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.
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?
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.
I have followed closely the research for many years and there has been false promise of good diagnostic tests previously. What I'm arguing for is that we need a test that is specific for ME/CFS. E.g. it will test positive for a patient with ME/CFS regardless of they are obese or not, but more importantly it will not test positive for everyone who is obese. This is known as the sensitivity and specificity of the test.
What I've seen in the past is some previous ME/CFS tests show positive for groups with related symptoms but who don't have ME/CFS. This then becomes a worthless diagnostic tool. For example this would not have helped your aunt.
Hope this explains my thoughts!
Thank you for clarifying and I wholeheartedly agree.
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?
Welcome to the powerful world of the placebo
> Peptides are a revolution and you don't need to know how they work to know that they work
But for self-use? Go right ahead.
Crack is really moreish.
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".
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.
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.
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 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.
Isn't one of the bigger problems with ChatGPT that it's much too supportive of whatever the human is talking about?
But it does require to know the bias that LLMs have ahead of testing this.
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.
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.
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.
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.
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!
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.