The first is collagen: I'd love to see Lowe's take on recent peer review which says boosting oral collagen does appear to show signs of improved joint pain and skin resilience. Obviously modulated through how protein deprived you are, but for older people, eating enough protein can be an issue: it's not rapidly absorbed so you need 3 squares a day to get to the higher numbers. Collagen powders and vitamin C (oj) at breakfast might kick start this.
The second contradictory point is that this entire thread makes me want to shout GELL MAN AMNESIA because it's an exercise in otherwise intelligent people who can distinguish between anecdata, their personal experience and some cold hard facts in their core field, but not when it's self injecting unknown chemicals from China bought off-script.
Note that there is research showing that whey protein powder has exactly the same effects as collagen, for much lower price.
Mechanistically it makes sense, as I understand the ingredients in Collagen are largely a subset of the ingredients in whey powder, albeit at different ratios.
it is the same if you base it just on the amino acid profiles, they are both just proteins with different amounts.
I always wondered if there were nutrients we can’t measure though, because collagen is typically made from skin or bones whereas whey protein is dairy. Even though both have similar “nutrition facts” maybe there are some unmeasurable differences. Both are highly processed though so who knows.
I think the idea is that some short peptides might survive the digestion and make it to the blood stream, but I'm doubtful there's any specific benefit to collagen.
It has a Mechanism section which explains that when collagen is digested, one of the products of that is Gly-Pro-Hyp, which is what has the effects. I don't think that conflicts anything in this post?
I assume they're referring to the brief bit in the post that indicates that oral ingestion leads to a breakdown that makes oral supplements of amino acids pointless. They say it very briefly and they don't really outright assert it, it's just a sort of implied aside.
That's not the exact quote lol you cut out the exact part I was referring to.
> because unless a really substantial amount of engineering has gone into it, any given peptide is going get the same treatment from your digestive system as a chicken breast does, i.e. a complete teardown
> Every single YouTube video and blog post I have read about peptites is exclusively about injectable supplements.
Collagen peptides, ghk-cu, and many other peptide supplements are often taken orally.
> Collagen peptides, ghk-cu, and many other peptide supplements are often taken orally.
And with very rare exceptions, it's as useful as watching someone workout when you want to gain muscle. Every meat we eat is awash in peptides, and to keep our body from getting hijacked by the signaling for, say a chicken, our body has to break down almost all peptides ingested orally.
There are a few exceptions, notably there's one that is produced by our own bile acid, that can be taken orally, and then SNAC, which was developed by Novo Nordisk over thirty years and has extremely limited capabilities and is fully patented and cannot be made by your fly by night distributers. SNAC achieves a whopping 1% bioavailability of the peptide, and it's ability to work depends on the size of the peptide, specifically the only commercially available use for this is Rybelsus.
Sweeping statements in biochemistry must be made with caution. It is well known that there are some small peptides that are absorbed following oral administration.
Interestingly enough, those two, as well as Gly-Pro-Hyp, are proline/hydroxyproline-rich, which might suggest that proline-rich small peptides are resistant to degradation in the gut.
Anyway, in general oral proteins and peptides are broken down prior to systemic absorption, but not always...
> It is well known that there are some small peptides that are absorbed following oral administration. ...BPC-157 itself is said to be among this class
Do you know of any studies that suggest BPC-157 absorption from gut?
Among others. If you read the paper, it's actually apparent that there's little difference between i.p. and oral administration in terms of efficacy -- both were roughly equally effective in improving MCL ligament healing.
Admittedly the paper's in rats -- as are 99% of the others -- as there's no incentive for anybody to run human trials.
You should note that your study is not controlled.
There are two groups, those with oral administration those with sub-q administration. There is not group without administration.
This means you can't say that oral vs injected is "equally effective" because you can't assert that BPC 157 is effective at all. You can't tease out the effect size because you don't know if any or all of the MCL ligament healing was done via normal pathways
You just read the abstract and didn't read the full paper.
There were control groups.
> Methods:
> [administration] as follows: (i) BPC 157 10 mg or 10 ng/kg or saline 5.0 ml/kg (controls), intraperitoneally, or (ii) BPC 157 in neutral cream (1.0 mg dissolved in distilled water/g commercial neutral cream) or commercial neutral cream (controls), as a thin layer, locally, at the site of injury, administered once daily with the first application 30 min after surgery and the final application 24 h before sacrifice; (iii) BPC 157 0.16 mg/ml or nothing (controls) in the drinking water (12 ml/day/rat) until sacrifice.
There was a big difference vs. the control groups.
> This means you can't say that oral vs injected is "equally effective" because you can't assert that BPC 157 is effective at all
Is that true? It seems that you can say that they were equally effective without quantifying an effect. It could be the case that both are equal in that neither has an effect, which this would validate. Then you can just point to other studies to claim effectiveness of injected.
I want to point out your own contradictory comments about absorption and specifically mentioning a typically highly processed food (orange juice), one which has been stripped of its natural fibers and flavors.
That age group (and all others) should be eating real/whole fruit or having the juice fresh (I.e. just juiced). They would be better served getting this advice than creating more anxiety about protein intake.
> Commercial orange juice with a long shelf life is made by pasteurizing the juice and removing the oxygen from it. This removes much of the taste, necessitating the later addition of a flavor pack, generally made from orange products.
> Commercial squeezed orange juice is pasteurized and filtered before being evaporated under vacuum and heat. After removal of most of the water, this concentrate, about 65% sugar by weight, is then stored at about 10 °F (−12 °C). Essences, Vitamin C, and oils extracted during the vacuum concentration process may be added back to restore flavor and nutrition.
So essentially there are components that vaporize during processing. The make sure to condense the same components and add them back in so that the orange juice contains all the components of fresh orange juice.
There is reason to think the differences are biotic vs. abiotic, between the two. Our digestive system is dependent on healthy microbiota. Pasteurization would be the difference here.
Raw milk is on the fringes of the same argument that whole foods play a more beneficial role in healthy gut microbiota and digestion, and that our current models focusing on nutrient composition are incomplete. It says that our measurements are off, and that there’s more to nutrition than composition alone. https://pmc.ncbi.nlm.nih.gov/articles/PMC11901572/
I think we are sort of in the worst of both worlds right now re: medicines/supplements/gray market.
FDA approval is expensive slow process. Doctors train for a long time and then work 40+ years entire careers, some without a ton of continuing education.
But then we have an entire gray market because enough legal and practical loopholes to drive a freight train through, such that people are self medicating with dubious substances of dubious origin of dubious purity sourced via dubious means.
Even if peptides work, you have no idea what side effects they have, or if the ones you are taking are even real, not contaminated/tainted in some manner, etc. Given a lot of the hype comes from social media for otherwise healthy people to take them for lifestyle / augmentation reasons.. to me the risks still outweigh the rewards.
Real solutions like regulatory reforms to find ways to bring down testing costs seem more important than reforms to make it easier to slap anything on the shelf at GNC as a completely untested “supplement”.
Where did you get this idea? I did a simple, five second Google search and learned that on average, US doctors are required to complete about 50 hours of continuing education for each one- to two-year recert cycle. (On HN, I also hear similar complaints about public school teachers. It isn't true. Public school teachers are required to do similar continuing education.)
Taking continuing education credits to check a box for retaining professional licensure and educating yourself about emerging and novel concepts in your field are two vastly different things. If anything, CE helps professionals update their knowledge base regarding existing processes and procedures.
Not US, but the seminars to fill in the hours in my country were closer to legal bribes and/or holidays in often exotic places. They usually were provided/funded by the medicine lobby.
Same in US only sometimes more banal. Signup sheet in front of the stacks of pizza at some research talk at the medical school. Back row entirely asleep. Talk had nothing to do with medical practice but the researcher holds an md phd. Might be talking about their work in yeast.
Compare how seriously many SWEs take mandatory HR/compliance trainings vs hanging out on HN, taking online courses, arguing about code, trying new frameworks, coding in spare time, etc.
I used retatrutide for weight loss and went from 199.3 lbs to just under 175 lbs. I kept daily notes through the process. Here's a quick AI one-paragraph summary if you're curious: https://pastebin.com/XACNYKvs
Overall I'm quite pleased with the effects and many of the properties of this treatment that people dislike are actually properties I was looking for. Essentially, for pharmacological interventions I want impermanent effects with a clear dose-response relationship and ideally minimal or no adaptation.
So the fact that people gain weight when they go off it and then lose weight again when they go on it was good. That meant it's fairly easily undoable. The fact that the more you take the more you lose also was pretty good to know though for the majority of the time I took less than any tested dose (and the effects were quite strong on those).
I did experience quite a bit of adaptation so I needed to up the dose until I was in the range tested by the end. I've been off it for a month now and been pretty much flat, but we've been traveling since I stopped and so a lot has changed (no more lifting, lots more eating, lots more walking).
When people talk about peptides, they typically mean either (1) GLP compounds like Reta that have successful phase 3 trial data and will be approved or (2) stuff like 157 which has no evidence or plausible mechanism to work.
Was cost the reason you went for it over tirzepitide? I feel like retatrutide is still way too early to mess with, it's giving me real "vioxx" vibes of messing with too much at once.
No, I had access to free tirzepatide. I chose retatrutide because early results seemed promising and safe and since I was going to run a short-term self-trial I wanted the most effective peptide.
Please be careful here, as Retatritude is not actually commercially available in most of the world, outside of research labs. And is not FDA approved to buy or use in the US (where most of HN readers are).
I fear this kind of post will encourage gullible people to go chasing reta on the grey market, where they might as well be getting a placebo, as there's no mechanism for your typical person to verify that they're getting what they think they're getting.
And given it's an injectable, and bacterial growth, or a variety of other toxins that can remain in poorly manufactured pharmaceuticals, can do a great deal of harm.
> there's no mechanism for your typical person to verify that they're getting what they think they're getting.
Think what would happen if there was one.
In the spirit of selling shovels in a gold rush, the first company to commercialize a tricorder is going to make bank off all the fitness fads and off-label/DIY medicine markets.
I know a couple of people that should know better (phds in biosciences but now doing corporate management) taking expensive weird Chinese peptides that would probably be better off if they did some cardio a few days per week and ate better.
I'm not inclined to be a guinea pig for these. I suspect maybe later in my child's life they will have been proven long-term safe (or not). I'll be old or dead at that point. I'm really wary of putting anything not known to be standard food or medicine into my body.
Care to share what those “other things” you’re concerned about are? If you mean what I suspect you do, then this is a complete false equivalence. But it’s hard to evaluate when you don’t actually state your claim or concerns.
I tried retatrutide for 10 weeks, here are my results:
Before:
5'7, ~182lb
Bench 1rm: 315
Squat: 5x10 225
Deadlift: 5x5 315
After:
same height lol, 154lb
Bench 1rm: 285
Squat: 5x10 205
Deadlift: 5x5 275
Suffered some anhedonia towards the end but that went away ~1wk after stopping.
Overall pretty good, not any side effects. Definitely fixed my food craving problem. I didn't have a high intake of protein during the 10 weeks, so I suspect thats why I lost muscle mass :/
I used a combo of low-dose retatrutide, tesamorelin, and ipamorelin and lost about 15lb over 45 days, including 60% of my visceral fat, and put on 4lb of muscle, per before-and-after DEXA scans. I lifted regularly, ate well, and prioritized protein, and while I definitely under-ate protein, I was very pleased to find that I was able to increase muscle mass while cutting the fat. My visceral fat was the primary target here, since I'd been unable to get it to budge despite consistent training and diet. Very pleased.
You lost muscle because you lost around 1.54% of body weight per week, which is way too aggressive. The maximum recommended amount for losing weight while retaining muscle is around 1%. You will also most likely experience a weight rebound.
Hasn't this mostly been debunked? You lose muscle mass because you lost mass overall, and whether you lost it too quickly or not is not the major factor. AFAIK maintaining muscle mass while losing fat is borderline impossible for anyone who isn't extremely fat and/or very disproportionate composition to begin with.
Not at all, this is a well-known and long-established risk of rapid weight loss. Even long before any of these drugs existed, medical guidance was to lose weight slowly to help limit lean muscle loss.
Not as far as I know. The ratio of fat-to-muscle loss depends on several factors, most notably the rate of weight loss (see https://pubmed.ncbi.nlm.nih.gov/34371981/). In fact, retatrutide is popular notably because it is known to preserve lean body mass better than other weight loss drugs.
Seems you are correct according to https://pubmed.ncbi.nlm.nih.gov/40609566/: "The proportion of lean mass loss to weight loss was similar to other obesity treatments."
You need to define how much muscle mass you expect to lose. The entire idea behind the bulk/cut cycle is that you want to net gain muscle after a full diet cycle.
It's also not borderline impossible to maintain the majority of your muscle mass, but it depends on how you eat and train. We don't know enough about the person above's diet, training, current body composition, etc. to say anything for certain.
Yeah, basically disinterested. Somewhat burnt out from doing things I normally love doing such as going on walks, programming on weekends, gaming, and work. It wasn't a really big problem, I only noticed it when looking retroactively at my experience.
How much of that is just from your hormones being trashed due to a severe deficit?
Large caloric deficits (1000+/day) in leaner people is known to tank T levels among other things. When I was on such large deficits, I had very weird mood/arousal swings. Nothing that problematic for someone with as much executive control as me but it was very weird to be held hostage to.
This is crazy. You lost 28 lbs (15% of your body weight) in 10 weeks. Why did your doctor to allow you to continue? By any common sense, that is an unhealthy pace to lose body weight.
It seems to be more complicated (or unpredictable?) than that:
> In this study, rapid weight loss was associated with the loss of kidney function in males with normal weight, and with improvement of kidney function in overweight males.
> Our study showed that BMI and BMI change were not associated with eGFR change in females.
This is untrue. There are 100s of YouTube videos of amateur body builders preparing for a show. They are able to maintain their muscle mass while in a calorie deficit. Yes, it is insanely hard, but it can be done.
Did you work out during those 10 weeks any? TBH if you went from regular lifting to not for 10 weeks I'd expect a similar decrease in your lifting numbers (though not a .4lb/day weight loss of course)
Given that many people experiment on themselves anyway, I feel it's a pity and a loss for science that the outcomes of those self-experiments are not collected and aggregated.
The article itself raises the issue of "lack of clinical data", given that these substances are relativelly new. But the lack of data may originate from a certain stiffness, or lack of accessibility and high cost of clinical trials. An alternative source of information are these people who self-experiment, but unfortunatelly this information is mostly lost instead of being captured.
How could this proposal work in practice? clearly the data would be noisy, contain some false reporting, biased, subjective etc. But statistical processing of a large number of reports (coming from hudreds of thousands or millions of self-reporting subjects) may still extract relevant scientific information; that we're dropping on the floor right now.
An example: I'm experimenting with a radical diet. I keep observations for myself, but they're not shared with anybody and don't contribute to science.
What the altervative would be: I would enroll on a web page, where I would describe the experiment I plan to do before I start it. I would be get a code for a blood/urine work for the "before" state, with the agreement that the results, anonimized, are shared with the platform. Weekly I would report on the platform observations, such as: got sick in this particular way, wheight variations, sleep eval, or any other changes.
At the end, or periodically I would get new free blood/urine work with the results shared.
Research institutes and pharma would get access to the data, to aggregate and denoise as they can to extract the latent information.
You REALLY don't want to open the door to "compulsory self-administration." You don't even want people to think about that door. For everyone else, there's clinical trials where you may get a $50 gift card if you're part of the test group.
Peptides are a revolution and you don't need to know how they work to know that they work (for various people for various conditions). There is a tension between empiricism and fundamentalism with much of medical science focusing on fundamentalism. Now with the ability to collect and search large amounts of empirical data and communicate it peer-to-peer people are picking up on a lot of things that work without knowing why they work. I think people are just going to circumvent the fundamentalist and chase after whatever works.
I owe my health to early adoption of experimental peptides, I have life long ME/CFS and there is no known treatment for this nor is there any on the horizon. At least they finally have a diagnostic test and know it's not psychosomatic but I could have told them that from day 1. Most doctors are not researchers and have little understanding on statistics instead preferring to rely on discrete classifications and simple decision tress. As someone with hEDS from TNXB I am a walking bag of symptoms and yet not a single doctor could figure it out. I had to research it myself which involved post-doc level textbooks and research journals. I came across the work done by Prof. Khavinson (USSR) and it did appear to me that peptides were incredibly under-explored. Given the poor quality of life with ME/CFS I was willing to take serious risks so previous trials were helpful to give an idea on dosing and lethality, I went through most of the research peptides one by one. I actually waited on semaglutide a bit because I suspected there was a small minority who would have hyper sensitivity and I both expected that to appear in the data, which it did, and I expected to have hypersensitivity, which I did. Others who were less careful ended up with pretty bad gastroenteritis. Semaglutide has been the most effective and with it and a few others I am largely able to lead a normal life. I was getting gray market from the US but now I get it direct from China.
> There is a tension between empiricism and fundamentalism with much of medical science focusing on fundamentalism.
This is a deeply unfair statement, and also a false dichotomy. Medical science is of course empiric. What you call "fundamentalism" is that compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people. And no, it's not just because of Thalidomide. Many, many compounds fail clinical trials because of severe side effects, like liver toxicity, severe immune reactions or heart problems. Then there's of course increased risk of cancer, which can take many years to manifest itself empirically. You argue that you prefer living with these uncertainties rather than ME/CFS, and that's of course entirely understandable, but disparaging the field of medical science as focused on "fundamentalism" because we do not give large patient cohorts untested compounds is polemic. I understand where you are coming from, and I'm sorry that you suffer from this terrible condition, but likewise, you should try to understand the other side.
Doctors have been maligning ME/CFS as psychosamatic for decades and generally still do despite a large amount of modern evidence to the contrary. If you have it it’s clearly not, you can get good and bad days that are clearly not dependent on psychological state. In addition I have it due to hEDS which is a condition that is almost never diagnosed due to aforementioned blind spots. Most doctors still think the prevalence rate is 1/50K despite continued research raising that number to 1/15K and 1/500. It takes a long time for this information to percolate through the system.
Doctors, like many professions, have institutional blind spots, I studied these in my search because I was looking for something that had not been found. Most doctors have to consider all people and all conditions, I only have to be concerned with one.
Notably they only recently adopted Bayesian statistics for medical trials despite that math being around for hundreds of years.
I completely understand your frustration with the lack of knowledge and research in ME/CFS. It's a scandal, given the prevalence and seriousness of the condition. Unfortunately, after Covid, ME/CFS was even more politicized as part of the long-Covid discussions and got caught up in the culture wars. I have several friends with ME/CFS and they basically say the same things you do - ignorant doctors, high cost due to medication usually being off-label and not covered by insurance, and even friends don't take the condition seriously.
ME/CFS research is severely underfunded. The reasons for this are not simple, it's partly due to the complexity of the disease which, as cynical as it is, does not make it an attractive research topic for ambitious scientists. Same goes for "Big Pharma". Clinical trials for ME/CFS are extremely complicated, and hence expensive, due to the myriad of symptoms in how the condition can appear. It makes research in this area very difficult and expensive. There's very little funding for ME/CFS research, and that needs to change. Unfortunately, especially in the US, this is not going to happen for Kennedy reasons.
The Bayesian statistics thing is a bit of red herring, though. While your are correct that the math is old, the needed compute resources for doing Bayesian modeling on large trials was simply not there until recently. But it is also correct that it also took a long time until there were official rules regarding this from FDA and EMA. These regulatory things move very, very slowly.
Unless you’ve had ME/CFS you cannot understand how bad it is, I’ve had it and I still have a hard time comprehending how bad it was, I am occasionally reminded and it’s easy to forget. While it won’t kill you it’ll destroy your life until you’re ready to kill yourself.
The UK led the world with explicit psychologizing of it in large part to prevent insurance companies being liable for such an expensive and debilitating condition. A legacy that continues to this day, the main people responsible are still very influential. Fauci was instrumental in diverting research away from the autoimmune aspect and preventing a lot of important research. The $1B set aside for LongCovid appears to largely have been wasted. The official classification for hEDS was explicitly changed to reduce the number found so that it could remain a rare disease and continue to have access to specific funding for rare diseases (goal seeking). I could go on and on. It is a highly dysfunctional industry with many perverse incentives pulling it in all sorts of directions. There was the healthy at any size movement despite obesity being a massive cause for mortality, perhaps the only stronger signal would be smoking and consider how long it took them to figure out smoking.
There have been insanely impressive improvements to medical science but this seems to be largely due to tooling and access to information rather than the lumbering bureaucracy which appears to do very little of benefit.
I don't really understand where you are going with the fundamentalist vs. empiricist holy war narrative. Medical science is very empiricist, but it is conservative.
Yes they will miss rare cases or where symptoms aren't quantifiable or where no understood biological mechanism exists. Yes you can take on research and treatment yourself with the risk associated. No a bunch of anecdotal evidence on experimental treatments do not substitute for structured research. No you won't come back here in 3 years if you develop serious side effects that would have been identified in clinical trials and tell everyone you were wrong.
’fundamentalist’ has religious connotations which I did not intend, I meant deduction from first principles not foundational orthodoxy. My expression was there was tension not completely discrete factions, there is clearly some empiricism used in medicine. One of the difficulties in getting published is defending a position and it’s easier to do this with a mechanism of action which I think slows things down too much. The pace of progress on my conditions might as well be none at all. Still no cure for a condition that’s been known about since Hippocrates.
So I’ve been doing this for over 4 years now, and commenting on this with this account for a bit less than that, so far no serious unwanted side effects other than the usual ones for semaglutide which went away. Of course that has a survivorship bias but in the forums people do often tell others what they’re about to try and we would notice if they stopped showing up.
> My expression was there was tension not completely discrete factions, there is clearly some empiricism used in medicine. One of the difficulties in getting published is defending a position and it’s easier to do this with a mechanism of action which I think slows things down too much.
There is always tension between objectives in real-world systems. There are essentially two frontiers in our healthcare system--a core of educated professionals that are conservative and move slowly with ample evidence behind decisions, and a wide range of laymen who are comfortable with personal risk (e.g. bodybuilding community). I have respect for both, and they work together. The core will always have too many false negatives and the horizon group will have too many false positives. Saying the balance right now slows things down too much needs more support as an argument, there will always be things on the roadmap for medicine and there will always be edge cases that can't get addressed perfectly
From what I've seen medical researchers are champing at the bit for new areas of treatment that they think are promising and they just need the smallest amount of convincing evidence to research. If they don't have it for something you think is valuable, collect the information in a systematic way and find someone to send it to.
>compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people
Particularly when the mechanism behind most of these peptides comes down to "promotes more rapid cell growth". The intent may be to repair the skin, muscles, or ligaments, but biology is rarely that specific.
I think the grandparent meant "fundamentalism" as "mechanistic", and lots of things we can know (as you say using the scientific method) to be useful long before we have a good mechanistic explanation of how they work.
Some examples: aspirin (willow bark used for thousands of years, drug synthesized in 1897 and mechanism explained almost 100y later), or general anesthesia used again since mid 1800s and the mechanism is quite still debated.
This is not to downplay all the long term, or developmental, risks that using something novel can result in. But we can empirically know something about the effects without having good mechanistic models.
But it is usually not necessary for approval of a compound to be able to describe how it works on a molecular or cellular level. What you need to show are three things: efficacy, safety and quality, so basically: the compound has the intended clinical benefit, has an acceptable safety profile and can be produced with a consistent manufacturing quality. Most compounds fail because of lack of efficacy (roughly half), and roughly a third because of lack of acceptable safety.
The vast majority of drug candidates don’t make it to the trial stage. Much of the research has to be defensible prior to the trial and what makes them defensible is having a mechanism for action. Of course once a drug is being used off label there starts to be some empirical data which can be used for trials, and it seems that we’ll get lucky with GLP1-As.
You are entirely correct. New compounds for trials do not come out of thin air, you usually derive them from compounds you already know how and why they work. For instance, we know very well how Semaglutide works, same goes for many other peptides that are currently being studied. However, you are correct that we do not understand why they would help for ME/CFS, simply because we do not understand ME/CFS in the first place. As I've written above, it's a severely neglected disease.
Anyway, I don't think we really disagree, I rather misunderstood your original post. It's good to hear that these new peptides are helping with your condition, and I wish you all the best!
Thanks for the feedback, I’m noticing that ‘fundamentalism’ didn’t translate properly and I should have referred to first principles and mechanisms of action. I need better words for these and I will try to find them.
As a fun aside, consider the effect of the birthday paradox on empiricism, as the pool of candidates grows larger the probability of a match increases substantially as potential matching candidates increases quadratically.
Non blinded self experimentation is not a useful branch of empiricism.
I had an ME/CFS patient that had tried 100s of things and documented the effects thoroughly. She had a quite impressive list. Roughly 30% had had an effect to begin with, but the trend she observed was that it lasted for around a month at most. Placebo was her overall conclusion, but she occasionally got relief anyways so we both agreed that there was no harm in continuing. I'm sure several "peptides" is on her list by now.
There is nothing new under the sun, and fad cures for diffuse conditions have come and gone many times before. This is especially the case for conditions involving pain or tiredness, which are extremely sensitive to both placebo and nocebo.
What would be revolutionary would be 2-3 double blinded RCTs showing a lasting effect. Which would be great if someone did! But you have to actually bother to do it. And personally I would put money on the outcome being "no effect".
What do you think about the mis-alignment between goals here?
For medical research, the goal is to find general practices that will broadly help, and identify risks with the intervention. Even then, with many interventions, it's understood that they will effect people differently.
For individuals, they don't care about variation in communities, or standard medical practices, they are looking for relief for their specific condition.
Of course, declaring that just because something worked for one person, it should work for others, is wrong in both camps.
I feel like a big part of the disconnect here, and a big reason why people are talking past each other, is that they actually have different goals, and aren't really aware of that difference.
Well, to be honest I think the primary disconnect is in epistemological understanding. The OP did not declare peptides to be a personal revolution, he/she seemingly generalised their own experience to be widely applicable.
Basic human thought patterns usually lead people to think that anecdotes about their personal experience is valuable for understanding the world, but this is wrong. The scientific revolution basically illustrated the flaw in this premise outside of hypothesis generation. It takes specific education to make human beings truly believe that their anecdotal experiences are mostly irrelevant beyond understanding their immediate circumstances. The proportion of humanity that truly think this way is relatively small.
Understanding the world through anecdotes still works okay-ish for a lot of areas, but ascertaining relatively subjective effects of experimental pharmaceuticals is not one of them. But to many people it's non obvious that this is the case. And as a general method of thinking about this issue, it is just the wrong way to go about things.
And that's the disconnect, in my opinion. The OP drew a conclusion from a thought pattern that comes easily to human beings, but that is just wrong in this situation. Of course, perhaps this is reinforced by underlying motivations, but that's not what makes people talk past each other. These kinds of discussion are usually driven by so called "deep disagreements" in epistemological understanding, in my experience.
I'm pretty sure there is no diagnostic test for ME/CFS. What are you referring to?
Also I don't understand how semaglutide did help you while you're at the same time part of a minority risk group with a hypersensitivity to it. Isn't that a contradiction?
Yes, sensitivity at over 10x normal, so I just took 10x less. I’m taking a more normal dose now after 4 years and I believe I have become desensitized as my body normalized. Other seemingly unrelated aspects also normalized such as thyroid, testosterone, and neutrophils also improved. I was taking medication for these and have been able to stop taking them. I am assuming a lack of GLP1-As to begin with caused the receptors become more sensitive to it. When I started there was no anecdotal information available just theory, in the 4 years since many people have now had very similar experiences including hypersensitivity. (https://www.healthrising.org/blog/2025/11/03/glp-1-agonist-m...)
There are now a number of very definitive tests, most related to immune system profiling. Prof. Ron Davis has some good research and has shown that plasma from someone with ME/CFS when combined with normal red blood cells will greatly diminish the ability for red blood cells to handle stress (pumping out salt).
I think I would need to see testing on a control group of housebound patients with other conditions to believe this. It's easy for ME testing to pick up markers for being housebound and limited exercise for an extended period of time.
You sound exactly like the tens of doctors that misdiagnosed my aunt (who passed away through euthanasia after her symptoms got too bad to live with late last year).
I understand that the symptoms of ME/CFS might be similar to being obese/depressed or housebound, but the problem is that doctors often jump to that conclusion too quickly and don’t take efforts to diagnose ME/CFS leading to situations like my aunt’s. She was also obese and depressed and has been struggling with those symptoms for about 30 years and has constantly been misdiagnosed the entire time because doctors didn’t figure out that those were symptoms of ME/CFS and not two unrelated conditions coming from two different diagnoses.
Thanks to long-covid putting the symptoms of ME/CFS on the forefront lately, there’s finally been some much needed research into the disease and people like my aunt finally get the diagnosis they should have been getting many years ago.
Well, reading the study, I'm not sure more patients could rescue it from methodological bias. They assumed the premise basically -- we should find a biomarker, which is kind of what this thread is discussing. Then they went trawling for biomarker in a sea of millions of biomarkers. They did this by training an model that produced the desired result, using a grid search for hyper parameters that even further expanded the available degrees of freedom here beyond what they had from the biology. No pre-registration; There are millions of places where the researchers could have made a different decision -- would they still have gotten a publishable result? Oh plus the authors mostly work for the company whose data they use, which is hoping to sell a diagnostic test.
I'm giving you a thorough response because I'm detecting a cavalier anti scientism which I think is sadly becoming more common. This stuff is hard; are you sure you understand it enough to have an informed opinion?
Im sorry for your quality of life problems but calling doctors bad at statistics and then giving anecdotal evidence as proof has to start ringing some logical bells right? You dont even have to take our word. Use an LLM as judge. Paste your comment into chatgpt and see what it says.
I didn't read their whole comment, but I worked in the Internal Research department of a medical school. I did their statistical studies and built software for analysis pipelines.
Doctors, at least 15 years ago, were definitely bad at statistics.
They were not required to take a statistics course at all. Most programs would require Algebra and Calculus as part of their science reqs.
Some would maybe take one basic research course, and they would then become obsessed with p values of 0.05.
They did not have a basic understanding of how to interpret research unless they were an auto didactic and went out of their way to improve. It's something my director (a doctor and software engineer), and the Dean complained about relentlessly.
I’ve not only visited many doctors personally I was also part of a team working on a medical diagnostic instrument, the result of the instrument was a probability distribution function and it was impossible to explain this to the doctors who really would only accept a small number discrete classifications, which in effect throws out about half of the data we had worked so hard to collect.
You reminded me about another idiosyncrasy:
Doctors are addicted to double blind randomized control trials.
Which yes, those are powerful. But good evidence can come from many other study designs. Especially when mechanisms and first principles are being studied.
I guess it depends on how you frame it. "I've just posted this comment, what do you think" vs "Someone online has just posted this comment, what do you think".
But it does require to know the bias that LLMs have ahead of testing this.
I agree with this, but we don't have a good understanding of the mechanisms of how most drugs work, and what else they do. That's why, generally speaking, we require actual observational safety data, and not just a thorough description of the mechanism(s) of a drug. And sometimes we find out years or even decades later we were badly wrong. "Safe" is a very qualified term when it comes to drugs. What actually distinguishes $randompeptide from $approveddrug is the safety data - there are papers all about the proposed mechanisms for most of them.
If a lot of people take the mediation and die is that evidence that the medication is unsafe? If they live is that evidence that the medication is safe? Either both are true or neither is true. The relative weight of evidence is dependent on priors but it is still evidence.
Your comment reads like someone with no experience in medical trials - neither pharmaceutical nor medical devices. Death is not the only negative outcome. Nor is a procedure that is commonly followed by death necessarily a bad procedure - many cancer treatments for example fall into this category.
You’re not understanding the point of the hypothetical, it was to illustrate a scenario in that most people would consider evidential and point out that by definition the opposite outcome must also be evidential even if that outcome was far more likely. It’s to highlight an unintuitive aspect of probability formalized as the bayes ratio. The strength of the evidence is dependent on the priors but it exists. Anecdotal evidence is not zero evidence it is weak evidence and with care a lot of anecdotal evidence can be combined to create stronger forms of evidence. Rounding it down to zero or up to one are both incorrect.
And yet neither of the sides are strong enough to term as evidence. I have no problem with self-experimentation. But citing a few anecdotes as evidence is a dangerous area that I discourage. Somedau we will understand why some people respond so favourably to the wolverine stack and others don't. And somebody will someday correlate what those hurt by BPC-157 all have in common. But until then, these peptides cannot be recommended to others in good conscious.
That is so dangerous, buying grey market replicas of pharmaceuticals.
Unless you have a research lab built out in your house, you have zero way of knowing what it is that you're actually getting. Whether the dosing matches the claimed dose. Whether there are bacterial growth, or other manufacturing chemical left in by bottom-of-the-barrel chinese manufacturer.
I understand your risk profile may be different than others, but when you can get the real thing officially, I'm not sure why anyone would risk this.
Clinical trials are not looking for fundamental mechanisms, they are there to ensure an effect is strong enough to say a product should be sold for that purpose. Otherwise you end up with snake oil salesmen. Because how can you be sure you are even injecting the thing the sellers claim it is?
I would encourage everyone interested in peptides to read about the state of medical science before the establishment of the Pure Food and Drug Act of 1906.
I have tried everything on just about every list of possible treatments, having been in the fortunate position to have made enough money that I can try things full time and being able to bypass doctors for access to medicine and being able to do my own research.
I don’t know the mechanism, I think ME/CFS is an autoimmune condition and semiglutide appears to help with autoimmune conditions in general. That was my reason for trying it. The improvements snuck up on me after many months as I noticed I was having fewer and fewer bad days.
If you felt improvements with semiglutide only after many months, how long did the other trials last? It sounds like you went through hundreds of trials. Did they all went on for many months? When did you determine that a drug wasn't effective and abort the trial? How come you didn't abort the semiglutide trial earlier?
Because I started at such low dose 0.025mg and ramped slowly I didn’t expect to see much of an effect until I got to more normal doses so I was unusually patient with it. Additionally extended water fasting (>5 days) was the only thing helping my headaches so I was focusing on ways to emulate this effect without an unmaintainable amount of fasting. I also had uncontrollable weight gain so I figured that was either related, or if not it would still help to lose weight anyway.
Most of the stuff I’ve tried that worked usually has an immediate or overnight effect. Notably Low Dose Naltrexone was overnight, Low Dose Abilify was near immediate. I believe this is due to their immunomodulator properties. So I studied psychopharmacology and focused in on finding weaker ligands than typical as a way to try and safely modulate my immune system. I landed on Modafinil in the morning and Amitryptiline at night, both off label treatments for the probably related dysautonomia.
The N of 1 with many overlapping signals and medications was of course very noisy but I treated it like a ML optimization problem. I could tell it was likely beneficial within the first week even with the small dose. I probably could have statistically determined it was working within a few months but I was distracted by work so it took a little longer to be sure.
Placebos would work with anything with a plausible story, since I’ve tried many hundreds of things and only a handful worked I’m highly confident that it’s not a placebo. People with ME/CFS are used to trying things and have them not work so the placebo effect where it exists has usually worn off.
For the vast majority of people “peptides” is a new word and they assume it’s new science that does something new. It’s like if they had never before heard the term “pill” or “injection” and now someone is marketing it to them. So you have a enthusiastic family member going “omg, I got this amazing injection, it can cure cancer, make you look like the rock, cure baldness and fill your bank account all at the same time!” And you go “I doubt that” and they’ll refer you to all the amazing science on injecting things and how injections are used broadly in the health industry and can treat so many different things. And they are not exactly wrong in that connection, they are just dumb, and of cause a given injection being able to treat diabetes says nothing about injections in general and absolutely nothing about cheap foreign snake oil injections.
I have the same feeling about the whole discussion. I know that colloquially we use terms like "protein" to refer to dietary protein rather than the class of mollecules.
But the way "peptide" is used by all the bro/gal-science influencers that push them online makes it blatantly obvious that they have next to no idea what they're talking about.
Cut and paste from New Yorker:
The human body produces thousands of peptides. Many are portions of proteins which send messages or regulate systems in the body, often in ways that scientists don’t fully understand. Researchers have known about some peptides for decades, and dozens have been turned into safe and effective drugs. The hormone insulin is a peptide that moves sugar from the bloodstream into cells; GLP-1, or glucagon-like peptide-1, spurs the pancreas to release insulin and slows the passage of food through the gut. (Peptides are usually defined as having about fifty amino acids or fewer; more than that and they’re proteins.)
The author is missing a massive segment of that gray market: people who buy FDA-approved weight loss drugs (e.g., semaglutide or tirzepatide) at 2–5% of the brand-name price. This route carries some risk, but there are ways to mitigate it, such as performing third-party testing. I assume most people who do this couldn't realistically afford the brand-name drug anyway, making this their only viable treatment.
Even if you test a batch once, do people who get testing done do testing on all batches?
The synthesis of peptides uses some NASTY chemicals. I would be worried about lax manufacturer policies leading to contamination, even if one batch passes. The costs of FDA certification are the effect of that protection.
But whatever, this is the same attitude that people have against owning insurance. It is hard to recognize the cost of risk.
Won't be anywhere near that. I don't have prices handy, but Lilly sells tirzepatide (a bit better than sema, and usually a bit more expensive) at 500/mo (maybe a bit less now on the trump rx site, I don't recall). Depending on dose, that'll be about 10 bucks a mg give or take. At 50c/mg for sema you were paying a bit of a premium. These days even tirz is only about 30-35c/mg.
I used to buy from Peptide Sciences so I was certainly paying a premium for reputation at $20/mg. I think Semaglutide is now at a bit of a premium due to it falling out of favour and most people switching to Triz and Reta. I only take a low dose and am happy to stick with what's working.
There must be an irony that it was Trumps crackdown on peptides, I presume to prop up his prescription company, that forced me to switch to Chinese supply. By doing it all at once it created a critical mass for that market.
IIRC the biggest impetus for cracking down was Lilly throwing a fit about the gray market supplying reta well before it even becomes available via the normal channels (who knows when that will be). But as you say, it just pushes people to buy direct from Chinese vendors (and it is basically impossible to stop direct imports like that). Would be safer if more reputable US-based sellers could supply it semi-openly as before. Nexaph is still selling it, but I figure the clock is ticking on that.
> and it is basically impossible to stop direct imports like that
How so? Is there a particular characteristic of the US that makes it so, or of the channels through which this is done? I get that in general it's impossible as with recreational drugs, but when you look at cocaine then at least to traffick it to most wealthy countries it takes a large amount of resources and is at high risk of getting caught. Which is why they're increasingly starting to use narco submarines. This greatly increases the price of the product. Why can't the same happen to peptide imports?
The US is a rather dysfunctional country along many axis and an inability to stop imports is one of them. The difference between drugs and peptides is that by weight peptides are much more valuable. 1kg of cocaine is $28K, fentanyl is $150K, and semaglutide is $500K.
High-Performance Liquid Chromatography so purity and concentration.
Back when I started few people were doing this and it was more of a risk, I was buying from research peptide vendors who had their own testing practices, but now a huge number of people are doing it and there are markets where reputations matter and it appears to be reasonably efficient.
I would prefer not to inject peptides from gray market China but practically all of the gray/black market supply is from there. I will likely switch to pharma grade when generics become available.
Im a libertarian at heart so cant argue too much with people's personal choices, but I can only say that given what I know can go wrong in even the best maintained lab, I wouldn't ever do what youre doing. Yes its all great today, but the day something goes wrong, you may not be happy finding out how its affecting you. Look up the bayer factor viii hiv incident.
Last I checked, Ozempic (Semaglutide) is around $1000/month in the US. A typical 1 month pen is 4-8mg, so around $250/mg to $500/mg. So yeah, I may have understated how much cheaper the gray market version is.
Novo Nordisk's drugs can be had as low as $250/month through third party (which is weird), though they'll probably honor those prices in direct sales before long.
I imagine it's legally risky to buy a large quantity, test it, and then resell smaller quantities. That's a shame because the alternative is probably that some folks settle for products of dubious quality and end up getting hurt.
Yes, I believe most people buy directly from somewhat shady Chinese factories. I tried contacting a few and they all refuse to meet or send samples from within China, so I assume what they're doing is illegal in China. In the US, it's legal to sell them as a "research chemical" but the FDA is cracking down on companies that are clearly engaging in b2c.
Right, but I don't know the people at those companies. I have local chemists that I trust. I'm just lamenting the fact that developing that kind of trust network everywhere, so everybody can be similarly sure of what they're putting in their body, is likely to run afoul of local laws.
FWIW, finnrick's claim to fame is being free. Someone is paying for it. They have also failed blind tests in the past, Janoshik (IIRC) never has. There are several US-based labs but none of them have the same reputation as Janoshik.
Actually, you just described most of the tele-health and compounding pharmacies that carry GLP1s!
Where do you think Hims, Ro, Brello, or the rest get the APIs they sell to their customers? They get them from grey market suppliers in China. They don't go to Ely Lilly or NovoNordisk and say, "politely sir, may I skirt around your IP and sell your drugs for 10x what they cost instead of 10,000x what they cost?" Hopefully, they test them and filter them and use sterile/pharma processes for what they sell to their customers. Well, except for the Medspas, those are just wild west snake oil farms.
We need to change the law so that the crime is selling mislabeled or contaminated drugs. If you can cook it well enough in your kitchen, you should be allowed to share it with a neighbor in need.
Things have changed a little, but during the time that compounding was explicitly allowed, the licensed pharmacies were buying from FDA approved manufacturers, sometimes in China, and sometimes the same manufacturers who also do contract manufacturing for Lilly.
Today ... who knows? It might just be the same gray market stuff us plebes can get.
It probably is, but that does not stop people from effectively doing it. There are a number of groups that specialize in conducting group buys, doing a bunch of testing on randomized samples, and then shipping out the product to individuals.
Also, if you plan to be on it a good long time, you can buy a bunch of kits yourself (a kit is 10 vials), run a bunch of tests, and then just have a nice stockpile that will last you years. The testing will likely cost as much or more than the product itself, but given how inexpensive the product is, you still come out way ahead financially.
>I imagine it's legally risky to buy a large quantity, test it, and then resell smaller quantities
It is illegal, but it doesn't stop people from doing it. In fact, if you don't have any sort of test results for your peptides people will absolutely avoid buying your wares until you have them. Purity and mg/ml are the 2 basic test results that any shop worth their stuff will have.
To be fair, most everyone I know who is buying on the gray market considers vendor tests to be minimally required, but still insufficient -- there is no assurance they tested the product they shipped to you. Plan on testing it yourself. I'm sure some people do trust nexaph enough, though, to not worry so much. Whether that trust is well placed, that is a separate discussion.
With most of these you can really tell if they work or not and there is a pretty predicable dose dependent reaction profile. With slow meds like semaglutide you'd maybe not notice it in the first week but you will by week 3. I had mine tested but if that wasn't available I probably would have considered the anecdotal evidence to be sufficient. It appears that most of the scamming is just people taking the money and not shipping anything.
The most dangerous failures I've seen have been sending the wrong peptide. 15 mg of tirzepatide and 15 mg of semaglutide is a very different experience.
After nearly getting hosed in a group buy (I did get refunded, but that is far from a guarantee) because of a product mismatch, I decided to just pay for nexaph. Love him or hate him, his popularity relies on his reputation and he has been more careful than most suppliers to cultivate it with more extensive testing and quality control.
That makes sense, I don't like that the bottles are unlabelled so the first thing I have to do is label them. The box is labelled and this seems to be standard practice. Semaglutide is falling out of favour so I guess they're substituting. I have 4 years supply now so I guess I'll check back then and see where the market is at.
I know a bunch of people with multi-year stockpiles. I've got ~5 years of reta and ~6 years of tirz. This is too much, of course, but I determined a while back that under no circumstances do I ever intend to find myself unable to source it. My life is immeasurably better after losing 110 pounds.
Could you direct me to some resources you used to figure out dosing and sourcing? I’ve been interested in trying it out (need to lose a lot of weight) but have been paralyzed by too much contradictory information.
Lowe has a point, but the FDA has painted itself into a corner by (a) forcing up the costs and the various bureaucratic demands associated with clinical trials, (b) allowing drug advertising , but then forcing those comical "may cause death" disclaimers, both of which have become totally ubiquitous, and (c) inconsistently following its own rules, and in some cases flouting its own rules.
At this point, broscience is considered no less valid than actual clinical trials, and the FDA should blame itself for this. Not "human nature being what it is in this fallen world" in a sort of general or abstract sense.
Another point I could raise is that telemedicine has turned the entire prescription system into nothing more than a parasitic middleman/gatekeeper.
FDA reform is very badly necessary. That ought to come before harsher enforcement, and I think that much of the populace already intuitively understands this.
People want GLP-1 drugs. They can't get them without a prescription. They pay $$$ to a "telemedicine" "doctor", recite a list of well-known symptoms, and buy the prescription.
The system is that you can't buy these drugs without the piece of paper, and the piece of paper is basically something that anybody can buy regardless of whether or not they actually need the drug. Wanting it is usually enough.
I think access is a good thing. The issue isn't with telemedicine but the fact that there's a prescription wall for helpful meds like GLP-1 in a country where we've failed people by creating one of the worst food environments.
Also, most doctor's visits aren't any different from getting it if you want it except it's gated on the mood/attitude of the doctor, maybe your ability to sell some sob story. And then you book a different doctor until you get it. Telemedicine just makes the process easier an arbitrary system.
GLP-1 prescriptions are easy to get in the US. It's filling the prescription that is the problem, because insurance rarely covers it and it is beyond the disposable income of most Americans.
The prescription hurdle is absolutely necessary -- these are not drugs that anyone can safely take without guidance. It's the price that needs to be fixed.
I actually think "informed" is almost definitely defined already. Doctors already need to provide informed consent, so I think it would borrow from that. As for "egregious", I also suspect that this is understood already in a similar vein, but perhaps not - I'd suggest that this is effectively "would near definitively cause imminent harm".
FWIW I do not think that most people agree with this.
There's a lot of definitions for both of those words.
I can tell you that the conversations I've had with people who take these drugs from telehealths or from med spas -- they generally don't understand how these drugs work, what the risk profiles, are or how dosing should be managed. There's a lot of misinformation going around about all these drugs.
"immiment" is a different word than "egregious" isn't it? Malnutrition, cancer, and death are pretty egregious as well, even if they occur maybe months or years in the future, aren't they?
Literally, enough people are fucking this stuff up that we have pop culture references to it: "ozempic face". Losing weight this rapidly is unsafe. Sure, a lot of people might consent to the idea of rapidly losing weight, but there's nothing "informed" about it.
> There's a lot of definitions for both of those words.
Sure. I don't think that that implies we have the right system currently or that we can't come up with good definitions. And again, "informed" is almost definitely already an understood term in medicine since "informed consent" is already understood.
> they generally don't understand how these drugs work, what the risk profiles, are or how dosing should be managed.
That's fine. I don't think they have to understand how they work. They have to have the risks conveyed appropriately to them. They might make a call that's ultimately harmful. Adults can do that, they should be allowed to do that.
> "immiment" is a different word than "egregious" isn't it?
Well, yes. If I had defined "egregious" as the same word, that wouldn't be very helpful.
> Malnutrition, cancer, and death are pretty egregious as well, even if they occur maybe months or years in the future, aren't they?
Not really. Things that take years to happen are a lot less serious, especially as they can be monitored for. But again, this can all be explained to the patient. I'd say the bar for "egregious" should be very, very high. When in doubt, give patients the power to choose.
> Literally, enough people are fucking this stuff up that we have pop culture references to it: "ozempic face". Losing weight this rapidly is unsafe.
That isn't compelling. How many of those people are getting ozempic from a nurse practitioner at one of these compound pharmacies? If anything, I'd bet that doctors taking the time to ensure patients are informed would lead to a reduction here.
I know a lot of people on GLP-1 meds and even took a dose myself out of curiosity.
You take a dose every two weeks. And if you accidentally double dose because you misread 1U to mean 1 dose, it just gives you some nausea.
Are we going to pretend it's hard to take this drug now too? Or that the doctor has some magical insight into your getting-on? Remember to eat. That's it. I guess a few people might need the doctor to go "you're eating, right?" but I don't believe in infantilizing everyone over that.
Weekly, if you are following guidelines correctly. The half-life of most GLP1 peptides is 5-6 days.
I otherwise agree with your point entirely. Though anecdotally, I may have given my brother-in-law a single small vial of tirzepatide at his request so that he could experience it, and the results were ... not good. Turns out he's an idiot, thought that 'more is better', 'drinking enough water is for weenies', and 'I am not an alcoholic even though I get plowed most evenings.' All against my very specific advice on how to give it a try. Whoops.
My fault, yes, I should have realized he was too stupid to do it without adult supervision. He made himself so sick he almost went to the ER. Nothing really dangerous, of course, tirzepatide is pretty safe stuff, but overdosing on it can make you feel very shitty for a few days until the blood concentration drops.
> Or that the doctor has some magical insight into your getting-on beyond a couple questions they ask you in your visit? Remember to eat. That's it.
Apparently we have forgotten people who died from eating disorders (previously called anorexia nervosa)?
There is a VAST difference between someone who weighs 300lbs asking for GLP-1 to combat morbidity and someone who is barely 100lbs asking for a GLP-1 to take off weight for bikini season. That's what needing to ask a doctor for a prescription is for.
One dose is one thing -- but there are other risks that can lead to complication or death here if taken improperly for a long period of time. Musculoskeletal issues, cardiac issues, thyroid issues, etc.
Additionally, getting the correct dose is not straightforward for a layperson as it is for other OTC drugs with standard doses.
There are similar risks, and probably more likely, to all sorts of consumables that aren't regulated at all. It is reasonable to ask whether the prescription regime for GLP-1s makes sense. It isn't the only substance posing that conundrum! Ondansetron is OTC in a lot of countries, but not in the US, Canada, or UK. But ondansetron is arguably less dangerous and more helpful than pseudoephedrine.
Pseudoephedrine, of course, isn't BTC because it's dangerous to take or complicated to dose. It's there because of the war on drugs. But I do agree that not all drugs are regulated appropriately. Marijuana also comes to mind.
I do think GLP-1s are just about right. It is appropriate to take them under personalized professional guidance.
Right, and I actually see the logic of that (unlike virtually everyone else on HN, and let's not rekindle that debate; the search bar avails). The point is you don't need a prescription to get it. People might be better off if GLP1s were also BTC. Hard to say!
Certainly you can abuse a GLP1 and get yourself very sick, or not abuse it and still end up with pancreatitis. But smoking and alcohol presumably cause way more cases of pancreatitis, and you don't need a script for a handle of Popov.
There used to be prescriptions for alcohol products and cigarettes have been sold as medical products -- the reason we accept them in society today is not because we think they have relative less risk to other things, but that their acceptance as recreational vices outweighs the harm that we know they cause.
> smoking and alcohol presumably cause way more cases of pancreatitis
Indeed. In fact, I think just recently there were updated studies for at least one of the popular GLP1s that disclaimed entirely a link to pancreatitis.
To be clear I don't think it's actually reasonable to suggest GLP1s should be OTC in 2026. Were that to happen it would be part of a regime change in drug regulation that I'd categorically oppose. The timeline on GLP1s (unlike Zofran) doesn't support it. There are arguments for why your doctors would want to know that you're taking it, and on what schedule. But it should be extremely easy to get.
Agree, it does feel like a class of medication that deserves more control than OTC would provide. I do think it should be largely voluntary, however, with doctors expected to provide it unless there is a specific contraindication that would make it harmful.
You're totally missing the point thought. The prescription hurdle effectively does not exist. It's just a paywall.
You pay your $100, get a 3 minute call with a NP/PA/whomever, and basically the robot writes you a prescription for whatever you want. The point is you pay and you get the prescription. Patient safety has nothing to do with anything.
It's cheaper for most people to get the prescription written at a PCP.
The advantage to a telehealth is not getting the prescription written -- it's that they'll fill it for cheap through a tiny compounding pharmacy that is making it, technically illegally, but are small enough to be off the FDAs enforcement radar for the moment.
I have used both my PCP and telehealth for prescription writing, never once have I used a compounding pharmacy.
It's slightly cheaper for me to use telehealth vs. billing through my insurance. The downside is it doesn't go towards my deductible of course.
The stuff you are describing are entire supply chains of a sort where you want a GLP-1 or perhaps a few other things like TRT. Those you are signing up for the drug itself, which happens to include the prescription part with it.
Telehealth can be used for any old medication you want. It removes the permission slip part of the process and replaces it with a payment gateway. If you have $75-150 you can just click some buttons and have a prescription for nearly anything you want at most a day later. This includes antibiotics, ADHD meds (getting harder on these), certain benzos, etc.
HIMS/HERS/etc. and their smaller ilk are super popular, but they are the tip of the iceberg.
Telehealth providers can certainly work with compounding pharmacies but not necessarily. If you are looking to get a prescription for Diazapam you are going to be getting that sent to your local Walgreens or whatnot.
> It's slightly cheaper for me to use telehealth vs. billing through my insurance.
How? Usually PCP visit are cheap and everyone gets one for free.
> HIMS/HERS/etc. and their smaller ilk are super popular, but they are the tip of the iceberg.
> Telehealth providers can certainly work with compounding pharmacies but not necessarily.
Yeah I’m aware there are a whole host of services telehealths provide but the primary reason people use them for GLP1s is to avoid the name brand cost.
It's that your health care system the doctor is in builds a few extra hurdles. I've talked to my (non-tele) doctor about GLP-1. I've tried losing weight before, with her, there's a long history.
To get approval, between the hospital my doc is in and the insurance, I need to:
1) Have a BMI of >30. Since it's only 29.5, I get to stuff my face if I want to lose weight.
2) Have six sessions with a nutritionist. Which are massively useless, their advice is roughly equivalent to reading Cosmopolitan. I know because I had prior conversations, and they're documented. But still, gotta do it again.
3) Do six months on Weight Watchers. Which is one massive scam leading you right to disordered eating. Also, I've tried for years to lose weight via diet changes, documented and talked through with my doc.
4) Before I can get tirzepatide, I have to get semaglutide for three months to see if it works. Never mind there's study over study over study showing it's slightly less effective and has massively more side effects.
Or I can just cough up the cash directly and buy from Eli Lilly, if somebody signs that receipt.
I'm fortunate enough I could afford that, so I did. (After a second consultation with my family's doctor back home - both they and my doctor agreed it was appropriate, so it's not just a case of "wanting is enough")
And after six months, my weight was in a much better region, lipid panels were much improved, other related biomarkers looked better as well - exactly as numerous studies and my doctors said one could expect.
So, as long as I cough up enough money, sure, I can bypass all the hoops. My health didn't enter the equation, just screw the poors (whose treatment for worse outcomes because they couldn't get access will cost a whole lot more than GLP-1 would've cost).
So, fuck the "prescription hurdle" and the medical system in the US with a hot white glowing iron rod right up the ass.
As for "these are not drugs that anyone can safely take without guidance", that's not really true either.
They're neither hard to take - "inject one vial once a week into the flabby part" isn't rocket science - nor does it cause massive health risks by itself. (And the hazard ratios for diabetes 2 and cardio events are so spectacularly low that they dwarf the other risks)
Yes, talking to a doc is a good idea. No, the current gatekeeping is in no way necessary.
Those are coverage requirements from your insurance company. Consider yourself lucky to even have any path to get these covered under insurance -- most insurance plans do not cover weight loss drugs under any circumstances.
The diagnostic criteria is simply (BMI > 30) OR (BMI > 27 + a weight related comorbidity like high blood pressure or high cholesterol)
> They're neither hard to take - "inject one vial once a week into the flabby part" isn't rocket science
It's not that they're difficult to administer, it's that dosage needs to be managed appropriately.
The "perscription system" used to be that you'd have to go see a doctor, the doctor knew who you were, and would make decisions on what prescriptions/medications you should be given.
Due to drug advertising rules, the prescription system has been turned on its head, and the patient now goes to their doctor asking for a specific prescription.
Telemedicine took advantage of this and has effectively removed the middleman (the doctor) in many cases and you just sign-up look at a person on a camera, and get your drugs sent to you.
> Telemedicine took advantage of this and has effectively removed the middleman (the doctor) in many cases and you just sign-up look at a person on a camera, and get your drugs sent to you.
This is only true for a handful of drugs that are basically OTC already (or that have OTC formulations). Additionally, telemedicine didn’t take advantage of drug advertising- that’s an odd assertion.
The system changed from the doctor deciding what drugs you should take to the patient asking for the drug by name from the doctor.
I think this enabled telemedicine to work in the way it does not. The patient says "I want wegovy" and the telemedicine platform says "ok, here you go".
Would telehealth pill-pushers exist without this mentality?
Go to doctor, get prescription for restricted medicine, pick up prescription.
If you can call up a teledoc and they give you a prescription based on your description why could you not just go buy the meds yourself without a prescription. You have essentially diagnosed yourself and just asked the doctor for permission to buy the drug you want.
That’s… not how actual telemedicine works. That’s how jackasses “disrupt” healthcare for very specific drugs. Mostly birth control, ED meds, and various hair regrowth meds.
It’s really clear that some of you are really mad about something you don’t understand.
I take certain medications--nothing interesting, nothing controlled, nothing abusable. I have to deal with a whole thing just to get refills, because my PCP forces me to come in every time--and even that is now just a telehealth call that is annoying.
In Mexico, for meds like mine, you can just buy them at the pharmacy. There's no reason for all this nonsense.
(Edit: same PCP refused to prescribe GLP-1s early, without any scientific or medical reason not to. Delayed my weightloss by months until I found a place that would.)
> I’m curious what you mean by this. I’m not sure what you mean by “prescription system” specifically.
They basically operate as a "pay for a prescription" service.
Figure out what drug you want, google the drug name and telehealth. You will be marketed in a wink wink sort of manner over how easy it is to get them, just hours away! Then if you are not a total idiot, you answer certain questions in the right manner on the intake form, the doctor (usually NP/PA or similar for most things) will quickly run through that and expect you to answer correctly - perhaps guide you a bit if you don't.
5 minutes later you have a prescription in the web portal and it's sent to your pharmacy of choice.
It really shows how the whole "permission slip" program is BS. I've used these services a couple times vs. my normal doctor just to save time and expense of an office visit. If I can click some buttons, have a call 30 minutes later, and be on my way to the pharmacy for $50 it's sometimes the path I take now vs. traditional route.
Someone used to the traditional doctor/patient relationship thing and prescriptions being "holy" would be shocked at how easy and gamed it all is.
Well that's a problem with the profit driven US health system (although admittedly other countries have similar problems to varying degrees) not prescriptions in general though? In particular the take home from this should be to make it more difficult to get the prescriptions not to do away with prescriptions.
So you are stating that there has been no change in how clinical trials are required to be run, and the associated costs, since the changes immediately following the thalidomide catastrophe?
Medicine doesn't really ignore nutrition, but the problem is:
1. Most people don't believe it anyway. People want to hear they can eat hamburgers and milkshakes and be healthy. Telling them "we know that gives you heart disease and cancer" does nothing.
2. Nutrition is complicated and different for every person, because everyone has different things they can tolerate. The "perfect" diet is actually worthless because it has a 0% success rate. Really, we have to optimize for how miserable people are willing to be.
3. Most people are unhealthy enough that nutrition is the least of their concerns. That sounds crazy, I know, but if you're obese (which most people are!), then priority is being not obese. Not your nutrition. I know those sound related but they're way less related than you think.
> hamburgers and milkshakes don’t give you heart disease and cancer
They absolutely do, particularly if you're getting most of your calories from them. If evidence-based medicine doesn't convince you, uh, hamburgers and supermarket milk tends to be processed.
They absolutely do not, unless you’re getting too many calories.
Individual foods are—with some exceptions—neither bad for you nor good for you. A healthy diet can occasionally include doughnuts, and milkshakes. Your overall diet is what matters.
Most green vegetables you can eat unlimited amount and stay healthy. They are absolutely "good" food. (Please don't reply with something trite like "oh, but what about the pesticide residues?") The same can be said for high fiber (soluable and insoluable) fruits like apples, oranges, and bananas. As long as eaten whole (minus skin for oranges and bananas), it is almost impossible to overeat these and they are absolutely "good" foods.
Sure, they are not mercury-level toxic. However, these recommendations are for people who consume way too much of these dishes, and it's a safe assumption that this is the case for a significant part of the population.
Sure. We’re saying roughly the same thing. For most Americans, hamburgers cause heart disease because we don’t exercise enough or eat enough plants. If you’re backpacking twenty miles a day, sure, eat whatever, you won’t suffer inflammation or obesity from it. (Though you may run nutritional deficiencies. And you’re building bad habits for when your activity necessarily tapers off.)
Hamburgers are not causing heart disease and diabetes for most Americans. Bad diets loaded with too many calories, too many saturated fats, and too many simple carbs are.
Messaging matters. When you tell people hamburgers and bacon and everything they love are bad, they stop listening, give up, or just eat some other junk that wasn’t prohibited. When you tell them some foods are good, they start buying into superfood marketing.
Diet is the only thing that matters. Lots of veggies are extremely useful because they add bulk without adding calories, and along with fresh fruits are great sources of fiber. Cheeseburgers can only come so often because they’re extremely calorie dense and send enormous reward signals to your brain.
Give people the tools they need to thrive, not just “don’t eat these specific bad foods, eat these specific good foods”.
Agreed (remember where I said overeating). Non-homogenized gently pasteurized milk/cream with minimally processed honey or maple syrup, and fresh ground hamburger, all of which which you can definitely get at supermarkets by the way, are much better for you than Big Macs and McFlurries. Ask yourself why? It’s obviously not “because they aren’t hamburgers and milkshakes”
I agree 100% with your follow-up. In the last 30 years of medical research, I do not recall anything but negative health results from eating red meat (beef). The real culprit is saturated fat. It is the cigarettes of food. There is almost no healthy level to consume, so keep it to 20g per day or less.
Reading this chain of responses from the original is making my internal bullshit alarm (Brandolini's law) go "wee woo wee woo".
> The real culprit is saturated fat. It is the cigarettes of food. There is almost no healthy level to consume
Not at all an expert, but from what I understood saturated fat isn't particularly good but it's not “no healthy level to consume” either (fortunately because you practically cannot avoid them).
I think you're confusing them with trans-insaturated fat (which I don't think are as bad as cigarettes either, but are still bad).
Everything is a carcinogen. Even water. Dose matters, and most of the "omg zomg causes cancer if you eat it!" dietary nonsense purposefully omits absolute amounts or base rates, lest you realize it's actually as likely to give you cancer as smiling at people.
I don't know what else to tell you. Except maybe that if one gets this single concept, that quantities matter, it becomes immediately apparent why most of the "healthy eating" / fitness fads is just pure bullshit.
Depends on the nutrients that comprise them to the extent they contain a lot of omega-6 or not. Not heart disease so much but the other killer - might as well mention in this context. 'A high omega-3, low omega-6 diet with FO for 1 year resulted in a significant reduction in Ki-67 index, a biomarker for prostate cancer'. https://doi.org/10.1200/JCO.24.00608.
Also Prostate Cancer and Prostatic Diseases (2024) 27:700 – 708 'Our preclinical findings provide rationale for clinical trials evaluating ω-3 fatty acids as a potential therapy for prostate cancer'.
Seed oils are not as bad as painted but some caution is needed given for instance the industrial processes used to bring them to market sometimes. Plus the way the oils are cooked when they create free radicals. This is not nonsense.
You don’t have to wonder. It’s public record that 45% of the FDA’s budget incomes from user fees that companies pay when they apply for approval of a medical device or drug.
In the drug division specifically, the number is about 75%.
Naive question: What is wrong with this? Lots of gov't agencies in highly developed countries operate similarly. User fees account for a non-trivial portion of department budgets. A more simple example: Should the Dept of Motor Vehicles (DMV) charge zero, low, medium, high, or infinity money to get a driver's license?
In principle there is nothing wrong with it, as long as the FDA or other testing body retains an appropriate impartiality or lack of bias (perceived or real). The issue, however, would be a lax system that allows revolving door access between the approval body and the industry that is seeking approval. Ironically, the common refrain becomes that their industry specific knowledge means they "must" be the only possible candidates for the role, which just so conveniently starts the revolving door swinging between leadership in industry and upper roles in regulatory bodies.
All but one I have had did not, and his suggestion to eat something other than cheeseburgers every day was less than revolutionary.
When I brought it up with other physicians the answer was always that I probably get all the nutrients I need from regular food. Whatever that may be.
Dietary changes have helped me feel better and healthier and perform better, and a few vitamin and other supplements as well.
I’m not selling a lifestyle. I’m criticizing the foolishness of a food and drug industry based in the idea that preventing death or lifelong disability is sufficient.
Nutrition is run on fads - see whole fitness and healthy food bullshit. Nutrition supplements ended up being a loophole that allows pharmacies and pharma companies to sell all kinds of random stuff that they can't or don't want to, show is safe, or doing anything at all.
> Nutrition is run on fads - see whole fitness and healthy food bullshit.
You raise an interesting point. I watched a YouTube video recently of someone walking around a large US supermarket pointing out all of the processed foods that now claimed to be high protein. It is nuts!
I wonder what will come after the protein boom? My guess: Fiber is back because you need to "fibermaxx" when taking GLP-1 antagonists. I can remember some of the funny adverts in the 1980s of old people taking fiber supplements to "stay regular". (See SNL comedy skit "Colon Blow" for a good laugh.)
Medicine doesn't ignore nutrition, you just don't like the answers.
And it shows on the research: e.g. does creatine help muscle building? No.[1] But cue some anecdote from someone where they also changed a dozen other things at the same time but are sure it was that.
Creatine is probably the most well-studied nutritional supplement we have, and one of the most efficacious. You are presenting a single study to counter that. Not even a meta-analysis, but a single study of just 54 participants who did not exercise at all previously (from the study; "Apparently healthy individuals, with a body mass index of ≤30 kg/m2 and not meeting current physical activity guidelines of at least 150 min of moderate-intensity exercise were included. Individuals who undertook [resistance training] within the previous 12 months were excluded"). The general consensus is that it is absolutely helpful in muscle-building. See, for example [0] and [1]. Beware the man of one study. https://slatestarcodex.com/2014/12/12/beware-the-man-of-one-...
[1]: https://www.mdpi.com/2072-6643/17/17/2748 - "A total of 69 studies with 1937 participants were included for analysis. Creatine plus resistance training produced small but statistically significant improvements... when compared to the placebo."
But there's a core problem with this, in many states doctors are legally forbidden to give nutrition advice. The academy of nutrition and dietetics has worked very hard to make it so that only dietitians can provide nutrition advice. Take Ohio for example, a medical doctor in Ohio is legally forbidden and actually in jeopardy of losing their license and going to jail if they were to provide nutrition advice without a dietetics license. Dietitians are not doctors, but the academy of nutrition and dietetics wants you to think they are.
Doctors in the US receive an average of under 20 hours of training in nutrition over four years of medical school. What little they do receive is often focused on nutrient deficiencies rather than on meal planning for health and chronic disease prevention. Less than 15% of residency programs include anything on nutrition.
To become a registered dietician requires at least a Master's degree in dietetics or nutrition or a related field, and at least 1000 hours of supervised internships.
PS: before any Europeans hold this up as an example of the poor US health care system, doctors in Europe average 24 hours of nutrition training.
Aren't doctors actually exempted specifically from such regulations in almost all states? AFAIK they can actually give nutritional advice legally in nearly every jurisdiction in the US.
To your first point, if you know where to look, you can get tens of vials of GLP-1s that have much higher dosing per vial for cheaper than you can get a third of the amount on the grey market. A lot of these sites even have purity testing to soothe consumers worries that they're getting garbage. For your third point, you have the FDA limiting HGH, yet you can buy the growth horomone releasing factor peptides (tesamorelin, sermorelin, ipamorelin) after doing a simple Google search.
As for broscience, moving into peptides was a logical next step after exhausting anabolic steroid "research". In fact, I'd say that biohackers are actually behind the bros when it comes to trying various peptides out and documenting experiences.
A lot of people are left alone with their health-issues, if you live in Canada and can only see a doctor if you are about to die, people try to change their health situation outside the "regulatory" system. These aren't health worriers, they are desperate to get their lifes back in order. Are there risks? For sure, but similarly untreated pain can damage more, especially mentally.
Wouldn't it be better to use verified medicine? Even if a patient could see a doctor at any time, the doctor would not prescribe such unverified peptides to the patient
I take a small issue with the claim that we don't test peptides. Some of us test them extensively before injecting. Granted, probably the same people who also understand how little science there is backing up most of the popular peptides today. I enjoy being able to buy my own GLP1s, however, at least those which have made it through phase III trials succesfully. As tempting as the claims are about things like BPC-157 and such ... no thanks, that is past my comfort level a good bit.
> My patient is refusing a drug studied in 170,000 people because of side effects that a 124,000-person analysis just confirmed do not exist — while injecting a compound studied in 14 humans, from unregulated sources, based on the recommendation of someone who profits from selling it. She’s probably not the only one. And those using it believe they are “doing their own research.”
Ok, and? At worst you waste a couple hundred dollars and deem the alternative therapy not worth it and go back to your doctor but I know dozens of people at my gym that used BPC 157 and TB 500 that fixed their chronic tendon/joint issues within weeks of starting the therapy that physios couldn't fix for years.
But I'm not saying everyone should be taking these peptides, I'm not coercing anyone, my original point was that people like the author of the article should mind their own business what other people choose to do with their own bodies.
It's very common when people start doing a new exercise regimen. Muscles can become significantly stronger on a timescale of months, while an equivalent increase in the strength of tendons happens on a timescale of a few years. Once somebody has a few years of training under their belt, muscle mass gains are way slower and the capacity of the ligaments will have caught up and these issues go away. However, with bodybuilders and strength athletes these problems can easily come back once anabolic steroids are involved and give big muscular gains without the same level of adaptations in connective tissues.
I don't doubt it. You make casual friends sometimes at certain gyms, especially if any sort of sports are involved like tennis or even group classes.
I am a super introvert and know at least half a dozen folks with such issues, more if you include my close friend group.
Any place that has a lot of physically active people stressing their limits a bit is going to have a lot of injured folks over a decent period of time. And of course it gets talked about quite a lot, since it limits performance and ability.
My trainer knows I have a chronic shoulder issue, and an adductor issue at the moment I'm working through that we need to avoid stressing too much. The few other folks who tend to work out around my schedule know of this, and I know of theirs.
My partner's grandfather died of cancer because when he was having pains they believed their homeopathic medicine would work. When he finally when in to see a real doctor it was too late. If he had gone in earlier, he would been able to have a chance. This is not a rare occurrence for these types.
Why would you stop going to a real doctor though? It's not one or the other.
I'm very on the fence over BPC-157/TB500, I really want to see some actual clinical trials ran on it. I have a feeling the effects are overstated, but I also have had a number of "insider" conversations where I know these and other compounds are very much being utilized in pro athlete injury recovery programs. Those athletes certainly are getting state of the art medical care via traditional sources, plus elite level physio therapy - so it's hard to say if the illicit injury recovery drugs are doing much or not.
I don’t think either of those are patentable so I doubt you’ll see studies or trials any time soon. A lot of strength athletes at all levels, not just elite, are absolutely convinced of their efficacy and their usage sometimes seems as common as ibuprofen.
I used those two in combination to fix pain after 3x surgeries to repair a torn pec + infection. They work and helped me heal from being at a 3/10 constant pain down to baseline.
Not something I would do at any point for fun. But anecdotally, it's materially better than other alternatives offered/available.
According to our new AI overlords, a short synopsis of potential risks of BPC 157 based on mechanistic and animal work to date (don't know human risks because there haven't been sufficient clinical studies):
* Possible pathologic angiogenesis (abnormal blood‑vessel growth), which theoretically could support tumor growth or inflammatory and autoimmune processes.
* Modulation of nitric‑oxide pathways that, at high levels, might contribute to anemia, altered drug metabolism (CYP enzyme activity), and possibly neurodegenerative processes in theory.
* Concerns that its pro‑healing, pro‑growth signalling (e.g., FAK–paxillin) could encourage cancer spread if malignant cells are already present; this remains theoretical, with no proof in humans.
* Possible liver and kidney toxicity suggested in some commentary and extrapolated from preclinical work, but not well characterized in people.
* Immune reactions or allergic responses, including fevers, rash, hives, muscle aches, or systemic inflammatory responses
These do not appear to be results that would appear overnight. It would be "nice" if the folks injecting random shit into their bodies also disclaimed any subsequent medical intervention as a result of said shit, but that I suspect that's unlikely.
We have no specific reason to believe there are concerns with GLP-1s for cancer or anything else, beyond the mildest signal in rodent studies around thyroids.
We do not have robust clinical data for things like BPC-157 but we do have strong preclinical data and an understanding of the mechanisms in play.
I use BPC-157/TB-500/Ghk-CU/KPV - so I'm certainly OK taking the risks. But those mechanisms mentioned before? The same things we're counting on for healing and inflammation reduction are the same things that we know can cause an increase in tumor growth rate and chance of metastasizing. VEGF/VEGFR2 expression are even suppression targets for some cancer therapies.
Are there powerful and useful medications out there, available today, that we both don't have good scientific data on and are free enough of serious side effects? For sure! Is everything out there that, though? No. Some things that work will have too serious of a side effect profile to be feasible. Some things won't work at all, despite however much anecdata is out there.
As for the general idea... I agree there's no law that says a medicine with a strong positive effect must also have strong side effects. And we have plenty that don't - statins, particularly the latest generation, like pitavastatin, are effectively side effect free for the hugely overwhelming majority of people and have great lipid lowering effects. Even older ones showed extremely minimal incidents of things like muscle pain - a vanishingly small number of people relative to the total amount on the medications report muscle pain, and when investigated, quite a lot of even that ends up being unrelated to the statins. Yet the narrative persists that make it sound like anyone on statins is going to have their muscles ache 24/7
I'm glad we have GLP-1, and I don't think there are really major side effects. But they are ineffective outside clinical trial setting for treating obesity.
It seems to be like treating alcoholism with disulfiram: it's a miracle in clinical trials but in the real world the patients just lower the doses or discontinue treatment after 1-2 years and go back to their old habits.
I hope it sounds less wild if you think obesity as disease of addiction. Reducing GLP1 dose can increase the enjoyment in eating, so it makes sense why treating obesity with GLP1 is like treating alcoholism with disulfiram: Effective in theory but hard to adhere outside trials.
Type 1 diabetes (or majority of diseases) doesn't involve addiction.
It is not ineffective outside of clinical trials. All the evidence says that people gain some weight back after they discontinue treatment - which is not a lack of efficacy. But they also usually gain back less then they lost.
I can't reply elsewhere so I will reply to this again.
> In my friends, all of them stopped taking GLP-1 drugs within 2 years because all of them lost the weight they wanted to. Out of curiosity, what sources lead you to believe this?
Anecdotes like this are interesting but in medicine they are not sufficient to make factual statements about drugs. In meta-analyses there is weight regain which is steeper as more weight is lost during treatment [1].
The weight regain seems to be rather slow, it can take years until the baseline weight is reached.
> In meta-analyses there is weight regain which is steeper as more weight is lost during treatment
What does "steeper" mean? The studies I've seen show a net weight loss, even after regain, for the median patient.
> The weight regain seems to be rather slow, it can take years until the baseline weight is reached
Maybe. Right now, however, the evidence shows solid effects outside clinical settings. Your original statement was wrong–your sources own refute the claim.
If you're arguing the effects in the real world haven't consistently been as ridiculous as they were in clinical trials, sure, you get a brownie point. But broadly speaking, these drugs are terrifically effective, both when taken for life and when taken intermittently.
If only there were a federal administration whose responsibility it was to collect data about food and drugs so we could rely on something more than anecdotes from random strangers on the Internet.
I emphasize it's like the drug disulfiram: Very effective as long as patients take the full dose, but the lack of real-world efficacy stems from the difficulty in adhering to the treatment.
> the lack of real-world efficacy stems from the difficulty in adhering to the treatment
Do you have a source for this "lack of real-world efficacy"?
> This study found that 84.4% non-diabetic patients stop taking GLP-1 drugs within two years
"With a with a median on-treatment weight change of −2.9%" [1]. Of those who discontinued and experienced "weight gain since discontinuation," they were "associated with an increased likelihood of GLP-1 RA reinitiation."
I'm genuinely struggling to see how this source shows real world inefficacy. In my friends, all of them stopped taking GLP-1 drugs within 2 years because all of them lost the weight they wanted to.
Out of curiosity, what sources lead you to believe this?
You mean the ones that are the result of experience through controlled clinical trials with statistical analyses and error bars, yep, sure. I guess I have a bit more faith in those leaflets and the testing regimes that generates them than the word of some gymbro or influencer who injected themselves and didn't immediately fall over dead.
Reminds me of some family members, all about organic, no seed oils, no plastics, no using 5G, no EMF, no fillers, no preservatives, no stabilizers, no emulsifiers, etc.
And yet they use unhealthy amounts of avocado oil, consume unhealthy amounts of “good fats.” They discount caloric intake and solely focus on eating loads of what they consider to be good food.
I think if you're a cloudflare customer they set a cookie in your browser that let's you bypass the waiting period. Just wait until next year when they show ads during the wait.
With India getting generic GLP-1s, the tech to "print" peptides will probably see costs fall off a cliff, so we're probably only looking at the tip of the iceberg with the amount of damages the reddit biohacker bros will accomplish. Men especially are feeling a lot more lonely and image-conscious and there are peptides people claim make them taller[1] or muscular[2].
Yeah I'm always amazed at what they can get people to pay for individual vials. I buy kits of 24mg reta for ~280. And that's not the cheapest, for certain.
> a patient who is discontinuing her statin therapy - very inadvisably, given the clinical presentation described - but is enthusiastic about “BPC-157”
This feels new. I thought the methylene-blue-for-cancer types continued their medicine while taking other things as extras.
Personally, I've swung over to the laissez-faire side of medicine. At the end of the day, if you're an adult, it's your body. You should be given the chance to educate yourself. But if you want to inject yourself with a prion, like, go for it. Maybe you won't fuck up your own research.
(Marketing should be tightly regulated, possibly banned.)
Exactly my point of view. Medications are like drugs, if we failed to forbid it we might as well allow it but regulate it, aka make seller accountable for the purity.
> Personally, I've swung over to the laissez-faire side of medicine.
Chesterton’s Fence rears its ugly head again. This is the same thing as vaccine skepticism (those diseases can’t be that bad, I never hear about them killing anyone these days) applied to a different context
Arguing for modern reforms is one thing, but there’s a reason we have the FDA. Statistically, most individuals do not have the medical expertise or the desire or ability to wade through enough clinical data to make these sorts of decisions with any hope of good outcomes, particularly in the face of an entire Internet of people trying to push questionable substances on them.
>I thought the methylene-blue-for-cancer types continued their medicine while taking other things as extras
There's no way you don't know that for example Steve Jobs ignored his cancer until it killed him because of absurd beliefs about "health". Surely you know about cancer patients dying because they found someone who promised them a cure rather than their doctor offering them a 60% chance through immense pain and struggle.
>Personally, I've swung over to the laissez-faire side of medicine.
We had laissez-faire medicine. It cured almost no one and killed hundreds for no reason. We HAVE laissez-faire medicine. There's almost no regulation in the "Supplements" aisle.
> For a chemist, “peptide” has a pretty clear definition: any relatively short chain of amino acids, and when they get longer we go ahead and call them “proteins”, although the dividing line is a matter of personal opinion.
So, it is not just chemist but molecular biologist too. And the above is also not entirely correct. Yes, the author refers to size as threshold, before something is called a "protein". But the term protein has additional meanings that a peptide does not automatically have. For instance, a protein typically has a specific 3D conformation. It may be "sticky" after degradation or unfolding, but for the most part a protein is something with a 3D structure. A peptide does not necessarily imply the same. A protein may also have several polypeptide chains - insulin is a simple example for that: https://en.wikipedia.org/wiki/Insulin#Structure (A and B chain)
> So the number of different possible peptides is just ridiculously huge.
That's no surprise either - that's due to the code used. You add to the code, so of course length plays a role, as does the variety. There is a DNA->aminoacid mapping. The first has four possibilities per slot; the latter 20 (or more if you include e. g. selenocystein or pyrrolysine; and you have various post-translational modifications too, so you have more variety per slot).
> For comparison, it has been about ten trillion seconds since Homo sapiens emerged as a separate species.
The whole species concept is IMO outdated. It was created before people knew that DNA codes for the complexity in pretty much any species (excluding RNA viruses but they have reverse transcriptase, at the least some viruses, so ultimately RNA->DNA).
> The other one (by Sarah Hood) relates all this to RFJ Jr.’s advocacy. The flip side of “the government shouldn’t be able to force me to vaccinate my kids” is “I should have the right to take whatever medicines I want to without the government getting in my way”.
I don't see why that would be questionable. Would people do as Trump tells them to do? I would not. If you see Trump as a lobbyist, how many private interests may his government have? If they have a commercial interest then their statements may be biased.
> You don’t have an LC/MS or an NMR machine in your garage, so you can’t be sure what it is you’re really injecting
Right, so the whole system depends on trust. This is already a problem because you have to trust not only the government but ALL who were involved in scientific publishing. There were lies told in science too: https://en.wikipedia.org/wiki/Retraction_in_academic_publish...
Is there any evidence supporting the claim there is a significant overlap between the group of people who "refuse injections the government recommends" and the group of people who take "peptides"? The article is carefully crafted to evoke this impression without clearly stating it, listing only anecdotal evidence.
“Blue dye stuff” meaning methylene blue? Ironically that is one of the most extensively studied compounds in medicine, with hundreds of clinical trials over 100 years…
He means the COVID vaccine but knows people will make fun of him if he says what he actually believes so he's playing pretend like there is some plague of untested vaccines being used instead of there being one fast tracked vaccine deployed in response to a massive pandemic
Indeed, but that’s not the point: many anti-vaxxers are against all vaccines, irrespective of how they were tested. (And will argue against e.g. the FRA approvals.)
Okay; noting that the argument has moved from "untested" to "relatively untested".
To clarify, is your concern the inadequacy of the approval process FDA uses for (all) vaccines (noting that many vaccines --e.g. influenza-- are refreshed on a fairly regular basis to account for new strains of viruses) or something specific to approval of the MRNA vaccines?
Or is it that MRNA vaccines were a new approach for vaccines more generally, and so there wasn't/isn't the same long-term data that there was/is for multiple generations of vaccines based on older technologies (viral vector, toxoid, etc.)?
It has a certain logic to it, and I think US tipping culture basically follows the same rules.
Even if you almost always end up paying the bill + 20% tip, Americans like the idea that they could not pay the tip if the service was bad.
The appearance of free action is appealing and preferable to being forced to pay the extra amount, even if you almost always pay the amount willingly anyway.
In my experience, everyone who defends tipping culture is defending not paying the tip. I don't buy this idea that someone likes tipping culture and still pays it. After all, you're free to tip anyone you want regardless of culture.
The problem is it is so ingrained in US culture that switching to tip-free has generally failed where tried, even in pro-labor lefty hoods in blue cities.
Numerous restaurants in NYC tried and flipped back over the last 10 years. Restauranteurs reported illogical / innumerate behavior where sales went down when they switched to untipped higher prices.
Well sure, it has to be mandated through law or underpaying workers will inevitably outcompete those that pay workers. I don't think that's an argument that anyone likes tipping culture (except wait staff in bougie cities).
I remember when Uber first came to Austin, one of the big draws was that a tip wasn't expected. The app didn't even allow it IIRC and Uber sort of advertised this as a feature. 15 years later, back to it, tips seem expected again?
Oddly enough, the fact that I was initially sold a product where a tip wasn't expected has made me continue to not tip Uber drivers. Not sure what that says about me.
I actually like tipping culture because it makes me feel generous and charitable, not because there's some kind of weird master/servant relationship. I even make it a point to passive aggressively tip well when service sucks because who gives a shit?
The world is full of people that confuse contrarianism for intelligence.
HN, in particular, loves anything that allows them to discredit science (like the constant banging on about the replication crisis) and replace it with their own pet theory.
Is HN particularly drawn to this over other platforms? I gotta say I don’t quite recognize this. In general, I think there’s a good dose of respect for science around these parts, but maybe I’m blind to it.
I see a particular strain more often here and in “rationalist”-adjacent spaces. It’s essentially anti-intellectualism dressed up as intellectual curiosity and debate.
I think it’s also that contrarianism generates an argument they can follow - it’s often much more simplistic along some axis. For example, flat earthers superficially have a really simple model. Throw a ball up, of course it comes down. You look straight ahead and it looks flat. Ask them how GPS works and they can’t follow the math anyways.
>The world is full of people that confuse contrarianism for intelligence.
I've been shouting this from the roof tops for years now and it's one of the biggest problems we face today. I live in a rural area and 100% of the Joe Rogan-ified men I know are mindless reactionaries. They aren't educated, they don't read books, they don't travel, heck, they barely leave the county. They think they're so smart because they say no to everything anyone else says. They never offer solutions. They never try to fix things. They barely even vote. If you say the sky is blue they will say it's green because they're just oh so smart. It's a massive massive problem.
I have recently been through the rabbit hole of peptides and most of the people engaged or involved in peptides seem to be healthy individuals. There are some exceptions like lookmaxxers and anti vaxers. The vast majority of people are normal and majority are outside of USA where anti vax sentiment are not in vogue. Some explore peptides for their dogs and cats too.
To assert that people are sad and anxious while not putting the effort to understand the people involved is such an intellectually lazy position to hold.
Extra points for people partying hard on shady synthetic drugs, but being actively anti-vax because government. Case in point, Miguel Bosé, a very well known spanish artist that spent the first 50 years of his life abusing everything except heroin (his own words), but now he is a vaccine negationist, for him and for his two children.
A lot of these peptides are designed to optimize bodies. And a lot of these people suffer from OCD - often a similar type to anorexia. No, it is not normal to intrusively think about your body every few minutes, most people that you see around you do not think about their bodies more than maybe once a day, when they look in the mirror after a shower. And maybe not even that.
"Antivaxxer*" here. I'm not injecting peptides for a similar reason - I'm not convinced the cost/benefit works out. That said, the issue for many is autonomy - if you want to put novel stuff in your body, go ahead. As long as you don't try to compel me to do it.
* Not if we're actually in literate company, but that seemed to be the common consensus after I skipped the jab, having recovered from covid right before the shots became available. Nevermind that my doctor was on board and I've had all the other ones (minus the flu shot). I was still a selfish grandma killing Republican who probably voted for trump to the commentariat.
Your right to swing a fist ends where the other fella's nose begins. That doesn't mean you aren't free, it just means you recognize that the right not to suffer grievous bodily harm trumps the right to swing your fist willy-nilly.
As a fist-swinger you may not always agree, and you may even get hurt one day because you couldn't swing your fist whenever you wanted, but that's just the cost of living in a world filled with other human beings.
I appreciate why you might feel that way. It's reasonable for reasonable people to disagree, but in this case the experts we trust to decide these things decided that you were the one who presented a danger to society. I seriously doubt that you have the sort of medical credentials that would be required to get any serious person to take your word over those of the world class epidemiologists, virologists, etc who said the opposite.
Regardless of correctness though, even if they'd been wrong it's just part of life that sometimes you have to go along to get along. There are a lot of things I disagree with society about, but I depend on society to live. It would childish to try not to participate.
You can at least draw a somewhat tortured connection between "anti vaccine" and opting out of receiving a specific vaccine (for logical reasons, with your doctors approval, though are they even a real doctor if they approved such a thing?).
But using the word "jab" or criticising the medical industry making you anti vaccine is the kind of thing I was talking about when I mentioned literacy.
The vibe you're getting is that I'm blaspheming. I'm saying things that probably hundreds of millions, possibly even billions of marketing dollars were spent to discourage being said.
No, all I have to do to make it clear is say "I'm not opposed to vaccines as some kind of principle, ideological or otherwise", and then you can either believe me or not.
That's what anti vaccine means, despite all the efforts to redefine it. It doesn't mean "won't recite the marketing materials for a specific pharmaceutical product when prompted".
Generally safe is meaningless in this context. That's not a reasonable way to talk about entire classes of drugs. All that matters is for a given person with a given medical history and context, does the specific drug have a net benefit.
Here's a good test case: have you had the rabies vaccine? If not, does that make you an antivaxxer? How about vaccines that have been pulled off the market? Are those no longer vaccines?
Something reasonable to say would be there are vaccines that have a net benefit, and you should take those if that applies to your situation.
This whole "say the slogan or you're an antivaxxer" is like giving kids the nontoxic glue because you know some of them are going to eat it. The adults in the room don't need this shit.
I don't care what "slogan" you say, I'm just trying to see if you hold the opinions of an antivaxxer and for some reason you refuse to make any claim that would help avail me of that position.
The article frames these supplements as being purely appealing to "anti science" people but I think that's really unfair. You can believe in medication, believe in science, trust government systems, etc, and still feel like you're not being served by the medically approved options.
It can also depend on people's politics vs who is on power. In general British anti-vaxers are left wing (very lefty affluent hippie types - you can see this from the areas with low MMR rates), and even more so during covid when a right wing government was in power. There is evidence for this in a survey KCL did of anti-vaccine beliefs during covid. I personally know of British students who declared they would not have covid vaccines because they "did not trust the Tories"
i mean, to be fair everything everyone is injecting, including prescribed medicines, are largely coming from Chinese (or Indian) factories. We don't manufacture much in the western world ourselves.
I think it's disingenuous to frame this exclusively in terms of the people who are turning down medically approved options for unknown supplements.
Dealing with doctors is kind of a pain in the ass. I was very sick a month ago and my doctor is pretty "anti antibiotics", he wanted me to go over for an in person check-in. This was after 10 days of having symptoms that I did everything reasonable to take care of. I got on a call with another doctor (at a perfectly reputable hospital) who immediately prescribed antibiotics. It took 5 days of antibiotics just to feel somewhat better - all while using saline rinses, showering, sleeping, eating properly, etc. I still have a lingering cough. I am very reluctant to take antibiotics unless it really feels necessary, this was easily the worst sinus infection of my adult life.
My friend wanted to try out a weight loss medication. Their doctor refused because they felt that my friend hadn't tried hard enough without it. So they got some from another friend who hadn't ended their prescription because they also were worried of being cut off. They've lost weight, which has motivated them to exercise more, eat better, and are generally happier and healthier.
From the article,
> Unfortunately, point two is that we barely have any of these effects worked out - at least not to the degree that you would want before you start injecting them into your leg.
This is what was said to a friend whose doctor took them off of one of those GLP medications, basically. They didn't have enough evidence to know the risks of continued use, even at lower doses.
The reality is simply that there's a big gap right now between what people want and what people have access to. The supplement industry exists to fill that gap.
Medical professionals can complain about users taking these peptides, but plenty of people are not "anti medicine" while still feeling underserved. If doctors aren't in a position to have these conversations, people will go to Youtube or wherever else to look for answers.
Personally, I have mixed feelings about a number of medications requiring a prescription. I frankly do not see why my doctor is involved in me taking a drug unless it would be negligent to allow me to or if it would have community health impacts (ie: antibiotic resistant strains etc). I'm an adult, if I've been properly informed of risks, etc, then I'm inclined to say that it should be up to me to pay full price for some medication or not.
I know plenty of people getting their GLP1 from compound pharmacies. None of them went their first, their doctors wouldn't give them the medication (sometimes they were just a pound under the BMI limit, often because they had been slowly losing weight) so they went elsewhere. These aren't anti-vaxxers who won't take their medication, they're people who want help and there's a gap that companies are taking advantage of. The medical establishment needs to find a way to address that. Right now the answer appears to be compound pharmacies and nurse practitioners.
> In my own view (and it ain’t just me) you also have regulatory agencies to force people to show that their drugs actually have some benefit before they can sell them, too. But that’s going further and further out of fashion. Can’t get ahold of the New Hotness to inject into your upper thigh if there are a bunch of stick-in-the-mud folks asking for human data, infringing on your freedom and all.
Many of us will be dead before there's a medically approved treatment for something. Hell, I got eye surgery before it was FDA approved - I'd probably be blind (or at least far worse off) if I'd waited the years it took.
How many people taking supplements are "naturopaths" who reject modern medicine as opposed to just people who want to be healthier? I really wonder that.
It seems we are treating Peptides like drugs here. It's my opinion that amino acids regardless of how they are chained do not belong under and stricter regulation than food given I eat peptides every day from my food. Then again I do not believe in the concept of prescription drugs. Everything with a NDC code should be at the grocery store and I should be able to stock up on it without permission especially given how fragile global shipping is these days. Drugs risks do not enter into the picture given the fact I can buy ammonia and bleach along with a myriad of other dangerous compounds. Worse, I could crush up apple seeds from the veggie isle. One can also make just about anything using fourth thieves vinegar. Maybe put expensive high demand things like cocaine behind locked glass along with the underwear and condoms.
As a side note more dangerous than any drug is stopping a prescription drug cold turkey. Watch what happens when global trade to/from China and India are cut off for a year. Attitudes will change.
This is briefly addressed in the article, but basically it's one thing to eat a peptide and quite another thing to inject it. Your digestive system is extremely adroit at taking peptides and proteins and breaking them down into individual amino acids, which are then absorbed via "transporters" in the gut. (e.g. SLC6A14 for glutamate and cysteine.)
If you eat insulin, absolutely nothing will happen. If you inject just a little bit too much, you're dead.
So, generally: Ingested proteins/peptides aren't drug-like, whereas they can be extremely potent drugs if administered via injection.
Granted, there are exceptions. If you accidentally get a drop of botox into your mouth, you'll be okay, but if you drink a vial, you'll be poisoned. And people have been trying to make orally-active peptides and proteins for decades, with some noteworthy successes, however few and far between in the general case.
I agree with some of this. There are most certainly orally active peptides such as BPC-157 and its replacement PDA penta deca arginate that can repair the gut and still circulate throughout the body especially in those with leaky gut. People with leaky gut should be able to buy a clean source of BPC-157 or PDA without a prescription and without visiting dark alleys. It is very safe and tolerable.
GLP's are all the rage these days. Doctors seem to be giving GLP peptides out like candy and those are injected. People are looking like zombies. That said if doctors are going to be so liberal with them I should be able to buy it in the grocery store and slap it down on the conveyor belt. Again I can buy things far more dangerous than any prescription drug. There are very dangerous supplements, some that are shilled heavily on youtube. For example, Glycine (for me specifically used without a specific process) is more dangerous than heroine and the vast majority of doctors would have no idea what I am talking about.
Also LOL at the notion "peptides are safe because GLP-1 exists".
Pretty much all venoms are mixes of short (10-15 base) peptide chains.
It's the naturalistic fallacy in an utterly perverse form ( and also goes to show why a regulatory system is good: the average person has no idea that they're dealing with or even common sense about it).
FDA is a money sink. People basically bribe to get their own self tests approved much like the airlines have their own FAA inspectors that approve their own self tests under duress and bribes. It's all a scam and everyone here knows this even if they won't admit it.
Nullify the FDA, FAA and at least half of the other orgs. Give at least half of those budgets to the people. Make aircraft smart enough to evade all obstacles. Make it technically damn near impossible to collide with anything. Make aircraft coordinate themselves. All doable. Force retire all FDA and FAA and give them a balloon, a golden wrist-watch and send them away.
Give people an app to paste in all the things they take or plan to take in terms of foods, supplements, drugs, their allergies. Let the best AI figure out what will happen.
Injected BPC-157 to a wound is a magic healing potion as far as I'm concerned. That it's not more broadly available is a crime, imo. If I had a billion dollars, I'd push so many things through the FDA.
This is entirely theorical, but the $2.6 billion figure that's commonly quoted accounts for all the failures as well. If I took something that's proven in Europe but wouldn't get a patent, it presumably would manage to pass FDA regulations, it's just that without the patent protection, there's no financial incentive for an existing company to do that.
> It seems we are treating Peptides like drugs here
That’s exactly what some biological drugs are too - peptides!
And peptides are just short chains of amino acids. Almost all the other biological drugs are just longer chains of amino acids - antibodies, enzymes, antigens, some hormones, and others.
Derek is right that the safety risks are exponentially higher when you inject peptides - you basically skip a bunch of protective mechanisms like enzymes that quickly break them down if taken orally or routes.
As a former R&D scientist there is no way I’d inject any peptide that hasn’t at least gone through a phase 1 safety study in humans. Otherwise you have no idea what it could be doing to your body.
A good example was a drug that was quickly pulled from market for causing fatal anaphylactic reactions. It wasn’t even caught in the clinical trials!
At the same time, I think people have the right to take whatever substance they want. But I worry a lot of people aren’t aware of the risks.
>As a former R&D scientist there is no way I’d inject any peptide that hasn’t at least gone through a phase 1 safety study in humans. Otherwise you have no idea what it could be doing to your body.
A lot of people do not understand the trial system or the value of Phase 0/1 tests when it comes to the substances that they put into their body. And thanks to the influencer/grifter/biohacker ecosystem that exists, more people would put their trust in accidental evidence, from people who's incentive it is to make money off of them, while complaining about the pharmaceutical industry operates off of a profit motive.
The regulation of drugs or most any consumer product is not due to the inherent danger of an item itself, but the danger presented to a consumer inside the context of societal mechanisms that influence behavior. You're right that many regulations don't make sense outside of a societal context -- but that's because they also don't exist outside of a societal context.
The reason we don't need tight regulations on bleach is because we don't have a societal issue causing people to drink it and hurt themselves... at least, not anymore: most of the locking lids on household cleaning chemicals are there by law.
Maybe so. Still one would be amazed at how many people will follow extremely dangerous and dumb trends on the interwebs. Don't get me wrong, I see it as just a small part in the great filter much like I think we should remove all warning labels.
I'm all for laxer regulation of substance control e.g. buying cocaine at the grocery store, but I think its also a bit misleading to describe arbitrary sequences of amino acids as if they're meaningfully comparable to food.
That's like saying that since neither one nor zero requires regulation, neither does software. Maybe software does or doesn't, but in either case its best based on the nature of the aggregate, not the nature of its components.
> It's my opinion that amino acids regardless of how they are chained do not belong under and stricter regulation than food given I eat peptides every day from my food.
I mean, why regulate anything? Everything is just different arrangements of hydrogen and time. It's so weird that certain arrangements of hydrogen and time try to claim to have things like "morals", and try to force other arrangements of hydrogen and time to not do arbitrary contrived concepts like "murder".
All is one. Just hydrogen and time. Therefore everything should be legal.
> Drugs risks do not enter into the picture given the fact I can buy ammonia and bleach along with a myriad of other dangerous compounds.
This is a deeply weird take. You think anyone ought to be able to buy, for instance, warfarin and freely take it without a doctor’s involvement? We should let parents self-diagnose diabetes and administer insulin without a prescription or discussion? We should just hope that patients heard their doctor say hydralazine and not hydroxyzine?
> As a side note more dangerous than any drug is stopping a prescription drug cold turkey.
Abject nonsense. It was very easy to stop my prescribed amoxicillin. It’s clear you don’t have any actual idea what “prescription drugs” are, in aggregate, and that should maybe inform your decision to have Big Opinions about them.
> Why do you think only the people taking it would be buying it?
I don't. But the cost of access is significant. And with pharmacies in India, China and Mexico willing to ship basically anything into America, it's a purely-cosmetic tax now.
No reason required. People can already buy incredibly dangerous things with a doctors permission, as if a doctor actually knows what other compounds a person is consuming to begin with. Doctors are not omniscient and patients lie. Most of them barely even know the compounds that are FDA approved to begin with. Be honest, most of them barely remember 10% of what they were taught in medical school and the schools even state that half of what they will be taught will not be relevant or will be entirely wrong by the time they graduate.
Again, I can buy apples and apricots without permission. There is nothing capable of more risk or harm that has ever been approved by the FDA than apples and apricots.
> This is a deeply weird take. You think anyone ought to be able to buy, for instance, warfarin and freely take it without a doctor’s involvement? We should let parents self-diagnose diabetes and administer insulin without a prescription or discussion? We should just hope that patients heard their doctor say hydralazine and not hydroxyzine?
Weird examples. You can buy insulin without a prescription today in the USA.
In much of the world -- including almost all of Asia, Africa, and much of Eastern Europe -- you can buy almost any drug without a prescription. The only exceptions are potent CNS stimulants or narcotics, and in some rare cases antibiotics.
This is legitimately a better system. Takes out the middleman.
In the US you can get any drug if you pay $120 and recite the magic words to a telemedicine "doctor."
Funny you mention this... I bumped into a VP of Merck at a conference and that's the exact example he gave: in the US, you can't adjust your own coumadin dosage without a M.D. consult, but here, have 200 doses of insulin to take home with you.
In much of the world -- including almost all of Asia, Africa, and much of Eastern Europe
Doctors in the US get a nice $200 to $500 per doctors visit, required to extend the prescription drug. I only notice because I pay cash. This is why they will argue against anything I am saying until they are code-blue in the face. I will leave them with my code brown.
In the US you can get any drug if you pay $120 and recite the magic words to a telemedicine "doctor."
That's how a number of us in a particular circle stock up on anti-biotics. That said anti-biotics are a last resort for me whereas I find doctors are quick to prescribe them.
Your argument is even worse lol. Obviously he's proposing that you can take your doctors note to the pharmacy and get what the doctor prescribed in addition to being allowed to self purchase behind the counter drugs.
I'm here for two probably contradictory comments.
The first is collagen: I'd love to see Lowe's take on recent peer review which says boosting oral collagen does appear to show signs of improved joint pain and skin resilience. Obviously modulated through how protein deprived you are, but for older people, eating enough protein can be an issue: it's not rapidly absorbed so you need 3 squares a day to get to the higher numbers. Collagen powders and vitamin C (oj) at breakfast might kick start this.
The second contradictory point is that this entire thread makes me want to shout GELL MAN AMNESIA because it's an exercise in otherwise intelligent people who can distinguish between anecdata, their personal experience and some cold hard facts in their core field, but not when it's self injecting unknown chemicals from China bought off-script.
Note that there is research showing that whey protein powder has exactly the same effects as collagen, for much lower price.
Mechanistically it makes sense, as I understand the ingredients in Collagen are largely a subset of the ingredients in whey powder, albeit at different ratios.
Afaik, not exactly, collagen has hydroxyproline which is attributed for skin\hair\joint improvement.
it is the same if you base it just on the amino acid profiles, they are both just proteins with different amounts.
I always wondered if there were nutrients we can’t measure though, because collagen is typically made from skin or bones whereas whey protein is dairy. Even though both have similar “nutrition facts” maybe there are some unmeasurable differences. Both are highly processed though so who knows.
I think the idea is that some short peptides might survive the digestion and make it to the blood stream, but I'm doubtful there's any specific benefit to collagen.
For the first one, I assume you mean a systematic review, not a peer review? I guess you're talking about this one:
https://pmc.ncbi.nlm.nih.gov/articles/PMC10180699/
It has a Mechanism section which explains that when collagen is digested, one of the products of that is Gly-Pro-Hyp, which is what has the effects. I don't think that conflicts anything in this post?
I assume they're referring to the brief bit in the post that indicates that oral ingestion leads to a breakdown that makes oral supplements of amino acids pointless. They say it very briefly and they don't really outright assert it, it's just a sort of implied aside.
Here is the exact quote:
Every single YouTube video and blog post I have read about peptites is exclusively about injectable supplements.That's not the exact quote lol you cut out the exact part I was referring to.
> because unless a really substantial amount of engineering has gone into it, any given peptide is going get the same treatment from your digestive system as a chicken breast does, i.e. a complete teardown
> Every single YouTube video and blog post I have read about peptites is exclusively about injectable supplements.
Collagen peptides, ghk-cu, and many other peptide supplements are often taken orally.
> Collagen peptides, ghk-cu, and many other peptide supplements are often taken orally.
And with very rare exceptions, it's as useful as watching someone workout when you want to gain muscle. Every meat we eat is awash in peptides, and to keep our body from getting hijacked by the signaling for, say a chicken, our body has to break down almost all peptides ingested orally.
There are a few exceptions, notably there's one that is produced by our own bile acid, that can be taken orally, and then SNAC, which was developed by Novo Nordisk over thirty years and has extremely limited capabilities and is fully patented and cannot be made by your fly by night distributers. SNAC achieves a whopping 1% bioavailability of the peptide, and it's ability to work depends on the size of the peptide, specifically the only commercially available use for this is Rybelsus.
Oral peptides are snake oil for the most part.
> And with very rare exceptions, it's as useful as watching someone workout when you want to gain muscle.
Who cares? I never made broad claims about their efficacy, the author did.
> Oral peptides are snake oil for the most part.
The author's claim is not nuanced by "for the most part", that's why I quoted it directly.
Besides, I was merely clarifying what the other poster was likely referring to.
Sweeping statements in biochemistry must be made with caution. It is well known that there are some small peptides that are absorbed following oral administration.
...BPC-157 itself is said to be among this class. As are certain milk tripeptides: https://en.wikipedia.org/wiki/Lactotripeptides
Interestingly enough, those two, as well as Gly-Pro-Hyp, are proline/hydroxyproline-rich, which might suggest that proline-rich small peptides are resistant to degradation in the gut.
Anyway, in general oral proteins and peptides are broken down prior to systemic absorption, but not always...
> It is well known that there are some small peptides that are absorbed following oral administration. ...BPC-157 itself is said to be among this class
Do you know of any studies that suggest BPC-157 absorption from gut?
https://onlinelibrary.wiley.com/doi/abs/10.1002/jor.21107
Among others. If you read the paper, it's actually apparent that there's little difference between i.p. and oral administration in terms of efficacy -- both were roughly equally effective in improving MCL ligament healing.
Admittedly the paper's in rats -- as are 99% of the others -- as there's no incentive for anybody to run human trials.
You should note that your study is not controlled.
There are two groups, those with oral administration those with sub-q administration. There is not group without administration.
This means you can't say that oral vs injected is "equally effective" because you can't assert that BPC 157 is effective at all. You can't tease out the effect size because you don't know if any or all of the MCL ligament healing was done via normal pathways
You just read the abstract and didn't read the full paper.
There were control groups.
> Methods:
> [administration] as follows: (i) BPC 157 10 mg or 10 ng/kg or saline 5.0 ml/kg (controls), intraperitoneally, or (ii) BPC 157 in neutral cream (1.0 mg dissolved in distilled water/g commercial neutral cream) or commercial neutral cream (controls), as a thin layer, locally, at the site of injury, administered once daily with the first application 30 min after surgery and the final application 24 h before sacrifice; (iii) BPC 157 0.16 mg/ml or nothing (controls) in the drinking water (12 ml/day/rat) until sacrifice.
There was a big difference vs. the control groups.
> This means you can't say that oral vs injected is "equally effective" because you can't assert that BPC 157 is effective at all
Is that true? It seems that you can say that they were equally effective without quantifying an effect. It could be the case that both are equal in that neither has an effect, which this would validate. Then you can just point to other studies to claim effectiveness of injected.
I'm in agreement. It's the article that made the sweeping statement.
> you need 3 squares a day to get to the higher numbers.
> Collagen powders
In that case if you're eating collagen powder you could be eating just regular protein powder then?
I want to point out your own contradictory comments about absorption and specifically mentioning a typically highly processed food (orange juice), one which has been stripped of its natural fibers and flavors.
That age group (and all others) should be eating real/whole fruit or having the juice fresh (I.e. just juiced). They would be better served getting this advice than creating more anxiety about protein intake.
Is there any reason to think that freshly squeezed juice is chemically different from, for example, frozen juice concentrate?
From the Wikipedia page on orange juice:
> Commercial orange juice with a long shelf life is made by pasteurizing the juice and removing the oxygen from it. This removes much of the taste, necessitating the later addition of a flavor pack, generally made from orange products.
https://en.wikipedia.org/wiki/Orange_juice
The same article goes into additional detail:
> Commercial squeezed orange juice is pasteurized and filtered before being evaporated under vacuum and heat. After removal of most of the water, this concentrate, about 65% sugar by weight, is then stored at about 10 °F (−12 °C). Essences, Vitamin C, and oils extracted during the vacuum concentration process may be added back to restore flavor and nutrition.
So essentially there are components that vaporize during processing. The make sure to condense the same components and add them back in so that the orange juice contains all the components of fresh orange juice.
There is reason to think the differences are biotic vs. abiotic, between the two. Our digestive system is dependent on healthy microbiota. Pasteurization would be the difference here.
So it's essentially the same argument as for raw milk, but at least it's less likely to make you sick (?).
Raw milk is on the fringes of the same argument that whole foods play a more beneficial role in healthy gut microbiota and digestion, and that our current models focusing on nutrient composition are incomplete. It says that our measurements are off, and that there’s more to nutrition than composition alone. https://pmc.ncbi.nlm.nih.gov/articles/PMC11901572/
yes it’s been frozen and concentrated..
You can freeze and concentrate a substance without chemically altering it
I think we are sort of in the worst of both worlds right now re: medicines/supplements/gray market.
FDA approval is expensive slow process. Doctors train for a long time and then work 40+ years entire careers, some without a ton of continuing education.
But then we have an entire gray market because enough legal and practical loopholes to drive a freight train through, such that people are self medicating with dubious substances of dubious origin of dubious purity sourced via dubious means.
Even if peptides work, you have no idea what side effects they have, or if the ones you are taking are even real, not contaminated/tainted in some manner, etc. Given a lot of the hype comes from social media for otherwise healthy people to take them for lifestyle / augmentation reasons.. to me the risks still outweigh the rewards.
Real solutions like regulatory reforms to find ways to bring down testing costs seem more important than reforms to make it easier to slap anything on the shelf at GNC as a completely untested “supplement”.
Taking continuing education credits to check a box for retaining professional licensure and educating yourself about emerging and novel concepts in your field are two vastly different things. If anything, CE helps professionals update their knowledge base regarding existing processes and procedures.
Not US, but the seminars to fill in the hours in my country were closer to legal bribes and/or holidays in often exotic places. They usually were provided/funded by the medicine lobby.
In Germany, at least for Dentists, it is exactly like this. Many training events are, in fact, hardly any different from sales events.
I am curious. Is dentistry considered poor in Germany? Or when compared to other similarly wealthy, highly-developed nations?
Same in US only sometimes more banal. Signup sheet in front of the stacks of pizza at some research talk at the medical school. Back row entirely asleep. Talk had nothing to do with medical practice but the researcher holds an md phd. Might be talking about their work in yeast.
Mandate vs interest.
Compare how seriously many SWEs take mandatory HR/compliance trainings vs hanging out on HN, taking online courses, arguing about code, trying new frameworks, coding in spare time, etc.
HN SWE's rarely do anything important. Doctors generally do.
Also doctors go to conferences and usually like doing it.
Neither teachers nor administrators take continuing education seriously, in my local experience.
I used retatrutide for weight loss and went from 199.3 lbs to just under 175 lbs. I kept daily notes through the process. Here's a quick AI one-paragraph summary if you're curious: https://pastebin.com/XACNYKvs
Overall I'm quite pleased with the effects and many of the properties of this treatment that people dislike are actually properties I was looking for. Essentially, for pharmacological interventions I want impermanent effects with a clear dose-response relationship and ideally minimal or no adaptation.
So the fact that people gain weight when they go off it and then lose weight again when they go on it was good. That meant it's fairly easily undoable. The fact that the more you take the more you lose also was pretty good to know though for the majority of the time I took less than any tested dose (and the effects were quite strong on those).
I did experience quite a bit of adaptation so I needed to up the dose until I was in the range tested by the end. I've been off it for a month now and been pretty much flat, but we've been traveling since I stopped and so a lot has changed (no more lifting, lots more eating, lots more walking).
Rough cost for the retatrutide is $1.25/mg.
When people talk about peptides, they typically mean either (1) GLP compounds like Reta that have successful phase 3 trial data and will be approved or (2) stuff like 157 which has no evidence or plausible mechanism to work.
Was cost the reason you went for it over tirzepitide? I feel like retatrutide is still way too early to mess with, it's giving me real "vioxx" vibes of messing with too much at once.
No, I had access to free tirzepatide. I chose retatrutide because early results seemed promising and safe and since I was going to run a short-term self-trial I wanted the most effective peptide.
Hey, fair enough! To each their own.
> Rough cost for the retatrutide is $1.25/mg.
Even with free healthcare that seems like a foolish place to save money when very widely used alternatives exist in the regulated market.
Ozempic in the US just had its price reduced to $499 for a pen with a few 2mg doses...
>when very widely used alternatives exist in the regulated market.
Which ones? Semiglutide costs orders of magnitude more.
op:
> had access to free tirzepatide
Please be careful here, as Retatritude is not actually commercially available in most of the world, outside of research labs. And is not FDA approved to buy or use in the US (where most of HN readers are).
I fear this kind of post will encourage gullible people to go chasing reta on the grey market, where they might as well be getting a placebo, as there's no mechanism for your typical person to verify that they're getting what they think they're getting.
And given it's an injectable, and bacterial growth, or a variety of other toxins that can remain in poorly manufactured pharmaceuticals, can do a great deal of harm.
> there's no mechanism for your typical person to verify that they're getting what they think they're getting.
Think what would happen if there was one.
In the spirit of selling shovels in a gold rush, the first company to commercialize a tricorder is going to make bank off all the fitness fads and off-label/DIY medicine markets.
I know a couple of people that should know better (phds in biosciences but now doing corporate management) taking expensive weird Chinese peptides that would probably be better off if they did some cardio a few days per week and ate better.
Exercise because you enjoy it (and it provides countless benefits) but for weight loss it is not going to do anything. Diet alone is enough.
I'm not inclined to be a guinea pig for these. I suspect maybe later in my child's life they will have been proven long-term safe (or not). I'll be old or dead at that point. I'm really wary of putting anything not known to be standard food or medicine into my body.
I feel this way about other things injected into the masses with little safety data and perverted informed consent.
Im not allowed to express that sentiment, without significant backlash.
Care to share what those “other things” you’re concerned about are? If you mean what I suspect you do, then this is a complete false equivalence. But it’s hard to evaluate when you don’t actually state your claim or concerns.
Social media
You should not be downvoted for expressing your concerns.
Didn’t express concerns. Just vaguebooked.
I tried retatrutide for 10 weeks, here are my results: Before: 5'7, ~182lb
Bench 1rm: 315
Squat: 5x10 225
Deadlift: 5x5 315
After: same height lol, 154lb
Bench 1rm: 285
Squat: 5x10 205
Deadlift: 5x5 275
Suffered some anhedonia towards the end but that went away ~1wk after stopping. Overall pretty good, not any side effects. Definitely fixed my food craving problem. I didn't have a high intake of protein during the 10 weeks, so I suspect thats why I lost muscle mass :/
I used a combo of low-dose retatrutide, tesamorelin, and ipamorelin and lost about 15lb over 45 days, including 60% of my visceral fat, and put on 4lb of muscle, per before-and-after DEXA scans. I lifted regularly, ate well, and prioritized protein, and while I definitely under-ate protein, I was very pleased to find that I was able to increase muscle mass while cutting the fat. My visceral fat was the primary target here, since I'd been unable to get it to budge despite consistent training and diet. Very pleased.
You lost muscle because you lost around 1.54% of body weight per week, which is way too aggressive. The maximum recommended amount for losing weight while retaining muscle is around 1%. You will also most likely experience a weight rebound.
Hasn't this mostly been debunked? You lose muscle mass because you lost mass overall, and whether you lost it too quickly or not is not the major factor. AFAIK maintaining muscle mass while losing fat is borderline impossible for anyone who isn't extremely fat and/or very disproportionate composition to begin with.
Not at all, this is a well-known and long-established risk of rapid weight loss. Even long before any of these drugs existed, medical guidance was to lose weight slowly to help limit lean muscle loss.
Not as far as I know. The ratio of fat-to-muscle loss depends on several factors, most notably the rate of weight loss (see https://pubmed.ncbi.nlm.nih.gov/34371981/). In fact, retatrutide is popular notably because it is known to preserve lean body mass better than other weight loss drugs.
> because it is known to
I thought that this was not yet substantiated in human trials? There's a plausible mechanism and, I think a mouse trial, right?
Seems you are correct according to https://pubmed.ncbi.nlm.nih.gov/40609566/: "The proportion of lean mass loss to weight loss was similar to other obesity treatments."
You need to define how much muscle mass you expect to lose. The entire idea behind the bulk/cut cycle is that you want to net gain muscle after a full diet cycle.
It's also not borderline impossible to maintain the majority of your muscle mass, but it depends on how you eat and train. We don't know enough about the person above's diet, training, current body composition, etc. to say anything for certain.
GLP1 destroy muscle tissue.
nope
It's interesting you mention this (anhedonia), since the guardian just published this article: https://www.theguardian.com/science/2026/apr/06/is-retatruti...
How did you actually feel? Disinterested in stuff, ennui, or other?
Yeah, basically disinterested. Somewhat burnt out from doing things I normally love doing such as going on walks, programming on weekends, gaming, and work. It wasn't a really big problem, I only noticed it when looking retroactively at my experience.
How much of that is just from your hormones being trashed due to a severe deficit?
Large caloric deficits (1000+/day) in leaner people is known to tank T levels among other things. When I was on such large deficits, I had very weird mood/arousal swings. Nothing that problematic for someone with as much executive control as me but it was very weird to be held hostage to.
This is crazy. You lost 28 lbs (15% of your body weight) in 10 weeks. Why did your doctor to allow you to continue? By any common sense, that is an unhealthy pace to lose body weight.
Why?
Your internal organs can't keep up with that kind of mass fluctuation, for one. Keep an eye on your kidneys.
It seems to be more complicated (or unpredictable?) than that:
> In this study, rapid weight loss was associated with the loss of kidney function in males with normal weight, and with improvement of kidney function in overweight males.
> Our study showed that BMI and BMI change were not associated with eGFR change in females.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4658128/
Those are sizable drops for 10 weeks unless you stopped lifting as well
Mentioned above, but "I worked out 6 days a week still, but swapped out 1 of my leg days for a run day (between 2-4 miles)"
Even if you hadn't lost any muscle mass, zero chance you're going to see the same exercise performance on a calorie deficit.
This is untrue. There are 100s of YouTube videos of amateur body builders preparing for a show. They are able to maintain their muscle mass while in a calorie deficit. Yes, it is insanely hard, but it can be done.
I didn't say that you can't maintain muscle mass. I'm saying your performance will suffer.
Did you try increasing protein intake during the cut?
Did you work out during those 10 weeks any? TBH if you went from regular lifting to not for 10 weeks I'd expect a similar decrease in your lifting numbers (though not a .4lb/day weight loss of course)
I worked out 6 days a week still, but swapped out 1 of my leg days for a run day (between 2-4 miles)
Dude, you must be jacked. Great lifts at those weights. Unreal bench haha. Good shit, dude.
solid bench brother
thank you:^)
Given that many people experiment on themselves anyway, I feel it's a pity and a loss for science that the outcomes of those self-experiments are not collected and aggregated.
The article itself raises the issue of "lack of clinical data", given that these substances are relativelly new. But the lack of data may originate from a certain stiffness, or lack of accessibility and high cost of clinical trials. An alternative source of information are these people who self-experiment, but unfortunatelly this information is mostly lost instead of being captured.
How could this proposal work in practice? clearly the data would be noisy, contain some false reporting, biased, subjective etc. But statistical processing of a large number of reports (coming from hudreds of thousands or millions of self-reporting subjects) may still extract relevant scientific information; that we're dropping on the floor right now.
An example: I'm experimenting with a radical diet. I keep observations for myself, but they're not shared with anybody and don't contribute to science.
What the altervative would be: I would enroll on a web page, where I would describe the experiment I plan to do before I start it. I would be get a code for a blood/urine work for the "before" state, with the agreement that the results, anonimized, are shared with the platform. Weekly I would report on the platform observations, such as: got sick in this particular way, wheight variations, sleep eval, or any other changes.
At the end, or periodically I would get new free blood/urine work with the results shared.
Research institutes and pharma would get access to the data, to aggregate and denoise as they can to extract the latent information.
You REALLY don't want to open the door to "compulsory self-administration." You don't even want people to think about that door. For everyone else, there's clinical trials where you may get a $50 gift card if you're part of the test group.
The quality of data really are too poor. To get enough sampling to achieve sufficient power to overcome these issues would be a pipe dream imo.
Peptides are a revolution and you don't need to know how they work to know that they work (for various people for various conditions). There is a tension between empiricism and fundamentalism with much of medical science focusing on fundamentalism. Now with the ability to collect and search large amounts of empirical data and communicate it peer-to-peer people are picking up on a lot of things that work without knowing why they work. I think people are just going to circumvent the fundamentalist and chase after whatever works.
I owe my health to early adoption of experimental peptides, I have life long ME/CFS and there is no known treatment for this nor is there any on the horizon. At least they finally have a diagnostic test and know it's not psychosomatic but I could have told them that from day 1. Most doctors are not researchers and have little understanding on statistics instead preferring to rely on discrete classifications and simple decision tress. As someone with hEDS from TNXB I am a walking bag of symptoms and yet not a single doctor could figure it out. I had to research it myself which involved post-doc level textbooks and research journals. I came across the work done by Prof. Khavinson (USSR) and it did appear to me that peptides were incredibly under-explored. Given the poor quality of life with ME/CFS I was willing to take serious risks so previous trials were helpful to give an idea on dosing and lethality, I went through most of the research peptides one by one. I actually waited on semaglutide a bit because I suspected there was a small minority who would have hyper sensitivity and I both expected that to appear in the data, which it did, and I expected to have hypersensitivity, which I did. Others who were less careful ended up with pretty bad gastroenteritis. Semaglutide has been the most effective and with it and a few others I am largely able to lead a normal life. I was getting gray market from the US but now I get it direct from China.
> There is a tension between empiricism and fundamentalism with much of medical science focusing on fundamentalism.
This is a deeply unfair statement, and also a false dichotomy. Medical science is of course empiric. What you call "fundamentalism" is that compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people. And no, it's not just because of Thalidomide. Many, many compounds fail clinical trials because of severe side effects, like liver toxicity, severe immune reactions or heart problems. Then there's of course increased risk of cancer, which can take many years to manifest itself empirically. You argue that you prefer living with these uncertainties rather than ME/CFS, and that's of course entirely understandable, but disparaging the field of medical science as focused on "fundamentalism" because we do not give large patient cohorts untested compounds is polemic. I understand where you are coming from, and I'm sorry that you suffer from this terrible condition, but likewise, you should try to understand the other side.
Doctors have been maligning ME/CFS as psychosamatic for decades and generally still do despite a large amount of modern evidence to the contrary. If you have it it’s clearly not, you can get good and bad days that are clearly not dependent on psychological state. In addition I have it due to hEDS which is a condition that is almost never diagnosed due to aforementioned blind spots. Most doctors still think the prevalence rate is 1/50K despite continued research raising that number to 1/15K and 1/500. It takes a long time for this information to percolate through the system.
Doctors, like many professions, have institutional blind spots, I studied these in my search because I was looking for something that had not been found. Most doctors have to consider all people and all conditions, I only have to be concerned with one.
Notably they only recently adopted Bayesian statistics for medical trials despite that math being around for hundreds of years.
I completely understand your frustration with the lack of knowledge and research in ME/CFS. It's a scandal, given the prevalence and seriousness of the condition. Unfortunately, after Covid, ME/CFS was even more politicized as part of the long-Covid discussions and got caught up in the culture wars. I have several friends with ME/CFS and they basically say the same things you do - ignorant doctors, high cost due to medication usually being off-label and not covered by insurance, and even friends don't take the condition seriously.
ME/CFS research is severely underfunded. The reasons for this are not simple, it's partly due to the complexity of the disease which, as cynical as it is, does not make it an attractive research topic for ambitious scientists. Same goes for "Big Pharma". Clinical trials for ME/CFS are extremely complicated, and hence expensive, due to the myriad of symptoms in how the condition can appear. It makes research in this area very difficult and expensive. There's very little funding for ME/CFS research, and that needs to change. Unfortunately, especially in the US, this is not going to happen for Kennedy reasons.
The Bayesian statistics thing is a bit of red herring, though. While your are correct that the math is old, the needed compute resources for doing Bayesian modeling on large trials was simply not there until recently. But it is also correct that it also took a long time until there were official rules regarding this from FDA and EMA. These regulatory things move very, very slowly.
Unless you’ve had ME/CFS you cannot understand how bad it is, I’ve had it and I still have a hard time comprehending how bad it was, I am occasionally reminded and it’s easy to forget. While it won’t kill you it’ll destroy your life until you’re ready to kill yourself.
The UK led the world with explicit psychologizing of it in large part to prevent insurance companies being liable for such an expensive and debilitating condition. A legacy that continues to this day, the main people responsible are still very influential. Fauci was instrumental in diverting research away from the autoimmune aspect and preventing a lot of important research. The $1B set aside for LongCovid appears to largely have been wasted. The official classification for hEDS was explicitly changed to reduce the number found so that it could remain a rare disease and continue to have access to specific funding for rare diseases (goal seeking). I could go on and on. It is a highly dysfunctional industry with many perverse incentives pulling it in all sorts of directions. There was the healthy at any size movement despite obesity being a massive cause for mortality, perhaps the only stronger signal would be smoking and consider how long it took them to figure out smoking.
There have been insanely impressive improvements to medical science but this seems to be largely due to tooling and access to information rather than the lumbering bureaucracy which appears to do very little of benefit.
I don't really understand where you are going with the fundamentalist vs. empiricist holy war narrative. Medical science is very empiricist, but it is conservative.
Yes they will miss rare cases or where symptoms aren't quantifiable or where no understood biological mechanism exists. Yes you can take on research and treatment yourself with the risk associated. No a bunch of anecdotal evidence on experimental treatments do not substitute for structured research. No you won't come back here in 3 years if you develop serious side effects that would have been identified in clinical trials and tell everyone you were wrong.
’fundamentalist’ has religious connotations which I did not intend, I meant deduction from first principles not foundational orthodoxy. My expression was there was tension not completely discrete factions, there is clearly some empiricism used in medicine. One of the difficulties in getting published is defending a position and it’s easier to do this with a mechanism of action which I think slows things down too much. The pace of progress on my conditions might as well be none at all. Still no cure for a condition that’s been known about since Hippocrates.
So I’ve been doing this for over 4 years now, and commenting on this with this account for a bit less than that, so far no serious unwanted side effects other than the usual ones for semaglutide which went away. Of course that has a survivorship bias but in the forums people do often tell others what they’re about to try and we would notice if they stopped showing up.
> My expression was there was tension not completely discrete factions, there is clearly some empiricism used in medicine. One of the difficulties in getting published is defending a position and it’s easier to do this with a mechanism of action which I think slows things down too much.
There is always tension between objectives in real-world systems. There are essentially two frontiers in our healthcare system--a core of educated professionals that are conservative and move slowly with ample evidence behind decisions, and a wide range of laymen who are comfortable with personal risk (e.g. bodybuilding community). I have respect for both, and they work together. The core will always have too many false negatives and the horizon group will have too many false positives. Saying the balance right now slows things down too much needs more support as an argument, there will always be things on the roadmap for medicine and there will always be edge cases that can't get addressed perfectly
From what I've seen medical researchers are champing at the bit for new areas of treatment that they think are promising and they just need the smallest amount of convincing evidence to research. If they don't have it for something you think is valuable, collect the information in a systematic way and find someone to send it to.
>compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people
Particularly when the mechanism behind most of these peptides comes down to "promotes more rapid cell growth". The intent may be to repair the skin, muscles, or ligaments, but biology is rarely that specific.
I think the grandparent meant "fundamentalism" as "mechanistic", and lots of things we can know (as you say using the scientific method) to be useful long before we have a good mechanistic explanation of how they work.
Some examples: aspirin (willow bark used for thousands of years, drug synthesized in 1897 and mechanism explained almost 100y later), or general anesthesia used again since mid 1800s and the mechanism is quite still debated.
This is not to downplay all the long term, or developmental, risks that using something novel can result in. But we can empirically know something about the effects without having good mechanistic models.
But it is usually not necessary for approval of a compound to be able to describe how it works on a molecular or cellular level. What you need to show are three things: efficacy, safety and quality, so basically: the compound has the intended clinical benefit, has an acceptable safety profile and can be produced with a consistent manufacturing quality. Most compounds fail because of lack of efficacy (roughly half), and roughly a third because of lack of acceptable safety.
The vast majority of drug candidates don’t make it to the trial stage. Much of the research has to be defensible prior to the trial and what makes them defensible is having a mechanism for action. Of course once a drug is being used off label there starts to be some empirical data which can be used for trials, and it seems that we’ll get lucky with GLP1-As.
You are entirely correct. New compounds for trials do not come out of thin air, you usually derive them from compounds you already know how and why they work. For instance, we know very well how Semaglutide works, same goes for many other peptides that are currently being studied. However, you are correct that we do not understand why they would help for ME/CFS, simply because we do not understand ME/CFS in the first place. As I've written above, it's a severely neglected disease.
Anyway, I don't think we really disagree, I rather misunderstood your original post. It's good to hear that these new peptides are helping with your condition, and I wish you all the best!
Thanks for the feedback, I’m noticing that ‘fundamentalism’ didn’t translate properly and I should have referred to first principles and mechanisms of action. I need better words for these and I will try to find them.
As a fun aside, consider the effect of the birthday paradox on empiricism, as the pool of candidates grows larger the probability of a match increases substantially as potential matching candidates increases quadratically.
Non blinded self experimentation is not a useful branch of empiricism.
I had an ME/CFS patient that had tried 100s of things and documented the effects thoroughly. She had a quite impressive list. Roughly 30% had had an effect to begin with, but the trend she observed was that it lasted for around a month at most. Placebo was her overall conclusion, but she occasionally got relief anyways so we both agreed that there was no harm in continuing. I'm sure several "peptides" is on her list by now.
There is nothing new under the sun, and fad cures for diffuse conditions have come and gone many times before. This is especially the case for conditions involving pain or tiredness, which are extremely sensitive to both placebo and nocebo.
What would be revolutionary would be 2-3 double blinded RCTs showing a lasting effect. Which would be great if someone did! But you have to actually bother to do it. And personally I would put money on the outcome being "no effect".
What do you think about the mis-alignment between goals here?
For medical research, the goal is to find general practices that will broadly help, and identify risks with the intervention. Even then, with many interventions, it's understood that they will effect people differently.
For individuals, they don't care about variation in communities, or standard medical practices, they are looking for relief for their specific condition.
Of course, declaring that just because something worked for one person, it should work for others, is wrong in both camps.
I feel like a big part of the disconnect here, and a big reason why people are talking past each other, is that they actually have different goals, and aren't really aware of that difference.
Well, to be honest I think the primary disconnect is in epistemological understanding. The OP did not declare peptides to be a personal revolution, he/she seemingly generalised their own experience to be widely applicable.
Basic human thought patterns usually lead people to think that anecdotes about their personal experience is valuable for understanding the world, but this is wrong. The scientific revolution basically illustrated the flaw in this premise outside of hypothesis generation. It takes specific education to make human beings truly believe that their anecdotal experiences are mostly irrelevant beyond understanding their immediate circumstances. The proportion of humanity that truly think this way is relatively small.
Understanding the world through anecdotes still works okay-ish for a lot of areas, but ascertaining relatively subjective effects of experimental pharmaceuticals is not one of them. But to many people it's non obvious that this is the case. And as a general method of thinking about this issue, it is just the wrong way to go about things.
And that's the disconnect, in my opinion. The OP drew a conclusion from a thought pattern that comes easily to human beings, but that is just wrong in this situation. Of course, perhaps this is reinforced by underlying motivations, but that's not what makes people talk past each other. These kinds of discussion are usually driven by so called "deep disagreements" in epistemological understanding, in my experience.
> Non blinded self experimentation is not a useful branch of empiricism.
Amen to this. The plural of anecdote is not data.
People have been hawking snake oil for centuries, and people have been believing snail oil cured them for centuries.
I'm pretty sure there is no diagnostic test for ME/CFS. What are you referring to?
Also I don't understand how semaglutide did help you while you're at the same time part of a minority risk group with a hypersensitivity to it. Isn't that a contradiction?
Doesn't it just mean GP needs to take less?
Yes, sensitivity at over 10x normal, so I just took 10x less. I’m taking a more normal dose now after 4 years and I believe I have become desensitized as my body normalized. Other seemingly unrelated aspects also normalized such as thyroid, testosterone, and neutrophils also improved. I was taking medication for these and have been able to stop taking them. I am assuming a lack of GLP1-As to begin with caused the receptors become more sensitive to it. When I started there was no anecdotal information available just theory, in the 4 years since many people have now had very similar experiences including hypersensitivity. (https://www.healthrising.org/blog/2025/11/03/glp-1-agonist-m...)
There are now a number of very definitive tests, most related to immune system profiling. Prof. Ron Davis has some good research and has shown that plasma from someone with ME/CFS when combined with normal red blood cells will greatly diminish the ability for red blood cells to handle stress (pumping out salt).
https://link.springer.com/article/10.1186/s12967-025-07203-w
I think I would need to see testing on a control group of housebound patients with other conditions to believe this. It's easy for ME testing to pick up markers for being housebound and limited exercise for an extended period of time.
You sound exactly like the tens of doctors that misdiagnosed my aunt (who passed away through euthanasia after her symptoms got too bad to live with late last year).
I understand that the symptoms of ME/CFS might be similar to being obese/depressed or housebound, but the problem is that doctors often jump to that conclusion too quickly and don’t take efforts to diagnose ME/CFS leading to situations like my aunt’s. She was also obese and depressed and has been struggling with those symptoms for about 30 years and has constantly been misdiagnosed the entire time because doctors didn’t figure out that those were symptoms of ME/CFS and not two unrelated conditions coming from two different diagnoses.
Thanks to long-covid putting the symptoms of ME/CFS on the forefront lately, there’s finally been some much needed research into the disease and people like my aunt finally get the diagnosis they should have been getting many years ago.
looks interesting, but has the classic "40 patients".
What would be enough? 400 patients, 4000, 40k, 400k, 4M?
Well, reading the study, I'm not sure more patients could rescue it from methodological bias. They assumed the premise basically -- we should find a biomarker, which is kind of what this thread is discussing. Then they went trawling for biomarker in a sea of millions of biomarkers. They did this by training an model that produced the desired result, using a grid search for hyper parameters that even further expanded the available degrees of freedom here beyond what they had from the biology. No pre-registration; There are millions of places where the researchers could have made a different decision -- would they still have gotten a publishable result? Oh plus the authors mostly work for the company whose data they use, which is hoping to sell a diagnostic test.
I'm giving you a thorough response because I'm detecting a cavalier anti scientism which I think is sadly becoming more common. This stuff is hard; are you sure you understand it enough to have an informed opinion?
Im sorry for your quality of life problems but calling doctors bad at statistics and then giving anecdotal evidence as proof has to start ringing some logical bells right? You dont even have to take our word. Use an LLM as judge. Paste your comment into chatgpt and see what it says.
I didn't read their whole comment, but I worked in the Internal Research department of a medical school. I did their statistical studies and built software for analysis pipelines.
Doctors, at least 15 years ago, were definitely bad at statistics.
They were not required to take a statistics course at all. Most programs would require Algebra and Calculus as part of their science reqs.
Some would maybe take one basic research course, and they would then become obsessed with p values of 0.05.
They did not have a basic understanding of how to interpret research unless they were an auto didactic and went out of their way to improve. It's something my director (a doctor and software engineer), and the Dean complained about relentlessly.
I’ve not only visited many doctors personally I was also part of a team working on a medical diagnostic instrument, the result of the instrument was a probability distribution function and it was impossible to explain this to the doctors who really would only accept a small number discrete classifications, which in effect throws out about half of the data we had worked so hard to collect.
Yes! good point, I have noticed this as well.
You reminded me about another idiosyncrasy: Doctors are addicted to double blind randomized control trials.
Which yes, those are powerful. But good evidence can come from many other study designs. Especially when mechanisms and first principles are being studied.
> Paste your comment into chatgpt and see what it says.
Isn't one of the bigger problems with ChatGPT that it's much too supportive of whatever the human is talking about?
Thats the point. If even such a sycophantic ai disagrees with your points you have a problem
I guess it depends on how you frame it. "I've just posted this comment, what do you think" vs "Someone online has just posted this comment, what do you think".
But it does require to know the bias that LLMs have ahead of testing this.
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I agree with this, but we don't have a good understanding of the mechanisms of how most drugs work, and what else they do. That's why, generally speaking, we require actual observational safety data, and not just a thorough description of the mechanism(s) of a drug. And sometimes we find out years or even decades later we were badly wrong. "Safe" is a very qualified term when it comes to drugs. What actually distinguishes $randompeptide from $approveddrug is the safety data - there are papers all about the proposed mechanisms for most of them.
If a lot of people take the mediation and die is that evidence that the medication is unsafe? If they live is that evidence that the medication is safe? Either both are true or neither is true. The relative weight of evidence is dependent on priors but it is still evidence.
Your comment reads like someone with no experience in medical trials - neither pharmaceutical nor medical devices. Death is not the only negative outcome. Nor is a procedure that is commonly followed by death necessarily a bad procedure - many cancer treatments for example fall into this category.
You’re not understanding the point of the hypothetical, it was to illustrate a scenario in that most people would consider evidential and point out that by definition the opposite outcome must also be evidential even if that outcome was far more likely. It’s to highlight an unintuitive aspect of probability formalized as the bayes ratio. The strength of the evidence is dependent on the priors but it exists. Anecdotal evidence is not zero evidence it is weak evidence and with care a lot of anecdotal evidence can be combined to create stronger forms of evidence. Rounding it down to zero or up to one are both incorrect.
And yet neither of the sides are strong enough to term as evidence. I have no problem with self-experimentation. But citing a few anecdotes as evidence is a dangerous area that I discourage. Somedau we will understand why some people respond so favourably to the wolverine stack and others don't. And somebody will someday correlate what those hurt by BPC-157 all have in common. But until then, these peptides cannot be recommended to others in good conscious.
But for self-use? Go right ahead.
That is so dangerous, buying grey market replicas of pharmaceuticals.
Unless you have a research lab built out in your house, you have zero way of knowing what it is that you're actually getting. Whether the dosing matches the claimed dose. Whether there are bacterial growth, or other manufacturing chemical left in by bottom-of-the-barrel chinese manufacturer.
I understand your risk profile may be different than others, but when you can get the real thing officially, I'm not sure why anyone would risk this.
> chase after whatever works
Crack is really moreish.
Clinical trials are not looking for fundamental mechanisms, they are there to ensure an effect is strong enough to say a product should be sold for that purpose. Otherwise you end up with snake oil salesmen. Because how can you be sure you are even injecting the thing the sellers claim it is?
I would encourage everyone interested in peptides to read about the state of medical science before the establishment of the Pure Food and Drug Act of 1906.
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Have you tried omega3? There were some improvements I was reading about.
I have tried everything on just about every list of possible treatments, having been in the fortunate position to have made enough money that I can try things full time and being able to bypass doctors for access to medicine and being able to do my own research.
can you talk about how semaglutide improves ME?
I don’t know the mechanism, I think ME/CFS is an autoimmune condition and semiglutide appears to help with autoimmune conditions in general. That was my reason for trying it. The improvements snuck up on me after many months as I noticed I was having fewer and fewer bad days.
If you felt improvements with semiglutide only after many months, how long did the other trials last? It sounds like you went through hundreds of trials. Did they all went on for many months? When did you determine that a drug wasn't effective and abort the trial? How come you didn't abort the semiglutide trial earlier?
Because I started at such low dose 0.025mg and ramped slowly I didn’t expect to see much of an effect until I got to more normal doses so I was unusually patient with it. Additionally extended water fasting (>5 days) was the only thing helping my headaches so I was focusing on ways to emulate this effect without an unmaintainable amount of fasting. I also had uncontrollable weight gain so I figured that was either related, or if not it would still help to lose weight anyway.
Most of the stuff I’ve tried that worked usually has an immediate or overnight effect. Notably Low Dose Naltrexone was overnight, Low Dose Abilify was near immediate. I believe this is due to their immunomodulator properties. So I studied psychopharmacology and focused in on finding weaker ligands than typical as a way to try and safely modulate my immune system. I landed on Modafinil in the morning and Amitryptiline at night, both off label treatments for the probably related dysautonomia.
The N of 1 with many overlapping signals and medications was of course very noisy but I treated it like a ML optimization problem. I could tell it was likely beneficial within the first week even with the small dose. I probably could have statistically determined it was working within a few months but I was distracted by work so it took a little longer to be sure.
> you don't need to know how they work to know that they work
Welcome to the powerful world of the placebo
Placebos would work with anything with a plausible story, since I’ve tried many hundreds of things and only a handful worked I’m highly confident that it’s not a placebo. People with ME/CFS are used to trying things and have them not work so the placebo effect where it exists has usually worn off.
For the vast majority of people “peptides” is a new word and they assume it’s new science that does something new. It’s like if they had never before heard the term “pill” or “injection” and now someone is marketing it to them. So you have a enthusiastic family member going “omg, I got this amazing injection, it can cure cancer, make you look like the rock, cure baldness and fill your bank account all at the same time!” And you go “I doubt that” and they’ll refer you to all the amazing science on injecting things and how injections are used broadly in the health industry and can treat so many different things. And they are not exactly wrong in that connection, they are just dumb, and of cause a given injection being able to treat diabetes says nothing about injections in general and absolutely nothing about cheap foreign snake oil injections.
I have the same feeling about the whole discussion. I know that colloquially we use terms like "protein" to refer to dietary protein rather than the class of mollecules.
But the way "peptide" is used by all the bro/gal-science influencers that push them online makes it blatantly obvious that they have next to no idea what they're talking about.
I read the article but didn't get the tl;dr about peptides. What are they and what are they used for?
Cut and paste from New Yorker: The human body produces thousands of peptides. Many are portions of proteins which send messages or regulate systems in the body, often in ways that scientists don’t fully understand. Researchers have known about some peptides for decades, and dozens have been turned into safe and effective drugs. The hormone insulin is a peptide that moves sugar from the bloodstream into cells; GLP-1, or glucagon-like peptide-1, spurs the pancreas to release insulin and slows the passage of food through the gut. (Peptides are usually defined as having about fifty amino acids or fewer; more than that and they’re proteins.)
https://www.newyorker.com/magazine/2026/04/13/why-are-people...
The author is missing a massive segment of that gray market: people who buy FDA-approved weight loss drugs (e.g., semaglutide or tirzepatide) at 2–5% of the brand-name price. This route carries some risk, but there are ways to mitigate it, such as performing third-party testing. I assume most people who do this couldn't realistically afford the brand-name drug anyway, making this their only viable treatment.
Even if you test a batch once, do people who get testing done do testing on all batches?
The synthesis of peptides uses some NASTY chemicals. I would be worried about lax manufacturer policies leading to contamination, even if one batch passes. The costs of FDA certification are the effect of that protection.
But whatever, this is the same attitude that people have against owning insurance. It is hard to recognize the cost of risk.
I bought Semaglutide at 50c/mg and had it tested, it's the real deal. What's the normal price, $100/mg?
My gf is in medicine so she had a friend test it through their work.
Won't be anywhere near that. I don't have prices handy, but Lilly sells tirzepatide (a bit better than sema, and usually a bit more expensive) at 500/mo (maybe a bit less now on the trump rx site, I don't recall). Depending on dose, that'll be about 10 bucks a mg give or take. At 50c/mg for sema you were paying a bit of a premium. These days even tirz is only about 30-35c/mg.
I'm paying $400/month currently, directly from Eli Lilly.
They drop ship a box containing cold packs and the meds.
You dont need the idiocy of trumprx to get these prices, just go directly to Eli Lilly or Novo Nordisk.
I used to buy from Peptide Sciences so I was certainly paying a premium for reputation at $20/mg. I think Semaglutide is now at a bit of a premium due to it falling out of favour and most people switching to Triz and Reta. I only take a low dose and am happy to stick with what's working.
There must be an irony that it was Trumps crackdown on peptides, I presume to prop up his prescription company, that forced me to switch to Chinese supply. By doing it all at once it created a critical mass for that market.
IIRC the biggest impetus for cracking down was Lilly throwing a fit about the gray market supplying reta well before it even becomes available via the normal channels (who knows when that will be). But as you say, it just pushes people to buy direct from Chinese vendors (and it is basically impossible to stop direct imports like that). Would be safer if more reputable US-based sellers could supply it semi-openly as before. Nexaph is still selling it, but I figure the clock is ticking on that.
> and it is basically impossible to stop direct imports like that
How so? Is there a particular characteristic of the US that makes it so, or of the channels through which this is done? I get that in general it's impossible as with recreational drugs, but when you look at cocaine then at least to traffick it to most wealthy countries it takes a large amount of resources and is at high risk of getting caught. Which is why they're increasingly starting to use narco submarines. This greatly increases the price of the product. Why can't the same happen to peptide imports?
The US is a rather dysfunctional country along many axis and an inability to stop imports is one of them. The difference between drugs and peptides is that by weight peptides are much more valuable. 1kg of cocaine is $28K, fentanyl is $150K, and semaglutide is $500K.
Test what, exactly? Purity? LPS contamination? They cant test for every last picogram of material in it. Did they test for viral contamination?
Even drug addicts heat up the thing they inject so theyre actually safer than you can ever be. Dont inject things from China into your blood!
High-Performance Liquid Chromatography so purity and concentration.
Back when I started few people were doing this and it was more of a risk, I was buying from research peptide vendors who had their own testing practices, but now a huge number of people are doing it and there are markets where reputations matter and it appears to be reasonably efficient.
I would prefer not to inject peptides from gray market China but practically all of the gray/black market supply is from there. I will likely switch to pharma grade when generics become available.
Im a libertarian at heart so cant argue too much with people's personal choices, but I can only say that given what I know can go wrong in even the best maintained lab, I wouldn't ever do what youre doing. Yes its all great today, but the day something goes wrong, you may not be happy finding out how its affecting you. Look up the bayer factor viii hiv incident.
Last I checked, Ozempic (Semaglutide) is around $1000/month in the US. A typical 1 month pen is 4-8mg, so around $250/mg to $500/mg. So yeah, I may have understated how much cheaper the gray market version is.
This is incorrect.
Tirzepatide is $400-450 (depending on dose) per month directly from Eli Lilly.
https://www.lilly.com/lillydirect/medicines/zepbound
Novo Nordisk's drugs can be had as low as $250/month through third party (which is weird), though they'll probably honor those prices in direct sales before long.
https://www.cnbc.com/2026/03/31/novo-nordisk-wegovy-subscrip...
These are all cash pay prices, no insurance.
Semaglutide is effectively $99/month in the US. Not from shady sources.
Do you mean with health insurance? Novo Nordisk still lists it at $1000+ on their website: https://www.novopricing.com/ozempic.html
I meant from the various compounding pharmacies. But in the worst-case you go with GoodRx and get it for $350/mo (after $199/mo for the first two).
> had it tested, it's the real deal
How did they test encapsulation? I thought the whole problem is your stomach acid breaking it down.
They’re presumably injecting it like normal.
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I imagine it's legally risky to buy a large quantity, test it, and then resell smaller quantities. That's a shame because the alternative is probably that some folks settle for products of dubious quality and end up getting hurt.
Yes, I believe most people buy directly from somewhat shady Chinese factories. I tried contacting a few and they all refuse to meet or send samples from within China, so I assume what they're doing is illegal in China. In the US, it's legal to sell them as a "research chemical" but the FDA is cracking down on companies that are clearly engaging in b2c.
There's this company that offers free testing: https://finnrick.com/
Another popular testing company is https://janoshik.com
Some other useful resources: https://graymarket.substack.com/ and https://glp1forum.com/
There are a few subreddits as well.
FWIW, I never ended up buying any myself.
Right, but I don't know the people at those companies. I have local chemists that I trust. I'm just lamenting the fact that developing that kind of trust network everywhere, so everybody can be similarly sure of what they're putting in their body, is likely to run afoul of local laws.
FWIW, finnrick's claim to fame is being free. Someone is paying for it. They have also failed blind tests in the past, Janoshik (IIRC) never has. There are several US-based labs but none of them have the same reputation as Janoshik.
Actually, you just described most of the tele-health and compounding pharmacies that carry GLP1s!
Where do you think Hims, Ro, Brello, or the rest get the APIs they sell to their customers? They get them from grey market suppliers in China. They don't go to Ely Lilly or NovoNordisk and say, "politely sir, may I skirt around your IP and sell your drugs for 10x what they cost instead of 10,000x what they cost?" Hopefully, they test them and filter them and use sterile/pharma processes for what they sell to their customers. Well, except for the Medspas, those are just wild west snake oil farms.
This actually isn't true. Hims compounded the GLP1s themselves. They broke/are breaking the law. Theres lawsuits.
They compounded them, which just means buying the API, reconstituting it, adding another compound (Vit B6), and putting it in sterile vials.
They did not make the peptides. They sourced them from China.
We need to change the law so that the crime is selling mislabeled or contaminated drugs. If you can cook it well enough in your kitchen, you should be allowed to share it with a neighbor in need.
Things have changed a little, but during the time that compounding was explicitly allowed, the licensed pharmacies were buying from FDA approved manufacturers, sometimes in China, and sometimes the same manufacturers who also do contract manufacturing for Lilly.
Today ... who knows? It might just be the same gray market stuff us plebes can get.
It probably is, but that does not stop people from effectively doing it. There are a number of groups that specialize in conducting group buys, doing a bunch of testing on randomized samples, and then shipping out the product to individuals.
Also, if you plan to be on it a good long time, you can buy a bunch of kits yourself (a kit is 10 vials), run a bunch of tests, and then just have a nice stockpile that will last you years. The testing will likely cost as much or more than the product itself, but given how inexpensive the product is, you still come out way ahead financially.
>I imagine it's legally risky to buy a large quantity, test it, and then resell smaller quantities
It is illegal, but it doesn't stop people from doing it. In fact, if you don't have any sort of test results for your peptides people will absolutely avoid buying your wares until you have them. Purity and mg/ml are the 2 basic test results that any shop worth their stuff will have.
To be fair, most everyone I know who is buying on the gray market considers vendor tests to be minimally required, but still insufficient -- there is no assurance they tested the product they shipped to you. Plan on testing it yourself. I'm sure some people do trust nexaph enough, though, to not worry so much. Whether that trust is well placed, that is a separate discussion.
With most of these you can really tell if they work or not and there is a pretty predicable dose dependent reaction profile. With slow meds like semaglutide you'd maybe not notice it in the first week but you will by week 3. I had mine tested but if that wasn't available I probably would have considered the anecdotal evidence to be sufficient. It appears that most of the scamming is just people taking the money and not shipping anything.
The most dangerous failures I've seen have been sending the wrong peptide. 15 mg of tirzepatide and 15 mg of semaglutide is a very different experience.
After nearly getting hosed in a group buy (I did get refunded, but that is far from a guarantee) because of a product mismatch, I decided to just pay for nexaph. Love him or hate him, his popularity relies on his reputation and he has been more careful than most suppliers to cultivate it with more extensive testing and quality control.
That makes sense, I don't like that the bottles are unlabelled so the first thing I have to do is label them. The box is labelled and this seems to be standard practice. Semaglutide is falling out of favour so I guess they're substituting. I have 4 years supply now so I guess I'll check back then and see where the market is at.
> I have 4 years supply now
<Insert that "one of us, one of us..." GIF here>
I know a bunch of people with multi-year stockpiles. I've got ~5 years of reta and ~6 years of tirz. This is too much, of course, but I determined a while back that under no circumstances do I ever intend to find myself unable to source it. My life is immeasurably better after losing 110 pounds.
Could you direct me to some resources you used to figure out dosing and sourcing? I’ve been interested in trying it out (need to lose a lot of weight) but have been paralyzed by too much contradictory information.
Lowe has a point, but the FDA has painted itself into a corner by (a) forcing up the costs and the various bureaucratic demands associated with clinical trials, (b) allowing drug advertising , but then forcing those comical "may cause death" disclaimers, both of which have become totally ubiquitous, and (c) inconsistently following its own rules, and in some cases flouting its own rules.
At this point, broscience is considered no less valid than actual clinical trials, and the FDA should blame itself for this. Not "human nature being what it is in this fallen world" in a sort of general or abstract sense.
Another point I could raise is that telemedicine has turned the entire prescription system into nothing more than a parasitic middleman/gatekeeper.
FDA reform is very badly necessary. That ought to come before harsher enforcement, and I think that much of the populace already intuitively understands this.
> prescription system into nothing more than a parasitic middleman/gatekeeper
Agree. Unless it's addictive or in short supply, you should be able to buy it OTC.
> Another point I could raise is that telemedicine has turned the entire prescription system into nothing more than a parasitic middleman/gatekeeper.
I’m curious what you mean by this. I’m not sure what you mean by “prescription system” specifically.
I'll give you a case in point. This article was discussed the other day:
> https://www.nytimes.com/2026/04/02/technology/ai-billion-dol...
People want GLP-1 drugs. They can't get them without a prescription. They pay $$$ to a "telemedicine" "doctor", recite a list of well-known symptoms, and buy the prescription.
The system is that you can't buy these drugs without the piece of paper, and the piece of paper is basically something that anybody can buy regardless of whether or not they actually need the drug. Wanting it is usually enough.
I think access is a good thing. The issue isn't with telemedicine but the fact that there's a prescription wall for helpful meds like GLP-1 in a country where we've failed people by creating one of the worst food environments.
Also, most doctor's visits aren't any different from getting it if you want it except it's gated on the mood/attitude of the doctor, maybe your ability to sell some sob story. And then you book a different doctor until you get it. Telemedicine just makes the process easier an arbitrary system.
GLP-1 prescriptions are easy to get in the US. It's filling the prescription that is the problem, because insurance rarely covers it and it is beyond the disposable income of most Americans.
The prescription hurdle is absolutely necessary -- these are not drugs that anyone can safely take without guidance. It's the price that needs to be fixed.
> these are not drugs that anyone can safely take without guidance.
Unless that risk is egregious, informed adults should be able to accept it if they so choose.
I think we all agree with that statement.
What we might not agree with is specifically what "informed" or "egregious" might mean.
I actually think "informed" is almost definitely defined already. Doctors already need to provide informed consent, so I think it would borrow from that. As for "egregious", I also suspect that this is understood already in a similar vein, but perhaps not - I'd suggest that this is effectively "would near definitively cause imminent harm".
FWIW I do not think that most people agree with this.
There's a lot of definitions for both of those words.
I can tell you that the conversations I've had with people who take these drugs from telehealths or from med spas -- they generally don't understand how these drugs work, what the risk profiles, are or how dosing should be managed. There's a lot of misinformation going around about all these drugs.
"immiment" is a different word than "egregious" isn't it? Malnutrition, cancer, and death are pretty egregious as well, even if they occur maybe months or years in the future, aren't they?
Literally, enough people are fucking this stuff up that we have pop culture references to it: "ozempic face". Losing weight this rapidly is unsafe. Sure, a lot of people might consent to the idea of rapidly losing weight, but there's nothing "informed" about it.
> There's a lot of definitions for both of those words.
Sure. I don't think that that implies we have the right system currently or that we can't come up with good definitions. And again, "informed" is almost definitely already an understood term in medicine since "informed consent" is already understood.
> they generally don't understand how these drugs work, what the risk profiles, are or how dosing should be managed.
That's fine. I don't think they have to understand how they work. They have to have the risks conveyed appropriately to them. They might make a call that's ultimately harmful. Adults can do that, they should be allowed to do that.
> "immiment" is a different word than "egregious" isn't it?
Well, yes. If I had defined "egregious" as the same word, that wouldn't be very helpful.
> Malnutrition, cancer, and death are pretty egregious as well, even if they occur maybe months or years in the future, aren't they?
Not really. Things that take years to happen are a lot less serious, especially as they can be monitored for. But again, this can all be explained to the patient. I'd say the bar for "egregious" should be very, very high. When in doubt, give patients the power to choose.
> Literally, enough people are fucking this stuff up that we have pop culture references to it: "ozempic face". Losing weight this rapidly is unsafe.
That isn't compelling. How many of those people are getting ozempic from a nurse practitioner at one of these compound pharmacies? If anything, I'd bet that doctors taking the time to ensure patients are informed would lead to a reduction here.
I know a lot of people on GLP-1 meds and even took a dose myself out of curiosity.
You take a dose every two weeks. And if you accidentally double dose because you misread 1U to mean 1 dose, it just gives you some nausea.
Are we going to pretend it's hard to take this drug now too? Or that the doctor has some magical insight into your getting-on? Remember to eat. That's it. I guess a few people might need the doctor to go "you're eating, right?" but I don't believe in infantilizing everyone over that.
> You take a dose every two weeks
Weekly, if you are following guidelines correctly. The half-life of most GLP1 peptides is 5-6 days.
I otherwise agree with your point entirely. Though anecdotally, I may have given my brother-in-law a single small vial of tirzepatide at his request so that he could experience it, and the results were ... not good. Turns out he's an idiot, thought that 'more is better', 'drinking enough water is for weenies', and 'I am not an alcoholic even though I get plowed most evenings.' All against my very specific advice on how to give it a try. Whoops.
My fault, yes, I should have realized he was too stupid to do it without adult supervision. He made himself so sick he almost went to the ER. Nothing really dangerous, of course, tirzepatide is pretty safe stuff, but overdosing on it can make you feel very shitty for a few days until the blood concentration drops.
> Or that the doctor has some magical insight into your getting-on beyond a couple questions they ask you in your visit? Remember to eat. That's it.
Apparently we have forgotten people who died from eating disorders (previously called anorexia nervosa)?
There is a VAST difference between someone who weighs 300lbs asking for GLP-1 to combat morbidity and someone who is barely 100lbs asking for a GLP-1 to take off weight for bikini season. That's what needing to ask a doctor for a prescription is for.
That sounds like people making an informed decision about their body to me. Doctors don't need to be inserted into every risky decision.
If you think that sounds like an informed decision then you might be proving their point.
One dose is one thing -- but there are other risks that can lead to complication or death here if taken improperly for a long period of time. Musculoskeletal issues, cardiac issues, thyroid issues, etc.
Additionally, getting the correct dose is not straightforward for a layperson as it is for other OTC drugs with standard doses.
There are similar risks, and probably more likely, to all sorts of consumables that aren't regulated at all. It is reasonable to ask whether the prescription regime for GLP-1s makes sense. It isn't the only substance posing that conundrum! Ondansetron is OTC in a lot of countries, but not in the US, Canada, or UK. But ondansetron is arguably less dangerous and more helpful than pseudoephedrine.
Pseudoephedrine, of course, isn't BTC because it's dangerous to take or complicated to dose. It's there because of the war on drugs. But I do agree that not all drugs are regulated appropriately. Marijuana also comes to mind.
I do think GLP-1s are just about right. It is appropriate to take them under personalized professional guidance.
Right, and I actually see the logic of that (unlike virtually everyone else on HN, and let's not rekindle that debate; the search bar avails). The point is you don't need a prescription to get it. People might be better off if GLP1s were also BTC. Hard to say!
Certainly you can abuse a GLP1 and get yourself very sick, or not abuse it and still end up with pancreatitis. But smoking and alcohol presumably cause way more cases of pancreatitis, and you don't need a script for a handle of Popov.
There used to be prescriptions for alcohol products and cigarettes have been sold as medical products -- the reason we accept them in society today is not because we think they have relative less risk to other things, but that their acceptance as recreational vices outweighs the harm that we know they cause.
> smoking and alcohol presumably cause way more cases of pancreatitis
Indeed. In fact, I think just recently there were updated studies for at least one of the popular GLP1s that disclaimed entirely a link to pancreatitis.
To be clear I don't think it's actually reasonable to suggest GLP1s should be OTC in 2026. Were that to happen it would be part of a regime change in drug regulation that I'd categorically oppose. The timeline on GLP1s (unlike Zofran) doesn't support it. There are arguments for why your doctors would want to know that you're taking it, and on what schedule. But it should be extremely easy to get.
Agree, it does feel like a class of medication that deserves more control than OTC would provide. I do think it should be largely voluntary, however, with doctors expected to provide it unless there is a specific contraindication that would make it harmful.
> The prescription hurdle is absolutely necessary
You're totally missing the point thought. The prescription hurdle effectively does not exist. It's just a paywall.
You pay your $100, get a 3 minute call with a NP/PA/whomever, and basically the robot writes you a prescription for whatever you want. The point is you pay and you get the prescription. Patient safety has nothing to do with anything.
It's cheaper for most people to get the prescription written at a PCP.
The advantage to a telehealth is not getting the prescription written -- it's that they'll fill it for cheap through a tiny compounding pharmacy that is making it, technically illegally, but are small enough to be off the FDAs enforcement radar for the moment.
I have used both my PCP and telehealth for prescription writing, never once have I used a compounding pharmacy.
It's slightly cheaper for me to use telehealth vs. billing through my insurance. The downside is it doesn't go towards my deductible of course.
The stuff you are describing are entire supply chains of a sort where you want a GLP-1 or perhaps a few other things like TRT. Those you are signing up for the drug itself, which happens to include the prescription part with it.
Telehealth can be used for any old medication you want. It removes the permission slip part of the process and replaces it with a payment gateway. If you have $75-150 you can just click some buttons and have a prescription for nearly anything you want at most a day later. This includes antibiotics, ADHD meds (getting harder on these), certain benzos, etc.
HIMS/HERS/etc. and their smaller ilk are super popular, but they are the tip of the iceberg.
Telehealth providers can certainly work with compounding pharmacies but not necessarily. If you are looking to get a prescription for Diazapam you are going to be getting that sent to your local Walgreens or whatnot.
> It's slightly cheaper for me to use telehealth vs. billing through my insurance.
How? Usually PCP visit are cheap and everyone gets one for free.
> HIMS/HERS/etc. and their smaller ilk are super popular, but they are the tip of the iceberg. > Telehealth providers can certainly work with compounding pharmacies but not necessarily.
Yeah I’m aware there are a whole host of services telehealths provide but the primary reason people use them for GLP1s is to avoid the name brand cost.
The issue isn't even just the prescription.
It's that your health care system the doctor is in builds a few extra hurdles. I've talked to my (non-tele) doctor about GLP-1. I've tried losing weight before, with her, there's a long history.
To get approval, between the hospital my doc is in and the insurance, I need to:
1) Have a BMI of >30. Since it's only 29.5, I get to stuff my face if I want to lose weight.
2) Have six sessions with a nutritionist. Which are massively useless, their advice is roughly equivalent to reading Cosmopolitan. I know because I had prior conversations, and they're documented. But still, gotta do it again.
3) Do six months on Weight Watchers. Which is one massive scam leading you right to disordered eating. Also, I've tried for years to lose weight via diet changes, documented and talked through with my doc.
4) Before I can get tirzepatide, I have to get semaglutide for three months to see if it works. Never mind there's study over study over study showing it's slightly less effective and has massively more side effects.
Or I can just cough up the cash directly and buy from Eli Lilly, if somebody signs that receipt.
I'm fortunate enough I could afford that, so I did. (After a second consultation with my family's doctor back home - both they and my doctor agreed it was appropriate, so it's not just a case of "wanting is enough")
And after six months, my weight was in a much better region, lipid panels were much improved, other related biomarkers looked better as well - exactly as numerous studies and my doctors said one could expect.
So, as long as I cough up enough money, sure, I can bypass all the hoops. My health didn't enter the equation, just screw the poors (whose treatment for worse outcomes because they couldn't get access will cost a whole lot more than GLP-1 would've cost).
So, fuck the "prescription hurdle" and the medical system in the US with a hot white glowing iron rod right up the ass.
As for "these are not drugs that anyone can safely take without guidance", that's not really true either.
They're neither hard to take - "inject one vial once a week into the flabby part" isn't rocket science - nor does it cause massive health risks by itself. (And the hazard ratios for diabetes 2 and cardio events are so spectacularly low that they dwarf the other risks)
Yes, talking to a doc is a good idea. No, the current gatekeeping is in no way necessary.
Those are coverage requirements from your insurance company. Consider yourself lucky to even have any path to get these covered under insurance -- most insurance plans do not cover weight loss drugs under any circumstances.
The diagnostic criteria is simply (BMI > 30) OR (BMI > 27 + a weight related comorbidity like high blood pressure or high cholesterol)
> They're neither hard to take - "inject one vial once a week into the flabby part" isn't rocket science
It's not that they're difficult to administer, it's that dosage needs to be managed appropriately.
The "perscription system" used to be that you'd have to go see a doctor, the doctor knew who you were, and would make decisions on what prescriptions/medications you should be given.
Due to drug advertising rules, the prescription system has been turned on its head, and the patient now goes to their doctor asking for a specific prescription.
Telemedicine took advantage of this and has effectively removed the middleman (the doctor) in many cases and you just sign-up look at a person on a camera, and get your drugs sent to you.
> Telemedicine took advantage of this and has effectively removed the middleman (the doctor) in many cases and you just sign-up look at a person on a camera, and get your drugs sent to you.
This is only true for a handful of drugs that are basically OTC already (or that have OTC formulations). Additionally, telemedicine didn’t take advantage of drug advertising- that’s an odd assertion.
The system changed from the doctor deciding what drugs you should take to the patient asking for the drug by name from the doctor.
I think this enabled telemedicine to work in the way it does not. The patient says "I want wegovy" and the telemedicine platform says "ok, here you go".
Would telehealth pill-pushers exist without this mentality?
Go to doctor, get prescription for restricted medicine, pick up prescription.
If you can call up a teledoc and they give you a prescription based on your description why could you not just go buy the meds yourself without a prescription. You have essentially diagnosed yourself and just asked the doctor for permission to buy the drug you want.
That’s… not how actual telemedicine works. That’s how jackasses “disrupt” healthcare for very specific drugs. Mostly birth control, ED meds, and various hair regrowth meds.
It’s really clear that some of you are really mad about something you don’t understand.
I take certain medications--nothing interesting, nothing controlled, nothing abusable. I have to deal with a whole thing just to get refills, because my PCP forces me to come in every time--and even that is now just a telehealth call that is annoying.
In Mexico, for meds like mine, you can just buy them at the pharmacy. There's no reason for all this nonsense.
(Edit: same PCP refused to prescribe GLP-1s early, without any scientific or medical reason not to. Delayed my weightloss by months until I found a place that would.)
> I’m curious what you mean by this. I’m not sure what you mean by “prescription system” specifically.
They basically operate as a "pay for a prescription" service.
Figure out what drug you want, google the drug name and telehealth. You will be marketed in a wink wink sort of manner over how easy it is to get them, just hours away! Then if you are not a total idiot, you answer certain questions in the right manner on the intake form, the doctor (usually NP/PA or similar for most things) will quickly run through that and expect you to answer correctly - perhaps guide you a bit if you don't.
5 minutes later you have a prescription in the web portal and it's sent to your pharmacy of choice.
It really shows how the whole "permission slip" program is BS. I've used these services a couple times vs. my normal doctor just to save time and expense of an office visit. If I can click some buttons, have a call 30 minutes later, and be on my way to the pharmacy for $50 it's sometimes the path I take now vs. traditional route.
Someone used to the traditional doctor/patient relationship thing and prescriptions being "holy" would be shocked at how easy and gamed it all is.
Well that's a problem with the profit driven US health system (although admittedly other countries have similar problems to varying degrees) not prescriptions in general though? In particular the take home from this should be to make it more difficult to get the prescriptions not to do away with prescriptions.
The FDA didn’t push up clinical trial costs, thalidomide did.
So you are stating that there has been no change in how clinical trials are required to be run, and the associated costs, since the changes immediately following the thalidomide catastrophe?
When medicine ignores nutrition entirely, and nutrient supplements are still complete unknowns, you have to wonder who the FDA is working for.
Medicine doesn't really ignore nutrition, but the problem is:
1. Most people don't believe it anyway. People want to hear they can eat hamburgers and milkshakes and be healthy. Telling them "we know that gives you heart disease and cancer" does nothing.
2. Nutrition is complicated and different for every person, because everyone has different things they can tolerate. The "perfect" diet is actually worthless because it has a 0% success rate. Really, we have to optimize for how miserable people are willing to be.
3. Most people are unhealthy enough that nutrition is the least of their concerns. That sounds crazy, I know, but if you're obese (which most people are!), then priority is being not obese. Not your nutrition. I know those sound related but they're way less related than you think.
> Most people don't believe it anyway
Maybe because so much of it is wrong, or (very charitably, as much is industry-biased) outdated?
Lifestyle modification is a definite challenge and I’m not dismissing it.
Still, hamburgers and milkshakes don’t give you heart disease and cancer. Overeating, oxidative stress from low-quality ingredients, etc might.
> hamburgers and milkshakes don’t give you heart disease and cancer
They absolutely do, particularly if you're getting most of your calories from them. If evidence-based medicine doesn't convince you, uh, hamburgers and supermarket milk tends to be processed.
They absolutely do not, unless you’re getting too many calories.
Individual foods are—with some exceptions—neither bad for you nor good for you. A healthy diet can occasionally include doughnuts, and milkshakes. Your overall diet is what matters.
Most green vegetables you can eat unlimited amount and stay healthy. They are absolutely "good" food. (Please don't reply with something trite like "oh, but what about the pesticide residues?") The same can be said for high fiber (soluable and insoluable) fruits like apples, oranges, and bananas. As long as eaten whole (minus skin for oranges and bananas), it is almost impossible to overeat these and they are absolutely "good" foods.
Sure, they are not mercury-level toxic. However, these recommendations are for people who consume way too much of these dishes, and it's a safe assumption that this is the case for a significant part of the population.
Sure. We’re saying roughly the same thing. For most Americans, hamburgers cause heart disease because we don’t exercise enough or eat enough plants. If you’re backpacking twenty miles a day, sure, eat whatever, you won’t suffer inflammation or obesity from it. (Though you may run nutritional deficiencies. And you’re building bad habits for when your activity necessarily tapers off.)
Hamburgers are not causing heart disease and diabetes for most Americans. Bad diets loaded with too many calories, too many saturated fats, and too many simple carbs are.
Messaging matters. When you tell people hamburgers and bacon and everything they love are bad, they stop listening, give up, or just eat some other junk that wasn’t prohibited. When you tell them some foods are good, they start buying into superfood marketing.
Diet is the only thing that matters. Lots of veggies are extremely useful because they add bulk without adding calories, and along with fresh fruits are great sources of fiber. Cheeseburgers can only come so often because they’re extremely calorie dense and send enormous reward signals to your brain.
Give people the tools they need to thrive, not just “don’t eat these specific bad foods, eat these specific good foods”.
Agreed (remember where I said overeating). Non-homogenized gently pasteurized milk/cream with minimally processed honey or maple syrup, and fresh ground hamburger, all of which which you can definitely get at supermarkets by the way, are much better for you than Big Macs and McFlurries. Ask yourself why? It’s obviously not “because they aren’t hamburgers and milkshakes”
I agree 100% with your follow-up. In the last 30 years of medical research, I do not recall anything but negative health results from eating red meat (beef). The real culprit is saturated fat. It is the cigarettes of food. There is almost no healthy level to consume, so keep it to 20g per day or less.
Reading this chain of responses from the original is making my internal bullshit alarm (Brandolini's law) go "wee woo wee woo".
> The real culprit is saturated fat. It is the cigarettes of food. There is almost no healthy level to consume
Not at all an expert, but from what I understood saturated fat isn't particularly good but it's not “no healthy level to consume” either (fortunately because you practically cannot avoid them).
I think you're confusing them with trans-insaturated fat (which I don't think are as bad as cigarettes either, but are still bad).
Hat tip. Good point about trans-fatty acids. That was all the rage to label and remove them about ten years ago.
> Still, hamburgers and milkshakes don’t give you heart disease and cancer. Overeating, oxidative stress from low-quality ingredients, etc might.
What? “Oxidative stress”? Oh come on, at least go full “seed oil” if we’re going to talk nonsense.
We already left the land of reason far behind by the time OP implied hamburgers and milkshakes give people cancer.
Red meat is a carcinogen, I don't know what to tell you.
Everything is a carcinogen. Even water. Dose matters, and most of the "omg zomg causes cancer if you eat it!" dietary nonsense purposefully omits absolute amounts or base rates, lest you realize it's actually as likely to give you cancer as smiling at people.
I don't know what else to tell you. Except maybe that if one gets this single concept, that quantities matter, it becomes immediately apparent why most of the "healthy eating" / fitness fads is just pure bullshit.
Depends on the nutrients that comprise them to the extent they contain a lot of omega-6 or not. Not heart disease so much but the other killer - might as well mention in this context. 'A high omega-3, low omega-6 diet with FO for 1 year resulted in a significant reduction in Ki-67 index, a biomarker for prostate cancer'. https://doi.org/10.1200/JCO.24.00608. Also Prostate Cancer and Prostatic Diseases (2024) 27:700 – 708 'Our preclinical findings provide rationale for clinical trials evaluating ω-3 fatty acids as a potential therapy for prostate cancer'.
Seed oils are not as bad as painted but some caution is needed given for instance the industrial processes used to bring them to market sometimes. Plus the way the oils are cooked when they create free radicals. This is not nonsense.
You don’t have to wonder. It’s public record that 45% of the FDA’s budget incomes from user fees that companies pay when they apply for approval of a medical device or drug.
In the drug division specifically, the number is about 75%.
Naive question: What is wrong with this? Lots of gov't agencies in highly developed countries operate similarly. User fees account for a non-trivial portion of department budgets. A more simple example: Should the Dept of Motor Vehicles (DMV) charge zero, low, medium, high, or infinity money to get a driver's license?
In principle there is nothing wrong with it, as long as the FDA or other testing body retains an appropriate impartiality or lack of bias (perceived or real). The issue, however, would be a lax system that allows revolving door access between the approval body and the industry that is seeking approval. Ironically, the common refrain becomes that their industry specific knowledge means they "must" be the only possible candidates for the role, which just so conveniently starts the revolving door swinging between leadership in industry and upper roles in regulatory bodies.
Every primary care physician I have ever had has discussed nutrition with me.
All but one I have had did not, and his suggestion to eat something other than cheeseburgers every day was less than revolutionary.
When I brought it up with other physicians the answer was always that I probably get all the nutrients I need from regular food. Whatever that may be.
Dietary changes have helped me feel better and healthier and perform better, and a few vitamin and other supplements as well.
I’m not selling a lifestyle. I’m criticizing the foolishness of a food and drug industry based in the idea that preventing death or lifelong disability is sufficient.
Nutrition is run on fads - see whole fitness and healthy food bullshit. Nutrition supplements ended up being a loophole that allows pharmacies and pharma companies to sell all kinds of random stuff that they can't or don't want to, show is safe, or doing anything at all.
I wonder what will come after the protein boom? My guess: Fiber is back because you need to "fibermaxx" when taking GLP-1 antagonists. I can remember some of the funny adverts in the 1980s of old people taking fiber supplements to "stay regular". (See SNL comedy skit "Colon Blow" for a good laugh.)
Medicine doesn't ignore nutrition, you just don't like the answers.
And it shows on the research: e.g. does creatine help muscle building? No.[1] But cue some anecdote from someone where they also changed a dozen other things at the same time but are sure it was that.
[1] https://www.unsw.edu.au/newsroom/news/2025/03/sports-supplem...
Creatine is probably the most well-studied nutritional supplement we have, and one of the most efficacious. You are presenting a single study to counter that. Not even a meta-analysis, but a single study of just 54 participants who did not exercise at all previously (from the study; "Apparently healthy individuals, with a body mass index of ≤30 kg/m2 and not meeting current physical activity guidelines of at least 150 min of moderate-intensity exercise were included. Individuals who undertook [resistance training] within the previous 12 months were excluded"). The general consensus is that it is absolutely helpful in muscle-building. See, for example [0] and [1]. Beware the man of one study. https://slatestarcodex.com/2014/12/12/beware-the-man-of-one-...
[0]: https://pmc.ncbi.nlm.nih.gov/articles/PMC12665265/ - Meta analysis results; "after intervention, the Cr group exhibited significant strength gains"
[1]: https://www.mdpi.com/2072-6643/17/17/2748 - "A total of 69 studies with 1937 participants were included for analysis. Creatine plus resistance training produced small but statistically significant improvements... when compared to the placebo."
But there's a core problem with this, in many states doctors are legally forbidden to give nutrition advice. The academy of nutrition and dietetics has worked very hard to make it so that only dietitians can provide nutrition advice. Take Ohio for example, a medical doctor in Ohio is legally forbidden and actually in jeopardy of losing their license and going to jail if they were to provide nutrition advice without a dietetics license. Dietitians are not doctors, but the academy of nutrition and dietetics wants you to think they are.
> Dietitians are not doctors
And doctors are not dietitians.
Doctors in the US receive an average of under 20 hours of training in nutrition over four years of medical school. What little they do receive is often focused on nutrient deficiencies rather than on meal planning for health and chronic disease prevention. Less than 15% of residency programs include anything on nutrition.
To become a registered dietician requires at least a Master's degree in dietetics or nutrition or a related field, and at least 1000 hours of supervised internships.
PS: before any Europeans hold this up as an example of the poor US health care system, doctors in Europe average 24 hours of nutrition training.
Aren't doctors actually exempted specifically from such regulations in almost all states? AFAIK they can actually give nutritional advice legally in nearly every jurisdiction in the US.
Mmmm, regulatory capture and rent seeking. Will it ever end?
To your first point, if you know where to look, you can get tens of vials of GLP-1s that have much higher dosing per vial for cheaper than you can get a third of the amount on the grey market. A lot of these sites even have purity testing to soothe consumers worries that they're getting garbage. For your third point, you have the FDA limiting HGH, yet you can buy the growth horomone releasing factor peptides (tesamorelin, sermorelin, ipamorelin) after doing a simple Google search.
As for broscience, moving into peptides was a logical next step after exhausting anabolic steroid "research". In fact, I'd say that biohackers are actually behind the bros when it comes to trying various peptides out and documenting experiences.
Many of us would appreciate if you could share one of those reputable vendors with such cheap prices
https://t.me/qsctgchannel https://t.me/c/2680146932/9
My Gmail username is the same as my HN username, for anybody who needs a reliable source with lab test results.
A lot of people are left alone with their health-issues, if you live in Canada and can only see a doctor if you are about to die, people try to change their health situation outside the "regulatory" system. These aren't health worriers, they are desperate to get their lifes back in order. Are there risks? For sure, but similarly untreated pain can damage more, especially mentally.
Wouldn't it be better to use verified medicine? Even if a patient could see a doctor at any time, the doctor would not prescribe such unverified peptides to the patient
I take a small issue with the claim that we don't test peptides. Some of us test them extensively before injecting. Granted, probably the same people who also understand how little science there is backing up most of the popular peptides today. I enjoy being able to buy my own GLP1s, however, at least those which have made it through phase III trials succesfully. As tempting as the claims are about things like BPC-157 and such ... no thanks, that is past my comfort level a good bit.
So you agree that this whole topic is in a sliding scale of lunacy, youre just on the saner side a bit?
The worst part that this article does not cover its kids and young adults who are sharing the "evidence" and "how to hide peptides from your parents".
Cellular peptide cakes are delicious with mint frosting.
I have it from good authority.
> My patient is refusing a drug studied in 170,000 people because of side effects that a 124,000-person analysis just confirmed do not exist — while injecting a compound studied in 14 humans, from unregulated sources, based on the recommendation of someone who profits from selling it. She’s probably not the only one. And those using it believe they are “doing their own research.”
Ok, and? At worst you waste a couple hundred dollars and deem the alternative therapy not worth it and go back to your doctor but I know dozens of people at my gym that used BPC 157 and TB 500 that fixed their chronic tendon/joint issues within weeks of starting the therapy that physios couldn't fix for years.
> At worst you waste a couple hundred dollars
At worst you inject unknown substances into your bloodstream that could do more or less anything.
> I know dozens of people at my gym
I don't think I even know dozens of people, full stop, let alone well enough to talk to them about their peptide use.
I go to a gym that has IFBB pros and people competing on elite powerlifting level, steroid and peptide use is an every day chit chat topic.
That does not seem like an environment we should use to determine if the rest of the world should take a substance lol
But I'm not saying everyone should be taking these peptides, I'm not coercing anyone, my original point was that people like the author of the article should mind their own business what other people choose to do with their own bodies.
The group of people that seem to be dying in their 30s of heart failure then
He's the guy that's selling them peptides.
You know dozens of people from a single place that have chronic tendon/joint issues?
Yes? These types of injuries are common among bodybuilders and powerlifters.
Pfft -- they're common among anyone over 30 who exercises!
> they're common among anyone over 30 who exercises
They shouldn't be. If someone has chronic tendon or joint issues, that's something to discuss with a doctor and a trainer.
It's very common when people start doing a new exercise regimen. Muscles can become significantly stronger on a timescale of months, while an equivalent increase in the strength of tendons happens on a timescale of a few years. Once somebody has a few years of training under their belt, muscle mass gains are way slower and the capacity of the ligaments will have caught up and these issues go away. However, with bodybuilders and strength athletes these problems can easily come back once anabolic steroids are involved and give big muscular gains without the same level of adaptations in connective tissues.
I think we are, and I'd presume that's why sports medicine centers are so common.
I don't doubt it. You make casual friends sometimes at certain gyms, especially if any sort of sports are involved like tennis or even group classes.
I am a super introvert and know at least half a dozen folks with such issues, more if you include my close friend group.
Any place that has a lot of physically active people stressing their limits a bit is going to have a lot of injured folks over a decent period of time. And of course it gets talked about quite a lot, since it limits performance and ability.
My trainer knows I have a chronic shoulder issue, and an adductor issue at the moment I'm working through that we need to avoid stressing too much. The few other folks who tend to work out around my schedule know of this, and I know of theirs.
Not very uncommon really.
Hang out at a BJJ or MMA gym for a bit, and you'll find plenty. Peptides are really popular in combat sports circles, with good reason.
Sure. He says that they commonly use steroids. It's no wonder they have degenerative joint disease.
You should hang out at a climbing gym sometime. There is nothing that unites climbers more than injury talk.
It's often part of the life if you're lifting competitively.
My partner's grandfather died of cancer because when he was having pains they believed their homeopathic medicine would work. When he finally when in to see a real doctor it was too late. If he had gone in earlier, he would been able to have a chance. This is not a rare occurrence for these types.
Why would you stop going to a real doctor though? It's not one or the other.
I'm very on the fence over BPC-157/TB500, I really want to see some actual clinical trials ran on it. I have a feeling the effects are overstated, but I also have had a number of "insider" conversations where I know these and other compounds are very much being utilized in pro athlete injury recovery programs. Those athletes certainly are getting state of the art medical care via traditional sources, plus elite level physio therapy - so it's hard to say if the illicit injury recovery drugs are doing much or not.
I don’t think either of those are patentable so I doubt you’ll see studies or trials any time soon. A lot of strength athletes at all levels, not just elite, are absolutely convinced of their efficacy and their usage sometimes seems as common as ibuprofen.
I used those two in combination to fix pain after 3x surgeries to repair a torn pec + infection. They work and helped me heal from being at a 3/10 constant pain down to baseline.
Not something I would do at any point for fun. But anecdotally, it's materially better than other alternatives offered/available.
> Ok, and?
According to our new AI overlords, a short synopsis of potential risks of BPC 157 based on mechanistic and animal work to date (don't know human risks because there haven't been sufficient clinical studies):
* Possible pathologic angiogenesis (abnormal blood‑vessel growth), which theoretically could support tumor growth or inflammatory and autoimmune processes. * Modulation of nitric‑oxide pathways that, at high levels, might contribute to anemia, altered drug metabolism (CYP enzyme activity), and possibly neurodegenerative processes in theory. * Concerns that its pro‑healing, pro‑growth signalling (e.g., FAK–paxillin) could encourage cancer spread if malignant cells are already present; this remains theoretical, with no proof in humans. * Possible liver and kidney toxicity suggested in some commentary and extrapolated from preclinical work, but not well characterized in people. * Immune reactions or allergic responses, including fevers, rash, hives, muscle aches, or systemic inflammatory responses
These do not appear to be results that would appear overnight. It would be "nice" if the folks injecting random shit into their bodies also disclaimed any subsequent medical intervention as a result of said shit, but that I suspect that's unlikely.
My total layman view is that powerful drugs often have powerful side effects.
That's because you grew up in a society still deeply coded to puritan moral viewpoints.
People for so upset that GLP-1 has no long term side effects.
There's still the crowd completely sure everyone will get HyperCancer in 10 years or something (they won't).
We have no specific reason to believe there are concerns with GLP-1s for cancer or anything else, beyond the mildest signal in rodent studies around thyroids.
We do not have robust clinical data for things like BPC-157 but we do have strong preclinical data and an understanding of the mechanisms in play.
I use BPC-157/TB-500/Ghk-CU/KPV - so I'm certainly OK taking the risks. But those mechanisms mentioned before? The same things we're counting on for healing and inflammation reduction are the same things that we know can cause an increase in tumor growth rate and chance of metastasizing. VEGF/VEGFR2 expression are even suppression targets for some cancer therapies.
Are there powerful and useful medications out there, available today, that we both don't have good scientific data on and are free enough of serious side effects? For sure! Is everything out there that, though? No. Some things that work will have too serious of a side effect profile to be feasible. Some things won't work at all, despite however much anecdata is out there.
As for the general idea... I agree there's no law that says a medicine with a strong positive effect must also have strong side effects. And we have plenty that don't - statins, particularly the latest generation, like pitavastatin, are effectively side effect free for the hugely overwhelming majority of people and have great lipid lowering effects. Even older ones showed extremely minimal incidents of things like muscle pain - a vanishingly small number of people relative to the total amount on the medications report muscle pain, and when investigated, quite a lot of even that ends up being unrelated to the statins. Yet the narrative persists that make it sound like anyone on statins is going to have their muscles ache 24/7
I'm glad we have GLP-1, and I don't think there are really major side effects. But they are ineffective outside clinical trial setting for treating obesity.
It seems to be like treating alcoholism with disulfiram: it's a miracle in clinical trials but in the real world the patients just lower the doses or discontinue treatment after 1-2 years and go back to their old habits.
> But they are ineffective outside clinical trial setting for treating obesity.
This is one of the wildest claims I have ever seen on this website.
Would you claim insulin is ineffective outside of clinical trials for treating type 1 diabetes because people have to keep injecting it?
I hope it sounds less wild if you think obesity as disease of addiction. Reducing GLP1 dose can increase the enjoyment in eating, so it makes sense why treating obesity with GLP1 is like treating alcoholism with disulfiram: Effective in theory but hard to adhere outside trials.
Type 1 diabetes (or majority of diseases) doesn't involve addiction.
It is not ineffective outside of clinical trials. All the evidence says that people gain some weight back after they discontinue treatment - which is not a lack of efficacy. But they also usually gain back less then they lost.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12361690/
It's kind of two separate topics: 1. Whether patients can adhere to GLP1. 2. Whether discontinuation leads to weight regain.
> they are ineffective outside clinical trial setting for treating obesity
This is totally false. I know a number of people who took GLP-1 to treat their obesity and then stopped and have stayed not obese.
I can't reply elsewhere so I will reply to this again.
> In my friends, all of them stopped taking GLP-1 drugs within 2 years because all of them lost the weight they wanted to. Out of curiosity, what sources lead you to believe this?
Anecdotes like this are interesting but in medicine they are not sufficient to make factual statements about drugs. In meta-analyses there is weight regain which is steeper as more weight is lost during treatment [1].
The weight regain seems to be rather slow, it can take years until the baseline weight is reached.
[1] https://www.bmj.com/content/392/bmj-2025-085304
> In meta-analyses there is weight regain which is steeper as more weight is lost during treatment
What does "steeper" mean? The studies I've seen show a net weight loss, even after regain, for the median patient.
> The weight regain seems to be rather slow, it can take years until the baseline weight is reached
Maybe. Right now, however, the evidence shows solid effects outside clinical settings. Your original statement was wrong–your sources own refute the claim.
If you're arguing the effects in the real world haven't consistently been as ridiculous as they were in clinical trials, sure, you get a brownie point. But broadly speaking, these drugs are terrifically effective, both when taken for life and when taken intermittently.
If only there were a federal administration whose responsibility it was to collect data about food and drugs so we could rely on something more than anecdotes from random strangers on the Internet.
Do you have a link to those data showing GLP-1 agonists are ineffective?
I emphasize it's like the drug disulfiram: Very effective as long as patients take the full dose, but the lack of real-world efficacy stems from the difficulty in adhering to the treatment.
This study found that 84.4% non-diabetic patients stop taking GLP-1 drugs within two years. https://jamanetwork.com/journals/jamanetworkopen/fullarticle...
> the lack of real-world efficacy stems from the difficulty in adhering to the treatment
Do you have a source for this "lack of real-world efficacy"?
> This study found that 84.4% non-diabetic patients stop taking GLP-1 drugs within two years
"With a with a median on-treatment weight change of −2.9%" [1]. Of those who discontinued and experienced "weight gain since discontinuation," they were "associated with an increased likelihood of GLP-1 RA reinitiation."
I'm genuinely struggling to see how this source shows real world inefficacy. In my friends, all of them stopped taking GLP-1 drugs within 2 years because all of them lost the weight they wanted to.
Out of curiosity, what sources lead you to believe this?
> it's like the drug disulfiram
Have clinicians made this connection?
[1] https://jamanetwork.com/journals/jamanetworkopen/fullarticle...
You didn’t come here with data. You came here with anecdotes and asserted that they were conclusive.
Have you ever looked at leaflets attached to any medicine prescribed by doctors?
You mean the ones that are the result of experience through controlled clinical trials with statistical analyses and error bars, yep, sure. I guess I have a bit more faith in those leaflets and the testing regimes that generates them than the word of some gymbro or influencer who injected themselves and didn't immediately fall over dead.
[dead]
Reminds me of some family members, all about organic, no seed oils, no plastics, no using 5G, no EMF, no fillers, no preservatives, no stabilizers, no emulsifiers, etc.
And yet they use unhealthy amounts of avocado oil, consume unhealthy amounts of “good fats.” They discount caloric intake and solely focus on eating loads of what they consider to be good food.
Patent Medicine
https://en.wikipedia.org/wiki/Patent_medicine
I really enjoyed having to wait 30 seconds for Cloudflare to let me into this website.
I think if you're a cloudflare customer they set a cookie in your browser that let's you bypass the waiting period. Just wait until next year when they show ads during the wait.
With India getting generic GLP-1s, the tech to "print" peptides will probably see costs fall off a cliff, so we're probably only looking at the tip of the iceberg with the amount of damages the reddit biohacker bros will accomplish. Men especially are feeling a lot more lonely and image-conscious and there are peptides people claim make them taller[1] or muscular[2].
1: https://www.reddit.com/r/endocrinology/comments/1jb2cce/grow...
2: https://r2medicalclinic.com/best-muscle-growth-peptides
These peptides are already relatively cheap, here's one US domestic source: https://imgur.com/a/OXOkSdR
$120 for 10mg of reta is highway robbery.
Yeah I'm always amazed at what they can get people to pay for individual vials. I buy kits of 24mg reta for ~280. And that's not the cheapest, for certain.
Pretty sure the last time I bought some it was more like $10 for 10mg.
> a patient who is discontinuing her statin therapy - very inadvisably, given the clinical presentation described - but is enthusiastic about “BPC-157”
This feels new. I thought the methylene-blue-for-cancer types continued their medicine while taking other things as extras.
Personally, I've swung over to the laissez-faire side of medicine. At the end of the day, if you're an adult, it's your body. You should be given the chance to educate yourself. But if you want to inject yourself with a prion, like, go for it. Maybe you won't fuck up your own research.
(Marketing should be tightly regulated, possibly banned.)
Exactly my point of view. Medications are like drugs, if we failed to forbid it we might as well allow it but regulate it, aka make seller accountable for the purity.
> Personally, I've swung over to the laissez-faire side of medicine.
Chesterton’s Fence rears its ugly head again. This is the same thing as vaccine skepticism (those diseases can’t be that bad, I never hear about them killing anyone these days) applied to a different context
Arguing for modern reforms is one thing, but there’s a reason we have the FDA. Statistically, most individuals do not have the medical expertise or the desire or ability to wade through enough clinical data to make these sorts of decisions with any hope of good outcomes, particularly in the face of an entire Internet of people trying to push questionable substances on them.
>I thought the methylene-blue-for-cancer types continued their medicine while taking other things as extras
There's no way you don't know that for example Steve Jobs ignored his cancer until it killed him because of absurd beliefs about "health". Surely you know about cancer patients dying because they found someone who promised them a cure rather than their doctor offering them a 60% chance through immense pain and struggle.
>Personally, I've swung over to the laissez-faire side of medicine.
We had laissez-faire medicine. It cured almost no one and killed hundreds for no reason. We HAVE laissez-faire medicine. There's almost no regulation in the "Supplements" aisle.
So why doesn't it work?
> For a chemist, “peptide” has a pretty clear definition: any relatively short chain of amino acids, and when they get longer we go ahead and call them “proteins”, although the dividing line is a matter of personal opinion.
So, it is not just chemist but molecular biologist too. And the above is also not entirely correct. Yes, the author refers to size as threshold, before something is called a "protein". But the term protein has additional meanings that a peptide does not automatically have. For instance, a protein typically has a specific 3D conformation. It may be "sticky" after degradation or unfolding, but for the most part a protein is something with a 3D structure. A peptide does not necessarily imply the same. A protein may also have several polypeptide chains - insulin is a simple example for that: https://en.wikipedia.org/wiki/Insulin#Structure (A and B chain)
> So the number of different possible peptides is just ridiculously huge.
That's no surprise either - that's due to the code used. You add to the code, so of course length plays a role, as does the variety. There is a DNA->aminoacid mapping. The first has four possibilities per slot; the latter 20 (or more if you include e. g. selenocystein or pyrrolysine; and you have various post-translational modifications too, so you have more variety per slot).
> For comparison, it has been about ten trillion seconds since Homo sapiens emerged as a separate species.
The whole species concept is IMO outdated. It was created before people knew that DNA codes for the complexity in pretty much any species (excluding RNA viruses but they have reverse transcriptase, at the least some viruses, so ultimately RNA->DNA).
> The other one (by Sarah Hood) relates all this to RFJ Jr.’s advocacy. The flip side of “the government shouldn’t be able to force me to vaccinate my kids” is “I should have the right to take whatever medicines I want to without the government getting in my way”.
I don't see why that would be questionable. Would people do as Trump tells them to do? I would not. If you see Trump as a lobbyist, how many private interests may his government have? If they have a commercial interest then their statements may be biased.
> You don’t have an LC/MS or an NMR machine in your garage, so you can’t be sure what it is you’re really injecting
Right, so the whole system depends on trust. This is already a problem because you have to trust not only the government but ALL who were involved in scientific publishing. There were lies told in science too: https://en.wikipedia.org/wiki/Retraction_in_academic_publish...
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Is there any evidence supporting the claim there is a significant overlap between the group of people who "refuse injections the government recommends" and the group of people who take "peptides"? The article is carefully crafted to evoke this impression without clearly stating it, listing only anecdotal evidence.
RFK Jr using the blue dye stuff for one thing
“Blue dye stuff” meaning methylene blue? Ironically that is one of the most extensively studied compounds in medicine, with hundreds of clinical trials over 100 years…
That doesn't support the claim that people who take peptides are anti-establishment.
How?
I imagine the entire Joe Rogan sphere with being anti vax (or vax skeptical)... While promoting a billion supplements.
*anti untested vaccines - people should be skeptical of untested vaccines, just like peptides.
Which untested vaccines are regularly given to patients?
He means the COVID vaccine but knows people will make fun of him if he says what he actually believes so he's playing pretend like there is some plague of untested vaccines being used instead of there being one fast tracked vaccine deployed in response to a massive pandemic
Indeed, but that’s not the point: many anti-vaxxers are against all vaccines, irrespective of how they were tested. (And will argue against e.g. the FRA approvals.)
But you confuse that set of people with people who don’t know want to inject untested vaccines into their body.
(I don’t)
I’m genuinely not aware of a DIY or grey market in vaccines. Peptides, yes, but vaccines?
In the absence of this, I suspect you’re either confused or straw-manning…
I was referring to the MRNA vaccines, which were relatively untested when released to the public. Suspicion of that is very reasonable.
Okay; noting that the argument has moved from "untested" to "relatively untested".
To clarify, is your concern the inadequacy of the approval process FDA uses for (all) vaccines (noting that many vaccines --e.g. influenza-- are refreshed on a fairly regular basis to account for new strains of viruses) or something specific to approval of the MRNA vaccines?
Or is it that MRNA vaccines were a new approach for vaccines more generally, and so there wasn't/isn't the same long-term data that there was/is for multiple generations of vaccines based on older technologies (viral vector, toxoid, etc.)?
It has a certain logic to it, and I think US tipping culture basically follows the same rules.
Even if you almost always end up paying the bill + 20% tip, Americans like the idea that they could not pay the tip if the service was bad.
The appearance of free action is appealing and preferable to being forced to pay the extra amount, even if you almost always pay the amount willingly anyway.
In my experience, everyone who defends tipping culture is defending not paying the tip. I don't buy this idea that someone likes tipping culture and still pays it. After all, you're free to tip anyone you want regardless of culture.
The problem is it is so ingrained in US culture that switching to tip-free has generally failed where tried, even in pro-labor lefty hoods in blue cities.
Numerous restaurants in NYC tried and flipped back over the last 10 years. Restauranteurs reported illogical / innumerate behavior where sales went down when they switched to untipped higher prices.
https://www.eater.com/21398973/restaurant-no-tipping-movemen...
The only restaurants that it stuck were Japanese restaurants that cater primarily to Japanese ex-pats, because culturally its familiar to them.
Well sure, it has to be mandated through law or underpaying workers will inevitably outcompete those that pay workers. I don't think that's an argument that anyone likes tipping culture (except wait staff in bougie cities).
I remember when Uber first came to Austin, one of the big draws was that a tip wasn't expected. The app didn't even allow it IIRC and Uber sort of advertised this as a feature. 15 years later, back to it, tips seem expected again?
Oddly enough, the fact that I was initially sold a product where a tip wasn't expected has made me continue to not tip Uber drivers. Not sure what that says about me.
I actually like tipping culture because it makes me feel generous and charitable, not because there's some kind of weird master/servant relationship. I even make it a point to passive aggressively tip well when service sucks because who gives a shit?
The world is full of people that confuse contrarianism for intelligence.
HN, in particular, loves anything that allows them to discredit science (like the constant banging on about the replication crisis) and replace it with their own pet theory.
Is HN particularly drawn to this over other platforms? I gotta say I don’t quite recognize this. In general, I think there’s a good dose of respect for science around these parts, but maybe I’m blind to it.
I don’t think HN discredits science a lot, especially when compared to other platforms.
I see a particular strain more often here and in “rationalist”-adjacent spaces. It’s essentially anti-intellectualism dressed up as intellectual curiosity and debate.
Come on, just admit that you are not able to follow the debate instead of criticizing it from the outside without understanding it.
I think it’s also that contrarianism generates an argument they can follow - it’s often much more simplistic along some axis. For example, flat earthers superficially have a really simple model. Throw a ball up, of course it comes down. You look straight ahead and it looks flat. Ask them how GPS works and they can’t follow the math anyways.
>The world is full of people that confuse contrarianism for intelligence.
I've been shouting this from the roof tops for years now and it's one of the biggest problems we face today. I live in a rural area and 100% of the Joe Rogan-ified men I know are mindless reactionaries. They aren't educated, they don't read books, they don't travel, heck, they barely leave the county. They think they're so smart because they say no to everything anyone else says. They never offer solutions. They never try to fix things. They barely even vote. If you say the sky is blue they will say it's green because they're just oh so smart. It's a massive massive problem.
As opposed to this, you have the mindless non-contrarians who unquestioningly believe any assertion by academia or authority, which is a problem too.
I feel like you're completely proving my point here.
Well I have a PhD and have published lots of papers, so I like to think I am educated lol.
And I should unquestioningly believe you? :P
I mean, from a position of critiquing non-contrarians you shouldn’t in general. But me specifically, everyone should believe me lol.
I have recently been through the rabbit hole of peptides and most of the people engaged or involved in peptides seem to be healthy individuals. There are some exceptions like lookmaxxers and anti vaxers. The vast majority of people are normal and majority are outside of USA where anti vax sentiment are not in vogue. Some explore peptides for their dogs and cats too.
To assert that people are sad and anxious while not putting the effort to understand the people involved is such an intellectually lazy position to hold.
Extra points for people partying hard on shady synthetic drugs, but being actively anti-vax because government. Case in point, Miguel Bosé, a very well known spanish artist that spent the first 50 years of his life abusing everything except heroin (his own words), but now he is a vaccine negationist, for him and for his two children.
A lot of these peptides are designed to optimize bodies. And a lot of these people suffer from OCD - often a similar type to anorexia. No, it is not normal to intrusively think about your body every few minutes, most people that you see around you do not think about their bodies more than maybe once a day, when they look in the mirror after a shower. And maybe not even that.
"Antivaxxer*" here. I'm not injecting peptides for a similar reason - I'm not convinced the cost/benefit works out. That said, the issue for many is autonomy - if you want to put novel stuff in your body, go ahead. As long as you don't try to compel me to do it.
* Not if we're actually in literate company, but that seemed to be the common consensus after I skipped the jab, having recovered from covid right before the shots became available. Nevermind that my doctor was on board and I've had all the other ones (minus the flu shot). I was still a selfish grandma killing Republican who probably voted for trump to the commentariat.
> That said, the issue for many is autonomy
Your right to swing a fist ends where the other fella's nose begins. That doesn't mean you aren't free, it just means you recognize that the right not to suffer grievous bodily harm trumps the right to swing your fist willy-nilly.
As a fist-swinger you may not always agree, and you may even get hurt one day because you couldn't swing your fist whenever you wanted, but that's just the cost of living in a world filled with other human beings.
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I appreciate why you might feel that way. It's reasonable for reasonable people to disagree, but in this case the experts we trust to decide these things decided that you were the one who presented a danger to society. I seriously doubt that you have the sort of medical credentials that would be required to get any serious person to take your word over those of the world class epidemiologists, virologists, etc who said the opposite.
Regardless of correctness though, even if they'd been wrong it's just part of life that sometimes you have to go along to get along. There are a lot of things I disagree with society about, but I depend on society to live. It would childish to try not to participate.
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You can at least draw a somewhat tortured connection between "anti vaccine" and opting out of receiving a specific vaccine (for logical reasons, with your doctors approval, though are they even a real doctor if they approved such a thing?).
But using the word "jab" or criticising the medical industry making you anti vaccine is the kind of thing I was talking about when I mentioned literacy.
The vibe you're getting is that I'm blaspheming. I'm saying things that probably hundreds of millions, possibly even billions of marketing dollars were spent to discourage being said.
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No, all I have to do to make it clear is say "I'm not opposed to vaccines as some kind of principle, ideological or otherwise", and then you can either believe me or not.
That's what anti vaccine means, despite all the efforts to redefine it. It doesn't mean "won't recite the marketing materials for a specific pharmaceutical product when prompted".
It sounds like you don't want to say that you think vaccines are generally safe. So, I'm going to go ahead and call you an anti-vaxxer.
Generally safe is meaningless in this context. That's not a reasonable way to talk about entire classes of drugs. All that matters is for a given person with a given medical history and context, does the specific drug have a net benefit.
Here's a good test case: have you had the rabies vaccine? If not, does that make you an antivaxxer? How about vaccines that have been pulled off the market? Are those no longer vaccines?
Something reasonable to say would be there are vaccines that have a net benefit, and you should take those if that applies to your situation.
This whole "say the slogan or you're an antivaxxer" is like giving kids the nontoxic glue because you know some of them are going to eat it. The adults in the room don't need this shit.
I don't care what "slogan" you say, I'm just trying to see if you hold the opinions of an antivaxxer and for some reason you refuse to make any claim that would help avail me of that position.
Did you miss this one?
> Something reasonable to say would be there are vaccines that have a net benefit, and you should take those if that applies to your situation.
It's a bit vague and I have to balance that out against a lot of stuff you've said so idk.
The article frames these supplements as being purely appealing to "anti science" people but I think that's really unfair. You can believe in medication, believe in science, trust government systems, etc, and still feel like you're not being served by the medically approved options.
It can also depend on people's politics vs who is on power. In general British anti-vaxers are left wing (very lefty affluent hippie types - you can see this from the areas with low MMR rates), and even more so during covid when a right wing government was in power. There is evidence for this in a survey KCL did of anti-vaccine beliefs during covid. I personally know of British students who declared they would not have covid vaccines because they "did not trust the Tories"
i mean, to be fair everything everyone is injecting, including prescribed medicines, are largely coming from Chinese (or Indian) factories. We don't manufacture much in the western world ourselves.
I think it's disingenuous to frame this exclusively in terms of the people who are turning down medically approved options for unknown supplements.
Dealing with doctors is kind of a pain in the ass. I was very sick a month ago and my doctor is pretty "anti antibiotics", he wanted me to go over for an in person check-in. This was after 10 days of having symptoms that I did everything reasonable to take care of. I got on a call with another doctor (at a perfectly reputable hospital) who immediately prescribed antibiotics. It took 5 days of antibiotics just to feel somewhat better - all while using saline rinses, showering, sleeping, eating properly, etc. I still have a lingering cough. I am very reluctant to take antibiotics unless it really feels necessary, this was easily the worst sinus infection of my adult life.
My friend wanted to try out a weight loss medication. Their doctor refused because they felt that my friend hadn't tried hard enough without it. So they got some from another friend who hadn't ended their prescription because they also were worried of being cut off. They've lost weight, which has motivated them to exercise more, eat better, and are generally happier and healthier.
From the article,
> Unfortunately, point two is that we barely have any of these effects worked out - at least not to the degree that you would want before you start injecting them into your leg.
This is what was said to a friend whose doctor took them off of one of those GLP medications, basically. They didn't have enough evidence to know the risks of continued use, even at lower doses.
The reality is simply that there's a big gap right now between what people want and what people have access to. The supplement industry exists to fill that gap.
Medical professionals can complain about users taking these peptides, but plenty of people are not "anti medicine" while still feeling underserved. If doctors aren't in a position to have these conversations, people will go to Youtube or wherever else to look for answers.
Personally, I have mixed feelings about a number of medications requiring a prescription. I frankly do not see why my doctor is involved in me taking a drug unless it would be negligent to allow me to or if it would have community health impacts (ie: antibiotic resistant strains etc). I'm an adult, if I've been properly informed of risks, etc, then I'm inclined to say that it should be up to me to pay full price for some medication or not.
I know plenty of people getting their GLP1 from compound pharmacies. None of them went their first, their doctors wouldn't give them the medication (sometimes they were just a pound under the BMI limit, often because they had been slowly losing weight) so they went elsewhere. These aren't anti-vaxxers who won't take their medication, they're people who want help and there's a gap that companies are taking advantage of. The medical establishment needs to find a way to address that. Right now the answer appears to be compound pharmacies and nurse practitioners.
> In my own view (and it ain’t just me) you also have regulatory agencies to force people to show that their drugs actually have some benefit before they can sell them, too. But that’s going further and further out of fashion. Can’t get ahold of the New Hotness to inject into your upper thigh if there are a bunch of stick-in-the-mud folks asking for human data, infringing on your freedom and all.
Many of us will be dead before there's a medically approved treatment for something. Hell, I got eye surgery before it was FDA approved - I'd probably be blind (or at least far worse off) if I'd waited the years it took.
How many people taking supplements are "naturopaths" who reject modern medicine as opposed to just people who want to be healthier? I really wonder that.
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It seems we are treating Peptides like drugs here. It's my opinion that amino acids regardless of how they are chained do not belong under and stricter regulation than food given I eat peptides every day from my food. Then again I do not believe in the concept of prescription drugs. Everything with a NDC code should be at the grocery store and I should be able to stock up on it without permission especially given how fragile global shipping is these days. Drugs risks do not enter into the picture given the fact I can buy ammonia and bleach along with a myriad of other dangerous compounds. Worse, I could crush up apple seeds from the veggie isle. One can also make just about anything using fourth thieves vinegar. Maybe put expensive high demand things like cocaine behind locked glass along with the underwear and condoms.
As a side note more dangerous than any drug is stopping a prescription drug cold turkey. Watch what happens when global trade to/from China and India are cut off for a year. Attitudes will change.
> given I eat peptides every day from my food
This is briefly addressed in the article, but basically it's one thing to eat a peptide and quite another thing to inject it. Your digestive system is extremely adroit at taking peptides and proteins and breaking them down into individual amino acids, which are then absorbed via "transporters" in the gut. (e.g. SLC6A14 for glutamate and cysteine.)
If you eat insulin, absolutely nothing will happen. If you inject just a little bit too much, you're dead.
So, generally: Ingested proteins/peptides aren't drug-like, whereas they can be extremely potent drugs if administered via injection.
Granted, there are exceptions. If you accidentally get a drop of botox into your mouth, you'll be okay, but if you drink a vial, you'll be poisoned. And people have been trying to make orally-active peptides and proteins for decades, with some noteworthy successes, however few and far between in the general case.
I agree with some of this. There are most certainly orally active peptides such as BPC-157 and its replacement PDA penta deca arginate that can repair the gut and still circulate throughout the body especially in those with leaky gut. People with leaky gut should be able to buy a clean source of BPC-157 or PDA without a prescription and without visiting dark alleys. It is very safe and tolerable.
GLP's are all the rage these days. Doctors seem to be giving GLP peptides out like candy and those are injected. People are looking like zombies. That said if doctors are going to be so liberal with them I should be able to buy it in the grocery store and slap it down on the conveyor belt. Again I can buy things far more dangerous than any prescription drug. There are very dangerous supplements, some that are shilled heavily on youtube. For example, Glycine (for me specifically used without a specific process) is more dangerous than heroine and the vast majority of doctors would have no idea what I am talking about.
> It is very safe and tolerable.
Can you point to the clinical trials that demonstrate this?
> Doctors seem to be giving GLP peptides out like candy and those are injected.
There have been several _thousand_ clinical trials that have shown GLP-1s to be safe and effective.
Also LOL at the notion "peptides are safe because GLP-1 exists".
Pretty much all venoms are mixes of short (10-15 base) peptide chains.
It's the naturalistic fallacy in an utterly perverse form ( and also goes to show why a regulatory system is good: the average person has no idea that they're dealing with or even common sense about it).
"Liquids are safe because water exists"
FDA is a money sink. People basically bribe to get their own self tests approved much like the airlines have their own FAA inspectors that approve their own self tests under duress and bribes. It's all a scam and everyone here knows this even if they won't admit it.
Nullify the FDA, FAA and at least half of the other orgs. Give at least half of those budgets to the people. Make aircraft smart enough to evade all obstacles. Make it technically damn near impossible to collide with anything. Make aircraft coordinate themselves. All doable. Force retire all FDA and FAA and give them a balloon, a golden wrist-watch and send them away.
Give people an app to paste in all the things they take or plan to take in terms of foods, supplements, drugs, their allergies. Let the best AI figure out what will happen.
Injected BPC-157 to a wound is a magic healing potion as far as I'm concerned. That it's not more broadly available is a crime, imo. If I had a billion dollars, I'd push so many things through the FDA.
If you had a billion dollars, you would need many billions more to push even a single thing through the FDA!
This is entirely theorical, but the $2.6 billion figure that's commonly quoted accounts for all the failures as well. If I took something that's proven in Europe but wouldn't get a patent, it presumably would manage to pass FDA regulations, it's just that without the patent protection, there's no financial incentive for an existing company to do that.
> > given I eat peptides every day from my food
It’s also just a silly rhetorical technique. The ability to construct a grammatical sentence of that form does not constitute a valid argument.
“Restricting nuclear material is silly given that nearly all the stuff I interact with every day contains atomic nuclei.”
> It seems we are treating Peptides like drugs here
That’s exactly what some biological drugs are too - peptides!
And peptides are just short chains of amino acids. Almost all the other biological drugs are just longer chains of amino acids - antibodies, enzymes, antigens, some hormones, and others.
Derek is right that the safety risks are exponentially higher when you inject peptides - you basically skip a bunch of protective mechanisms like enzymes that quickly break them down if taken orally or routes.
As a former R&D scientist there is no way I’d inject any peptide that hasn’t at least gone through a phase 1 safety study in humans. Otherwise you have no idea what it could be doing to your body.
A good example was a drug that was quickly pulled from market for causing fatal anaphylactic reactions. It wasn’t even caught in the clinical trials!
At the same time, I think people have the right to take whatever substance they want. But I worry a lot of people aren’t aware of the risks.
>As a former R&D scientist there is no way I’d inject any peptide that hasn’t at least gone through a phase 1 safety study in humans. Otherwise you have no idea what it could be doing to your body.
A lot of people do not understand the trial system or the value of Phase 0/1 tests when it comes to the substances that they put into their body. And thanks to the influencer/grifter/biohacker ecosystem that exists, more people would put their trust in accidental evidence, from people who's incentive it is to make money off of them, while complaining about the pharmaceutical industry operates off of a profit motive.
Yeah, but my mum is an eye surgeon and she wouldn't get LASIK. That's just how it is with people involved in the field.
The regulation of drugs or most any consumer product is not due to the inherent danger of an item itself, but the danger presented to a consumer inside the context of societal mechanisms that influence behavior. You're right that many regulations don't make sense outside of a societal context -- but that's because they also don't exist outside of a societal context.
The reason we don't need tight regulations on bleach is because we don't have a societal issue causing people to drink it and hurt themselves... at least, not anymore: most of the locking lids on household cleaning chemicals are there by law.
The reason we don't need tight regulations on bleach is because we don't have a societal issue causing people to drink it and hurt themselves..
I think you missed out on a long time period of 4chan. They managed to get a number of people to mix ammonia and bleach.
More people do this accidentally trying to clean something than have ever done it because 4chan told them to. Still, the incidence rate is low.
Maybe so. Still one would be amazed at how many people will follow extremely dangerous and dumb trends on the interwebs. Don't get me wrong, I see it as just a small part in the great filter much like I think we should remove all warning labels.
I'm all for laxer regulation of substance control e.g. buying cocaine at the grocery store, but I think its also a bit misleading to describe arbitrary sequences of amino acids as if they're meaningfully comparable to food.
That's like saying that since neither one nor zero requires regulation, neither does software. Maybe software does or doesn't, but in either case its best based on the nature of the aggregate, not the nature of its components.
> It's my opinion that amino acids regardless of how they are chained do not belong under and stricter regulation than food given I eat peptides every day from my food.
I mean, why regulate anything? Everything is just different arrangements of hydrogen and time. It's so weird that certain arrangements of hydrogen and time try to claim to have things like "morals", and try to force other arrangements of hydrogen and time to not do arbitrary contrived concepts like "murder".
All is one. Just hydrogen and time. Therefore everything should be legal.
> Drugs risks do not enter into the picture given the fact I can buy ammonia and bleach along with a myriad of other dangerous compounds.
This is a deeply weird take. You think anyone ought to be able to buy, for instance, warfarin and freely take it without a doctor’s involvement? We should let parents self-diagnose diabetes and administer insulin without a prescription or discussion? We should just hope that patients heard their doctor say hydralazine and not hydroxyzine?
> As a side note more dangerous than any drug is stopping a prescription drug cold turkey.
Abject nonsense. It was very easy to stop my prescribed amoxicillin. It’s clear you don’t have any actual idea what “prescription drugs” are, in aggregate, and that should maybe inform your decision to have Big Opinions about them.
You think anyone ought to be able to buy, for instance, warfarin and freely take it without a doctor’s involvement?
Yes.
Triple yes! Most of the people buying it have been buying it and using it for years.
Why do you think only the people taking it would be buying it?
> Why do you think only the people taking it would be buying it?
I don't. But the cost of access is significant. And with pharmacies in India, China and Mexico willing to ship basically anything into America, it's a purely-cosmetic tax now.
Why? Why, specifically, do you think an adult without HF should be able to buy a random drug, likely by accident, and start taking it?
I guess I don’t hate everyone else enough to agree with that.
Why?
No reason required. People can already buy incredibly dangerous things with a doctors permission, as if a doctor actually knows what other compounds a person is consuming to begin with. Doctors are not omniscient and patients lie. Most of them barely even know the compounds that are FDA approved to begin with. Be honest, most of them barely remember 10% of what they were taught in medical school and the schools even state that half of what they will be taught will not be relevant or will be entirely wrong by the time they graduate.
Again, I can buy apples and apricots without permission. There is nothing capable of more risk or harm that has ever been approved by the FDA than apples and apricots.
> This is a deeply weird take. You think anyone ought to be able to buy, for instance, warfarin and freely take it without a doctor’s involvement? We should let parents self-diagnose diabetes and administer insulin without a prescription or discussion? We should just hope that patients heard their doctor say hydralazine and not hydroxyzine?
Weird examples. You can buy insulin without a prescription today in the USA.
In much of the world -- including almost all of Asia, Africa, and much of Eastern Europe -- you can buy almost any drug without a prescription. The only exceptions are potent CNS stimulants or narcotics, and in some rare cases antibiotics.
This is legitimately a better system. Takes out the middleman.
In the US you can get any drug if you pay $120 and recite the magic words to a telemedicine "doctor."
Funny you mention this... I bumped into a VP of Merck at a conference and that's the exact example he gave: in the US, you can't adjust your own coumadin dosage without a M.D. consult, but here, have 200 doses of insulin to take home with you.
In much of the world -- including almost all of Asia, Africa, and much of Eastern Europe
Doctors in the US get a nice $200 to $500 per doctors visit, required to extend the prescription drug. I only notice because I pay cash. This is why they will argue against anything I am saying until they are code-blue in the face. I will leave them with my code brown.
In the US you can get any drug if you pay $120 and recite the magic words to a telemedicine "doctor."
That's how a number of us in a particular circle stock up on anti-biotics. That said anti-biotics are a last resort for me whereas I find doctors are quick to prescribe them.
Your argument is even worse lol. Obviously he's proposing that you can take your doctors note to the pharmacy and get what the doctor prescribed in addition to being allowed to self purchase behind the counter drugs.