Your Experience with GW-501516

[BigGuy1980]

Hello --

I dont have enough posts yet to comment in the sponsor section regarding GW-501516... JohnJuan mentioned that GW-501516 has been shown to increase HDL levels, something I find very intriguing.

I would like those you are researching this to post results, much like I intend to. Researchers are using 5mg/day... If possible I would like to see actual lipid profile results over the course of time.

The only way we will be able to learn and discern the effectiveness of these new products is by researching and discussing.

Thank you for your cooperation.

 

[johnjuanb1]

Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% in rhesus monkeys and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans.

 

[donjoy]

I'm really curious to research as my rats are big on running and I hear that people can improve their cardio load with this. The only part that scares me is the potential for it to exacerbate a cancerous growth. I'm not keen on hurting my rats.

Anyone know of more studies on the issue? It's a really interesting looking peptide that I don't want to write off immediately.

Cross-talk between Peroxisome Proliferator-Activated Receptor

 

[oktome]

my last hdl was 77

I wonder if my monkey improved 79% it would set a world record.

 

[johnjuanb1]

My last HDL was 8. My chimp is in need of this product.

 

[donjoy]

I think this is the study that jj was talking about. Still looking for the final write-up.


GW501516 In Subjects Who Have Low Level Of High-Density Lipoprotein Cholesterol - Full Text View - ClinicalTrials.gov

 

[johnjuanb1]

A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport.
Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM.
Source
Metabolic Diseases Drug Discovery and Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
Abstract
The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the alpha (NR1C1) and gamma (NR1C3) subtypes, respectively. By contrast, the therapeutic potential of the delta (NR1C2) subtype is unknown, due in part to the lack of selective ligands. We have used combinatorial chemistry and structure-based drug design to develop a potent and subtype-selective PPARdelta agonist, GW501516. In macrophages, fibroblasts, and intestinal cells, GW501516 increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin. Our results suggest that PPARdelta agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X.

 

[donjoy]

Thanks jj! Good read. I also found another one where they tested 10mg/day orally on humans.

Triglyceride: High-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor δ agonist, Dennis L. Sprecher, Christine Massien, Greg Pearce, Andrew N. Billin, Itay Perlstein, Timothy M. Willson, David G. Hassall, Nicolas Ancellin, Scott D. Patterson, David C. Lobe, Tony G. Johnson, Arteriosclerosis, Thrombosis, and Vascular Biology Volume 27, Issue 2, February 2007, Pages 359-365


Abstract

OBJECTIVES - Exercise increases fatty acid oxidation (FAO), improves serum high density lipoprotein cholesterol (HDLc) and triglycerides (TG), and upregulates skeletal muscle peroxisome proliferator activated receptor (PPAR)d expression. In parallel, PPARd agonist-upregulated FAO would induce fatty-acid uptake (via peripheral lipolysis), and influence HDLc and TG-rich lipoprotein particle metabolism, as suggested in preclinical models.

METHODS AND RESULTS - Healthy volunteers were allocated placebo (n=6) or PPARd agonist (GW501516) at 2.5 mg (n=9) or 10 mg (n=9), orally, once-daily for 2 weeks while hospitalized and sedentary. Standard lipid/lipoproteins were measured and in vivo fat feeding studies were conducted. Human skeletal muscle cells were treated with GW501516 in vitro and evaluated for lipid-related gene expression and FAO. Serum TG trended downwards (P=0.08, 10 mg), whereas TG clearance post fat-feeding improved with drug (P=0.02). HDLc was enhanced in both treatment groups (2.5 mg P=0.004, 10 mg P<0.001) when compared with the decrease in the placebo group (-11.5±1.6%, P=0.002). These findings complimented in vitro cell culture results whereby GW501516 induced FAO and upregulated CPT1 and CD36 expression, in addition to a 2-fold increase in ABCA1 (P=0.002). However, LpL expression remained unchanged.

CONCLUSIONS - This is the first report of a PPARd agonist administered to man. In this small study, GW501516 significantly influenced HDLc and TGs in healthy volunteers. Enhanced in vivo serum fat clearance, and the first demonstrated in vitro upregulation in human skeletal muscle fat utilization and ABCA1 expression, suggests peripheral fat utilization and lipidation as potential mechanisms toward these HDL:TG effects.


Discussion

The PPARδ agonist-induced lipoprotein effects (eg, an increase in HDLc of up to 16.8%) were observed as the dose increased to 10 mg of GW501516. Closer inspection of the placebo cohort within this small trial revealed the physiologically expected reduction in HDLc (-11.5%, P=0.002) when requiring the study participants to be in-house and sedentary. Previous preclinical studies demonstrated that administration of GW501516 in obese rhesus monkeys at doses of 0.6 and 2.0 mg/kg/d produced a significant increase in HDLc and a reduction in TG values14 at similar GW501516 plasma exposure levels observed in our human experiment at daily doses of 2.5 mg and 10.0 mg, respectively. The most dramatic results observed in these animals were at the 6.0 mg/kg/d, with exposure level considerably above those observed in humans at the 10.0 mg dose. These pharmacodynamic (PD) results were recently corroborated by similar findings in Vervet monkeys administered with 3.0 mg/kg/d dose of GW501516, leading to over 3-fold higher exposure level than observed in human at the 10.0 mg dose.15 However, the pathophysiologic mechanisms for these changes remain unclear. The comparable HDL:TG modifications with both exercise and PPARδ agonism are conducive to theories surrounding lipolytic activity.

I'm still curious about the cancer aspect of things but the research seems to be conflicting on the matter. Some say it proliferates and others say it actually inhibits

Either way I'm no doctor but would love to hear others chime in.

 

[johnjuanb1]

I'm still curious about the cancer aspect of things but the research seems to be conflicting on the matter. Some say it proliferates and others say it actually inhibits

Either way I'm no doctor but would love to hear others chime in.

I just read that AICAR inhibits cancer cells. AICAR and GW-501516 work synergistically to improve endurance and reduce body fat. Both help HDL, I believe.

 

[BigGuy1980]

I wonder if my monkey improved 79% it would set a world record.

That is sooo sexy... I have been hovering around 30 for the past couple of years... Bad genetics coupled with TRT... I have been trying everything to get it up... This is something I am excited about...

So GW-501516 is shown to help with endurance... Any reported draw backs... Im not really interested in developing a runner type body.... nor do I plan on training for a marathon.

 

[johnjuanb1]

"GW501516" - Reduces fat & greatly produces slow twitch muscle
Mice which can run almost twice the distance of normal mice have been genetically engineered by US scientists.

"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.

But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.

Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.

The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.

In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes

So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.

But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.

"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.

It is unclear whether boosting PPARdelta levels later in life - or in people - would similarly enhance endurance. But, by coincidence, a drug called GW501516 which activates PPARdelta directly - is being clinically tested as a treatment to lower blood cholesterol and fat by the pharmaceutical company GlaxoSmithKline.

Evans has already shown the new drug causes many of the same genetic changes in muscle cells triggered by increasing levels of PPARdelta protein.
Therapeutic purposes

The question that remains is whether the drug alone will be enough to increase endurance "I suspect that animals training with the drug will increase endurance more rapidly," predicts Evans.

Evans says he has no affiliation with GlaxoSmithKline. And the company has so far been able to provide any comment on the work.

Farnaz Khadem, a spokesperson for the World Anti-Doping Agency, which strives to make sporting competitions drug-free, says she would not be surprised if cheating athletes would try taking GW501516, if it becomes available.

"Most doping involves a substance developed for therapeutic purposes being used for a sports purpose," she says. "Medical science is moving forward, which is good. But it also means we've got to be on our toes."

 

[spartan]

I will be following as I would like to see the results on the HDL levels could always use an increase there.

 

[aphextwin]

That's sounds very promising. My animal is going to need to get his HDL levels up

 

[cell911]

Starting tomorrow...will also chime in when on:headbang:

 

[firebirdz97]

Great read! May have try this

 

[ABO-for-2012]

GW

I took GW with MK for 16 weeks and my results were crazy. My endurance and recovery were off the chart. I stopped getting sore after all workouts and my muscles would not burn or fatigue during.

Since I have been off (ABOUT 4-5 WEEKS) I notice muscle burn during training and I definitely get sore. It takes me a few seconds more to recover between sets but overall I am in way better shape now than before the GW

Whether taking GW or MK I would recommend taking Omega 3's and Niacin to help keep all levels in check.

 

[donjoy]

I took GW with MK for 16 weeks and my results were crazy. My endurance and recovery were off the chart. I stopped getting sore after all workouts and my muscles would not burn or fatigue during.

Since I have been off (ABOUT 4-5 WEEKS) I notice muscle burn during training and I definitely get sore. It takes me a few seconds more to recover between sets but overall I am in way better shape now than before the GW

Whether taking GW or MK I would recommend taking Omega 3's and Niacin to help keep all levels in check.

What doses were you researching on your rat ABO? Sounds interesting as the human study at 10mg per day only tested for the HDL levels. I know the "exercise" rats were at much higher dosages but it's obvious that 10mg is beneficial at the very least for HDL.

 

[communistkiller]

I took GW with MK for 16 weeks and my results were crazy. My endurance and recovery were off the chart. I stopped getting sore after all workouts and my muscles would not burn or fatigue during.

Since I have been off (ABOUT 4-5 WEEKS) I notice muscle burn during training and I definitely get sore. It takes me a few seconds more to recover between sets but overall I am in way better shape now than before the GW

Whether taking GW or MK I would recommend taking Omega 3's and Niacin to help keep all levels in check.

Great tips... Why did you stop researching? Did you ever check your lipids? What was your dosage?

 

[oktome]

Quit dosing

I think he quit because there is some concern with polyps and cancer with extended use so he is being cautious. Probably smart with something this new.

 

[ABO-for-2012]

GW and MK

Initially quit because my cholesterol got out of wack. The good chol was low and the bad started to climb. I really did not know if it was from the GW or MK so to be safe I quit both and started high dose Omega 3 and niacin.

AFTER I quit is when my derm suggested a colonoscopy based on a pin head sized growth in my cheek. She said people with these growths need to get their ass checked. I did and all was cool. Thank GOD!

I will be starting back up on both but for 6 weeks on and 2-weeks off and repeat. Dosing was GW 5mg per day and MK 39 mg per day.

T know the GW dosing was low but the shit works...PERIOD. My endurance went crazy and for that to happen like that is unheard of.

I would not do more than 10 mg of GW PD. You don't need it. Just make sure you get good stuff.