# GW-501516 opinions



## DrBanner (Apr 10, 2015)

I've read a good bit on this material and had a short term trial. The test subjects reponded well to it, but wanted to get input from others on whether they would deem GW-501516 worthy of another trial. Only asking because I haven't seen much said about it in the past couple of years. So worth another trial or waste of time?


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## gymrat827 (Apr 10, 2015)

it works, but you need to bust your ass doing cardio.  bust your ass cardio.


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## DrBanner (Apr 10, 2015)

It seemed like it worked pretty well on first trial of it, just wanted to get others take on it. Thanks for the input. I read the old thread you posted in about it, but that thread is a couple years old and just making sure nothing negative has come about from it.


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## TheLupinator (Apr 11, 2015)

Shit works great for endurance, which in turn will help you lose fat.


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## goodfella (Apr 12, 2015)

Bump! I've always been interested in this but have seen so many mixed reviews, then I think I saw POB mention something about tumors? :/ Was't really sure if it's worth a hundred bucks if thats what it still goes for... More feedback much appreciated


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## Ggeneral (Apr 13, 2015)

> A 2004 article in The Wall Street Journal noted that a study published in Nature Medicine had found that GW501516 increased polyps in specially-bred mice,[3][31] but GSK originally said that they had not identified any safety problems with the compound and would continue to develop it.[14] However, researchers from GSK later presented findings of the adverse effects of giving GW501516 to rats and mice for two years at the 2009 meeting of the Society of Toxicology. The compound was found to significantly increase the chances of developing cancer and development of the drug was subsequently halted.



http://en.wikipedia.org/wiki/GW501516#Safety

I really wouldn't take my chances, but that decision is up to you.

~Ggeneral


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## TheLupinator (Apr 13, 2015)

Ggeneral said:


> http://en.wikipedia.org/wiki/GW501516#Safety
> 
> I really wouldn't take my chances, but that decision is up to you.
> 
> ~Ggeneral




http://carcin.oxfordjournals.org/content/28/12/2641.short

http://www.sciencedirect.com/science/article/pii/S0300483X07007524


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## goodfella (Apr 13, 2015)

So it looks like its not able to pass through our cancer cell lines/walls on us, which would make it safer? Also on that study on mice, have to wonder how often and how much they were giving to those mice and if they cycled it on them or just ran it constant year round after year... :? 

Also thank you guys for posting up! and DrBanner sorry we using ur thread, but I've also been interested in this as well.


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## TheLupinator (Apr 13, 2015)

The lowest dose used in mice that showed carcinogenicity was 5mg / kg... a 185lb man (84kg) would be dosing 420mg / day to be equivalent. Not saying small doses are not harmful, but it's not proven and not something I worry about. 10mg / day total will do the trick




RAT CARCINOGENICITY STUDY WITH GW501516, A PPAR DELTA AGONIST.
L. E. Geiger1 , W. S. Dunsford2 , D. J. Lewis2 , C. Brennan3 , K. C. Liu3 and S. J. Newsholme1 . 1 Safety Assessment, GlaxoSmithKline, King of Prussia, PA, 2 Safety Assessment, GlaxoSmithKline, Ware, United Kingdom and 3 Huntingdon Life Sciences, Huntingdon, United Kingdom.

GW501516, a non-genotoxic PPARδ agonist, was assessed for carcinogenic potential by daily administration (oral gavage) to Han Wistar rats for a period of 104 weeks. Males were given 0, 5, 15 or 30 mg/kg/day for the first 6 weeks of the study. For the remainder of the study males were given 0, 5, 20 or 40 mg/kg/day. Females were given 0, 3, 10 or 20 mg/kg/day for the entire study. GW501516 produced test article-related neoplastic findings in multiple tissues at all doses. Increased mortality was seen with females given GW501516 at all doses and uterine endometrial adenocarcinoma contributed to death in a high proportion of these animals. Neoplasms considered test-article related occurred in the liver (hepatocellular adenoma at ≥ 10 mg/kg/day), urinary bladder (transitional cell carcinoma in males given 20 and 40 mg/kg/day), thyroid (follicular cell adenoma at ≥ 3 mg/kg/day and carcinoma in males at ≥ 20 mg/kg/day), tongue (squamous cell papilloma in males at 5 mg/kg/day and 40 mg/kg/day), stomach (squamous cell papilloma in males at ≥ 5 mg/kg/day and a female at 20 mg/kg/day, and carcinoma in a male at 40 mg/kg/day and a female at 3 mg/kg/day), skin (inverted squamous cell papilloma in males at ≥ 5 mg/kg/day and females at 3 or 20 mg/kg/day), Harderian glands (adenoma in males at ≥ 5 mg/kg/day and adenocarcinoma in a male at 40 mg/kg/day), testes (interstitial cell adenoma at 40 mg/kg/day), ovary (Sertoli cell adenoma at ≥ 10 mg/kg/day) and uterus (polyp and endometrial adenocarcinoma at ≥ 3 mg/kg/day). Some of the tumor types observed in this study have not been reported with either PPARα or PPARγ agonists and may reflect tumor promotion mediated through PPARδ agonism.




MOUSE CARCINOGENICITY STUDY WITH GW501516, A PPAR DELTA AGONIST.
S. J. Newsholme1 , W. S. Dunsford2 , T. Brodie2 , C. Brennan3 , M. Brown3 and L. E. Geiger1 . 1 Safety Assessment, GlaxoSmithKline, King of Prussia, PA, 2 Safety Assessment, GlaxoSmithKline, Ware, United Kingdom and 3 Huntingdon Life Sciences, Huntingdon, United Kingdom.

GW501516, a non-genotoxic PPARδ agonist, was assessed for carcinogenic potential by daily administration (oral gavage) to CD1 mice for 104 weeks at doses of 0, 10, 30, 60 or 80 mg/kg/day. Survival was decreased at doses ≥ 30 mg/kg/day. 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). There have been conflicting reports in the literature regarding the effects of PPARδ on epithelial cell proliferation. The results of this study demonstrate an increase in proliferation in certain epithelial cell populations, but do not support a role for PPARδ in colon carcinogenesis. The squamous cell tumors observed in this study have not been reported with either PPARα or PPARγ agonists and may reflect tumor promotion mediated through PPARδ agonism.




LIGAND-ACTIVATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-BETA/DELTA INHIBITS THE PROLIFERATION OF HUMAN PANCREATIC CANCER CELLS.
J. D. Coleman and J. Vanden Heuvel. Pennsylvania State University, State College, PA.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, owing to its extremely aggressive nature and resistance to chemotherapeutic regimens In the present study we report that activation of the nuclear receptor PPAR-β/δ decreases human pancreatic cancer cell growth. The proliferation of three human pancreatic cancer cell lines - BxPc-3 (high COX-2 expression), Panc- 1 and MIA PaCa-2 (COX-2 negative) - was inhibited by the PPAR-α and PPAR-γ- selective agonists, Ciprofibrate and Rosiglitazone, respectively, but most effectively by the PPAR-β/δ-selective agonist GW501516. Treatment of pancreatic cancer cells with a PPAR-β/δ-selective agonist significantly decreased mRNA levels of the cell cycle regulatory gene, cyclin D2, compared with control cells at 24 hours. Furthermore, GW501516 treatment significantly reduced the TNF-α-induced mRNA expression of pro-inflammatory mediators in MIA PaCa-2 and BxPc-3 cells, several of which are known to influence cell proliferation. PPAR-β/δ interacts with NF-κB p50 subunit, although this was not dependent on ligand. PPAR-β/δ is unique among the PPAR isoforms in its association with the transcriptional repressor, Bcl-6. We hypothesize that PPAR-β/δ activation results in Bcl-6 shuttling from the receptor complex to its known consensus sequence in the cyclin D2 promoter where it influences pancreatic cancer cell proliferation.


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## goodfella (Apr 13, 2015)

Good find Lupinator! Yeah, thats a huge dose for mice to be taking and is what I've heard others mention. Thanks again brother!


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## DrBanner (Apr 13, 2015)

Yeah the tumor issue was my worry. The first trial had significant increase in endurance which resulted in increased ability for cardio.


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## DrBanner (Apr 13, 2015)

goodfella said:


> So it looks like its not able to pass through our cancer cell lines/walls on us, which would make it safer? Also on that study on mice, have to wonder how often and how much they were giving to those mice and if they cycled it on them or just ran it constant year round after year... :?
> 
> Also thank you guys for posting up! and DrBanner sorry we using ur thread, but I've also been interested in this as well.



Not a problem. The more information the better. Also the price is reasonable, it's come down quite a bit.


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## grizzldsealpoacher (Apr 13, 2015)

I ran it once it worked wonders for my cardio dropped a bunch of pounds and didn't really see a drop off in cardio after I stopped using it my runs were still equally as strong


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## j2048b (Apr 13, 2015)

Hmmmm so in essence if it i creases ur capacity for cardio and thus cardio will help ur heart health as well as lower ur h&h = WINNER WINNER CHICKEN DINNER???


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