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GW501516 for performance enhancement.

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GW501516 for performance enhancement.

23 Mar 2013 13:30

Please put your comments here on how this drug will effect endurance athletes and what the dangers are for endurance athletes.

Please no baiting posts
del1962
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23 Mar 2013 13:32

What Dirtyworks said about it

DirtyWorks wrote:With the sports federation now in total control of testing and test processing, who will ever find out if they got a positive? Remember, the system is anti-doping controversy, not anti-doping.

The compound has yet to be named a controlled or prohibited substance by any nation's drug enforcement or regulation agency.

An AICAR cocktail with GW-501516 would explain the super-duper weight loss and contradictory sustained power we've seen recently. It's not a crime to take either...
del1962
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23 Mar 2013 13:33

Maxmartin said

"GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone."

But taking GW is an offence, The World Anti-Doping Agency has also begun work on a test for GW-501516 and other related PPARδ modulators, and they have been added to the prohibited list from 2009 onwards.

I think simply there is no robust method to detect this compound up to today. Correct me on this, if I am wrong.
del1962
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23 Mar 2013 13:56

del1962 wrote:Maxmartin said

"GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone."

But taking GW is an offence, The World Anti-Doping Agency has also begun work on a test for GW-501516 and other related PPARδ modulators, and they have been added to the prohibited list from 2009 onwards.

I think simply there is no robust method to detect this compound up to today. Correct me on this, if I am wrong.


These have been around for a while and are readily detectable using standard means [see below - 2009] - nothing new here. 0 evidence of efficacy in elite athletes.

Doping control analysis of emerging drugs in human plasma - identification of GW501516, S-107, JTV-519, and S-40503. Rapid Commun Mass Spectrom. 2009 Apr;23(8):1139-46.

Thevis M, Beuck S, Thomas A, Kortner B, Kohler M, Rodchenkov G, Schänzer W.

Abstract

An important aspect of preventive doping research is the rapid implementation of tests for emerging drugs with potential for misuse into routine doping control assays. New therapeutics of different classes such as PPARdelta-agonists (e.g. GW501516), ryanodine-calstabin-complex stabilizers (e.g. S-107 and JTV-519), and selective androgen receptor modulators (SARMs, e.g. S-40503) are currently used for the treatment of particular medical conditions such as metabolic syndrome, cardiac arrhythmia, debilitating diseases and osteoporosis, respectively. Due to their being at an early stage of clinical trials and the limited availability of data on the metabolism and possible renal elimination of the active drugs, the development of protocols for doping control analyses of plasma specimens could be an option for the detection of the circulating agents. The mass spectrometric fragmentation of four emerging drug candidates (GW501516, S-107, JTV-519, and S-40503) was elucidated by positive electrospray ionization and collision-induced dissociation using a high resolution/high accuracy mass spectrometer. A screening and confirmation procedure was established based on liquid chromatography/tandem mass spectrometry requiring a volume of 100 microL of plasma. Proteins were precipitated using acetonitrile, the specimens were centrifuged and the supernatant analyzed using a triple-quadrupole mass spectrometer employing multiple reaction monitoring of diagnostic ion transitions. The method was validated with regard to specificity, limits of detection (0.4-8.3 ng/mL), recoveries (72-98%), intraday and interday precisions (12-21%), and ion suppression/enhancement effects.
mastersracer
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23 Mar 2013 14:13

In addition to possibly killing you, there are also mixed findings - including reduction in oxidative capacity in oxidative muscle.

Cresser, Justin, et al. "Oral administration of a PPAR-delta agonist to rodents worsens, not improves, maximal insulin-stimulated glucose transport in skeletal muscle of different fibers." American journal of physiology. Regulatory, integrative and comparative physiology 299.2 (2010):R470-R479.

excerpts:

"This is the first study to examine the effects of chronic in vivo treatment with a PPAR-δ agonist (GW 501516) on insulin-stimulated glucose transport in skeletal muscle of different fiber types."

"Our major finding was that oral administration of the PPAR-δ agonist, GW 501516, significantly reduced maximal insulin-stimulated glucose transport and insulin signaling in skeletal muscle."

"Several studies have implicated PPAR-δ as a regulator of oxidative capacity in skeletal muscle (29, 50). However, the studies reporting this finding have generally used muscles composed primarily of glycolytic fibers (50); information pertaining to oxidative muscle is limited. On the basis of our results, it would appear that glycolytic fibers respond more robustly than oxidative fibers to treatment with GW 501516 in terms of increasing their capacity for oxidative metabolism."
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23 Mar 2013 14:29

What is the detection window?
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23 Mar 2013 15:00

del1962 wrote:Please put your comments here on how this drug will effect endurance athletes and what the dangers are for endurance athletes.

Please no baiting posts


SINCE I read this first
http://playtrue.wada-ama.org/news/wada-issues-alert-on-gw501516/

I thought you were joking

here are the relevant abstracts from toxicology.org

895 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. 1Safety Assessment, GlaxoSmithKline, King of Prussia, PA, 2Safety Assessment, GlaxoSmithKline, Ware, United Kingdom and 3Huntingdon Life Sciences, Huntingdon, United Kingdom.

GW501516, a non-genotoxic PPAR? agonist, was assessed for carcinogenic poten- tial 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 mortal- ity 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 ade- noma 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 (ade- noma 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 PPAR? or PPAR? agonists and may reflect tumor promotion mediated through PPAR? agonism.

896 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. 1Safety Assessment, GlaxoSmithKline, King of Prussia, PA, 2Safety Assessment, GlaxoSmithKline, Ware, United Kingdom and 3Huntingdon Life Sciences, Huntingdon, United Kingdom.

GW501516, a non-genotoxic PPAR? agonist, was assessed for carcinogenic poten- tial 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 carci- noma 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 (squa- mous cell papilloma and carcinoma, and keratoacanthoma). There have been con- flicting reports in the literature regarding the effects of PPAR? 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 PPAR? in colon carcinogenesis. The squamous cell tumors observed in this study have not been re- ported with either PPAR? or PPAR? agonists and may reflect tumor promotion mediated through PPAR? agonism.
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Gw 501516

23 Mar 2013 15:12

GW 501516 was initially thought to be able to improve lipid profiles and be an effective anti-obesity drug, however it looks to be DOA. Most likely it won't make it past phase II trials.

There is a cancer risk:
http://www.hindawi.com/journals/ppar/2010/571783/
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016215

It also worsens the liver fibrogenic response:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519722/

As far as improved performance goes, it allows for a shift toward using lipids rather than glycogen as fuel. Improving the 'lipid power'. Obviously this may lead to weight loss and a reduced need for glycogen utilization. I would also suspect this causes improved recovery. No studies on athletes I could find.

A drug test is available:
http://link.springer.com/article/10.1007%2Fs00216-009-3283-x
It is a urine test, and if I remember correctly it is detectable up to four days after taking 20mg. I didn't read the full article just now and could be wrong. Whether this test is being implemented I don't know. The drug is definitely being used somewhere and no one has been caught. http://onlinelibrary.wiley.com/doi/10.1002/dta.283/abstract;jsessionid=5CB28FAE6373C2B0C93FA4768C5D711C.d04t03
sideshadow
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23 Mar 2013 22:03

sideshadow wrote:GW 501516 was initially thought to be able to improve lipid profiles and be an effective anti-obesity drug, however it looks to be DOA. Most likely it won't make it past phase II trials.

There is a cancer risk:
http://www.hindawi.com/journals/ppar/2010/571783/
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016215

It also worsens the liver fibrogenic response:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519722/

As far as improved performance goes, it allows for a shift toward using lipids rather than glycogen as fuel. Improving the 'lipid power'. Obviously this may lead to weight loss and a reduced need for glycogen utilization. I would also suspect this causes improved recovery. No studies on athletes I could find.

A drug test is available:
http://link.springer.com/article/10.1007%2Fs00216-009-3283-x
It is a urine test, and if I remember correctly it is detectable up to four days after taking 20mg. I didn't read the full article just now and could be wrong. Whether this test is being implemented I don't know. The drug is definitely being used somewhere and no one has been caught. http://onlinelibrary.wiley.com/doi/10.1002/dta.283/abstract;jsessionid=5CB28FAE6373C2B0C93FA4768C5D711C.d04t03


Does this mean that Lance will be able to buy up all of the supply, just like he has done before with Hemassist?

Dave.
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23 Mar 2013 22:38

D-Queued wrote:Does this mean that Lance will be able to buy up all of the supply, just like he has done before with Hemassist?

Dave.


no Lance would never ever pump his body full of chemicals which could cause cancer after just surviving it once.
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23 Mar 2013 22:51

If you guys think cyclists, or any other elite athletes looking for an edge, are going to sit around and wait for double-blind tests to be done by researchers (which usually takes years) to either measure the efficacy of the drug as a performance enhancer or its' risks, you'd be mistaken.

According to what I've read here in "the Clinic" this drug never made it the past the initial trials into the pharmaceutical retail marketplace, so if anyone IS using it, where is the supply coming from?
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24 Mar 2013 02:57

Berzin wrote:If you guys think cyclists, or any other elite athletes looking for an edge, are going to sit around and wait for double-blind tests to be done by researchers (which usually takes years) to either measure the efficacy of the drug as a performance enhancer or its' risks, you'd be mistaken.

According to what I've read here in "the Clinic" this drug never made it the past the initial trials into the pharmaceutical retail marketplace, so if anyone IS using it, where is the supply coming from?


From those who first made it... They didn't manage to get in the market, they sell it for doping purposes..

But the thing is the win at any price mentality that most of these athlete have.
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24 Mar 2013 03:00

Alpechraxler wrote:no Lance would never ever pump his body full of chemicals which could cause cancer after just surviving it once.


What makes you think that he didn't get the cancer from some other dope that he used in the past?? Growth hormone is carcinogenic.. I have read that he used this among other substances..
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24 Mar 2013 03:07

When I read about the warnings I can't help but think of a very successful rider from the 2012 season who said he couldn't keep up the same regimen for another year. On the surface it seems like the reference to training, but maybe the unsaid scope of the statement was much broader? It doesn't seem so far fetched that a rider might be willing to brush up against the danger zone for a period of time, notch the big wins for the palmares, then ramp it down to mitigate risks.
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24 Mar 2013 03:40

alitogata wrote:What makes you think that he didn't get the cancer from some other dope that he used in the past?? Growth hormone is carcinogenic.. I have read that he used this among other substances..


He was being sarcastic ;-)
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24 Mar 2013 04:50

Berzin wrote:If you guys think cyclists, or any other elite athletes looking for an edge, are going to sit around and wait for double-blind tests to be done by researchers (which usually takes years) to either measure the efficacy of the drug as a performance enhancer or its' risks, you'd be mistaken.

According to what I've read here in "the Clinic" this drug never made it the past the initial trials into the pharmaceutical retail marketplace, so if anyone IS using it, where is the supply coming from?

joe papp might have stock?

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24 Mar 2013 12:39

Dear Wiggo wrote:He was being sarcastic ;-)



Indeed :o But anyway a seminoma is a seminoma.
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24 Mar 2013 20:10

sideshadow wrote:As far as improved performance goes, it allows for a shift toward using lipids rather than glycogen as fuel. Improving the 'lipid power'. Obviously this may lead to weight loss and a reduced need for glycogen utilization. I would also suspect this causes improved recovery.


It should also improve endurance by sparing glycogen.

A limitation to the duration and intensity of exercise is fatigue. Running low on glycogen stores is one reason that you may feel fatigue during exercise. As an adaptation to a regular exercise program, your body makes changes to metabolism. Regular exercise causes an increase in the mitochondria of your muscle cells. This allows for a more rapid use of fat as fuel. Turning to fat as the primary fuel source during exercise allows you to work harder and longer without feeling fatigue. This is known as muscle glycogen sparing. Part of glycogen sparing means that your body relies more on fat for fuel. This mechanism slows the rate of glycogen use.


http://www.livestrong.com/article/487122-the-body-can-use-glycogen-as-an-energy-source-when-aerobic-exercise-lasts-how-long/

Ferrari wrote:Every cyclist should have the interest in improving his own lipid power: increasing fats consumption at medium intensities allows the rider to spare precious glycogen stores, saving them for the highest efforts or the final part of the race.


http://www.53x12.com/do/show?page=article&id=50

Ferrari wrote:“]

http://www.53x12.com/do/show?page=article&id=37

Ferrari wrote:Since the maximum amount of glycogen that can be stored in the muscles for an athlete of 70 kg is around 700-800g, it is difficult to explain how an athlete can run for 42 km at 16 km/h with glycogen stores almost totally depleted by the previous cycling performance.

Running at this speed requires an oxygen consumption of 53ml/kg/min, which corresponds to 70%]

http://www.53x12.com/do/show?page=article&id=110

Ferrari wrote:Richard Virenque confirms himself as one of the best endurance athletes of the peloton: more than 200 km of getaway, 4000 m of total elevation climbed at an average of 40 km/h!

His engine is not so powerful, but an optimal use and distribution of the fuel allows him to maintain a constantly elevated intensity for many hours.

Together with a perhaps too generous Axel Merckx for 130 km, the French rider gave his best in the last 2 hours of the stage: while Axel ran out of fuel (read: glycogen), Virenque's metabolism, privileging the use of fat as energetic source, allowed him to spare glycogen stores for the final part of the race.


http://www.53x12.com/do/show?page=indepth.view&id=50

GW501516 also spares muscle protein and increases glucose uptake in muscle tissue.

It may allow you to:

* Improve power to weight ratio by effortlessly getting bf% very low.

* Improve day-to-day recovery by sparing muscle protein and glycogen and increasing glycogen uptake in muscle.

* Increase time to exhaustion at sub-threshold intensities by sparing glycogen.
Tyler'sTwin
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24 Mar 2013 23:28

* It may allow you to go from this...

Image

to this...

Image

* It may allow your doms to ride at the front of the peloton all day long.

* It may allow your leaders to arrive at the final climb with fresh legs, prepared to crank out those 6 'plausible' W per kg.

* It may allow them to do it day after day after day.
Tyler'sTwin
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25 Mar 2013 00:23

Tyler'sTwin wrote:* It may allow you to go from this...

Image




This is not Froome.
That's him, pre-Sky:


Image
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