuge doesn’t exactly inspire confidence, especially considering what we’ve already learned about not every telehealth company, compounding pharmacy, or RUO site being created equally. But then these small businesses aren’t alone in being deceptive. In the fall of 2025, the FDA sent Eli Lilly warning letters for false or misleading claims the manufacturer made about Zepbound and Mounjaro; the agency also sent Novo Nordisk a warning letter for false or misleading claims made about the medications Wegovy, Ozempic, and Victoza. It seems not even FDA approval, patent ownership or brand-name recognition are safeguards against slipping into salesmanship.

Let’s revisit the plight of the hypothetical patient I described at the very beginning of this essay. This strange convergence of circumstances places her in something of a bind: if she can’t trust the medical establishment, the rapidly diversifying cash-pay telehealth sector, the RUO site, nor the gray market group buy, then who can she trust?

The only answer is herself. There’s certainly plenty of snake oil in the wellness and longevity worlds, but there’s also plenty of expertise – not everyone’s the guy who blended a generic bottle of tea and claimed it could cure COVID “within minutes.” There are experts like biogerontologist Dr. Matt Kaeberlein who readily acknowledges the immense research potential of peptides alongside facts about their unscientific misuse and even abuse. There are clinicians like Dr. Tyna Moore, who has guided a number of patients through GLP-1 protocols while remaining vigilant about patient safety and maintaining that all successful peptide therapies must also include substantial lifestyle changes (sleep, diet, exercise, etc.). There are research vendors like Peptide Partners, a group I am happy to work with because of their well-documented commitments to lab safety and evidence-based science.

We may all fantasize about being that rare type of human being: someone who can’t be persuaded, whose loyalty can’t be purchased, or who would never dream of helel-turning from one cause to sell her loyalty to the highest bidder. But the fact of the matter is that our messy and highly subjective human psychology is prohibitive to this kind of stoic objectivity. We all desire, and we all want to be desired in some capacity – each of us will have a different notion of what these things mean. We are hopelessly social creatures, which is not necessarily a bad thing. It’s not a bad thing to be loyal, either, nor to want to believe in a cause, nor to care about the needs and feelings of others, nor to want the basic features of a good life. The trouble only arises when that good life is promised and then retracted, remaining forever just out of reach; when your discernment is questioned and then invalidated for another party’s obvious gain.

This is all to say we ought to seek answers and solutions, even as we remain realists about the conflicted medical landscape we find ourselves in. Discernment is the enemy of blind consumption.

Stay tuned next week for part 4 of this series, in which we’ll learn more about the risks of unscientific peptide use and lapses in oversight before revisiting the need for taking an empirical approach to research compounds.

This is part two of a multi-part investigative series. Read part one here:

Part Two: Telehealth, Ease of Access, and the Medical Consumer Boom

Jordan1 realized he wanted to transition during the pandemic – not an uncommon phenomenon, he told me.

“You know, you’re at home on your phone, just scrolling through Instagram, and you’re seeing the same stuff you would have before, but now it’s basically intensified,” he said. “If you don’t have much else going on, the message that would normally be coming at you as like a little hint, a little reminder, is now coming at you with flashing red lights. This was the case for me and a lot of people I know.”

And what was that message? For Jordan, a longtime member of the Chicago queer community and therapist-in-training, it was about the freedom resulting from gender transition. “Alignment, acceptance, euphoria,” he told me.

Gender conformity and transition weren’t unfamiliar topics for Jordan. Prior to the pandemic, he had lived as a butch lesbian, and he had many friends who identified similarly. During a graduate school practicum, he’d learned about pediatric gender-nonconformity, and his class had even watched video content by the young drag performer Desi Napoles. Going to live drag shows and chatting about RuPaul’s Drag Race were both things Jordan did frequently.

“I knew plenty of trans people – like, tons of them – just living normal, happy lives. But even then, I think it was kind of scary to consider that I might be one of them,” he said.

It wasn’t until Jordan’s classes shifted online with the arrival of lockdown that he allowed himself the mental space to consider this intimidating prospect. He found himself lingering longer and longer over each video, infographic, and meme he encountered on the topic of transness or transgender rights. Had he always been uncomfortable in his body, sometimes to the degree that it negatively impacted his ability to function? Yes, he had. Growing up, had he been more inclined toward typically “boyish” or “masculine” pursuits than feminine ones? Yes. Did he feel that the misalignment of his body with his gender identity had impacted his social or romantic lives?

This last question hit home with particular intensity for Jordan. A few years before the pandemic, he had been engaged to a woman back in his progressive hometown on the East Coast. He’d felt sure they were destined to live a long and happy life together, if only they could overcome the intimacy issues they were having.

“I started binding in high school,” Jordan told me, referring to the practice of compressing one’s breasts in order to achieve the appearance of a flat chest. “And I’ve been pretty religious about wearing some form of chest binder ever since. And that didn’t always fly with my ex.”

Jordan’s fiancée couldn’t understand why he wanted to wear the binder at all times, including in the bedroom. When things came to a head, he’d floated the idea of gender transition. His fiancée didn’t take it well, and the relationship ended. “After that ugliness, the question of my gender identity kind of just stayed locked up in a little box.”

Jordan couldn’t have guessed that a global pandemic would be precisely the thing to start him questioning again. But here he was, scrolling his feed, watching YouTube videos, and following countless trans influencers on Instagram and TikTok. He described consuming this content as “liberating,” as though he’d been holding his breath for years and was finally allowing himself to exhale again.

By early 2021, Jordan had made up his mind to transition: “I had gotten to the point where I wasn’t just decided on it, but I felt like I couldn’t wait a second longer.” But the pandemic was still raging, and most gender-affirming care clinics had staggeringly long waitlists. With many hospital administrators working remotely, Jordan found it was a struggle just to get a real human being on the phone. He waited nearly an hour on hold at a popular LGBTQ+ primary care clinic with locations throughout Chicago, only to be told that the next available appointment wasn’t for another four months.

“I hit a real low point then,” he told me. “My thoughts went really dark.” Jordan feared he would become another statistic, one of the many trans people denied the right to live as their chosen gender who, according to sources like the Trevor Project and the Human Rights Campaign, choose to end their lives as a result.

But then one day Jordan’s feed offered a glimmer of hope: trans influencer Schuyler Bailar released a video promoting a popular LGBTQ+ telehealth company with a business model similar to popular telehealth sites like Hims, Hers, and Fridays: a medical patient signs up for an account, completes a medical history intake form, and is then connected via live chat, video, or telephone to a healthcare professional licensed in their state. After the telehealth visit, the clinician identifies a treatment plan, typically involving prescription medications manufactured by a U.S.-based compounding pharmacy licensed to work with the telehealth company; depending on the state the patient resides in, they may pay for their treatment plan out of pocket or qualify for insurance coverage.

Most telehealth companies endeavor to streamline care for common medical issues: anxiety, depression, weight loss, sexual dysfunction, etc. But this one was unique in that it specialized in LGBTQ+ healthcare – gender-affirming healthcare in particular. Jordan was elated. He’d finally found a way to access the HRT that would help him begin his gender transition without the interminable wait. “The idea that I wouldn’t even need to leave my house to get gender-affirming care was just so exciting to me,” he told me.

Jordan signed up, and within a week he was scheduled for his first appointment. He was feeling on track at last, finally moving towards a goal he’d had most of his adult life but had only recently allowed himself to embrace. He didn’t expect what happened next: a telehealth consultation so disorienting that he would only describe it to me on the condition that I anonymized him in this article.

“It was really weird, like something out of an episode of TV,” he told me, and proceeded to describe sitting down to a video chat with a licensed nurse practitioner who was a trans woman. This in and of itself was not unexpected – the company boasts that the lion’s share of its providers identify as some form of LGBTQ+ – but her bullishness about getting Jordan on testosterone was.

“I sat down and told her I wanted to start, and that I had some questions,” Jordan said. “Like my mind was made up, but I also wanted to know about side effects, safe administration, stuff like that. And she kind of just hurried me through it. She was so focused on making sure I answered yes to all her questions, posing them differently if I hesitated and sometimes even approaching me like I was naive and hadn’t done my research and if I had, I’d be saying yes faster. When I asked her what dosage she thought would be best for me with my height and weight, she told me I should be on the highest one to see results the fastest because I had been binding for over a decade. That didn’t make sense to me: I wanted to know about, you know, the medical side of things. Testosterone wasn’t like a car I was trying to buy.”

Jordan received what he’d wanted – a prescription for testosterone cypionate – but the provider’s saleswoman-like approach was so off-putting that it took him several weeks to start injections. And even after he’d begun to see the physical changes he’d longed for – muscles, a squarer jaw, hair on his chin – there was still a sense of uncertainty clawing at the back of his mind. Was he on the right dose? Was he moving too fast? Was there something he needed to know about his body’s reaction to the testosterone that the provider hadn’t told him? No amount of reminding himself that he’d met with a licensed medical practitioner could negate how uneasy it made him that he had to remind himself of this fact in the first place.

“It feels weird even sharing this because, like, this was supposed to be a happy outcome,” Jordan told me. “I got what I wanted, and I got it quickly. I don’t want to badmouth a company that’s apparently doing good, especially when trans rights are so viciously under attack across the country. But it’s hard not to feel kind of like a science experiment. Did I get medical treatment, or did I get a pitch? And who’s going to follow up with me?”

Shortly after his first appointment, Jordan’s care was switched to a different medical practitioner. Jordan appreciated that this new doctor was not as sales-forward as the LNP had been, but still found their meetings too short: he disliked having to offer a rapid-fire “CliffNotes” of his experience on T, and would sometimes stumble when the doctor deferred to him on matters of dosage. He appreciates having his point of view considered – a rarity in the medical field, where past paradigms saw patient testimony overwritten by expert knowledge – but he says he’d be more comfortable with a treatment plan that integrates a combination of his view and the doctor’s, especially when it comes to medical advancements about which he lacks expert knowledge.

“I’m in school to be a therapist, not a doctor – maybe that’s why I have this hypochondriac reaction every time my joints are creaky or I feel depressed or angry or I’m sick for longer than a week,” Jordan said. “I’m always like Oh god, is it the T? It’s made this very euphoric process of my transition have this kind of anxious tinge to it.”

Jordan is not alone in feeling like something is lost in the patient-forward model of telehealth: the “informed” part of the phrase “informed consent,” a requirement for any medical protocol and a necessary component of medical ethics. When a patient consents to a given medical treatment, they want to know what they’re consenting to: side effects, failure rates, and all. Though any medical intervention will always carry with it some degree of risk, it’s reasonable to expect that a given patient will want to take far more conservative risks when it comes to her health than she might take with her investments – provided she has the capital, of course – or, say, the software she’s patenting.

The body is not a startup, though this would be news to the health optimizers and self-experimenters of the tech and wellness worlds. There, the desire for bodily sovereignty converges with our down-and-out culture’s sense of urgency to produce a milieu that fetishizes taking high – and frequently uninformed – risks in pursuit of elusive rewards. For a paradigmatic example of this, one need look no further than tech founder and “immortal unc” Bryan Johnson, a centimillionaire whose stated sole purpose is “not dying.” Johnson reportedly spends over $2 million a year on longevity efforts for himself, and has drawn criticism for allegedly “snorting” stem cells and drafting his own son to serve as his “blood boy.”

In the documentary film about Johnson’s quest for immortality, Don’t Die: The Man Who Wants to Live Forever, Johnson frames his endeavors as a practical, even heroic, response to a set of unjust conditions. He was, like the rest of America, so overworked that his health was in a shambles and he barely knew his own family; he was estranged from the Mormon religious community he’d grown up in and struggling to conceal the fractures in his marriage; he was seeking professional help yet only finding professional self-interest. So he decided to take his health into his own hands and start experimenting on himself with gene therapies, fat injections, and a course of rapamycin, which is a drug typically used to slow cell growth in cancer patients.

Johnson postulates that his self-experimenting could maybe someday be of help to the non-millionaire public. How this could happen is unclear, given that Johnson is in the habit of blocking longevity scientists who suggest he allocate some of his personal fortune to fund medical research that could replicate his findings in a laboratory setting – first, by expanding his experimental group of one.

In many ways, Johnson is like the telehealth patient who arrives at his scheduled video chat with an exact sense of the treatments he wants. But unlike a telehealth patient, Johnson’s wealth places him in a realm beyond that of the average consumer of virtual medicine. He works with a team of specialists in the field of longevity, some of whom look so young it renders their research interest in looking younger a tad suspect. These specialists are compensated very well by Johnson to sustain his experimental enterprise; they function less as empirical researchers than as doctors-on-demand to suggest ways Johnson might go about not dying, and – more importantly – to prevent him from dropping dead in the process.

The subjectivity of the medical consumer emerges as a cross between the cavalier founder/self-experimenter and the pay-on-demand viewer of digital entertainment. There’s a desired outcome, a sense of urgency, and a willingness to endure a little risk in order to bypass the indignities of achieving that outcome via more traditional routes. If a consumer knows she wants to lose weight, has struggled her entire life to do it, and knows there’s a product that can alleviate her life’s struggle, what’s the sense in forcing herself to endure the embarrassment of an in-person visit to a doctor who may or may not be sympathetic to that struggle, who may throw up guardrails or even gaslight the consumer for a set of totally arbitrary professional reasons?

Medical care is not a social service in the United States: it’s a consumer good whose affordability, like any consumer good’s, is dictated by market forces of supply and demand. The availability of medical care – from the basics of primary care to the costly personalized longevity protocol of Bryan Johnson – hinges upon the financial resources (and often social standing), of a given consumer. Naturally, this reality exposes the medical field to the many conflicts of interest and iniquities one might find in any realm of the profit-driven private sector. So the medical consumer thinks something like the following: If medicine is already stacked against me, and in the interest of doctors and pharmaceutical companies, why should I play their game? She willingly enters a different paradigm, one in which she pays for the health she wants on demand, without any of the unnecessary friction.

I recently asked a friend who’s active in the peptide gray market how difficult it would be to get a prescription for retatrutide, a non-FDA approved GLP-1 agonist, from a telehealth platform like Hers or Fridays. “Very easy,” she said, without batting an eye. “Today, you can have an RX within the hour. You join, have a telehealth call or FaceTime, and that’s it.”

There’s no doubting the convenience of this, and it certainly fits neatly with the aims of the medical consumer. But as my friend and I spoke, I couldn’t help remembering Jordan’s ordeal. When I checked in with him again recently, he’d just celebrated two years on testosterone. He was seeing plenty of the physical changes he’d longed for, but he was also experiencing symptoms that worried him. Rapid fat gain totaling nearly 80 pounds despite no changes in diet or exercise. Irregular thyroid levels. Periods of insomnia or “sped up” cognitive activity that were causing him to miss whole nights of sleep in a row.

“Do I think it’s the T?” he wondered to me via text. “I don’t know. I don’t want to believe it is. There are so many ways that HRT’s helped me, too – like really helped me become who I am. But at the same time, that hypochondriac at the back of my head can’t stop worrying. And I just feel like I can’t ask. Some trans friends, when I’ve brought this up, tell me asking would be like setting our entire cause back. I can’t imagine going so far down this rabbit hole and then realizing that I need to detransition or something. That would be the ultimate mindfuck.”

Jordan is in a bind not altogether different from any consumer of peptides. With FDA approval for many compounds either far on the horizon or nonexistent, average consumers who have been able to gain access to these compounds have felt their connections tenuous at best. Raising complaints or even bringing up symptoms can sometimes feel like a surefire way to jeopardize one’s access to a compound that has now become an immensely valuable facet of the consumer’s life. Telehealth is convenient and practically frictionless, but the costs are still prohibitive for many. At Hims, insurance isn’t accepted; at Hers, consumers are warned that weight loss drugs are only covered for those with type 2 diabetes. Medical expertise is also out of reach for vast swaths of the population, and regarded as a fiction (and a friction) by many.

So, what’s the answer? What’s the affordable, readily accessible treatment plan that strikes the perfect balance between doctor and consumer, expert knowledge and lived experience? Is there such a thing as unbiased expert knowledge? What about unmanipulated lived experience? (We can certainly be sure that there’s no such thing as objective subjectivity.)

These are probing philosophical questions with no ready answers, but they do reflect the state of affairs in today’s peptide world. There’s no contesting that medical consumerism rules the day in the ever-expanding frontiers of wellness and longevity, a fact which has its upsides and downsides. The real threat to the longevity – pun intended – of peptides in the research world isn’t so much public enthusiasm for them, or even the willingness to experiment with compounds whose long-term effects are unproven. It’s the senses of urgency and desperation, the influencer marketing pushes and the cognitive biases, the distortions of the truth and the abandonment of the scientific method in favor of shoddy experimental practices, the dogged pursuit of instant results. It’s the experimentation without guardrails, the ubermensch approach that willfully forgets why every randomized controlled trial requires not only time, but experimental and control groups and well calibrated tools of measurement.

It’s certainly true that there are corruption and self-interest aplenty in the medical and research fields. Doctors who brush off patient concerns or not-so-subtly pressure them into opting for the prescription du jour are complicit in the more coercive aspects of medical consumerism. When the doctor becomes a yes man – or worse, a salesperson – then it’s safe to say any pretense of expertise has long since flown out the window.

Still, the existence of such cynicism doesn’t mean the entire medical field is deserving of condemnation, nor the scientific method. Failures to practice ethical medicine are precisely that: failures in the practice, not evidence of failure in the practice itself. As a culture, we find ourselves at a crossroads: How do we restore a panicked public’s faith in science? How do we separate research interests from consumer ones and remind clinicians that healthcare is, at base, about health?

Stay tuned next week for part 3 of this series, we’ll learn more about the medical consumer to gray market pipeline, and how certain Research Use Only sites have been dodging FDA warnings to continue peddling untested cures.

For those of you new to the journalistic side of the Peptide Partners Corner, welcome! For those of you returning: it’s good to see you again!

You may be wondering why a Substack known for its articles about evidence-based findings in the world of peptide research would also publish journalism about topics like the dangerous peptide gray market and the numerous risks of unregulated peptide use. This is because Peptide Partners and its affiliates are committed to an understanding of peptides as research compounds with powerful medical and scientific potential. And in order to better understand how peptides can function as a public good, it is necessary to investigate instances of peptide misuse – not just so these increasingly popular trends can be warned against, but so the safe and regulated study of peptides can continue unimpeded.

What does this mean for you, reader of the Peptide Partners Corner? What it means is that along with our usual reportage about scientific advancements and safety protocols in the research peptide world, you can also expect to find investigative reports highlighting the perils of ignoring those advancements and protocols. In our investigative work, we aim to ask the following questions:

• What happens when a skeptical consumer base decides that “sovereign health” is more valuable than heeding the guidance of medical and scientific experts?

• What happens when medical consumerism allows any patient to become her own prescribing doctor for a price?

• What does it mean for profit and ideology to overtake proven scientific methodology?

We ask these questions not just because the research value of peptides is evident, but because the reckless misuse of peptides threatens to obfuscate that value and undermine scientific progress. Nowhere is this more evident than in the realm of consumer medicine, where health is in demand and “solutions” are in supply but expertise runs woefully short.

The following investigative series tackles this issue with regards to the manufacture and sale of peptides, exploring how some Research Use Only (RUO) sales sites, motivated by consumer demand and an increasingly laissez faire medical market, are thumbing their noses at regulatory oversight — even some that could actually protect consumers.

How can you know who to trust? Read this series to find out.

Part 1: Willpower Is Out, Biohacking Is In

In September of last year, the FDA announced “sweeping reforms to rein in misleading direct-to-consumer pharmaceutical advertisements.” In the ensuing months, the regulatory agency sent thousands of letters warning pharmaceutical companies to remove misleading ads, and approximately 100 cease and desist letters.

“For far too long, the FDA has permitted misleading drug advertisements, distorting the doctor-patient relationship and creating increased demand for medications regardless of clinical appropriateness,” said FDA Commissioner Marty Makary. “Drug companies spend up to 25% of their budget on advertising. Those billions of dollars would be better spent on lowering drug prices for millions of Americans.”

Dr. Makary’s point is a cogent one, and to fully understand the ramifications of the market forces he’s objecting to, it’s necessary to understand the strange ecosystem formed by direct-to-consumer pharmaceutical companies and the public’s waning faith in scientific best practices.

In an essay titled “Testosterone Gave Me My Life Back,” former professional poker player and current Astera CEO Cate Hall recounts the numerous ways beginning testosterone replacement therapy (TRT) has improved her life after 40. What began as an effort to restore a waning sex drive transformed into a large-scale solution to a variety of problems: sleep disturbances, cognitive issues, and dysregulated moods.

“The best way I can describe it is that it uniformly lowered the activation energy required for pretty much every activity,” Hall writes, going on to describe her new exercise habits, personal records for the Times crossword puzzles, and marked decrease in her anxiety levels. Why had she been trying for so many years to change her bad habits, only to encounter more and more resistance from her mind, body, and the world around her? Why try to make a broken system work for yourself when a better life wasn’t just close, but ready to hand? “Willpower is overrated; biochemistry is king,” Hall concludes.

And Hall isn’t the only one. Ours has always been a convenience-obsessed culture, keen to maximize impact while minimizing effort. The pejorative way to describe this tendency might be with the word “laziness,” but another way to think of it would be in terms of efficiency, or cost-benefit optimization. There is value in hard work, certainly, but not in hard work with ill-defined or poorly matched outcomes. And if a high-performing CEO of a multibillion dollar private foundation like Cate Hall is encountering resistance to effecting positive changes in her life, then what hope is there for the average American?

The answer is very little, or else this is how people seem to feel. A 2025 Gallup poll revealed that only 48.9 percent of respondents categorized their quality of life as “thriving,” only one of three sub-50 percent rates ever to be measured outside of the Great Recession and the COVID-19 pandemic. While these rates were informed by the outcome of the 2024 election – Democrats saw a thriving rate decrease of 11 points, whereas Republicans jumped 5 points and Independents stayed roughly the same – it’s worth noting that the overall thriving rate was also 48.9 percent when it was measured in Q3 2023 during Joe Biden’s presidency.

Why such low rates? Gallup’s National Health and Wellbeing Index approaches the question of whether one is “thriving,” “struggling” or “suffering” with a battery of questions concerning topics like material stability and hope for the future. Tellingly, it was the following two questions that have driven the drop in the thriving rate: “Have you worried about money in the past seven days?” and “Is there a leader in your life who makes you enthusiastic about the future?” As it turns out, Americans were feeling just as cash-strapped and in want of competent leadership in 2023 as they were in 2025.

Material instability and political uncertainty combine to create an overall feeling of helplessness and precariousness. How can consumers be expected to afford the space and time to improve themselves when they can barely afford rising gas prices? Why invest in long-term solutions like diet, exercise, and meditation when the very idea of the long-term itself is in question? And why trust the clinical guidance of an expert, when the so-called “experts” elected to lead the country and its most time-honored institutions have proven feckless at best? When factoring the questions of happiness, agency and trust into the larger equation, it’s easy to see that it’s much more than laziness driving consumers’ search for easy solutions: it’s urgency fueled by widespread fear and uncertainty.

“The universe rewards calculated risk and passion,” noted wellness enthusiast and BPC-157 promoter Joe Rogan told his millions of podcast listeners. And what does biohacking promise, if not a reclamation of agency and a vanquishing of uncertainty? Optimize your biology with direct-to-consumer research compounds and you won’t have to worry about a good life that’s forever vanishing on the horizon. You can have it now, and you can have it with zero resistance, as long as you’re willing to take a little calculated risk and approach the project of your health with passion.

The only problem with this approach is that without the medical or scientific knowledge required for understanding what peptides are and how they function in the human body, there is no way to distinguish a calculated risk from a reckless one. The truth is that, while peptides can have an enormously positive impact on biological systems that influence longevity – e.g. growth hormone release, metabolism, and inflammation repair – that impact will only last when a given peptide protocol is done in concert with a healthy lifestyle. “Can peptides replace a healthy lifestyle?” writes Dr. Khanh Nguyen of Austin Regenerative Therapy. “Never. Peptides work best with lifestyle optimization–nutrition, exercise, sleep, and mindset are the foundation.”

This is something that’s often forgotten in the consumer public’s rush to find a silver bullet for all their problems with the aid of a little “calculated risk” – silver bullets don’t exist. Peptides are complex proteins that support our bodies’ natural systems, but cannot override or rewire them. As Nguyen observes, peptides “encourage cells to repair, rejuvenate, and function more efficiently” and optimize existing systems by “helping the human body ‘remember’ how to heal and renew itself.” They cannot replace those systems in cyborgian fashion. This is what it means for peptides to be “naturally occurring.”

The aforementioned urgency, desperation, and promise of ease are all working against a more nuanced public understanding of these compounds. So are declining trust in medically trained experts and the regulatory guidance and oversight of the FDA. Unfortunately, these are conditions that certain major players in the direct-to-consumer pharmaceutical world have been all too keen to take advantage of.

Stay tuned next week for part 2 of this series, we’ll learn how telehealth companies and rapidly unfolding medical consumerist trends have contributed to the rise of untrustworthy peptide peddlers.

This is the fourth installment of a four-part series. Read the other installments here:

Inside the Strange World of Peptide Group Buys

Peptide Cults and Cartel Bosses: Down the Group Buy Rabbit Hole

Wellness Optimizers and Self-Experimenters: The Peptide Wild West

Part 4: Restoring Faith in Science: the Importance of FDA Oversight

Dr. Matt Kaeberlein is a biogerontologist, which is a fancy way of saying that he’s a biologist who studies how the human body ages, and what mechanisms of aging are conserved across our evolutionary patterns. He’s also a professor of pathology at the University of Washington in Seattle, and he believes that peptides ought to be rigorously studied before being administered in a clinical setting, much less self-administered from an untested, grey market purchase.

“Broadly speaking, peptides are bioactive molecules, and some peptides will definitely have beneficial effects, [like] GLP-1 agonists for people who have obesity or diabetes,” Kaeberlein said recently on his Optispan podcast. “But I think for a variety of reasons, the scientific research has not actually been done to be able to use [other popular peptides] in an effective way medically.”

Kaeberlein asserts that randomized controlled trials (RCTs) over long periods of time are the gold standard for determining a given treatment’s effectiveness. This would involve the recruitment of a statistically significant number of individuals, the random assignment of those individuals to control and experimental groups, and the monitoring of those individuals’ reactions to peptide treatments over time. Unlike Bryan Johnson snorting stem cells in the Bahamas, an RCT would produce empirical data about the impact of a given treatment on a group of individuals, and would inform safety protocol for future clinical use. Though an RCT takes time, in other words, it pays massive dividends: more people get safe and affordable access to a potentially life-changing treatment.

It’s easy to imagine the cavalier self-optimizer laughing this off as so much pointless noise. I’m sure you’ll recall the “high risk tolerance” tech founders Jasmine Sun encountered in San Francisco. The guy who just founded a startup valued in the hundreds of millions and feels impervious to the realities of the world. The guy who’s sick of being a pale ginger and so starts injecting melanotan he ordered from his “guy in China.” But no matter how rich you are, or how much you trust pepbrother888 in Beijing, it doesn’t change the fact that regulatory agencies like the FDA exist for a reason. Without rigorous RCTs and the FDA overseeing when and how drugs that have cleared all phases of clinical trials enter the mainstream for public consumption, we’re left with what Verge reporter Victoria Song calls the “wellness wild west.”

But how to remind a distrustful population that the scientific method is, in fact, the consumer’s friend?

Though clinical trials are slow-moving, they are still happening.

Contrary to RFK Jr.’s conspiratorial sabre-rattling about the FDA “suppressing” helpful peptides, a number of them are currently in clinical trials to determine their safety and efficacy for medical use. These include tirzepatide, retaglutide, and peptide-based radiopharmaceuticals for use in the diagnosis of neuroendocrine tumors. Data from these studies will help inform how to safely administer peptides that are already popular on the gray market. Even better: if and when these compounds are approved by the FDA, they’ll be more affordable for pharmaceutical companies to manufacture and for consumers to obtain, and even more affordable/widely available when specific drug patents expire.

FDA guidance and oversight means high-purity, non-toxic peptides.

China’s comparatively lax regulatory climate has facilitated the quick manufacture of many peptides, including the gray market varieties that aren’t up for clinical review in the United States. And it’s that same regulatory climate that has resulted in the manufacture and shipment of untested and potentially impure research chemicals.

It’s certainly unnerving to receive a vial of peptides that tests low on purity, or has a falsified COA. But, as we’ve seen before, a high-purity test result isn’t a complete guarantee of safety. Even the purest peptides are susceptible to developing endotoxins, or lipopolysaccharides from the gram-negative bacteria used to synthesize amino acid chains. Endotoxins are some of the most potent biological toxins in existence, and are very harmful – even fatal – if ingested.

The facts are clear: taking peptides that haven’t been submitted to third-party testing and independently verified to be safe and non-toxic is like playing Russian roulette with your health. The path to the normalization and standardization of these practices will come through scientific research and the guidance and oversight of the FDA.

The relationship between clinicians and scientists is a symbiotic one.

While many clinicians do currently offer therapies using peptides that are still undergoing clinical trials, these therapies must be informed by scientific findings in order to yield any sort of efficacy. A good clinician is someone who stays abreast of current scientific literature and weighs the risks and the benefits for individual patients before initiating a given health protocol – risks and benefits that should not be informed by the patient’s emotions, the political climate, pressure from colleagues, or any other social or economic interests. We would all do well to remember that clinicians are in service roles, not research ones: they don’t have access to the mechanisms for producing empirical data. Rather, it’s their job to implement the data researchers produce in lab settings.

Finally, a clinician’s willingness to explore new peptide therapies is not a guarantee alone of his or her trustworthiness. We’ve seen this with the case of Dr. Kent Holtorf, whose peptide injections at last year’s RAADFest in Las Vegas left two attendees in critical condition. Holtorf also received a warning from the Federal Trade Commission after making scientifically unfounded claims that certain peptides could “protect” patients from and even “cure” COVID.

There are only two things that can protect the health of consumers: research and regulatory oversight. If we abandon our faith in empirical data, then we render ourselves vulnerable to the whims of profit-driven manufacturers, vengeful vendors, and a Bay Area startup culture convinced it can move faster than the scientific method. The problem with all this lies in the major fallacy of its logic: it was the scientific method – rigorous testing, close observation, trial and error – that gave us these peptides in the first place.

In our next research peptide deep dive, we’ll learn more about Research Use Only sites, how they work (or don’t) with compounding pharmacies, and how they’ve responded to FDA warnings.

This is part three of a four-part series. Read parts one and two below:

Peptide Partners Corner

Inside the Strange World of Peptide Group Buys

If you’re reading this, then you probably already know which peptides have been approved for human use by the FDA. As is frequently the case for cutting-edge pharmaceutical compounds, peptides have entered the clinical world as treatments for serious diseases: e.g. semaglutide for diabetes management (Wegovy, Ozempic), teriparatide for osteoporosis (For…

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4 months ago · 4 likes · 2 comments · Peptide Reporter

Part 3: Wellness Optimizers and Self-Experimenters

A sense of “outsiderly” desperation is just one of many factors driving people to purchase peptides in the ethically dubious and potentially dangerous world of gray market group buys. There’s also been a marked cultural shift in how Americans think of health and longevity – a shift that shares some ideological DNA with attitudes infallibility emerging from Silicon Valley’s risk-hardy culture of innovation at all costs.

In an interview on the Bloomberg podcast Odd Lots, San Francisco tech and culture reporter Jasmine Sun described the prevailing attitude she’d observed among young tech founders as one of “high risk tolerance.” Sun had witnessed members of the tech community taking non-FDA approved peptides purchased through gray market Chinese vendors. Some had even boasted about “having a guy in China” or knowing a “peptide dealer.” Sun admitted to being a bit weirded out by the cavalier vibe, especially when it comes to injecting one’s body with foreign substances of debatable provenance.

“Almost everyone I spoke to [about this], I’d ask, ‘Hey, are you scared? Are you worried?” Sun told Odd Lots. “And most of them would tell me, ‘I have a higher risk tolerance than most people…I’m the kind of person who doesn’t really need to wait until I’m given permission to do something, whether that’s by a regulator, or by some boss.”

This is a mentality that we’ve seen serve founders well since the early days of the tech boom in the mid-aughts: wresting expertise from the hands of experts (and questioning the very notion of “expertise” altogether); forging ahead with experiments, pitches, and prototypes instead of waiting for a senior partner’s advice or approval. Moving fast and breaking things, in other words – an approach that requires more than a little arrogance and foolhardiness, but has been proven time and time again to generate massive payoffs. Why not take a risk – even an extraordinary one – and get rich? Order a Tesla robotaxi, start a Zoosk profile, buy a self-driving car? Use yourself as the human test subject, like Blueprint founder Bryan Johnson did by taking the cancer drug rapamycin or injecting stem cells? Embrace the future, in other words, instead of trying to recapture a swiftly vanishing past?

“I think San Francisco is really leaning into its identity these days of not being the place that’s suffering under the regulatory decelerationist burden that’s plaguing the rest of the Western world,” Sun said. “And I think peptides are a part of that.”

Innovation, futurity, and an enthusiasm for deregulation are parts of the Silicon Valley Weltanschauung that have never had trouble gaining purchase in the U.S. government, or in the broader culture at large. Secretary of Health and Human Services RFK Jr. has been an outspoken proponent of sovereignty on the national and individual levels when it comes to matters of health. In addition to his famously controversial views on vaccine mandates, he also opposes WHO mandates that would grant unelected international bodies the ability to interfere with American self-reliance, and supports both Indigenous self-determination and tribal sovereignty, especially when it comes to bodily integrity.

Notably, RFK Jr. is also an enthusiastic proponent of peptides. He has strongly advocated the benefits of BPC-157, and claimed that the FDA is suppressing useful peptides. RFK Jr. is good friends with biohacker, longevity enthusiast, and Ultimate Human founder Gary Brecka, who is well-known for his support of both BPC-157 and Sermorelin, which stimulates the production of HGH. RFK Jr. and Brecka have engaged in other wellness practices together, like trying a hyperbaric oxygen chamber and intravenous nutrition drips at Brecka’s penthouse.

Influencers like Brecka and RFK Jr. interlocutor Joe Rogan are for many the public face not just of peptide use, but of the broader wellness movement. Some may know it as MAHA (Make America Healthy Again), an RFK Jr. term they picked up not from the HHS Secretary himself, but from the constellation of influencers and podcasters surrounding him. “Momfluencers” like Vani Hari – whose Food Babe blog intends to expose harmful food additives not disclosed on product labels, among other things – and Zen Honeycutt – founder of the anti-GMO nonprofit Moms Across America – provide a feminine compliment to the decidedly male-dominated longevity and wellness sphere online. But Hari and Honeycutt share something crucial in common with popular biohackers like Andrew Huberman and “immortal unc” Bryan Johnson: a deep and abiding suspicion of “big pharma” and federal regulatory agencies like the FDA and CDC.

In many ways, this attitude is a mirror of a broad public sentiment that has been percolating since COVID. We all watched while half the country assiduously embraced masking mandates while the other half rejected them. And then we all watched with increasing anxiety as the pandemic progressed and the masked camp claimed non-maskers were inflicting a “genocide” upon the imnunocompromised, while the unmasked camp claimed masking mandates were “unconstitutional,” and an infringement of their civil rights. For many of us, that anxiety became horror pursuant to the following: 1) the CDC changed its recommended COVID isolation period from ten days to five, citing only “what we currently know about the Omicron variant”; 2) medical practitioners began opening up about the impact of ruthless market incentives on FDA-approved COVID treatments.

On the heels of unmitigated public health emergencies like the opioid crisis, the twin epidemics of depression and loneliness, and working class/impoverished America’s persistent lack of access to nutritious food, public faith in the federal government’s ability to protect the health of the American populace is at an all-time low. An Axios/Ipsos American Health Index poll taken in October of last year revealed that only 54% of respondents found the CDC trustworthy (as opposed to 66% in December 2024), and only 47% still trust federal food safety standards as advanced by the FDA.

Add to all of this the distrust of clinical expertise emerging from within medical spaces. Naturopath and chiropractic physician Dr. Tyna Moore has decades of experience working with peptides, hormone replacement therapy, and other anti-aging and anti-inflammatory protocols. On a recent episode of her podcast, she reports being badgered by colleagues who didn’t understand why she turned some patients away for treatment. They accused her of “taking away hope” from her patients, which struck Moore as a dangerous thing to say. “These procedures are not covered by insurance under any circumstances, they are expensive, they are invasive, they are potentially risky…why would I put someone through that if they weren’t primed and ready to receive that treatment, and have the best outcomes possible?”

Moore is keen to remind potential patients that peptides should be taken under clinical supervision, and that the most effective peptide protocols are the ones administered to patients who have made lifestyle chances – eating, sleeping, activity – that will prime their bodies to benefit from those treatments. But Moore is one of very few voices in a sea of influencers crowing about their weight loss and pushing their peptide affiliate links.

In many ways, the cultural stew of post-COVID America has done much to aid and abet unregulated peptide use. Tech innovation and cavalier self-experimentation combined with a deep distrust of federal regulatory agencies – a distrust that extends to members of the federal government itself – means that more and more Americans are feeling empowered to take matters of their health into their own hands.

At base, this isn’t necessarily a bad thing: there’s nothing wrong with staying abreast of scientific findings and learning more about what is and isn’t right for your health. In fact, there’s nothing stopping us average Americans from absorbing enough knowledge to claim a sort of armchair expertise. And it’s certainly true that there’s no one more knowledgeable about the lived experience of our individual bodies than we are: this sentiment has been a popular rejoinder to the misogyny and underdiagnosis encountered by many women in medical settings, and even undergirds feminist and postcolonial theories of oppression and liberation that have gained widespread currency since the 2020 George Floyd protests.

But all of this leaves a crucial question unanswered: If Americans no longer trust the guidance and oversight of federal regulatory agencies staffed by medical and scientific experts with vast stores of experience in their respective fields, what makes us more inclined to trust wellness influencers hocking their merch, gray market Chinese peptide manufacturers, or faceless GB organizers like Sandy, accountable to no one and incentivized solely by profit? Is it the novelty of these “experts” who aren’t experts in the least? Is it the desperation and lack of belonging Em identified in last week’s installment? Or is it a dangerous combination of both?

Next week, we’ll explore how fear trumps science and revisit why FDA oversight and medical expertise are critical when it comes to peptide therapies.

PT-141 is a synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH), a naturally occurring peptide that plays a role in everything from skin pigmentation to appetite. Specifically, PT-141 is a metabolite of Melanotan II, the actual sunless tanning agent from which it was derived. During the initial clinical trials for Melanotan II, researchers noted that a significant number of male subjects were experiencing spontaneous erections. This unexpected observation prompted a shift in research focus, leading to the isolation and development of PT-141 as a dedicated sexual health therapeutic [2].

What makes PT-141 so significant is its unique mechanism of action. Unlike blockbuster drugs like Viagra or Cialis, which target the vascular system to improve blood flow, PT-141 works directly on the central nervous system. It is a melanocortin receptor agonist, primarily targeting the MC3R and MC4R receptors in the brain, which are known to be involved in the regulation of sexual desire and arousal. This central mechanism allows PT-141 to address the psychological and emotional aspects of sexual function, not just the physiological ones [3].

This novel approach culminated in the 2019 FDA approval of Bremelanotide, marketed as Vyleesi, for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This was a landmark achievement, providing a much-needed therapeutic option for a condition that had long been underserved by the pharmaceutical industry. While its journey began with the cosmetic goal of a sunless tan, PT-141’s ultimate destination was the far more complex and important landscape of human sexual health [4].

The Central Nervous System Approach to Arousal

The therapeutic innovation of PT-141 lies in its departure from the traditional, vascular-focused approach to treating sexual dysfunction. Instead of targeting the plumbing, it targets the brain, the true epicenter of sexual desire and arousal. This central nervous system (CNS) mechanism is what distinguishes PT-141 from all other approved sexual health medications and allows it to address a different and arguably more fundamental aspect of sexual function.

PT-141 is a non-selective agonist of the melanocortin receptors, with a particular affinity for MC3R and MC4R, which are densely expressed in areas of the brain associated with sexual behavior, such as the hypothalamus. When PT-141 binds to these receptors, it initiates a cascade of downstream signaling events that are thought to modulate the activity of key neurotransmitter systems involved in sexual arousal, including dopamine, norepinephrine, and serotonin. The precise details of this cascade are still being elucidated, but the net effect is an increase in sexual desire and a heightened state of arousal [3, 5].

This is a fundamentally different approach from that of phosphodiesterase type 5 (PDE5) inhibitors like sildenafil (Viagra). PDE5 inhibitors work by enhancing the effects of nitric oxide in the corpus cavernosum of the penis, leading to increased blood flow and facilitating an erection. This is a purely mechanical effect, and it requires the presence of sexual stimulation to be effective. If the desire is not there to begin with, PDE5 inhibitors are of little use. PT-141, on the other hand, works to generate that desire in the first place. It is a starter, not just a facilitator [2].

This central mechanism has important implications for the treatment of both male and female sexual dysfunction. For men with erectile dysfunction (ED) who do not respond to PDE5 inhibitors, PT-141 offers a potential alternative or synergistic therapy. Many cases of so-called “Viagra failure” are not due to a vascular issue but to a lack of underlying desire, a problem that PT-141 is uniquely equipped to address. For women with HSDD, a condition characterized by a persistent lack of sexual thoughts, fantasies, and desire, PT-141 provides the first-ever on-demand treatment that targets the neurological roots of the condition [4, 6].

The development of PT-141 represents a significant step forward in our understanding of the neurobiology of sexual function. It has validated the melanocortin system as a key therapeutic target and has opened the door to a new class of centrally-acting drugs for the treatment of sexual dysfunction. By shifting the focus from the periphery to the brain, PT-141 has not only provided a new therapeutic option but has also deepened our appreciation for the complex interplay of mind and body in human sexuality.

A Landmark Achievement in Women’s Health

The FDA approval of Bremelanotide (Vyleesi) in 2019 for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women was a watershed moment in sexual medicine. It marked the culmination of a long and often challenging development process and provided a much-needed, on-demand treatment for a condition that affects millions of women and had long been neglected by the pharmaceutical industry. The clinical trial program that led to this approval, known as the RECONNECT studies, provides a clear picture of PT-141’s efficacy and safety in this population [4, 7].

The RECONNECT studies were two large, randomized, placebo-controlled Phase 3 trials that enrolled over 1,200 premenopausal women with HSDD. The primary endpoints of these studies were an increase in the Female Sexual Function Index (FSFI) desire score and a decrease in the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) Item 13 score, which measures the level of distress associated with low sexual desire. The results were statistically significant and clinically meaningful. Women treated with PT-141 experienced a significant improvement in their sexual desire and a significant reduction in the distress caused by their condition compared to those treated with placebo [8].

These results were particularly impressive given the challenges of studying a condition like HSDD, where subjective endpoints and a high placebo response rate can make it difficult to demonstrate efficacy. The fact that PT-141 was able to show a consistent and statistically significant benefit across two large trials provided strong evidence of its therapeutic value. The most common side effects reported in the trials were nausea, flushing, and headache, which were generally mild to moderate in severity and tended to decrease with repeated use. The development of an autoinjector for subcutaneous administration also improved the convenience and tolerability of the treatment [7, 8].

While the FDA approval is limited to premenopausal women with HSDD, the potential applications of PT-141 extend to other populations as well. The off-label use of PT-141 for the treatment of erectile dysfunction in men is widespread, particularly for those who do not respond to PDE5 inhibitors. The rationale is clear: if the underlying issue is a lack of desire rather than a vascular problem, a centrally-acting agent like PT-141 is a more appropriate therapeutic choice. While large-scale clinical trials in this population are still needed, the wealth of anecdotal evidence and the strong biological plausibility suggest that PT-141 could be a valuable tool in the management of male sexual dysfunction [6].

The potential for PT-141 to be used in combination with other sexual health medications is another exciting area of exploration. For men with mixed-etiology ED (i.e., both vascular and psychological components), a combination of PT-141 and a PDE5 inhibitor could be a particularly effective strategy, addressing both the central and peripheral aspects of the condition. For women, the possibility of combining PT-141 with other therapies to address different aspects of sexual dysfunction, such as arousal or orgasm, is also an area of active interest. The 2025 research landscape continues to evolve, with ongoing studies exploring new formulations and applications for this versatile peptide [9].

The Future of Centrally-Acting Sexual Health Therapies

The story of PT-141 is a powerful illustration of how a single, serendipitous observation can reshape a field of medicine. Its journey from a failed sunless tanning agent to a landmark FDA-approved treatment for female sexual dysfunction has not only provided a new therapeutic option but has also fundamentally changed the way we think about the treatment of sexual disorders. By validating the melanocortin system as a key therapeutic target, PT-141 has paved the way for a new generation of centrally-acting drugs that promise to be more effective and more personalized than ever before.

The future of PT-141 and other melanocortin agonists will likely involve several key areas of development. First, the expansion of its approved indications to include men with erectile dysfunction and postmenopausal women with HSDD is a logical next step. The biological rationale is strong, and the unmet medical need is significant. Second, the development of new formulations with improved tolerability and convenience, such as oral or intranasal delivery systems, could further enhance its clinical utility. Third, the exploration of combination therapies, pairing PT-141 with other agents to address the multifaceted nature of sexual dysfunction, holds great promise.

Perhaps most importantly, the success of PT-141 has reinvigorated research into the neurobiology of sexual desire and arousal. It has reminded us that sexual function is not just a matter of plumbing and blood flow but a complex interplay of neurochemistry, emotion, and psychology. As we continue to unravel the intricate workings of the brain’s sexual circuitry, we can expect to see the development of even more sophisticated and targeted therapies that build on the foundation laid by this remarkable peptide.

PT-141 is more than just a drug; it is a proof of concept. It has demonstrated that it is possible to develop safe and effective treatments for the central components of sexual dysfunction, opening up new avenues of hope for millions of people who have been let down by traditional, peripherally-acting therapies. Its legacy will be not only the lives it has changed but also the scientific and medical innovation it has inspired.

References

[1] Dhillon, S. (2019). Bremelanotide: First Approval. Drugs. https://pubmed.ncbi.nlm.nih.gov/31429064/

[2] King, S. H., et al. (2007). Melanocortin Receptors, Melanotropic Peptides and Penile Erection. Current Topics in Medicinal Chemistry. https://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000011/art00007

[3] Bremelanotide: Uses, Interactions, Mechanism of Action. DrugBank. https://go.drugbank.com/drugs/DB11653

[4] Vyleesi (bremelanotide) FDA Label. (2019). https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf

[5] Ückert, S., et al. (2014). Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies. Expert Opinion on Investigational Drugs. https://www.tandfonline.com/doi/abs/10.1517/13543784.2014.934805

[6] PT-141 for Men: A New Drug to Treat Erectile Dysfunction and Low Libido. Men’s Reproductive Health. https://mensreproductivehealth.com/pt-141-for-men-a-new-drug-to-treat-erectile-dysfunction-and-low-libido/

[7] FDA Approves New Drug Application for Vyleesi (bremelanotide injection). (2019). Palatin Technologies. https://palatin.com/press_releases/fda-approves-new-drug-application-for-vyleesi-bremelanotide-injection-2/

[8] Diamond, L. E., et al. (2006). An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. The Journal of Sexual Medicine. https://academic.oup.com/jsm/article-abstract/3/4/628/6882956

[9] Ila, V., et al. (2025). Intravenous peptides and amino acids for erectile dysfunction: a narrative review of current applications and future directions. Expert Opinion on Pharmacotherapy. https://www.tandfonline.com/doi/full/10.1080/14656566.2025.2478912

This finding was a landmark in peptide research. It demonstrated that the complex biological activity of a large hormone could be distilled down to a simple, three-amino-acid sequence. This had significant implications for drug development. The small size of KPV makes it easier and cheaper to synthesize than its parent hormone, and its focused mechanism of action means it can deliver the anti-inflammatory benefits of α-MSH without the other, often unwanted, hormonal effects. It is a case of molecular reductionism at its finest, isolating the signal from the noise [2].

KPV’s primary mechanism is the potent inhibition of the pro-inflammatory NF-κB signaling pathway. By preventing the activation of this master regulator of inflammation, KPV can effectively shut down the production of a wide range of inflammatory cytokines and mediators. This makes it a powerful tool for treating a variety of inflammatory conditions, from inflammatory bowel disease (IBD) to skin disorders like psoriasis and eczema. Its ability to be administered orally and topically further enhances its versatility as a therapeutic agent [3].

Recent research has continued to expand our understanding of KPV’s capabilities. A 2025 study highlighted its ability to protect skin cells from damage caused by environmental pollutants, while other 2025 research explores its role in novel drug delivery systems for treating vascular calcification. These findings underscore the broad potential of this simple tripeptide, a molecule that proves that in the world of biology, size does not always determine strength [4, 5].

The Intracellular Anti-Inflammatory Pathway

KPV’s therapeutic power lies in its ability to penetrate cells and directly modulate the intracellular machinery of inflammation. Unlike many anti-inflammatory drugs that work by blocking cell surface receptors or neutralizing extracellular cytokines, KPV gets to the very heart of the inflammatory process, shutting it down from the inside out. This intracellular mechanism is a key to its potency and its broad spectrum of activity.

The primary target of KPV is the NF-κB (nuclear factor kappa B) signaling pathway. NF-κB is a protein complex that acts as a master switch for the inflammatory response. In a resting cell, NF-κB is held inactive in the cytoplasm. When the cell is stimulated by an inflammatory signal, a cascade of events is initiated that leads to the activation of NF-κB and its translocation into the nucleus. Once in the nucleus, NF-κB binds to the DNA and switches on the genes for a host of pro-inflammatory molecules, including cytokines like TNF-α, IL-1β, and IL-6. KPV has been shown to potently inhibit this process, preventing the activation and nuclear translocation of NF-κB and thereby blocking the production of these key inflammatory mediators [1, 3].

This is a fundamentally different approach from that of many conventional anti-inflammatory drugs. For example, monoclonal antibodies like infliximab (Remicade) work by binding to and neutralizing a single cytokine, TNF-α, in the extracellular space. While this can be effective, it is a highly specific intervention that only addresses one piece of the inflammatory puzzle. KPV, by targeting the master switch, can simultaneously suppress the production of a wide range of inflammatory molecules, leading to a more comprehensive and robust anti-inflammatory effect.

Another key aspect of KPV’s mechanism is its ability to be taken up by cells via the peptide transporter PepT1. This transporter is highly expressed in the gut, which allows KPV to be administered orally and still exert a potent local anti-inflammatory effect in the intestines. This is a significant advantage for the treatment of inflammatory bowel disease (IBD), as it allows for targeted delivery of the therapeutic to the site of inflammation without the need for injections. The expression of PepT1 is also upregulated in inflamed tissues, which means that KPV is preferentially taken up by the very cells that need it most [6, 7].

In addition to its anti-inflammatory effects, KPV also possesses antimicrobial properties. It has been shown to be effective against a range of bacteria and fungi, including Staphylococcus aureus and Candida albicans. This dual action is particularly beneficial in conditions like IBD, where a breakdown of the gut barrier can lead to microbial translocation and secondary infections. By both suppressing inflammation and fighting off invading microbes, KPV can help to restore the integrity of the gut and promote healing [8].

From Gut Health to Skin Care

The potent anti-inflammatory and antimicrobial properties of KPV have made it a promising therapeutic candidate for a wide range of clinical applications, from the complex and debilitating world of inflammatory bowel disease to the more common but no less challenging realm of inflammatory skin conditions. Its versatility, safety, and ease of administration have positioned it as a unique tool in the management of chronic inflammation.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is perhaps the most well-studied application for KPV. The ability of KPV to be administered orally and its preferential uptake by inflamed gut tissue via the PepT1 transporter make it an ideal candidate for treating this chronic and often debilitating condition. Numerous preclinical studies have demonstrated that oral administration of KPV can significantly reduce the severity of colitis in animal models, decreasing inflammation, promoting mucosal healing, and restoring the integrity of the gut barrier. While large-scale human trials are still needed, the strong preclinical data and the compelling biological rationale have generated significant excitement about KPV’s potential as a new, non-steroidal therapy for IBD [3, 6, 7].

The application of KPV in dermatology is another area of active research and development. Inflammatory skin conditions like psoriasis, eczema, and rosacea are all characterized by chronic inflammation and immune dysregulation. The ability of KPV to be formulated into topical creams and lotions allows for direct application to the affected skin, delivering a potent anti-inflammatory effect with minimal systemic exposure. This localized approach can reduce the risk of side effects associated with systemic anti-inflammatory drugs. A 2025 study further highlighted KPV’s dermatological potential by demonstrating its ability to protect skin keratinocytes from inflammation and cell death induced by environmental pollutants like fine dust, suggesting a role for KPV in both the treatment and prevention of environmentally-triggered skin conditions [4].

Beyond the gut and the skin, KPV’s systemic anti-inflammatory effects make it a potential therapy for a wide range of other inflammatory and autoimmune conditions. Its ability to suppress the NF-κB pathway has implications for diseases like rheumatoid arthritis, multiple sclerosis, and even the chronic, low-grade inflammation that is now recognized as a key driver of aging and age-related diseases. The development of novel drug delivery systems, such as the 2025 research on KPV-containing nanoparticles for the treatment of vascular calcification, is further expanding the potential applications of this versatile peptide [5].

The antimicrobial properties of KPV also open up a range of therapeutic possibilities. In an era of growing antibiotic resistance, the development of new antimicrobial agents is a global health priority. KPV’s ability to kill a range of common pathogens, combined with its anti-inflammatory effects, makes it an attractive candidate for the treatment of infected wounds and other conditions where both inflammation and infection are present. This dual-action profile is a rare and valuable asset in a therapeutic agent [8].

The Power of Simplicity

KPV is a testament to the power of simplicity in biological design. In a world where we often equate complexity with sophistication, this humble tripeptide reminds us that sometimes the most elegant solutions are the most elemental. By isolating the anti-inflammatory core of a large and complex hormone, researchers have created a therapeutic tool of remarkable potency and versatility. Its ability to target the master switch of inflammation from within the cell, its dual anti-inflammatory and antimicrobial properties, and its adaptability to oral, topical, and systemic administration make it a unique and valuable asset in the fight against a wide range of diseases.

The future of KPV is bright. As our understanding of the central role of inflammation in chronic disease continues to grow, the demand for safe and effective anti-inflammatory therapies will only increase. The ongoing development of KPV for the treatment of IBD, inflammatory skin conditions, and other autoimmune disorders is likely to be just the beginning. The exploration of novel delivery systems and the investigation of its potential in new therapeutic areas, from aging to cardiovascular disease, will continue to expand the clinical utility of this remarkable molecule.

KPV is more than just a fragment of a hormone. It is a proof of principle, a demonstration that by understanding the fundamental building blocks of biology, we can create therapies that are not only effective but also elegant and efficient. It is a story of molecular reductionism, of finding the essential signal within the noise, and of harnessing the power of simplicity to address some of medicine’s most complex challenges.

References

[1] Luger, T. A., et al. (2007). α-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Annals of the Rheumatic Diseases. https://ard.bmj.com/content/66/suppl_3/iii52

[2] Getting, S. J., et al. (2003). Dissection of the Anti-Inflammatory Effect of the Core and C-Terminal (KPV) α-Melanocyte-Stimulating Hormone Peptides. Journal of Pharmacology and Experimental Therapeutics. https://jpet.aspetjournals.org/content/308/3/1053

[3] Kannengiesser, K., et al. (2008). Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. https://academic.oup.com/ibdjournal/article/14/3/324/4653598

[4] Sung, J., et al. (2025). Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway. Toxicology and Applied Pharmacology. https://www.sciencedirect.com/science/article/pii/S004081662500117X

[5] Zhao, Y., et al. (2025). KPV and RAPA Self-Assembled into Carrier-Free Nanodrugs for Vascular Calcification Therapy. Advanced Healthcare Materials. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202402320

[6] Dalmasso, G., et al. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. https://www.gastrojournal.org/article/S0016-5085(07)01852-5/fulltext

[7] Viennois, E., et al. (2016). Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-Inflammatory PepT1-Mediated Tripeptide KPV in a Murine Model. Cellular and Molecular Gastroenterology and Hepatology. https://www.cmghjournal.org/article/S2352-345X(16)00015-1/fulltext

[8] Cutuli, M., et al. (2000). Antimicrobial effects of alpha-MSH peptides. Journal of Leukocyte Biology. https://jlb.onlinelibrary.wiley.com/doi/10.1002/jlb.67.2.233

This is the second installment of a four-part series. Read the first installment here:

Part 2: Down the Rabbit Hole

Em joined a GB Discord server called WellnessBuy1. “Even though I was new, I could tell the server owner/GB organizer was a bit shady,” they said.

And they weren’t wrong. From the get-go, “Sandy”2 appeared more than willing to play fast and loose with her customers and their peptides. First, she claimed to have a trusted relationship with a reputable Chinese vendor, but would not disclose the name of that vendor. Then, she informed the GB members that there had been a raid on the factory in China where the peptides were being manufactured – not an uncommon occurrence, given that Chinese chemical manufacturers have come under fire by the FDA before for synthesizing compounds of unknown/untested purity and selling them via gray market methods to buyers with questionable intent.

In fact, one notorious example of this phenomenon is the manufacture and sale of chemical precursors like protonitazene to the powerful drug fentanyl: in October of 2024, the DEA found that eight China-based chemical manufacturers had been manufacturing and selling the substance via gray market methods, and using pseudonymous cryptocurrency transfers like Bitcoin. Drug cartels in the United States and Mexico were among the buyers; they subsequently synthesized the highly addictive opioid and distributed it to individual users in the U.S., feeding the country’s ongoing crisis of fentanyl overdoses.

When Sandy reported the raid, the members of the GB server didn’t find it particularly unusual. It was what happened next that threw them for a loop: she informed them that they wouldn’t be refunded for the peptides they’d purchased in bulk through her.

“Most trustworthy or reputable vendors will often state in their vendor statements” – disclaimers at the top of GB order forms – “that they would offer refunds or remake [the batch of peptides] if anything happened,” Em said. Sandy was no exception.

But it didn’t matter either way, because Sandy had no intention of redistributing the GB members’ funds. Em and a few other members of the WellnessBuy server did some sleuthing, and what they found was damning. Sandy hadn’t been lying about the factory raid, but she had been lying about the refund: the Chinese manufacturer had refunded her the full amount in Bitcoin she and the GB members had collectively paid for the peptide shipment, but Sandy had endeavored to conceal that fact via a poorly doctored “message exchange” in which the vendor appeared to be denying her the refund they’d already sent her.

It was clear she was lying, but it didn’t stop her from shutting down the WellnessBuy server and absconding with over 28,000 BTC. Disturbing but predictable behavior, especially from a scammer. Em was less surprised by Sandy’s role in the debacle than by the strange behavior she witnessed from WellnessBuy members next.

“Even with evidence showing she was lying, people were still defending her and grouping together to bully the ones asking questions and showing that she was lying.” Using only a Discord server and the promise of high-quality Chinese peptides, Sandy had managed to construct such a powerful cult of personality that other server members were willing to launder her reputation for her – and viciously so. The result: even after she fled Discord with tens of thousands in Bitcoin, Sandy was able to re-establish her GB on Facebook with a coterie of her loyal followers. The story doesn’t end there, however. Sandy was vengeful, and would settle for nothing less than a public pillorying of those who’d “wronged” her. It was, Em told me, a harrowing experience for everyone involved.

Retaliatory behaviors like doxxing or sending threatening emails are common for scammers in the gray market peptide world. Before shutting down – or “nuking,” in gray market parlance – one’s Discord server, aggrieved scammers will freely post the names, emails, and personal addresses of those they blame for their exposure. This is dangerous – especially in a digital environment where paranoia is already running high. Add some threatening personal emails to the mix, and you have a full battery of intimidation tactics that cynical organizers can weaponize against GB members from afar.

Nowadays, Em makes their peptide purchases through Telegram, only dipping into Discord for an occasional GB if the organizer happened to be making a purchase from one of Em’s favorite vendors. While Em recognizes that the bulk discount price of the typical GB is one of the lowest – if not the lowest – prices for peptides around, the risks of dealing with potential scammers outweigh the financial benefits of the GB.

“Essentially it’s a blind following, a blind faith [people place] in these resellers,” they said. “They’re very friendly, and do a good job to create a space for people in these servers where it’s a very community-oriented, ‘we’re all in this together’-kind of vibe.”

Em suspects that part of the reason charismatic GB organizers have such an easy time building their cults of personality is that they’re working with a population especially vulnerable to such grooming: “It’s playing on people’s insecurities, self-esteem issues, and lack of friendship or community due to obesity/sickness that comes with being on the outskirts of society.”

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Here, Em has landed on a truth that reveals not just why peptide group buys continue proliferating despite the prevalence of scammers, but something arguably more sinister: under-resourced people seeking peptides for myriad health issues but shut out of clinical or research treatment will still find ways to pay for and consume peptides – except these peptides will be synthesized without FDA guidance and oversight. This means that Chinese vendors and GB organizers could be colluding to send impure product rife with endotoxins or heavy metals to unsuspecting buyers. They could be mixing batches of peptides, falsifying test results, or sending illegal controlled substances in place of what they claimed to be sending.

In fact, all of these things have happened. Uncapped: Stories from the Grey Market is an anonymous podcast – it’s credited to a creator named “krysia” with no other credits – that claims to “dive deep into the underground world of grey market peptides, research compounds, and the Discord and Telegram communities that operate just outside the lines.” Uncapped is a bizarre and hyper-specific drama in many acts, told with a roundtable of AI-robo voices. Strange though it is, I ended up bingeing the entire thing. I found its granularity impressive, and couldn’t help noticing how thoroughly it corroborated much of what Em had described to me about the GB world.

One season of Uncapped is dedicated entirely to a debacle endured by members of a European Union GB seeking North American prices, but ultimately defrauded by a vendor who’d sold them an impure and dubiously compounded product. “The Tinky Winky Quadrilogy” is the oddly captivating story of a shameless scammer who shows up on a Peppys-like server touting hundreds of milligrams-worth of peptides at fire sale prices – later on, he’s exposed as a Chinese hacker who’d stolen a major peptide player’s Instagram avatar, disappearing from the server only to resurface shortly thereafter using the appropriated persona of a health-obsessed peptide saleswoman. Yet another season tells the harrowing story of a disgruntled vendor who sends “hot packs” of illegal steroids to GB members who dare to speak out about his shady business practices.

Paranoia, profit, revenge, and “nuking” (i.e. the sudden disappearance of a server, whether because of detection by the platform itself or a tip-off from a competitor): there’s a kind of cloak-and-dagger drama to it all, poison-tongued infighting one would sooner expect to encounter on Blackbeard’s ship or at El Chapo’s ranch than on a server frequented by a bunch of millennials who know the chemical makeup of a carboxyl chain.

But the unregulated peptide grey market is a strange world, bringing together individuals from across the globe eager to close the supply-side gap for these powerful amino acid chains that more and more consumers want affordable access to. While the research value of peptides is undeniable, a compound has to be more than just scientifically compelling to capture the popular imagination the way peptides have.

For unregulated experimentation with a pharmaceutical to take off, that substance has to arrive into the popular consciousness in the right way, at the right time, and with the right set of evangelists.

Next week, we’ll learn more about how wellness influencers, U.S. government officials, and Silicon Valley’s culture of self-optimization have contributed to the “peptide craze.”

This piece will explore the science behind Retatrutide’s unique mechanism, dive into the groundbreaking results from its most recent clinical trials, and discuss what these findings mean for the future of functional and anti-aging medicine. We will examine three particularly impactful studies from the last year that highlight its potential not just for weight reduction, but for resolving serious associated conditions like fatty liver disease and osteoarthritis, and for modifying the very behaviors that drive weight gain.

Summary of Key Retatrutide Clinical Findings (2024-2025)

The Power of Three: What Makes Retatrutide Different?

The excitement surrounding Retatrutide stems from its novel design as a “triple agonist” or “tri-agonist.” Unlike its predecessors, which target one or two metabolic pathways, Retatrutide engages three critical hormone receptors involved in appetite, energy balance, and glucose control: the glucagon-like peptide-1 (GLP-1) receptor, the glucose-dependent insulinotropic polypeptide (GIP) receptor, and the glucagon (GCG) receptor [1]. This triple-action mechanism is what sets it apart and underpins its remarkable efficacy.

To appreciate the innovation, consider the evolution of this class of medicine. The first wave, including drugs like Semaglutide (found in Ozempic and Wegovy), focused solely on GLP-1 receptor agonism. These were effective, primarily working by suppressing appetite, slowing digestion, and promoting insulin secretion. The next generation, exemplified by Tirzepatide (Mounjaro and Zepbound), added a second target, the GIP receptor, creating a dual-agonist effect that led to even greater weight loss and improved glycemic control [2].

Retatrutide represents the third wave, incorporating the glucagon receptor into this synergistic symphony. The addition of glucagon agonism is a strategic masterstroke. While GLP-1 and GIP primarily regulate appetite and insulin, the glucagon receptor plays a key role in energy expenditure. Activating this receptor is believed to increase thermogenesis (the body’s production of heat) and promote fat oxidation, effectively turning up the metabolic furnace [3]. The result is a powerful combination: GLP-1 and GIP reduce energy intake, while glucagon increases energy expenditure. This dual approach of eating less and burning more is the holy grail of weight management, and Retatrutide is the first single molecule engineered to achieve it so effectively.

A New Benchmark in Weight Loss: The TRIUMPH-4 Trial

Just as the scientific community was beginning to process the impressive outcomes of dual-agonist peptides, the first Phase 3 results for Retatrutide set a new, almost unbelievably high bar. In December 2025, Eli Lilly announced topline results from the TRIUMPH-4 trial, a study that evaluated the peptide in adults with obesity and knee osteoarthritis. The findings were nothing short of spectacular.

Participants taking the highest dose of Retatrutide (12 mg) for 68 weeks achieved an average weight loss of 28.7% [4]. To put that in perspective, an individual weighing 250 pounds would have lost, on average, over 71 pounds. These figures represent the highest level of weight loss ever recorded in a large-scale, late-stage pharmaceutical trial for an obesity treatment, surpassing even the impressive results of its dual-agonist predecessor, Tirzepatide.

Source: Eli Lilly and Company, TRIUMPH-4 Topline Results, December 2025 [4]

Perhaps more importantly, the benefits extended far beyond the scale. The trial specifically enrolled patients suffering from knee osteoarthritis, a painful and debilitating condition often exacerbated by excess weight. The results showed that Retatrutide delivered substantial relief. Participants experienced up to a 75.8% reduction in their WOMAC pain scores, a standardized measure of osteoarthritis pain. In a remarkable post-hoc finding, more than one in eight patients treated with Retatrutide were completely free from knee pain by the end of the trial [4]. This demonstrates that the benefits of such profound weight loss are not merely cosmetic but can lead to life-altering improvements in mobility and quality of life, potentially delaying or even preventing the need for joint replacement surgery.

The Psychology of Weight Loss: Changing Eating Behaviors

The remarkable weight loss achieved with Retatrutide is not solely due to enhanced metabolism; it is also rooted in the peptide’s influence on the brain’s control of appetite and eating behavior. While the physiological effects on energy expenditure are significant, the psychological impact on hunger, cravings, and dietary choices is equally crucial. A study published in Diabetes, Obesity and Metabolism in September 2025 provided the first detailed look into these behavioral changes in adults with type 2 diabetes treated with Retatrutide [8].

The researchers used validated questionnaires to track changes in appetite and eating behaviors over 36 weeks. The results demonstrated a clear, dose-dependent effect. Participants on higher doses of Retatrutide (8 mg and 12 mg) reported significant reductions in both perceived hunger and “disinhibition”—the tendency to overeat in response to environmental cues or emotional triggers. Compared to placebo, these individuals felt less hungry and had more control over their food intake [8].

Crucially, these self-reported behavioral changes were directly correlated with weight loss. The study found that greater reductions in body weight were significantly associated with decreased perceived hunger and lower disinhibition scores. Furthermore, participants on the highest dose of Retatrutide showed an increase in “dietary restraint,” indicating a more conscious effort to control food intake. This suggests that Retatrutide creates a powerful positive feedback loop: the peptide directly reduces the physiological drive to eat, which in turn makes it easier for individuals to adopt and maintain healthier eating habits, leading to more successful and sustainable weight loss. This synergy between physiology and psychology is a key component of Retatrutide’s success, empowering individuals to not just lose weight, but to fundamentally change their relationship with food.

Beyond the Scale: Tackling Liver Fat with Precision

While the weight loss numbers are headline-grabbing, some of Retatrutide’s most profound benefits may lie in its ability to resolve other metabolic dysfunctions. A prime example is its effect on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). MASLD is a silent epidemic, affecting an estimated 38% of the global population, and can progress to a more severe form, MASH, which can lead to cirrhosis and liver failure [5].

In a landmark Phase 2a substudy published in Nature Medicine in June 2024, researchers used advanced imaging (MRI-PDFF) to quantify changes in liver fat in participants with MASLD treated with Retatrutide. The results were stunning. After just 24 weeks, participants on the higher doses of Retatrutide saw a dramatic reduction in liver fat.

Source: Sanyal AJ, et al. Nature Medicine, 2024 [5]

By 48 weeks, an incredible 93% of participants on the 12 mg dose had achieved a normal liver fat content of less than 5%. The treatment effectively resolved the steatosis in nearly all subjects. This effect is likely driven by the glucagon receptor agonism, which is known to enhance fat metabolism directly within the liver. These findings suggest that Retatrutide could become a frontline therapy for MASLD, potentially halting or reversing a disease that currently has no approved pharmacological treatments in the US or Europe. By addressing the root metabolic drivers, Retatrutide is not just managing a symptom; it is resolving a dangerous underlying pathology.

Quality Over Quantity: The Body Composition Question

A reasonable concern with any therapy that produces substantial and rapid weight loss is the nature of that weight. Is it primarily fat, or is a significant amount of metabolically crucial lean muscle mass also being lost? This question is paramount for long-term health and wellness, as preserving muscle is key to maintaining metabolic rate and physical function.

A substudy of the Phase 2 trial, published in The Lancet Diabetes & Endocrinology in June 2025, specifically addressed this question using DXA scans to analyze changes in body composition [6]. The researchers sought to determine if the powerful weight loss from Retatrutide came at the cost of disproportionate muscle loss.

The findings provided crucial reassurance. While any significant weight loss will involve some reduction in lean mass, the study concluded that the proportion of lean mass loss relative to total weight loss with Retatrutide was similar to that seen with other incretin-based obesity treatments. In other words, despite causing much greater overall weight loss, Retatrutide did not appear to be selectively catabolizing muscle tissue. A commentary on the study noted that, for the 12 mg dose, the placebo-subtracted weight loss of 15.4 kg comprised approximately 8.8 kg of fat mass and 5.8 kg of lean mass [7]. This suggests that most of the weight lost is indeed fat, and that the therapy maintains a favorable body composition profile. This is a critical finding, indicating that Retatrutide achieves its powerful effects by preferentially targeting adipose tissue, preserving the lean mass that is vital for a healthy metabolism.

The Horizon for Retatrutide

The clinical data emerging on Retatrutide is painting a clear picture of a peptide with transformative potential. The unprecedented level of weight loss, combined with profound improvements in comorbidities like osteoarthritis and fatty liver disease, and a reassuring body composition profile, places it in a class of its own. The ongoing TRIUMPH clinical trial program, with seven additional Phase 3 readouts expected in 2026, will further clarify its role in the treatment of obesity and type 2 diabetes [4].

For those in the wellness and longevity space, Retatrutide represents more than just a powerful tool. It is a validation of a systems-based approach to health. By targeting multiple interconnected metabolic pathways, it demonstrates that we can achieve holistic improvements that go far beyond a number on a scale, enhancing quality of life, reducing pain, and resolving organ-specific pathologies. The era of the tri-agonist has arrived, and the future of metabolic medicine looks brighter than ever.

References

[1] Coskun, T., Urva, S., Roell, W. C., Qu, H., Loghin, C., Moyers, J. S., O’Farrell, L. S., Briere, D. A., Cui, X., & Haupt, A. (2022). LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism, 34(9), 1234-1247.e9. https://doi.org/10.1016/j.cmet.2022.07.013

[2] Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., & Stefanski, A. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387(3), 205–216. https://doi.org/10.1056/NEJMoa2206038

[3] Gnad, T., Scheibler, S., von Kügelgen, I., Scheele, C., Kilić, A., Glöde, A., Hoffmann, L. S., Reverte-Salisa, L., Horn, P., Mutlu, S., El-Tayeb, A., Ku, M., Kretz, O., Rulands, S., Bange, T., Vogl, F. M., Hrabě de Angelis, M., Schürmann, A., Müller, T. D., & Pfeifer, A. (2016). Glucagon-induced browning of white adipose tissue is a FGF21-dependent process. Cell Metabolism, 24(6), 849-862. https://doi.org/10.1016/j.cmet.2016.10.005

[4] Eli Lilly and Company. (2025, December 11). Lilly’s triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial [Press release]. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average

[5] Sanyal, A. J., Kaplan, L. M., Frias, J. P., Brouwers, B., Wu, Q., Thomas, M. K., Harris, C., Schloot, N. C., Du, Y., Mather, K. J., Haupt, A., & Hartman, M. L. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine, 30(7), 2037–2048. https://doi.org/10.1038/s41591-024-03018-2

[6] Coskun, T., Wu, Q., Schloot, N. C., Haupt, A., Milicevic, Z., Khouli, C., & Harris, C. (2025). Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. The Lancet Diabetes & Endocrinology, 13(8), 674-684. https://doi.org/10.1016/S2213-8587(25)00092-0

[7] Dirksen, C., & Madsbad, S. (2025). Body composition during major incretin-based weight loss. The Lancet Diabetes & Endocrinology, 13(8), 622-624. https://doi.org/10.1016/S2213-8587(25)00122-6

[8] Kanu, C., Boye, K. S., Poon, J. L., Goetz, I., Williamson, S., Lou, J., Hartman, M. L., Martin, C. K., & Coskun, T. (2025). Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study. Diabetes, Obesity and Metabolism, 27(12), 6988-6998. https://doi.org/10.1111/dom.70097

If you’re reading this, then you probably already know which peptides have been approved for human use by the FDA. As is frequently the case for cutting-edge pharmaceutical compounds, peptides have entered the clinical world as treatments for serious diseases: e.g. semaglutide for diabetes management (Wegovy, Ozempic), teriparatide for osteoporosis (Forteo), enfuvirtide for HIV (Fuzeon), and so on.

And more likely than not, you also have a sense of the peptides that haven’t been approved by the FDA, but are nevertheless being buzzed about everywhere online. Maybe you’ve heard of retatrutide, the Eli Lilly-manufactured GLP-1, GIP, and glucagon triple agonist designed to assist patients with weight loss, sleep apnea, and osteoarthritis. The fact that it’s still in a number of Phase 3 scientific trials hasn’t stopped TikTok influencers from promoting it as a miracle drug under the just-barely-indemnifying codename “ratatouille.” Or maybe you’ve seen musclehead Reddit users enthusing about the deadlifting miracles made possible by the “Wolverine stack,” a combination of BPC-157 and TB-500, both experimental peptides with limited peer-reviewed data in humans.

It wouldn’t require a massive leap of deduction to conclude that the wellness influencer on TikTok and gymbro647 aren’t medical researchers who’ve acquired their peptides for the purpose of setting up a rigorous, placebo-controlled empirical study to determine a given peptide’s long-term clinical efficacy. So where are they getting their research peptides?

The answers are multifarious. Given the consent of the patient, there are situations in which licensed clinicians can legally prescribe experimental peptides as part of a given health protocol. One can always become part of a study, or seek a specific dispensation through a trusted compounding pharmacy. But of course all these things require time, oversight, and – most crucially – money.

While money doesn’t exist in limitless supply for all of us, it’s safe to say that the desires for health and longevity do. And wherever a demand arises, a supply chain is sure to form.

For gray market peptides, the strangest supply chain comes through the world of “group buys” (GBs) on messaging apps like Telegram, Discord and WhatsApp. Spearheaded by organizers with the resources to purchase peptides in large quantities from foreign vendors, GB members congregate on messaging servers in order to split the cost of the peptide kit purchase and the independent materials testing. GBs promise peptides that would have cost thousands or been otherwise impossible to find for prices as low as $200. It seems like an ideal option for the non-millionaire peptide user – but does it come with a cost?

The answer is yes, and a high one. GBs are the digital wild west of the peptide world, as full of schemes, scams, and cults of personality as they are of earnest buyers and sellers. And for anyone interested in the considerable research potential of peptides and their value to the medical and scientific communities, it’s worth taking a moment to understand the social and economic implications of GBs, and the “peptide craze” they’ve helped fuel.

Part 1: The Supply-Side Gap

For Em1, it started at a local med spa: a 2.5 mg shot of tirzepatide to facilitate weight loss and inflammation reduction. The weekly shot cost $150, and was compounded not by Eli Lilly but by an independent compounding pharmacy. The compounding pharmacy had added B12 to the shot to avoid legal repercussions from the pharmaceutical manufacturing heavyweight, whose sales of injectable tirzepatide under the brand names Zepbound and Mounjaro totaled over $16 billion in 2024 alone.

The protocol was immensely effective. Within a couple weeks, Em told me, they “started seeing weight loss, and no more ‘food noise’” — the colloquial term for the clinically observed phenomenon of excessive rumination about/preoccupation with food. “My skin looked better, I felt less puffy, and I felt more stable overall – like my body was functioning more smoothly instead of constantly playing catch-up.”

Em wanted to keep up the tirzepatide protocol, but without having to pay $600/month and make the trip into the office every week. They researched independent compounding pharmacies like HERS and FRIDAYS that also manufacture tirzepatide injections and sublingual tablets, but those proved out of their price range as well.

Like many who’d benefit from the anti-inflammatory and stress-reduction properties of peptides, Em works a mentally and physically demanding job in the service industry. And while they aren’t struggling financially, the high price points of peptides like tirzepatide – sold by FRIDAYS in injectable form starting at $240/month before taxes, shipping, and any other add-ons – place regular access to the compounds out of their reach, and out of the reach of countless other Americans in positions similar to theirs.

“I kept looking for a more direct route,” Em told me via email. “I knew there had to be a cheaper, better, more self-sufficient way of acquiring the tirzepatide.”

Like many an internet native with a complex research question, Em took to Reddit. There, they were linked to vendor sites like Peptide Sciences, Core Peptides, and BioLongevity Labs. The peptides these manufacturers were selling had the advantages of being synthesized in the U.S. and boasting independently verified Certificates of Analysis (COAs) with purity levels in excess of 99%. The only problem was that these manufacturers stipulated their peptides were for research and scientific use – not human use – in accordance with FDA guidance and oversight. Em wasn’t a researcher, and even if they were willing to fudge the truth and pretend to be one, the price point was still far too high.

And then it came: an invitation via a Reddit thread to join Peppys, a chat server billed as an “exclusive peptide community.” Em accepted, and found themself plunged into a vast international network of peptides being bought, sold, and traded. They were impressed by the possibilities: “It opened up a whole new world…within a group of people just like me who had started [taking peptides] within the past year, as the Eli Lilly GLP-1s started coming out.”

Em began digging around on the Peppys server, taking note of what they found. The messaging channels were numerous, and seemed to keep proliferating. Admins had compiled whole digital libraries of documents to help users stay abreast of the latest research, with categories like “Incretin Memetics,” “Bioregulators,” “Other Peptides,” “Testing and Manufacturing” and “Health and Wellness.” There were channels to vet foreign peptide vendors – the vast majority were Chinese – and countless fora to discuss changes in health and appearance over the course of individual peptide-use journeys.

Scientifically minded and genuinely eager to learn more about the chains of amino acids that had positively impacted their health and others’, Em became an active participant on Peppys. Soon enough, they started receiving invitations to join Discord servers hosted by GB organizers. The group buy was at last on the table, and the prices were right: $400 for a 10-vial kit of 30mg tirzepatide vials. (Just one year later, that price has now dropped to $100.)

So Em started digging again, searching for transparent organizers offering quality products from well-vetted vendors. But what they found was more like a group of mini-cults run by a faceless battalion of mean girl cliques and low-ranking cartel members.

In Part 2, take a plunge down the GB rabbit hole and learn more about the growing – and potentially dangerous – unregulated gray market for peptides:

In the grand theater of cellular biology, where proteins perform their ancient choreography and genes conduct their molecular symphonies, a new player has emerged from the most unexpected corner of the stage—not from the nucleus with its vast library of genetic instructions, but from the mitochondria, those cellular powerhouses we thought we understood completely

The year 2015 marked a quiet revolution in our understanding of how cells communicate with themselves. When Changhan Lee, Kelvin Kim, and Pinchas Cohen at USC first identified MOTS-c—a mere 16-amino acid peptide encoded by mitochondrial DNA—they weren’t just discovering another cellular component. They were uncovering evidence of an entirely new form of biological communication that challenged fundamental assumptions about how genetic information flows within our cells.

For decades, the scientific orthodoxy held that mitochondria were essentially cellular servants, dutifully producing ATP while taking orders from the nuclear command center. The mitochondrial genome, we believed, encoded only 13 proteins dedicated to the mundane but essential task of energy production. MOTS-c shattered this paradigm by demonstrating that mitochondria don’t just follow orders—they send messages back to headquarters, and those messages can fundamentally alter how cells respond to stress, aging, and metabolic challenges.

What makes MOTS-c particularly fascinating is not just what it does, but how it represents a completely novel form of retrograde signaling—communication that flows from mitochondria to nucleus rather than the traditional nuclear-to-mitochondrial direction. This discovery has opened an entirely new chapter in cellular biology, one where mitochondria emerge as sophisticated communicators capable of coordinating cellular responses to metabolic stress with a precision that rivals the most advanced biological systems.

The implications extend far beyond academic curiosity. As we grapple with an aging global population and rising rates of metabolic disease, MOTS-c offers a tantalizing glimpse into therapeutic possibilities that work with, rather than against, our cellular machinery. From its role in exercise adaptation to its potential applications in chronic fatigue syndrome, from its protective effects against muscle wasting to its emerging promise in cardiovascular disease, MOTS-c represents a new frontier in precision medicine—one where we harness the wisdom of our own mitochondria to promote health and longevity.

The Molecular Architecture of Mitochondrial Wisdom

Understanding MOTS-c requires appreciating the elegant simplicity that often characterizes nature’s most profound innovations. At just 16 amino acids, MOTS-c is remarkably compact, yet this brevity belies its sophisticated mechanism of action and far-reaching biological effects. The peptide’s discovery emerged from the recognition that mitochondrial DNA contains short open reading frames that had been overlooked in traditional genetic analyses—a reminder that even i [1].

The peptide’s name itself tells a story: Mitochondrial Open Reading Frame of the 12S ribosomal RNA type-c. This designation reflects its origin in the mitochondrial 12S rRNA gene, a location that traditional molecular biology would have considered unlikely to encode a functional peptide. The discovery required researchers to look beyond conventional protein-coding sequences and consider the possibility that evolution had hidden functional peptides in what appeared to be structural RNA genes [2].

MOTS-c’s molecular structure reveals several key features that enable its unique biological functions. The peptide contains a hydrophobic core region, specifically the 8YIFY11 sequence, which appears crucial for its ability to interact with other proteins and facilitate its nuclear translocation during stress conditions. This hydrophobic region acts as a molecular key, enabling MOTS-c to unlock specific cellular pathways when metabolic conditions demand adaptive responses [3].

The peptide’s stability and bioavailability represent another layer of evolutionary optimization. Unlike many small peptides that are rapidly degraded in biological systems, MOTS-c demonstrates remarkable stability, allowing it to function effectively as a signaling molecule across different cellular compartments. This stability is particularly important given its role as a stress-responsive messenger that must maintain its function during the very conditions—oxidative stress, energy depletion, metabolic dysfunction—that typically compromise cellular processes [4].

Perhaps most remarkably, MOTS-c exhibits tissue-specific expression patterns that suggest sophisticated regulatory mechanisms governing its production and activity. The peptide is most highly expressed in metabolically active tissues, particularly skeletal muscle, where its effects on glucose metabolism and stress adaptation are most pronounced. This tissue specificity indicates that MOTS-c production is not a random cellular event but rather a carefully orchestrated response to metabolic demands [5].

The peptide’s mechanism of action centers on its ability to undergo stress-induced nuclear translocation, a process that represents one of the most elegant examples of cellular communication discovered in recent years. Under normal conditions, MOTS-c remains primarily in the cytoplasm, but when cells encounter metabolic stress—glucose restriction, oxidative damage, or energy depletion—the peptide rapidly translocates to the nucleus within 30 minutes. This translocation is not passive but requires active transport mechanisms and specific protein interactions [6].

Once in the nucleus, MOTS-c functions as a transcriptional regulator, binding to promoter regions of genes involved in stress adaptation and antioxidant defense. The peptide specifically interacts with antioxidant response elements (ARE) and influences the expression of genes regulated by transcription factors like NRF2, ATF1, ATF7, and JUND. This nuclear activity transforms MOTS-c from a simple peptide into a sophisticated coordinator of cellular stress responses [7].

The Folate-AICAR-AMPK pathway represents the primary mechanism through which MOTS-c exerts its metabolic effects. The peptide directly influences the folate-methionine cycle and de novo purine biosynthesis, leading to increased levels of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide). AICAR then activates AMPK, the master regulator of cellular energy homeostasis, creating a cascade of beneficial metabolic effects including enhanced glucose uptake, increased fatty acid oxidation, and improved mitochondrial biogenesis [8].

The Clinical Renaissance of Mitochondrial Medicine

The transition of MOTS-c from laboratory curiosity to clinical reality represents one of the most compelling stories in modern translational medicine. What began as a basic science discovery about mitochondrial genetics has evolved into a therapeutic approach with applications spanning metabolic disease, aging, muscle wasting, and even chronic fatigue syndrome. This evolution reflects both the peptide’s remarkable versatility and the growing recognition that mitochondrial dysfunction underlies many of the health challenges facing our aging population [9].

The clinical journey of MOTS-c began with animal studies that demonstrated its profound effects on metabolic health. Early research showed that MOTS-c administration could prevent age-dependent and high-fat diet-induced insulin resistance while also protecting against diet-induced obesity. These findings were particularly striking because they suggested that a single intervention could address multiple aspects of metabolic dysfunction simultaneously—a holy grail in metabolic medicine [10].

The peptide’s effects on exercise adaptation provided another compelling avenue for clinical development. Research demonstrated that MOTS-c levels increase in response to exercise and that the peptide can mimic many of the beneficial effects of physical activity at the cellular level. This “exercise mimetic” property has profound implications for populations who cannot engage in traditional exercise due to age, disability, or illness, offering a potential pharmacological approach to capturing exercise benefits [11].

Perhaps most remarkably, recent clinical developments have seen MOTS-c analogs progress to human trials, with Phase 1 studies suggesting both safety and potential efficacy. This progression from basic discovery to clinical testing in less than a decade represents an unusually rapid translation for a novel therapeutic approach, reflecting both the compelling preclinical data and the significant unmet medical need in metabolic and aging-related diseases [12].

The 2024-2025 research developments have been particularly exciting, with studies demonstrating MOTS-c’s direct binding to casein kinase 2 (CK2) and its ability to modulate skeletal muscle function through this interaction. This discovery provided the first direct molecular target for MOTS-c action, moving beyond correlative studies to demonstrate specific protein-protein interactions that explain the peptide’s biological effects. The CK2 interaction is particularly significant because this kinase plays crucial roles in muscle metabolism and protein synthesis [13].

Clinical applications have expanded beyond metabolic disease to include potential treatments for chronic fatigue syndrome and myalgic encephalomyelitis (ME/CFS). The 2025 research proposing MOTS-c as a disease-modifying therapy for ME/CFS represents a paradigm shift in how we think about these debilitating conditions. Rather than treating symptoms, MOTS-c offers the possibility of addressing the underlying mitochondrial dysfunction that many researchers believe drives chronic fatigue [14].

The peptide’s emerging role in cardiovascular medicine has added another dimension to its clinical potential. Studies in chronic hemodialysis patients have shown that MOTS-c levels may help predict mortality and cardiovascular risk, while research in diabetic cardiomyopathy suggests that MOTS-c therapy could help restore mitochondrial function in damaged heart tissue. These cardiovascular applications could significantly expand the peptide’s therapeutic reach [15].

Cancer research has revealed yet another potential application, with studies showing that MOTS-c levels are reduced in ovarian cancer patients and that low levels correlate with poor prognosis. This finding suggests that MOTS-c might serve both as a biomarker for cancer outcomes and as a potential adjuvant therapy to support patients undergoing conventional cancer treatment [16].

The age-related macular degeneration research represents perhaps the most unexpected clinical application, demonstrating that MOTS-c’s benefits extend beyond metabolic tissues to include specialized cells like retinal pigment epithelium. The finding that MOTS-c can modulate inflammatory responses in eye tissue opens possibilities for treating age-related vision loss, a major cause of disability in older adults [17].

The Stress Response Revolution

MOTS-c’s role as a cellular stress sensor and adaptive coordinator represents a fundamental advance in our understanding of how cells maintain homeostasis in the face of metabolic challenges. This stress response system operates with remarkable sophistication, integrating multiple cellular signals to orchestrate appropriate adaptive responses that enhance cellular resilience and promote survival under adverse conditions [18].

The peptide’s stress-sensing mechanism begins with its ability to detect cellular energy status through the AMPK pathway. When cells experience energy depletion, glucose restriction, or oxidative stress, AMPK activation triggers a cascade of events that includes MOTS-c nuclear translocation. This process represents a direct link between cellular energy status and gene expression, allowing cells to rapidly adjust their metabolic programming in response to changing conditions [19].

The nuclear translocation process itself demonstrates remarkable precision and timing. MOTS-c can translocate to the nucleus within 30 minutes of stress induction, allowing for rapid transcriptional responses to metabolic challenges. Equally important, the peptide returns to its baseline extranuclear localization within 24 hours, preventing excessive or prolonged stress responses that could be harmful to cellular function [20].

The transcriptional programs activated by nuclear MOTS-c focus heavily on antioxidant defense and stress adaptation. The peptide’s interaction with NRF2, the master regulator of antioxidant response, enables cells to upregulate protective enzymes and signaling proteins that neutralize reactive oxygen species and repair oxidative damage. This antioxidant response is particularly important in aging and metabolic disease, where oxidative stress plays a central role in tissue damage [21].

MOTS-c’s influence on the folate-methionine cycle adds another layer to its stress response capabilities. This metabolic pathway is crucial for DNA synthesis, methylation reactions, and cellular repair processes. By modulating this cycle, MOTS-c can influence cellular capacity for repair and regeneration, potentially explaining its beneficial effects on aging and tissue maintenance [22].

The peptide’s role in exercise adaptation represents a particularly elegant example of beneficial stress response. Exercise creates controlled metabolic stress that triggers MOTS-c activation, leading to improved mitochondrial function, enhanced glucose metabolism, and increased stress resistance. This process explains how exercise promotes health and longevity at the cellular level, while also suggesting that MOTS-c supplementation might provide similar benefits for those unable to exercise [23].

The hormetic effects of MOTS-c—where mild stress leads to beneficial adaptations—reflect a fundamental principle of biological resilience. By activating stress response pathways in a controlled manner, MOTS-c helps cells develop greater resistance to future stressors, a process that may contribute to healthy aging and disease prevention. This hormetic response is similar to the beneficial effects of caloric restriction and intermittent fasting, suggesting that MOTS-c might provide a pharmacological approach to capturing these longevity benefits [24].

The Future Landscape of Mitochondrial Therapeutics

As MOTS-c continues its journey from laboratory discovery to clinical reality, the peptide represents more than just another therapeutic option—it embodies a new paradigm in medicine that recognizes mitochondria as sophisticated communicators rather than simple energy producers. This paradigm shift has profound implications for how we approach aging, metabolic disease, and cellular health in the coming decades [25].

The immediate future holds significant promise for MOTS-c clinical development, with multiple research groups advancing toward larger clinical trials. The successful completion of Phase 1 safety studies provides a foundation for efficacy trials in specific disease populations, while the growing understanding of MOTS-c’s molecular mechanisms enables more targeted therapeutic approaches. The development of MOTS-c analogs with improved stability or tissue specificity could further enhance therapeutic potential [26].

The peptide’s applications in precision medicine represent a particularly exciting frontier. As we develop better understanding of genetic polymorphisms that affect MOTS-c function—such as the K14Q variant that influences muscle health in older adults—we may be able to identify patients who would benefit most from MOTS-c therapy. This personalized approach could maximize therapeutic benefits while minimizing unnecessary treatment [27].

Combination therapies offer another avenue for expanding MOTS-c’s therapeutic utility. The peptide’s mechanism of action suggests potential synergies with other mitochondrial interventions, metabolic therapies, and even lifestyle modifications like exercise and dietary interventions. These combination approaches could provide more comprehensive treatment strategies for complex conditions like metabolic syndrome and age-related decline [28].

The manufacturing and delivery challenges facing MOTS-c development are significant but not insurmountable. As a peptide therapy, MOTS-c requires sophisticated production and formulation approaches to ensure stability and bioavailability. However, advances in peptide chemistry and drug delivery systems provide multiple pathways for overcoming these challenges, while the peptide’s relatively small size makes it more manageable than larger protein therapeutics [29].

The regulatory pathway for MOTS-c approval will likely focus on establishing clear efficacy endpoints and long-term safety profiles. The peptide’s novel mechanism of action may require new approaches to clinical trial design and regulatory evaluation, but the growing acceptance of peptide therapeutics and the compelling preclinical data provide a favorable environment for development [30].

Perhaps most importantly, MOTS-c represents the beginning rather than the end of mitochondrial medicine. The discovery that mitochondria encode functional peptides beyond the traditional 13 proteins has opened an entirely new field of investigation. Other mitochondrial-derived peptides like humanin and the SHLP family are showing their own therapeutic potential, suggesting that we may be on the verge of discovering an entire pharmacopeia encoded within our own mitochondria [31].

The implications extend beyond individual therapies to encompass a new understanding of aging and disease. If mitochondrial communication plays a central role in cellular health and longevity, then interventions that enhance this communication could provide broad-spectrum benefits for age-related conditions. MOTS-c may be the first of many mitochondrial messengers that we learn to harness for therapeutic benefit [32].

References

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[2] MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC9905433/

[3] Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging. E-DMJ. https://www.e-dmj.org/journal/view.php?number=2725

[4] MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Science Direct. https://www.sciencedirect.com/science/article/abs/pii/S0891584916302507

[5] The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis. Cell Metabolism. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(15)00061-3

[6] Mitochondria-derived peptide MOTS-c restores mitochondrial function. Frontiers in Physiology. https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1602271/full

[7] The mitochondrial‐derived peptide MOTS‐c: a player in exceptional longevity. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC4693465/

[8] MOTS-c modulates skeletal muscle function by directly binding and activating CK2. Science Direct. https://www.sciencedirect.com/science/article/pii/S2589004224024374

[9] MOTS-c For Beginners: Benefits, Dosage, Stacking, and Side Effects. Swolverine. https://swolverine.com/blogs/blog/mots-c-for-beginners-benefits-dosage-stacking-and-side-effects

[10] How to Improve Health with Peptides: MOTS-c, Mitochondrial Magic. Intricate Art Seminars. https://intricateartseminars.com/how-to-improve-health-with-peptides-mots-c-mitochondrial-magic/

[11] MOTS-c Peptide for Metabolism, Energy & Longevity. LIVV Natural. https://livvnatural.com/mots-c-peptide-benefits-metabolism-energy-longevity/

[12] A Powerhouse of Innovation. USC Gero. https://gero.usc.edu/2024/11/25/mitochondria-microproteins-cohen-usc/

[13] MOTS-c modulates skeletal muscle function by directly binding and activating CK2. Tohoku University. https://tohoku.elsevierpure.com/en/publications/mots-c-modulates-skeletal-muscle-function-by-directly-binding-and

[14] Redefining Mitochondrial Therapy for ME/CFS: The Case for MOTS-c. Preprints. https://www.preprints.org/manuscript/202507.0058/v1

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[16] Mitochondrial‐Derived Peptide MOTS‐c Suppresses Ovarian Cancer. Advanced Science. https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202405620

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[19] MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. PubMed. https://pubmed.ncbi.nlm.nih.gov/36761202/

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[24] MOTS-c functionally prevents metabolic disorders. Metabolites. https://www.mdpi.com/2218-1989/13/1/125

[25] The Relationship Between MOTS-c K14Q Polymorphism and Sarcopenia. Biomedicines. https://www.mdpi.com/2227-9059/12/10/2384

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