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03-27-2018, 11:02 AM #1
GW501516 - where are we now?
Okay, so I’m wondering about GW501516 aka Cardarine / Endurobol.
(Yes I know it’s now a steroid , but it ain’t a peptide either)
So, basically what i am contemplating about it is ofcourse cancer risk.
What really concerns me about this is that I read several places that the study showing rats forming cancer from GW501516 is cited as being equivalent of humans taking enormous dosages of aspirin.
As someone with over the average molecular biology know how, I can tell you that you DO NOT convert mg/kg in a rat to the same mg/kg in a human.
So if a rat dies after taking 100mg/kg, and is fine with 50mg/kg, IT DOES NOT mean that a human can take 50mg/kg and be fine. Not at all.
When you translate from animals to humans you take size and surface volume (and maybe other factors) into consideration as well.
If you look at LD50 (lethal dose for 50% of test subjects) for a given drug, and see what it is for different animals, you’ll often see something like this;
Rat: 100mg/kg
Rabbit: 80mg/kg
Dog: 60mg/kg
...
Elephant: LOL
You see where this is going right?
But other arguments against the cancer thing I’ve heard that makes more sense is that peroxisome proliferators act very different in rats vs humans.
I’ve also heard the studies saying it causes cancer to be methodologically flawed, however, unless I hear that from a doctor or molecular biologist directly I take that with a grain of salt, as I don’t know if the individual even understand animal to human conversion of drug dosages.
Sooo, what are your opinions folks?
This looks like a so fucking nice chem, except the cancer thing.
And that’s a big thing IMO.
I’m thinking of the star in the Spartacus series f.ex; who died after season 1. He was quite ripped and it wouldn’t suprise me if he had used tons of GW501516,
but that’s pretty much mere speculation on my part.
Point is, you never know, and cancer is a sneaky bitch.
Input from users and anyone having done their homework on this is most welcome.
And users, please tell me how much for how long. Hehe.
(Total)
Be happy and have a great Easter!!
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03-27-2018, 12:18 PM #2
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03-27-2018, 12:26 PM #3
The explanation i was given a lomg time ago was that there is a close genetic and biological comparison to humans and that there are alot of conditions in humans that could be replicated in mice and rats.
I havent done my homework on this one Doc, not very familiar, but interesting. Thanks for the heads up, Will keep my eyes open.
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03-27-2018, 12:32 PM #4
That’s a good point, it would actually be better.
But having had a first hand peek at animal experiments, there’s several difficulties.
The experiment has to be reproducible, and it has to be “ethical”.
That means that even rats has to be put under anesthesia not only for operations, but in an experiment for resistance training for ex. the rats were out under anesthesia when they electronically stimulated their muscles.
(And I totally agree with that)
Even though this isn’t painful as such, it isn’t comfortable either, and for a rat it surely is scary.
Also it’s cheaper.
An experiment with 100 rats is “better” than 10 pigs.
Except there are instances you don’t discover what you need in rats.
F.ex there was a drug called thalidomide that seemed like a wonder sedative drug... in rats.
Had they used pigs they would have seen the issue, or that is, had they used pregnant pigs.
So they prescribed thalidomide for morning sickness and anxiety in pregnant women.
Well, that caused the most massive incident of birth defects seen in the western world.
Babies born without arms and legs... yeah, they should have used pregnant pigs for that one...
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03-27-2018, 12:37 PM #5Productive Member
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The reason why i will never try it is....
Why would a big pharma company pull funding on such a great drug (it sounds absolutely terrific)?
If there was money to be made, and believe me there would have been, why pull funding?
Numbere gave the best explanation ill see if i can find his post.
The guys researching this drug will be the a+ scientists. The top of their field so i would think they would account for the fact that rats are lighter than humans and doses would vary accordingly.
Have a hard think before you use it.
Just my opinion obviously
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03-27-2018, 12:41 PM #6
I do remember reading about another ppar qgonist, gft505, that was a multiple sub ppar agonist, alpha-gamma-delta, that was in phase 3 trials in 2016. That could potentially be another one to watch if it gets through to the market. Not too much info out yet on that one either though
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03-27-2018, 12:59 PM #7
Big pharma pulls funding on drugs that compete with others or have the potential to do so.
They pressure the fda and countries drug regulation bureas into labeling them as harmful. You are seeing it with kratom. Already schedule nine in Austrailia and will soon be illegal in the US.
This is also why there hasn't been a cure since polio.
The polio vaccine only happened because the creator went behind the medical communities back and once he had the cure... He gave away the info to all interested.
Big pharma is a disgrace to medicine of all kinds.
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03-27-2018, 01:06 PM #8
Drugs allowed on the market only reach the market if if it is economically viable to the interests already in place.
This is why most people in the US who can, go to Mexico to get their medications for serious illness.
My grandmother for example has horrible, untreatable, acid reflux. She got meds in Mexico that totally made her normal until she ran out and now cannot even get it there any more.
Cancer awaits her now because of this.
$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$
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03-27-2018, 01:10 PM #9
This is the cure to disease and the way great medicine is made... A good man, circumventing the system, and not being greedy.
Salk could have made millions.
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03-27-2018, 03:05 PM #10
Zeus, they intentionally pulled funding with no explanation at the time. GSK took it to phase 2, i believe, trials and once that happened they had to pay a million dollars to thw originating company. Well they drop the trials not too long after with no explanation. No details came out until a while later, when it was found out that the drug induced cancer in multiple organs. So it couldnt make it to phase 3 trials and they had to pull the plig on it immediately.
I hadnt really researched the effects of the drug much, but i do remember when it first came to be, then shortly after the plug got pulled, it popped up on the black market and was being ised by athletes because there was no testing for it. Finally the fopimg agencoes caught on and some olympians, i believe from central or south america, got busted for using it.
From what i heqrd it was supposed to be a crazy phenomenal drug for performance, but no way i would touch it with the possible results
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03-27-2018, 05:50 PM #11
That’s a very valid concern.
As Obs say though, they usually only complete development on drugs they think will make money, or at least more money than the research and development necessary and then some profit.
With this drug however, it has to have commercial applications; from cholesterol to type 2 diabetes and probably cardiac issues as well I would suspect.
But question remains; how much would there be made in these areas when competing with other drugs, but I still suspect it would.
That they dropped it after the trial was a natural reaction when test animals die. Ofcourse, they drop it to not lose even more money, after they have encountered something they naturally see as a fucking big obstacle; the rats are dying from cancer.
So that makes perfect sense.
The only question that then remains is;
Is the mechanism of causing cancer explained? And if not, are there enough proof available from other trials that discredit their study, is this effect is not seen in other types of test animals?
It has been used for quite some time now, by humans, so and have they a higher incidence of cancer or earlier onset than the norm. Unfortunately it hasn’t been that long on the market, so all we can say from that is;
It doesn’t cause cancer very rapidly in humans. And is the carcinogenic effect lasting or only when the drug is in our system?
There’s so many questions I’d like to know more about this drug.
I would suspect that if it is carcinogenic, it is by the PPAR activation which turn things into overdrive, and that when the drug is out there isn’t massive damage on DNA in certain cells, but again, I need a lot more info to say anything about it.
I haven’t even really begun researching this myself yet, but would like to start by gathering anecdotal evidence.
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03-27-2018, 06:02 PM #12
Doc, im not 100% but pretty sure thos drug never hit the market. Only way to get it as far as i know was black market. That i remember, there was no other study done. GSK had sole rights to the drug at the time, and probably for so many years. And if they terminated trials, its not likely that anyone else would pick up where they left off, thatbwould be takimg a huge risk to throw good money after bad.
So no there wouldnt be any contradicting i fo or anything from another source in regards to results or efficacy. So it would stand that this drug would most likely never be studied again in actual trials.
Instead, they went back to the drawing board and came up with gft505, which does basically all the same things with regards to type 2 diabetes, cholesterol, etc, in much the same way, working with the ppar alpha, gamma, and delta instead of just the delta. So its kinda a blind chance you take if you decide to take it. I havent checked but i would guess there isnt going to be too much actual scientific info on it
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03-27-2018, 06:07 PM #13
Lol nerd alerts!
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03-27-2018, 06:52 PM #14
I would dig for some European studies Doc. I am embroiled in some professional recertification so have negative time on my hands but see if you can’t find something not US researched. They tend to be more objective and the studies aren’t driven by pharma or profit goals.
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03-27-2018, 09:52 PM #15
Killin me Obs.
Trail- there are some studies that have been done. I havent really had time to go through much of it, but there are arguments on both sides from what i can tell. I just dont know that the benefit of usage would justify the risks that obviously exist
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The reason they use rats or mice over pigs and such is a couple things.
1. Short life cycle, and extremely high metabolic rate
A white rat has a typical life span of 3-5 years.
Thus any long term effect of a drug is sped up in
Real time and shows up in the rat. So instead of doing 10-20 year studies you do a year study on the rat.
2. Cost and easy of raising and controlling variables
They are much more easy to handle and need not nearly the space you would need with other animals.
Here is a really good study that talks about a lot of this.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733029/“If you can't explain it to a second grader, you probably don't understand it yourself.” Albert Einstein
"Juice slow, train smart, it's a long journey."
BG
"In a world full of pussies, being a redneck is not a bad thing."
OB
Body building is a way of life..........but can not get in the way of your life.
BG
No Source Check Please, I don't know of any.
Depressed? Healthy Way Out!
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03-28-2018, 05:40 AM #17
Better explanation than I did on why they use rats MS.
Problem remains that while rats tell you much, they can’t replace bigger mammals in all circumstances.
If there’s a valid argument to actually use GW501516 in spite of the what GSK found, well it isn’t for me yet, that’s for sure.
I really would like to use this stuff, and even have some in the fridge as we speak. But I have no intention of using it now. I can’t justify it.
But that’s not to mean I won’t change my mind if I find more data.
Still it has to be a bit more than just a sarm site on the web saying; people have used this for 10years now and they are all fine!
I do kinda suspect it’s not as dangerous as one would think, but cancer is such a sneaky bitxt it’s not a risk I would take without knowing much much more.
What I do know is that even the ramipril (ACE inhibitor) I like to take for BP on any blast is a PPAR agonist. (But much weaker, yet still enough to elicit some positive effects)
If there’s anther PPAR agonist (for more subtypes of the receptors) being in use, that leads me to think the PPAR agonist activity was not the cause of cancer. Which doesn’t really say much at all, maybe GW501516 has some toxic metabolites in rats, or some other effects than PPAR agonism, or maybe the PPAR really is implicit in the cancer cause after all.
I’ll see what else i can find on this.
Sucks tho. Would have been great if this could be disproved.
One argument against it is that Sil was very much a fan. Hehe, no but I remember this was one thing he really claimed was better than rain water for the liver, heart rate, and so on.
Then I think, what is my most probable cause of death?
And I just right away know it is cardiac issues. Why?
Cause my heart is big, (and healthy), and family members struggle when they get old. Not that they die that young anymore, but that’s because if modern medicine.
And that’s a key word right now; medicine.
It is far easier to treat cardiac issues (up to a point) than to treat cancer.
So that’s why I can’t justify it, even if it would reduce the risk factors I’m most likely gonna die from.
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03-28-2018, 05:57 AM #18
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I mean is it better than an already established AAS compound? If not why risk getting cancer when another compound might produce just as good or similar results?
“If you can't explain it to a second grader, you probably don't understand it yourself.” Albert Einstein
"Juice slow, train smart, it's a long journey."
BG
"In a world full of pussies, being a redneck is not a bad thing."
OB
Body building is a way of life..........but can not get in the way of your life.
BG
No Source Check Please, I don't know of any.
Depressed? Healthy Way Out!
Tips For Young Lifters
MuscleScience Training Log
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850978/
Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits and pitfalls
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03-28-2018, 09:58 AM #21
Doc, the way i understand it is this was a ppar delta agonist. Im not clear on the distinctions. But the info i could find, it was dosed at 3mg/kg/day, 30mg/kg/day and 100mg/kg/day and all 3 groups developed cancer. I would have to look at the allometric conversion to see what that comes out to in humans, but tge lower ranges are not crazy doses. They are currently working on a ppar beta/gamma/delta agonist that is supposed to be in phase 3.
I think the biggest argument against it after the cancer risk, is exactly what Muscle said-is it so kuch better than the proven compounds we have already that the reward out weighs the risk? My .02 is no. Especially since they are working on another very similar drug that should be comparable and should pass clinical trials. Just seems like a big roll of the dice for something that isnt gonna give you magic in return
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03-28-2018, 12:07 PM #22
I think the question still remains is the cancer risk valid in humans. I don’t think I’ve seen definitive proof that it is. And can’t really trust US studies, as they fast-tracked aspartame onto the market and it has possible links to brain tumors and other issues, but when $$ is the issue, the waters get muddy very quickly because studies go away or are refuted, etc. Even some research with the CDC was tainted recently. That is why I recommend the european studies. For that matter GH has an inherent risk of cancer issues if you happen to have something undiagnosed, so I think it’s unclear at this point unless someone comes up with a large study offshore
The benefits of Cardarine are pretty extensive if there is low relative risk. And it is available from a number of reputable peptide sources.
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03-28-2018, 01:19 PM #23
Oh i get ya man. If i thought the risk was low i would jump on it. I just get thst bad feeling in my gut about it. No way they will ever test on humans if it cant get out of fda or rodent type trials. I guess it doesnt sit right with me because of the extensive cancer at a lower dose. Just makes me think that at sone point in time, a month or 5 years, the odds are good it would do the same in humans. Ill wait for the next version, gft505, to hopefully finish trials and see the comparison.
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03-28-2018, 03:21 PM #24
No you can’t even compare this to any AAS on the market.
Completely different animal.
Unlike AAS this would pretty much decrease all risk factors associated with AAS, and I’m not looking at it for its lipolysis effect either, rather it’s effects on stamina and muscle protein expression.
So no, I don’t really think there is an alternative on the market.
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03-28-2018, 03:22 PM #25
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03-28-2018, 03:25 PM #26
It’s available, but that doesn’t make it safe.
But yeah, it doesn’t cause cancer very quickly at least. That would have been noticed by now. Or at least if it did to a large degree.
Problem is, colorectal cancer can normally take up to 30years to develop.
And once it has progressed, 90% won’t survive it.
If it’s detected early, very early (Which it usually isn’t), then almost 90% survive it.
And that’s one of the cancer forms it seemed to cause.
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03-28-2018, 07:38 PM #27
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03-28-2018, 08:59 PM #28
Thats true scotch, but theres a reason they use rats for clinical trials. Our "genetic, biological and behavior characteristics closely resemble each other and many symptoms of human conditions can be replicated in mice and rats" - yet that doesnt always mean the opposite.
If a drug inhibits cancer in multiple organs in rats at 3mg/kg and a major pharma company abandons trials after paying a chunk of change to get the trials in the first place- enough for me to stay away from it.
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03-29-2018, 03:31 AM #29
This is true and it might very well be the case here.
Rats do after all get cancer quite easy in some ways. And I’ve heard the argument before that PPAR agonists work differently in the than humans regarding this very issue.
I have however not heard any deeper explanation, and while it may NOT be the case in humans, it’s also true that it MAY be true, unless there’s evidence to the contrary.
Have you ever used it yourself Scotch?
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Any difference in bioavailability/effect on this if injected compared to ingested?
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03-29-2018, 11:29 AM #31
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03-29-2018, 11:34 AM #32
What you're saying true and I present another reason why a pharma might drop the product. Even if there is no medical evidence of cancer in humans due to the inter-species barrier, some enterprising lawyer will take a cancer that is totally unrelated to the cardarine and because a lab rat got cancer, he's going to pin it on the pharma. Why not, they have deep pockets he's thinking. The potential liability is too great because the general public doesn't read the pharmacological report and even if they did, they wouldn't understand it. This lack of knowledge gives lawyer a fertile ground to position the drug to their advantage. America used to lead the world in new pharmacological discoveries. Now we just combine existing drug so you only have to take one pill instead of two. It's sad.
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03-29-2018, 01:48 PM #33
You are def right scotch, theres alot of different angles to it. And the point of usa pharmacology is correct and very sad.
Ive never known anyone to use it, so i never had much info on results. I guess i always got the results i was lookin for other places so never really had too much of an interest to begin with.
I am keeping an eye on follistatin and myo inhibitors though. Curious to see what comes out of that
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03-30-2018, 04:50 AM #34
I dont really care about fat loss, but how did it impact endurance?
Is this something that would (and I wouldn’t run anymore than 20mg myself) help me for a competition to a great degree? (I’m thinking martial arts here, where endurance is key)
Would just a single or 3 days use give a noticeable boost in stamina / endurance?
If it doesn’t really help that much Then my interest is more limited.
I’ve read to much hype abouT it;
Claiming it gives more endurance than anything, and without the sides from stims.
(Stims can actually reduce endurance In me; if it’s high intensity, due to just emptying me to quick)
They marketed it as endurobol after all. What’s your experience?
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03-30-2018, 06:59 AM #35
Doc, do stims affect you that way - empty you out quicker- during workouts as well? I dont do pre w/o drinks or anything like that, but i am an avid coffee drinker. I ran into a few times where i had the same prob, kinda ran outta steam sooner than usual during my workout, and could never really pinpoint why one day i would and most other days i was fine. I cant remember the specific days but wondering if coffee too close to a workout could be the prob
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03-30-2018, 12:18 PM #36
Yeah stims can absolutely drain me quicker. It depends though, caffeine might be ok, again depending on dose. But I notice that f.ex Ritalin really doesn’t help and will drain my batteries much quicker if doing sparring f.ex, and that muscle relaxers can actually improve my endurance.
It’s easy enough to explain really;
If you tense up you use more energy, and in top of that there might be some increase in metabolism that require more oxygen and produce more lactic acid.
A very small dose of insulin will actually also help prevent lactic acid buildup.
But it’s not always like that, but now I’d say it is more often than not.
I know lots of guys that have tried training on amphetamine and found that this just depleted them very quickly, and it’s not just about eating less and such.
Some stims might be better than others in this regard, and it might also be a tolerance issue in some cases, but yeah, I think generally it just increases focus and will and actually saps endurance if doing intense activity.
But for more medium level activity stims work great and increase stamina a lot.
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I found that 10mg halotestin helps a power-workout alot... not great for a cardio workout tho.. .
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03-30-2018, 01:24 PM #38
Halo is alright, and I don’t mind it before cardio either , though I haven’t tried that much. Will have to do that.
But this is what I wonder about when it comes to GW501516, how much does it help endurance?
Is it that noticeable? And does the effect come on quickly, or is this something that has to build up like when starting an AAS cycle?
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03-30-2018, 05:25 PM #39
Im not a big cardio fan anyway. I know, i gotta do it. I do some, just not too much. Ive heard that about halo, been thinkin bout givin it a go and see how it works out, and gonna cut the coffee a couple hrs before workout and see how that works.
Scoth is the only one ive ever talked to thats used it so im sure he can shed some light. Testimonials and shit online isnt worth much. Im still gonna look into the next one up, gft505. Its a dual agonist so may not have the same benefits, but may be interesting to see.
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03-30-2018, 09:18 PM #40
Awesome read guys thank you
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