Talk:GW501516

Cancer risk revisited
User:71.218.216.109 left the following message on my talk page SmartSE (talk) 21:45, 20 July 2015 (UTC):


 * About your undoing my changes on the page: GW501516


 * You said: "Not in agreement with the majority of sources and this is inappopriate citing of a primary source."


 * I don't want anymore wiki fights; however, in the opening paragraph, there are things that are just plain wrong.


 * To my knowledge, there is no study that shows that GW501516 causes cancer by itself: ONLY one study mentions cancer, and ONLY when it is combined with the intentional carcinogen DMBA. There aren't any sources that say that GW501516 causes cancer, and only one other mentions polyps (which aren't cancer). This stuff is uncommon enough, that the sources will be mostly primary ones. This can't be helped.


 * In fact, mentioning cancer should probably be left out. It DOESN'T cause cancer by itself.


 * One of the previous writers said "rats". The referenced studies were of mice, NOT rats.


 * The most common name for this stuff is Cardarine, and should be included in with the other names.


 * I would really appreciate it, if you would let my next edit remain. Karl 71.218.216.109 (talk) 21:28, 20 July 2015 (UTC)


 * The sources listed in the 'Safety' section of the article seem pretty clear cut to me and nothing seems to have changed in the last two years since this was previously discussed. This reference is the best that I could find before and states that the research that found it caused cancer was presented at a conference and in "two rather obscure short abstracts published in The Toxicologist" which is why you won't be able to find the full studies . We don't need to have a reference to original research 'proving' that it causes cancer by itself though when we have other very reliable sources (e.g. New Scientist and WADA) repeating the primary research findings of GSK. Our policy on the sourcing of medical information is rightly very strict on what we can use as sources and unless there is definitive evidence that the secondary sources which say that it does cause are incorrect, we should follow what they do say. I agree that cardarine is widely used online, but I haven't found any remotely reliable sources which could be added here. Including what is apparently a brand name could also be seen to legitimise the use of it. SmartSE (talk) 21:45, 20 July 2015 (UTC)
 * Oops, didn't end a sentence so I've fixed that and underlined what I added. SmartSE (talk) 22:05, 20 July 2015 (UTC)


 * Cardarine is not a brand name. Do a search, and you will see it used on many, many sites. It receives about 40% as many hits, as the name "Endurobol", on Google, so it's use is certainly valid (and the name "Endurobol" got worldwide exposure, because of the sports drug aspect). There are not much in the way of secondary sources on ANY of this, mostly just primary. Somewhere in Wikipedia editing tips, it says that you don't have to say that the sky is blue. I think that this falls under that category. If it gets 40% as many hits, as  the name "Endurobol" (which had worldwide exposure), it should be included among the names.


 * The link you give above, is from, as far as I can tell, a very poor secondary source. In a Google search, it only gets a little over 800 hits! I would take a primary source, over this source. The parent site, runswimthrowcheat.com, only gets a little under 1,500 Google hits. This is a very, very, very tiny site. This should not be used as a reference in this article.


 * The source link within the article going to the actual abstracts, is broken, and doesn't work. http://www.toxicology.org/AI/Pub/Tox/2009Tox.pdf  I wanted to see this, as I have seen no research showing cancer being actually caused by this, only polyps (not cancerous). I have done Google searches, and CANNOT find these abstracts. All that says what the abstracts supposedly said, is this tiny site. It does not appear on Google searches.


 * The studies were with mice, NOT rats.


 * I have checked all of the links under Safety. One goes to the tiny, tiny site you quoted, and almost certainly should be removed as a reference. I cannot find any info they mentioned, in Google searches where I can actually check the research or abstracts. Another, called "895 - Rat carcinogenicity study with GW501516, a PPAR delta agonist", goes to a broken link. A Google search on this study brings up only a tiny number of hits, probably having to do with the Wiki article. This link should be removed. This link, "896 - Mouse carcinogenicity study with GW501516, a PPAR delta agonist.", is broken, and should be removed. (Is this just the same link, twice?) Same tiny number of Google hits. This link in Safety, "The Role of PPARs in Cancer", I also checked every reference to GW501516 in. It said this "GW501516 and GW0742, highly specific PPARδ ligands, did not increase the growth of human colon cancer cell lines" It quoted many references. NOT ONE said that GW501516 caused cancer in anything. The polyp study was mentioned, and one where you got some extra cell growth, BUT no cancer. Several research studies mentioned here mentioned a DECREASE in polyps, or cell growth. The link, In Two Generations, Drug Research Sees a Big Shift, mentions the polyp research a FOURTH time. The link to, "Anti-doping agency warns athletes of black market drug", is broken, and should be removed. This link to "Anti-doping agency warns cheats on the health risks of Endurobol", works. On this page, however, the only reason given for a problem is "a developmental drug that was withdrawn from research by the pharmaceutical company and terminated when serious toxicities were discovered in pre-clinical studies." This says nothing. This link almost certainly should be removed. Presumably, they are talking about GW501516 combined with the carcinogen DMBA, already referenced in the first paragraph. The last link, "WADA issues alert on GW501516", is broken, and should be removed.


 * The "Safety" section is so horrible, it should probably be removed in it's entirety, or completely rewritten.


 * Please, if you could, redo my edit that you undid. OR, please, put the correct facts into your own words. Thank you. Karl 71.218.216.109 (talk) 22:54, 20 July 2015 (UTC)


 * I worked this over today. hopefully is acceptable to all. Jytdog (talk) 01:26, 21 July 2015 (UTC)


 * In addition to the secondary source provided by Jytdog, the abstracts of the rodent carcinogenicity studies are still available from the Wayback machine.  There were two studies, one done in rats (abstract # PS895) and the second in mice (abstract # PS896).  As stated in the secondary source, tumors were seen in multiple organs.  In addition, the primary sources state these tumors were observed at all doses. Boghog (talk) 05:50, 21 July 2015 (UTC)


 * "The sky is blue" doesn't apply here to an obscure chemical compound being known as cardarine and unless there are reliable sources calling it that, we shouldn't include it here however many google hits something gets.
 * Regarding inaccessible sources, see WP:DEADLINK. A link not working isn't cause to remove the information and as Boghog has pointed out the abstracts are still available at archive.org. As the studies that led to GSK discontinuing development, it seems highly relevant to include them here, even though the abstracts contain little information. Although the runswimthrowcheat source doesn't at first glance appear to be reliable, it is written by an expert on doping and therefore can be included per the policy on self-published sources. When I researched this before, this was the only source I could find that actually explained why GSK abandoned the development and I don't think it should have been removed. can you please review this again? I also think you have down-played the risks compared to what the sources state e.g. "a risk that it could cause cancer" (current article) versus "at all doses, the drug rapidly causes cancers in a multitude of organs" (new scientist quote, now removed). It's tricky when there are so few RS but particularly when we know that this compound is being used in doping I think we should err on the side of caution (as the RS do) rather than saying there is only a risk. It seems to me that the only people who'd want to downplay the risk are those selling it. SmartSE (talk) 12:21, 21 July 2015 (UTC)
 * I updated the lead to the match the body, where the content is well sourced. OK? Jytdog (talk) 12:28, 21 July 2015 (UTC)


 * Boghog said: "carcinogenicity studies are still available from the Wayback machine." I did numerous web searches that failed to pull these abstracts up. Plus the number of hits was tiny. Usually this implies that the research is bogus, and not a real study (normally, even if you can't find the study or abstract, it will be referenced in other studies, at least). The site in the Wiki article that briefly mentioned these abstracts, whose links had gone dead, was tiny, and should never have been used as a reference in the first place. I have now read the abstracts.
 * -Boghog said: "In addition, the primary sources state these tumors were observed at all doses." Here is the exact quote: "Neoplasms considered related to test article occurred in liver (hepatocellular carcinoma at ≥ 30 mg/kg/day and adenoma at ≥ 10 mg/kg/day), stomach (squamous cell carcinoma at all doses) and combined squamous cell tumours at all doses (squamous cell papilloma and carcinoma, and keratoacanthoma)." (Not all of these cancers are tumorous cancers.) These rats were very old (2 years), and cancers regularly develop in old rats on even normal diets. While they indicated a control group in the abstract, the cancer rate from the control group was not contrasted with the group receiving GW501516. The text implies the cancer rate was higher, but, by how much? Without the actual research study, who knows? And even the low doses, are quite high, compared with what humans would consume (and yes, I've done the correct animal/human conversion to get a correct human dose).


 * Smartse said: "It seems to me that the only people who'd want to downplay the risk are those selling it." Presumably, this comment is aimed directly at me, for wanting to "downplay" risks. I do not sell this stuff, and only became aware of it just a few weeks ago. I am ONLY interested in the truth. ONLY truth. I do not want to downplay risks; neither do I want to unduly exaggerate risks. Virtually ANY substance will cause cancer, in large enough doses, or if combined with the wrong things. You must keep perspective on this, when writing about potential risks. For example, NSAIDs cause over 100,000 hospitalizations a year in the US. They are estimated to kill over 16,000 arthritis users a year, in the US alone. YET, a multitude of them are available over the counter, without a prescription. So far, the number of deaths from GW501516 is zero. Which is the bigger hazard? Please, these "risks", must be kept in proper perspective.
 * -Smartse said: "expert on doping" Chris Cooper was interviewed by the Guardian simply because he had written a book on a hot topic. Nowhere in the article, is he called an "expert". He is simply called, by the Guardian, a "biologist and sports scientist". Is everyone who has ever written a non-fiction book, qualified under the Wiki self-published policy? I don't think so. Is Chris Cooper qualified? I don't know.
 * -Smartse said: "A link not working isn't cause to remove the information" If you re-read what I actually wrote, mostly I just said to remove the dead links. Also, I still think the addition of the term Cardarine is valid. I, myself, first searched on this term in Wikipedia to find out more about it. I thought there was no article. Only later, did I stumble across the Wiki article, by doing a Google search on "GW501516".


 * Jytdog said this: "was abandoned in 2007 because animal testing showed that the drug caused cancer to develop rapidly in several organs." This is wildly misleading. The research you are paraphrasing, is that GW501516 COMBINED with the intentional, known carcinogen DMBA did this. In the VERY SAME research study, control mice treated with GW501516 alone, developed NO cancer. You could just as well have said that GW501516 caused no cancer, which is actually more correct. (Plus this research is not referenced in your lead.) Here is how I said it, before my portion of the lead was undone:
 * -"GW501516 (also known as GW-501,516, GW1516, GSK-516, Cardarine and Endurobol[2]) is a PPARd receptor agonist that was previously investigated for drug use by GlaxoSmithKline. The drug worsened or caused cancer in mice, only when administered with the carcinogen DMBA, "...whereas treatment with either GW501516 or DMBA alone was not tumorigenic...". Administration in mice "resulted in a significant increase in the number and size of intestinal polyps." GlaxoSmithKline has ceased development." (I did have proper references in there.)
 * -Let me tell you a story that illustrates this problem. Decades ago, a research study was done that got the sweetener cyclamate banned in the US. What they did was clever. They used a large amount of cyclamate, PLUS a small amount of saccharin. After the study showed cancer, they said that, well, it was obviously the large amount of cyclamates that did it. Their buddies at the FDA agreed (although this was obviously stupid), and POOF!, cyclamates were banned. Only later, was it revealed that it was the small amount of saccharin, NOT the cyclamate, that caused the cancer. Today, decades later? Saccharin is available at your local grocery store, cyclamate is still banned (although it is legal in almost every other country in the world.) GW501516 combined with the intentional, known carcinogen DMBA, is NOT GW501516 by itself; which this same research study showed to cause no cancer in mice when administered alone.
 * -If you want the most damaging thing that I have seen (which seems to be what everyone wants), try the abstracts that Boghog tracked down. This quote is probably what you are looking for: "Neoplasms considered related to test article occurred in liver (hepatocellular carcinoma at ≥ 30 mg/kg/day and adenoma at ≥ 10 mg/kg/day), stomach (squamous cell carcinoma at all doses) and combined squamous cell tumours at all doses (squamous cell papilloma and carcinoma, and keratoacanthoma)." (Do be aware, even the smallest dose used in these studies is quite large compared to a(n) (accurately adjusted) human dose.) Please also check out the comments I made to Smartse and Boghog. Also, "black market", is certainly not a neutral term. GW501516 is not illegal in the US, is not a controlled substance, and is widely available (legally!) on the web. There is no "black market" in this. If you are bound and determined to use this term, it would be best done in a direct quote from an authority. This term was used 3 times in the body of the article.
 * -Other than the comments above, I consider the re-write of the article a big improvement over the old. Thank you. Karl 71.218.216.109 (talk) 20:03, 21 July 2015 (UTC)
 * Here for the cancer "sources" too.. The say absolutely nothing about "cancer" you can click each link and use ctrl+f for "cancer" there is nothing at all whatsoever. 2601:1C2:4F00:3D00:F428:9490:542C:2D14 (talk) 22:10, 20 July 2022 (UTC)

There is a whole lot of disinformation above that needs to be cleared up. The carcinogenicity studies (two years in two different rodent species) were performed by the drug's sponsor, GSK as part of the drug approval process and are required by regulatory agencies (see for example Guidance for Industry: Carcinogenicity Testing). GSK was highly motivated to perform these studies at a high standard according to the guidelines since a clean rodent carcinogenicity test that passes regulatory muster is a prerequisite for drug approval. Or are you suggesting GSK did a hack study to kill their own drug candidate? This makes no sense. Furthermore, a reliable secondary source in turn cited the two abstracts which strongly argues that the abstracts are not bogus.

The abstract states "GW501516 produced test article-related neoplastic findings in multiple tissues at all doses." Of course, the "test article-related neoplastic findings" are relative to the vehicle control as this is required by the guidelines. Furthermore why else would one include a control group?

No where in the abstracts nor in the guidelines is mentioned DMBA. DMBA was used in a much shorter one month carcinogenicity tumor initiator (DMBA) / tumor promoter (GW501516) study but not in the two year carcinogenicity studies. The reason DMBA was used in the one month study is to demonstrate that GW501516 is a promoter and not an initiator and also to shorten the length of the study.

The low dose in the carcinogenicity studies (5 mgs/kg/day) corresponds closely to the performance enhancing dose (2–5 mg/kg/day; ). The fact that some athletes have been using GW501516 to enhance their performance is scary and no wonder WADA banned its use. Boghog (talk) 03:59, 22 July 2015 (UTC)

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Page protection
Have temporarily protected the page to halt the current edit war. This is not an endorsement of whatever the current version is, it's just the version in place at the time I came by.

The protection will expire in a day, so please use this time to resolve the dispute through discussion and consensus on this page. -- Euryalus (talk) 08:56, 18 March 2017 (UTC)

Cardarine
User: 50.187.63.48 - Cardarine is apparently a  proprietary name for this "research reagent". I have looked and found no reliable sources that use this name to describe this chemical. Lots of spem sites tho, which we don't use in WP. If you have a non-spam ref that would be great. Jytdog (talk) 08:59, 18 March 2017 (UTC)