Tag Archive for GW1516

The Ultimate Performance Enhancer GW-501516

The Ultimate Performance Enhancer GW-501516

The Ultimate Performance Enhancer GW-501516

GW501516 is a drug that acts as a PPARδ modulator. GW501516 is a selective agonist (activator) of the PPARδ receptor. It displays high affinity (Ki = 1 nM) and potency (EC50 = 1 nM) for PPARδ with > 1000 fold selectivity over PPARα and PPARγ. GW 501516 activates the AMP-activated protein kinase and stimulates glucose uptake in skeletal muscle tissue.

GW 501516 has been demonstrated to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation. It has been proposed as a potential treatment for obesity and related conditions.

GW has also shown to dramatically increase endurance and recovery. In rats, binding of GW501516 to PPARδ recruits the co-activator PGC-1a. The PPARδ/coactivator complex in turn up regulates the expression of proteins involved in energy expenditure.

In obese rhesus monkeys, GW501516 increased high-density lipoprotein (HDL) and lowered very-low-density lipoprotein (VLDL). The mechanism by which PPARδ agonists increase HDL appears to be a result of increased expression of the cholesterol transporter ABCA1.

GW-501516 Various Uses

GW has many benefits but has two primary uses. The most common use of GW consists of the extreme amount of endurance and recovery increase. The results with GW use regarding endurance increase are staggering. GW was banned by the WADA (World Anti Doping Association) in 2009 because it provided such a large advantage to users over their competition. GW has shown to be fast acting with drastic results. A user can expect to see an endurance increase within a few days of use. GW provides continuous increases in the VO2MAX, allowing an individual to provide maximal output during exercise, thus obtaining the name, “The Ultimate Performance Enhancer.” The common dosage for this type of result is 20 mg a day with 14 weeks of continuous use

The other main use of GW is to aid in fat loss. GW has shown to melt away fat at a rapid pace. Another strong component of GW is that it is non catabolic, meaning it allows a user to lose fat and not have to sacrifice muscle. Many people that are on a fat burning diet are sacrificing a lot of muscle. GW allows a user to hold on to much more muscle than a standard fat lass diet or other fat loss compound would allow. GW also shines when ran in conjunction with other SARMS. When stacking GW with Ostarine and S4, users can add lean muscle while still losing weight and body fat. This makes GW highly desirable for many. The most optimal dosage for fat loss is 20 mg a day but users will still be able to receive this benefit at 10 mg a day.

GW 501516 can be ran in 8-12 cycles and can also be ran in conjunction with any SARM, steroid or supplement. As with any other steroid or supplement, it should be cycled properly to avoid any possible side effects and the keep it as effective as possible.

The Science behind GW-501516 Fat Burning

GW-50156 regulates fat burning through a number of widespread mechanisms. GW increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization. This shift changes the body’s metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar. GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity.


GW501516 is a selective agonist (activator) of the PPARδ receptor. It displays high affinity (Ki = 1 nM) and potency (EC50 = 1 nM) for PPARδ with > 1000 fold selectivity over PPARα and PPARγ.

In rats, binding of GW501516 to PPARδ recruits the co activator PGC-1a. The PPARδ/coactivator complex in turn up regulates the expression of proteins involved in energy expenditure. Furthermore in rats treated with GW501516, increased fatty acid metabolism in skeletal muscle and protection against diet-induced obesity and type II diabetes was observed. In obese rhesus monkeys, GW501516 increased high-density lipoprotein (HDL) and lowered very-low-density lipoprotein (VLDL). The mechanism by which PPARδ agonists increase HDL appears to be a result of increased expression of the cholesterol transporter ABCA1.

Cholesterol Improvement from GW501516

An often overlooked benefit of GW use is the ability to treat poor cholesterol. GW was originally formulated to treat people suffering from cholesterol problems and has shown to significantly increase HDL (good cholesterol) whle reducing LDL (bad cholesterol).

GW501516 Dosing and Timing

GW also has a very long half life, so it can be dosed once a day or split 12 hours apart. The most effective method of dosing is to take it in one serving, 30 minutes prior to working out. On non workout days, once a day dosing in the morning is the best method. If a split dosage is used, 10-12 hour splits are optimal.

GW501516 Side effects

There are constant debates and many studies arguing the potential side effects for a user. There are studies showing that GW has caused cancer in rats while other studies refute it. The ONE study that was conducted that showed this issue was deeply flawed and refuted time and time again. GW dosing was not only abused but ran at insurmountable amounts of time within this study. When ran properly, it has actually been used as a cancer treatment. There are no known side effects associated with GW use and the only need to cycle off is so that one’s body does not acclimate or desensitize to use. There is no suppression, no toxicity and no other common side effects. This makes GW even more desirable amongst the bodybuilding community.

Benefits of GW 501516

Extreme increases in endurance and recovery
Extreme fat melting
Long Half Life Making Dosing Optimal
Lowering of Bad Cholesterol and Increasing Good Cholesterol
Minimal Side Effects
Can be ran up to 12 weeks
Stacks well with everything
Non catabolic
Excellent energy
Excellent overall sense of well-being and feeling

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AICAR, GW1516 Are An Exercise In A Pill

AICAR, GW1516 Are An Exercise In A Pill

AICAR and GW1516 experiments suggest that these two drugs, also called exercise in a pill, might protect against gaining weight on a high-fat diet, which might make it useful for treating obesity.

Researchers have identified two drugs, AICAR and GW1516, that mimic many of the physiological effects of exercise. The drugs increase the ability of cells to burn fat and are the first compounds that have been shown to enhance exercise endurance.

Both AICAR and GW1516 can be given orally and work by genetically reprogramming muscle fibers so they use energy better and contract repeatedly without fatigue. In laboratory experiments, mice taking the drugs ran faster and longer than normal mice on treadmill tests. Animals that were given AICAR, one of the two drugs, ran 44 percent longer than untreated animals. The second compound, GW1516, had a more dramatic impact on endurance, but only when combined with exercise.

Ronald M. Evans, the Howard Hughes Medical Institute investigator who led the study, said drugs that mimic exercise could offer potent protection against obesity and related metabolic disorders. They could also help counter the effects of devastating muscle-wasting diseases like muscular dystrophy. Evans and his colleagues, who are at the Salk Institute for Biological Studies, published their findings on July 31, 2008, in an advance online publication in the journal Cell.

Concerned about the potential for abuse of the two performance-enhancing drugs AICAR and GW1516, Evans has also developed a test to detect the substances in the blood and urine of athletes who may be looking for way to gain an edge on the competition.

In 2004, Evans and his colleagues genetically engineered mice that had altered muscle composition and enough physical endurance to run twice as far as normal mice. These “marathon mice” had an innate resistance to weight gain, even when fed a high-fat diet. “We made these mice and they had low blood sugar, they resisted weight gain, they had low fats in their blood. They were much healthier animals,” Evans said. “And when we put them on a treadmill, the engineered mice ran twice as far than normal mice – they transformed into remarkable runners.”

The scientists achieved these effects by modifying a gene called PPAR-delta, a master regulator of numerous genes. Evans and his colleagues showed that by enhancing PPAR-delta’s activity, they had shifted the genetic network in muscle cells to favor burning fat over sugar as their energy source. But the effects seen in the marathon mice were caused by a genetic manipulation that was present in their bodies as their muscles were developing. Evans’s group began to wonder whether they could duplicate these effects by turning on PPAR-delta in adult mice.

“We had shown that we could pre-program muscle using genetic engineering. If you express this gene while the muscle is being formed, you can increase the amount of non-fatiguing muscle fibers,” Evans says. “But what about reprogramming in an adult? When all the muscles are in place, can you give a drug that washes over the muscle for a few hours at a time and reprograms existing muscle fibers? That’s a very different question.”

PPAR-delta has long been an attractive drug target because of its central role in metabolism, so Evans and his colleagues had no shortage of chemical compounds available to test. They began by testing a compound called GW1516. They treated young adult mice with the drug for five weeks. “We measured gene changes and the muscles looked like they were responding, so we knew the drug was working.”

Thus, while fully expecting the drug to dramatically increase endurance – Evans says, “There was no change at all in running performance. Nothing — not even a percent.”

Surprised by this spectacular failure, Evans and his colleagues decided to try a different approach, based on real-life experience. “If you’re out of shape – and most of us are – and you want to change, you have to do some exercise. The way we reprogram muscle in adults is by training.”

So the scientists subjected two groups of mice — one that received the drug and one that did not — to interval training. The mice ran for 30 minutes on a slow treadmill five days a week for a total of four weeks. At the end of the training period, all of the mice – regardless of whether they had received GW1516 – had improved their performance. Those that had received GW1516, however, ran 68 percent longer than those that had only done the exercise training. “The dramatic effect of the drug was stunning,” Evans said.

The scientists were intrigued by this synergistic interaction and wanted to know how exercise allowed the drug to work. One possibility was an enzyme called AMP kinase (AMPK). During exercise, cells burn ATP as their primary source of energy. In the process, they create a by-product called AMP. When cells sense the presence of AMP, they activate AMPK. Activation of AMPK creates more ATP for the cell to burn. AMPK also triggers changes that lower blood sugar, sensitize cells to insulin, enable cells to burn more fat, suppress inflammation, and otherwise influence metabolic pathways. This is one reason that exercise is so beneficial.

Evans’s team found that in addition to replenishing the cell’s energy stores, AMPK also assists PPAR-delta in activating its gene targets. “It hops onto PPAR-delta in the nucleus and turbo-charges its transcriptional activity,” Evans explained. “We think AMPK activity is the secret to allowing PPAR-delta drugs to work.”

The critical question was whether chemical activation of AMPK is sufficient to trick the muscle into thinking it has been exercised. The second drug, called AICAR, enabled them to answer that question. AICAR mimics AMP, Evans said, “so muscle thinks it’s burning fat.” The researchers were encouraged when they found that when they gave the drug to mice, they activated many of the genes in muscle that are turned on by exercise.

After four weeks of treatment with AICAR, Evans and his colleagues once again challenged sedentary mice to run on the treadmill. They found that mice that had received AICAR were able to run 44 percent longer than untreated mice. “This is a drug that is like pharmacological exercise,” Evans says. “After four weeks of receiving the drug, the mice were behaving as if they’d been exercised.” In fact, he says, those that got the drug actually ran longer and further than animals that received exercise training.

The animals receiving AICAR improved their running performance and their ability to burn fat. None of these effects, however, were as strong as they were in the animals that received both exercise and activation of PPAR-delta via GW1516.

Evans said this indicates that the benefits are likely due to collaboration between cells’ AMPK and PPAR-delta signaling pathways. The team’s genetic analyses supported this hypothesis; they found that AICAR and GW1516 alone activated a subset of exercise-induced genes, but activating both pathways (by combining GW1516 with exercise) activated a larger group of genes. Many of those genes regulate metabolism and muscle remodeling. Evans and his colleagues called this the “endurance gene signature.”

Like exercise, AICAR and GW1516 trigger a variety of changes that contribute to muscles cells’ improved endurance and ability to burn fat. These changes include an increase in mitochondria, the structures responsible for producing energy; a shift in metabolism that takes advantage of lipids as an energy source; and an increase in blood flow, which enables the steady delivery of fat to burn. While the scientists only examined the drugs’ effects on muscle cells in this study, Evans says it is likely that they confer benefits on other systems impacted by exercise, such as the heart and lungs.

Based on his group’s findings, Evans is optimistic about using small molecules that mimic exercise to treat and prevent a variety of common conditions. For example, the way in which AICAR and GW1516 transformed the muscle fibers of mice suggests they might help reverse the muscle frailty associated with aging or diseases like muscular dystrophy. “We have now created the potential for a really simple intervention in an area of major health problems for which there is no intervention,” he says.

More broadly, AICAR and GW1516 could offer the benefits of exercise to people who do not get enough. “Almost no one gets the recommended 40 minutes to an hour per day of exercise,” he says. “For this group of people, if there was a way to mimic exercise, it would make the quality of exercise that they do much more efficient. This might be enough to move people out of the `danger zone’ toward a lower risk, healthier set point. By intervening early, you may forestall the emergence of more serious problems.”

Evans expects these types of drugs will be attractive to a variety of individuals. “If you like exercise, you like the idea of getting more bang for your buck,” he says of GW1516. “If you don’t like exercise, you love the idea of getting the benefits from a pill,” as with AICAR. So, while Evans sees tremendous opportunities for health benefits from drugs that mimic exercise, he also sees serious potential for abuse.

“Drugs that improve health are not only going to be used by people who have medical problems. They may also be used by people who are healthy – or by athletes who want an edge,” said Evans. He noted that the sports world has long been aware of his lab’s work demonstrating a link between PPAR-delta and endurance. What’s more, GW1516 has a relatively simple chemical structure and can be synthesized easily. Evans anticipates that athletes will seek their own sources of the drug – if they haven’t already.

Concerned about the potential for abuse, Evans thought it was important to develop a test that could detect whether the drug was being used as a performance-enhancing substance. With HHMI support, his group has created a highly sensitive test that uses mass spectrometry to detect the two drugs and their metabolic by-products in the blood or urine. While the test is very reliable in mice, Evans says that further analyses are needed to ensure that it is accurate in humans. Evans, HHMI and the World Anti-Doping Agency are now working to certify the detection system and make it available in time to retroactively test athletes who compete in the 2008 Olympics

Submitted by Armen Hareyan

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