# New GW-501516 studies done!



## cybrsage (May 8, 2017)

The May issue of Cell Metabolism has a study that looked much deeper into GW and how it works, etc. Their results are a bit surprising. I will quote the study and then give an overview of what it says. The source is here: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30211-5



> In addition to stimulating fatty acid metabolism in sedentary mice, PPARδ activation potently suppresses glucose catabolism and does so without affecting either muscle fiber type or mitochondrial content. By preserving systemic glucose levels, PPARδ acts to delay the onset of hypoglycemia and extends running time by ∼100 min in treated mice.



 This basically says PPAR activation causes the body to use up its glucose stores much slower, thereby allowing for greater endurance. It does this by causing the body to use fat as its energy source.




> Exercise training enhances endurance, in part, by delaying the depletion of carbohydrate stores (mainly glycogen in liver and muscle). The adaptive benefits of exercise training are commonly attributed to the glycolytic-to-oxidative fiber-type transformation and increased mitochondrial energetic capacity (Holloszy and Booth, 1976xBiochemical adaptations to endurance exercise in muscle. Holloszy, J.O. and Booth, F.W. Annu. Rev. Physiol. 1976; 38: 273–291
> 
> Crossref | PubMedSee all ReferencesHolloszy and Booth, 1976), programs in which the AMPK-PGC1α signaling pathway is now known to play a major role. At the same time, exercise also enhances muscle fatty acid (FA) oxidation



 If you exercise, your body will make new muscle fibers that are designed to not use as much glycogen, use the glycogen more efficiently, and cause the body to use fat as its primary energy source. I think we all already understood this even if we did not know the nitty gritty as to why.




> small molecule ligands that specifically activate PPARδ, including GW501516 (GW), have revealed multiple beneficial metabolic effects, including
> (1) increased energy expenditure
> (2) elevated FA oxidation(
> (3) reduced obesity and insulin resistance(
> ...



 I think that is clear enough. Anything that activates PPAR, such as exercise and GW, have amazingly powerful benefits for you.




> Despite the requirement for muscle PPARδ in exercise-induced metabolic adaptations and endurance enhancement, the glycolytic-to-oxidative fiber-type switch and mitochondrial biogenesis are still achieved in PDmKO mice. Furthermore, sedentary PDmKO mice are indistinguishable from WT mice in terms of mitochondrial content and oxidative phosphorylation (OXPHOS) capacity as well as muscle fiber-type composition. In addition, whole-body energy expenditure (measured as oxygen consumption rate [VO2];, energy substrate utilization are all independent of muscle PPARδ expression. This indicates a role for PPARδ in adaptive, but not innate, muscle activity and stands in contrast to previous reports.



 Ok, this is starting to get exciting. The two types of mice are PDmKO mice and WT mice. WT mice are normal mice used in laboratories. PDmKO mice have been genetically altered to be unable to increase endurance via exercise. The study shows that BOTH groups of mice had reduced glycogen use and increased fat use while using GW!!! This means it acts independently of your genetic makeup.




> Previous studies showed that treatment of mice with the PPARδ agonist GW dramatically increased running endurance, but only when combined with daily exercise. Based on the above, we re-examined the impact of GW on muscle energy substrate usage and endurance in fully sedentary mice. Unexpectedly, treatment of WT mice with GW (40 mg/kg in food) for a longer time (8 weeks compared to 4 weeks) reduced RER to a level similar to exercise training, indicative of increased FA metabolism. Consistent with an energy substrate shift, the longer 8 week GW treatment of sedentary mice was sufficient to confer ∼1.5 hr longer running time than untreated controls. This endurance benefit is lost in PDmKO mice and thus dependent on muscle PPARδ activation and muscle fiber-type composition—changes commonly associated with endurance enhancement—were not affected by GW treatment. Thus, while establishing that ligand activation of PPARδ can enhance endurance in sedentary mice, these findings implicate a novel mechanism of action.



 Endurance increase was found even in the mice that DID NOT EXERCISE! That is quite different from the previous study...but the previous study only went on for 4 weeks while this one went on for 8 weeks. Apparently, continued use provides increased benefits over time. The mice who genetically cannot increase endurance did not see endurance increases. Still, quite awesome that you can be a couch potato and STILL get benefits from GW on your endurance!




> Interestingly, while the blood glucose in the control mice started dropping after 90–120 min of running, GW-treated mice were able to maintain normal glycemic levels for extended periods and delay the onset of blood glucose reduction even after 180 min of running. It is important to note that the glucose-sparing effects of GW treatment parallel those seen with exercise training, suggesting a common underlying mechanism. Blood lactate was also monitored during our run-to-exhaustion tests, which showed minimal fluctuation in both control and GW-treated mice, indicating that the endurance regimen did not exceed the aerobic threshold of the tested mice. In combination, our data describe a PPARδ-controlled muscle reprogramming that boosts exercise endurance by inversely regulating fat and glucose metabolism, thereby preserving circulating glucose to support other tissues such as the brain.



 GW mirrors the effects of endurance training in the body, even to the point where it does not reduce the glucose levels being sent to the brain and other organs while actively reducing the amount sent to the muscles. This is awesome!




> Global transcriptional analyses in the glycolytic white quadriceps muscle (WQ) identified 975 genes with altered expression upon GW treatment, with 492 up- and 483 downregulated. In addition to the key mitochondrial genes Pdk4 and Cpt1b described above, gene ontology (GO) analysis of upregulated genes revealed significant enrichment in the PPAR signaling pathway as well as lipid and FA catabolism. Interestingly, lipogenic genes including PPARγ (master adipogenic regulator) and FA synthase (Fasn) were also induced, which would theoretically lead to a futile cycle of lipid catabolism and anabolism. Additionally, genes involved in antioxidant defense and glutathione synthesis (including Cat, Sod3, and Gpx1) were highly upregulated. Counterintuitively, pathways in carbohydrate metabolism, including the hexose metabolic process, pentose-phosphate shunt, and insulin signaling, were also significantly enriched is consistent with the induction of an anabolic program, suggesting a possible role in muscle repair.
> 
> Conversely, pathways of insulin signaling, glycolysis, and carbohydrate catabolism were significantly enriched in the downregulated gene set. Notably, these transcriptional changes, combined with the suppression of the recently identified mitochondrial pyruvate carrier Mpc1, coordinately reduce muscle glucose catabolism. These studies reveal that PPARδ reprograms muscle metabolism for endurance by reciprocal regulation of gene programs promoting FA oxidation and suppressing glucose metabolism.



 GW causes genes to "flip" their state, allowing for up and down regulation of specific body functions. Of interest is that antioxidants and glutathione synthesis was enhanced, as well as muscle repair pathways, which muscle glucose metabolism was suppressed. Also, insulin signally was significantly enriched.




> Activation of muscle PPARδ either genetically or pharmacologically is sufficient to dramatically improve endurance capacity. However, fiber-type changes and mitochondrial biogenesis found in the PPARδ transgenic models were not seen in “ligand-only” activation. Instead, we find that PPARδ ligand prioritizes energy substrate usage to increase FA catabolism while lowering glycolysis with the net effect of preserving systemic glucose.
> 
> Notably, pharmacologic activation of PPARδ replicates the exercise-induced changes in substrate utilization to preserve systemic glucose and thereby delay the onset of hypoglycemia, or “hitting the wall.” While exercise-induced muscle remodeling is well documented, the health benefits have been largely attributed to mitochondrial biogenesis and fiber-type transformation. In contrast, pharmacophores that activate PPARδ promote endurance through preserving glucose, essentially “pushing back the wall,” without affecting mitochondrial biogenesis or fiber-type transformation. This ability to chemically activate energetic circuits regulated by PPARδ has the potential to confer health benefits in a variety of human diseases.



 Endurance training literally changes your muscle fiber type so they use less glycogen and more fat as their energy source. GW does not change your muscle fiber type, but it replicates all the changes CAUSED by the new muscle fiber type, thereby giving you the same benefit as if you had performed endurance training.



 What this means, in a nutshell, is that you can take GW and be a couch potato and, after 8 weeks, your body will act as if you had been doing 8 weeks of endurance training. The downside is that it goes away when you stop. The extra fat you lose does not return (provided you have a proper diet), but since you do not form the new muscle fibers you will lose the benefits when you stop taking GW whereas you keep them if you stop exercising (slowly losing it over time). My recommendation is to take GW to increase your endurance AND do endurance training. You will have a synergistic effect of the two, helping you to create MORE of the new muscle fiber type in a shorter period of time.






In other news, it appears GW actually is being looked at as a way to kill cancer, not cause it.



> GW501516 is a selective and high-affinity synthetic agonist of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). This molecule promoted the inhibition of proliferation and apoptosis in a few cancer cell lines, but its anticancer action has never been investigated in bladder tumor cells. Thus, this study was undertaken to determine whether GW501516 had antiproliferative and/or apoptotic effects on RT4 and T24 urothelial cancer cells and to explore the molecular mechanisms involved. Our results indicated that, in RT4 cells (derived from a low-grade papillary tumor), GW501516 did not induce cell death. On the other hand, in T24 cells (derived from an undifferentiated high-grade carcinoma), this PPARβ/δ agonist induced cytotoxic effects including cell morphological changes, a decrease of cell viability, a G2/M cell cycle arrest, and the cell death as evidenced by the increase of the sub-G1 cell population. Furthermore, GW501516 triggered T24 cell apoptosis in a caspase-dependent manner including both extrinsic and intrinsic apoptotic pathways through Bid cleavage. In addition, the drug led to an increase of the Bax/Bcl-2 ratio, a mitochondrial dysfunction associated with the dissipation of ΔΨm, and the release of cytochrome c from the mitochondria to the cytosol. GW501516 induced also ROS generation which was not responsible for T24 cell death since NAC did not rescue cells upon PPARβ/δ agonist exposure. For the first time, our data highlight the capacity of GW501516 to induce apoptosis in invasive bladder cancer cells. This molecule could be relevant as a therapeutic drug for high-grade urothelial cancers.


https://www.ncbi.nlm.nih.gov/pubmed/27638828

GW is able to kill many kinds of cancer cells WITHOUT harming the non-cancerous cells around it.  A papillary tumor is a non-cancerous tumor (benign), for those who do not know (I had to look it up).  Only one study has shown GW to cause cancer while none of the others have shown GW to cause cancer in any of their test subjects.


----------



## Nattydread (May 9, 2017)

Very cool read. Thanks for posting


----------



## 456 (Jun 8, 2017)

cybrsage said:


> In other news, it appears GW actually is being looked at as a way to kill cancer, not cause it.
> 
> 
> https://www.ncbi.nlm.nih.gov/pubmed/27638828
> ...




Very interesting. Thanks for sharing. Everyone seems to reference the "study" that says that it causes cancer.

Some other good info as well.


----------



## lycan Venom (Jun 8, 2017)

Damn, exciting to say the least.


----------



## jamescb77 (Jun 8, 2017)

I think I'll
Hold off till there is more research done. 


Sent from my iPhone using Tapatalk


----------



## Sully (Jun 8, 2017)

Glad to see there is still research being done on this compound. Looking forward to logging my run with it for you.


----------



## jamescb77 (Jun 8, 2017)

I agree the new research on dnp is pretty neat as well 


Sent from my iPhone using Tapatalk


----------



## Sully (Jun 9, 2017)

jamescb77 said:


> I agree the new research on dnp is pretty neat as well
> 
> 
> Sent from my iPhone using Tapatalk



I haven't seen that. You should start a thread and link to it.


----------



## odin (Oct 9, 2017)

Good read. Always good to learn more. GW was good for me and I plan to use it again.


----------



## Viking (Oct 10, 2017)

I was put off by the cancer studies on this. Otherwise I may have tried it.


----------



## Thaistick (Oct 10, 2017)

Thanks for posting. I haven't been able to find much solid info on this before.


----------



## Thaistick (Oct 13, 2017)

Anyone have experience or information on sr9009? I think that's its name.


----------



## cybrsage (Nov 17, 2017)

Thaistick said:


> Anyone have experience or information on sr9009? I think that's its name.



Here is a writeup I did on it.

http://www.anasci.org/vB/peptides-h...1993-sr9009-what-what-does-do.html#post310964


----------



## striffe (Nov 18, 2017)

Very cool read.


----------



## Victory (Nov 25, 2017)

Good read. I plan to add this into my preworkout stack.


----------



## muj (Nov 25, 2017)

Hopefully I'll get to try this compound soon, the recovery and cardio benefits of it are exactly what I'm looking for


----------



## Thaistick (Dec 17, 2017)

cybrsage said:


> Here is a writeup I did on it.
> 
> http://www.anasci.org/vB/peptides-h...1993-sr9009-what-what-does-do.html#post310964


Thanks you. That's the one I'd most like to try, but I'll wait awhile and see what happens with the research being done on it.


----------



## El Hereje (Dec 17, 2017)

Cancer risk kept me away from this one as well.  Going to keep an eye on future studies for sure


Sent from my iPhone using Tapatalk


----------



## ELIMINATOR (Mar 1, 2018)

El Hereje said:


> Cancer risk kept me away from this one as well.  Going to keep an eye on future studies for sure
> 
> 
> Sent from my iPhone using Tapatalk



Me too, but now I think those studies were over doing the dosage.


----------



## muj (Mar 17, 2018)

This is on my to try list for sure. Especially to test it's effects on HDL and see if I can raise it with GW


----------



## AGGRO (Mar 20, 2018)

Most of the cancer talk came from massive doses and later studies showed it's not a cancer risk. It's impossible to know for certain but I think we are safe using this at the standard doses.


----------



## Lon Chaney (Mar 21, 2018)

El Hereje said:


> Cancer risk kept me away from this one as well.  Going to keep an eye on future studies for sure
> Sent from my iPhone using Tapatalk



found these qoutes...

"the rat study actually used outrageous levels of Cardarine, not normal amounts. I believe the amount was around 10,000 times the normal dosage. The equivalent amount of aspirin to a human would be deadly. The rat study was way off and men have now used Cardarine every day for over a decade without side effects. can prevent the average male from needing a series of cardiovascular meds, ED meds, Cholesterol Meds, etc etc. This is the reason they are suppressed by the FDA. Big pharma knows the results."

"as far as the cancer link goes, not only is the dose high, but PPAR agonists are known to cause cancer in rats and not humans. If you give a rat one of the fibrate drugs like lopid, their livers fill with cancerous too."


also you know GW501516 Cardarine - often gets grouped with SARMS however it is technically a PPAR Modulator.

so...

"this doesn’t happen in humans because PPAR agonism doesn’t actually cause proliferation of peroxisomes. That only happens in some lower life forms like rats. Their number of peroxisomes shoots up, causing vastly increased oxidative stress which fries their dna and causes cancer."


----------



## ASHOP (Mar 22, 2018)

Other than the supposed cancer risk any other noticeable side effects with it's use?


----------



## G-FLUX (Mar 22, 2018)

ASHOP said:


> Other than the supposed cancer risk any other noticeable side effects with it's use?



Actually if you read the study its an anti-cancer if anything

Big fan of GW


----------



## rmtt (Mar 24, 2018)

G-FLUX said:


> Actually if you read the study its an anti-cancer if anything
> 
> Big fan of GW


Exactly. Just another "Big Pharm" tactic to keep people away.

I don't even use this stuff for the cardiovascular effects....and it gives them no doubt.

I use it for the lipid effects.

This is my 3rd run with it since last year. In that time frame....I put on 30+ lbs of weight (muscle memory) and my lipids improved.

LDL and Triglycerides dropped....and pretty much maintained my HDL during my 8 week "blasts".

Granted I don't use orals and stay on the safer side of compounds I do use.....but it's the first time I ever had total cholesterol drop while gaining so much bodyweight.

Sent from my LG-H871 using Tapatalk


----------



## jackjones (Apr 26, 2018)

Big fan of the GW and Sarms Search....good stuff


----------



## Aton (Apr 26, 2018)

Very interesting read. Thank you for posting. 


Sent from my iPhone using Tapatalk


----------



## cybrsage (Jun 5, 2018)

I still use GW50 on a regular basis.  It really helps my cardio and, as RMTT mentioned, it can really help your lipids.  Remember this when you go to use lipid crushing things, like SDrol and such.

Also, I think it should be considered a must include item when using Tren, since Tren smashes your cardio endurance.  I think adding some Kratom when using Tren should also be required - it will reduce divorces and jail times.


----------



## goalieguru (Jun 10, 2018)

tried it before but then backed off..anyone with experience can back up what they say?


----------



## fishboy (Jun 10, 2018)

cybrsage said:


> I still use GW50 on a regular basis.  It really helps my cardio and, as RMTT mentioned, it can really help your lipids.  Remember this when you go to use lipid crushing things, like SDrol and such.
> 
> Also, I think it should be considered a must include item when using Tren, since Tren smashes your cardio endurance.  I think adding some Kratom when using Tren should also be required - it will reduce divorces and jail times.



I started using it for the cardio endurance but haven’t noticed any difference. I’ve continued to use it hoping it is helping  with lipids.  What amount are you taking that you notice a difference in cardio?


----------



## cybrsage (Jul 10, 2018)

fishboy said:


> I started using it for the cardio endurance but haven’t noticed any difference. I’ve continued to use it hoping it is helping  with lipids.  What amount are you taking that you notice a difference in cardio?



I see good results at 20mg a day, but I found my personal best bang for the buck is at 30mg a day.

There are non-responders to GW50, so it is possible you are one of them.  That would be sad, I love it.


----------



## Sparkss (Aug 23, 2018)

Any known plans for human studies? Or all rat and/or invitro studies at this point?


----------



## Sparkss (Aug 23, 2018)

I just answered my own question: https://clinicaltrials.gov/ct2/show/study/NCT00158899

*Detailed Description*	A multicentre, two-staged with interim analysis, parallel, randomised, double blind, placebo-controlled, dose-ranging study of the safety, tolerability, and effects on plasma high-density lipoprotein cholesterol (HDLc) of 12 weeks treatment with 2.5mg, 5mg and 10mg daily doses of GW501516 in subjects with low HDLc
*Study Type  ICMJE*	Interventional
*Study Phase*	Phase 2
*Actual Enrollment  ICMJE* 	424


----------



## ASHOP (Sep 9, 2018)

G-FLUX said:


> Actually if you read the study its an anti-cancer if anything
> 
> Big fan of GW



Most of the articles I had read early on read otherwise but now I'm seeing the complete opposite, a possible anti-cancer like effect. This stuff is interesting and I've still yet to run it myself.


----------



## Anne.ST (Sep 30, 2018)

That's a lot of info, cool !


----------



## Jtooswol (Oct 20, 2018)

Swear by this stuff!


----------



## phoenix13 (Nov 20, 2018)

What is extremely encouraging is that it is in Phase 2 clinical trials.  That means it was safe enough to continue pumping money into researching it.   If it was linked to causing cancer as the older (super high dose) study made it out to be, it would have never made it to Phase 2.  

Phase 1 is for basic safety.

Phase 2 is for further research into safety AND how well it works for what they want it to work for.

Phase 3 is to compare the new treatment (the drug being studied) to what is currently being used and available.

Phase 4 is for long term effects of a drug, and starts after FDA approval.

(This may be common knowledge to  you guys, but I only learned it recently.)


----------



## teejey (Nov 21, 2018)

Interesting good read.

Sent from my VS835 using Tapatalk


----------

