akn
Musclechemistry Member
by Mike Arnold
Accelerated fat loss, increased muscular endurance, improved metabolic health; these are just a few of the ways in which GW-5015156 can benefit our bodybuilding progress. So, it wasn’t surprising when it became all the rage back when it was first released 5 or so years ago, but what was surprising was its relatively quick fall from grace. Despite possessing a list of benefits applicable to nearly every bodybuilding goal, its time in the limelight was cut short when W.A.D.A (World Anti-Doping Agency) announced that GW-501516 had been “withdrawn from research by the pharmaceutical company and terminated when serious toxicities were discovered in pre-clinical studies”.
Supposedly, GW-501516 was carcinogenic, causing tumors in rat test subjects. Initial reports revealed that tumor formation had occurred in numerous organs at all dosage levels, affecting the liver, bladder, stomach, skin, thyroid, tongue, testes, ovaries and womb. This really put a damper on its résumé and before long, warnings started popping up all over the place, admonishing prospective users to stay away. As one might expect, the kneejerk reaction was to stop using the stuff, which at the time seemed fairly reasonable. After all, if W.A.D.A thought it was dangerous enough to release an official statement warning athletes of its potential side effects, there was probably a good reason for it, or so it was assumed.
With the study results having been confirmed, GW’s popularity plummeted—the general consensus being that it was too risky to use, but was this conclusion premature? At the time, the decision to abstain was probably a wise one, at least until we found out a little bit more about the stuff. Since then, additional information has come to light. A more accurate interpretation of the study results, as well as a meta-analysis of the available anecdotal evidence, has helped shape a more favorable view of this S.A.R.M.
When evaluating the clinical trials, we need to understand that while animal studies can serve as a useful guide, alerting us to potential issues in human beings, we shouldn’t automatically assume that we will be affected in the same way. Extrapolation of this sort is never entertained by scientists, as animal physiology—in this case rat physiology—is often quite different from people.
Clenbuterol, a commonly used bodybuilding drug, is a great example. Not only are animals able to metabolize massive dosages (relative to humans) of clen without dying, but it imparts an extreme anabolic effect, increasing muscle mass up to 30% within a short period of time. Furthermore, these animals did not weight train, eat huge quantities of protein, or engage in any of the other practices typically employed by bodybuilders attempting to grow muscle tissue. They were simply given large doses of the drug and they grew like weeds.
By comparison, human tolerance is very low, allowing us to use just a tiny fraction of the doses administered in animals. Likewise, our anabolic response is comparatively poor, with little to no muscle gain occurring even when using large doses in the presence of beta blockers (beta blockers can be used to help us tolerate large doses of clenbuterol by preventing lethal heart rate acceleration). This difference in physiological response shows us very clearly that animal studies are often an unreliable indicator of human response. Of course, this does not mean we should automatically discount the results, but we cannot draw any conclusions from them.
Equally important are the variables of relative dose and duration of use. The rats in the study (there were actually two studies) were administered doses ranging from 5-80 mg/kg of bodyweight, per day With Wistar rats (the type of rat used in the study) usually weighing 1 pound or less, the following figures will be based on a rat weight of ½ kg (slightly over 1 lb). Using that figure, the rats were given a dose of GW ranging from 2.5-40 mg daily. Applying those same dosing guidelines to humans, an equivalent dose for a 100 kg male would be 500-8,000 mg per day. Most bodybuilders only use 5-20 mg/day, meaning the rat dose was 25-160X higher than what is normally used in humans.
Furthermore, this study lasted 104 weeks; exactly 2 years. With Wistar rats having a lifespan of 2-3 years, these rats were subjected to treatment for 66-100% of their lifetime. If we put this in human terms (a typical bottle of GW-501516 contains 30 servings of 10 mg each), it would be like giving a newborn baby 1.66-27 bottles of GW-501516 per day and continuing treatment through adulthood for all, or most of its life. With an average bodybuilding dose of 1/30th of a bottle per day for 30-60 days, only a moron would equate the two. Factor in cross-species differences in physiological response and any faith in extrapolation becomes incredibly difficult to sustain.
Given the seriousness of the accusations (that GW-501516 causes cancer), even though it has little to stand on, we still need to take it seriously. Fortunately, we are not left in the dark regarding the real-world use of this drug, as 1,000’s of bodybuilders and other athletes have now been using it for over a half-decade without experiencing any medical problems, let alone cancer. There is also independent research being conducted, with no signs of cancer in sight, even when exceeding the dosages used in the above referenced study.
When looking at the evidence as a whole, it seem as if the initial cancer scare was nothing more than that—a scare. Let’s not forget all the other chemicals/drugs which were shown to cause cancer in research animals under similar circumstances, but were subsequently approved by the FDA and have now been in use by the general public for decades. Artificial sweeteners, anyone? Although I hate to pull the honesty card here, let’s also not forget that Big Pharma isn’t known for being the most moral/honest entity around town. Self-interest is Big Pharma’s middle name, but I digress. At this point, although one cannot state definitively that GW-501516 is safe (the same can be said for many other commonly used bodybuilding drugs), it appears that the risk is minimal, especially when adhering to conventional cycling guidelines.
Questions of safety aside, what makes this such a great bodybuilding drug? Although it does not provide overly dramatic results in any single area (except for perhaps its positive effect on metabolic health), the totality of its effects are nothing short of impressive. One of its most desirable benefits is its ability to stimulate fat loss. While I am not going to get into the science of “how” this stuff works (there are already plenty of articles available on the subject), I do want to touch on what differentiates GW-501516 from its peers.
Unlike most of the fat loss drugs today, GW does not stimulate the nervous system. Personally, I find this to be a relief, as there are plenty of times I don’t feel like having to contend with the jitters, nervousness, anxiety, or post-use crash, all of which are common occurrences with drugs like clenbuterol, ephedrine, caffeine, and every other stimulant drug out there. Similar to growth hormone, the fat loss effects of GW are not rapid, but they are consistent and ongoing, allowing us to accelerate fat loss over the long haul without any of the typical side effects associated with nervous system stimulation. This alone makes it worthy of consideration.
It is also one of the few non-stimulant drugs which induces fat loss via an increased rate of oxidation (the use of fat for energy—fat burning). There are two primary steps involved in the fat loss process: oxidation and lipolysis. Lipolysis is a term used to describe the release of fatty acids from the fat cell into the bloodstream, making them more likely to be used by the body for energy. Oxidation describes the use/burning of fat for energy. Both of these steps must occur in order for fat loss to take place. If fat is not first released from the fat cell, it cannot be used for energy. In the same way, if newly released fat is not used for energy, it will simply be re-deposited into the fat cell.
If one of these processes begins to exceed the other, the slower process is said to be the rate-limiting factor. In other words, the rate of fat loss is limited by the weakest link. When it comes to fat loss, oxidation is usually the rate-limiting factor. This make GW-501516 an excellent stacker with growth hormone, as its ability to increase oxidation pairs well with GH’s lipolytic effect, increasing the rate of fat loss beyond what can be achieved with either one alone.
But this is not the only reason GW-501516 makes a good match with growth hormone. As many of you probably know, as awesome a drug as GH is, it has some pretty significant downsides, especially those related to metabolic health. When used at replacement doses, it is a strictly positive addition to one’s program, leading to improvements in metabolic health and overall functioning, but at the doses normally used by bodybuilders, its injurious effects are undeniable.
Most notably, GH causes a decrease in insulin sensitivity and has been shown to result in clinical insulin resistance at doses as low as 5 IU/day. This has a barrage of negative effects on the body, such as impaired glucose metabolism, diminished fat loss, and visceral fat build-up, to name a few. You may be wondering how decreased fat loss made the list, being that growth hormone is specifically known to increase the rate of fat loss. The explanation is simple. Growth hormone has a very potent lipolytic effect, which overpowers the negative effect that insulin resistance has on fat loss. It’s like taking 4 steps forward and 2 steps back. You will still end up in the green after all is said and done, but maximum results are not obtained.
PPARδ agonists, such as GW-501516, have also been show to reverse the effects of metabolic syndrome by increasing insulin sensitivity. By re-establishing a normal degree of insulin sensitivity, not only are we able to mitigate GH’s harmful effects on metabolic health, but its fat loss effect is optimized as well. As an added benefit, GW-501516 also helps prevent “GH gut”. Contrary to popular belief, organ growth is not the primary mechanism by which GH causes stomach distension. The real problem is insulin resistance. Insulin resistance causes stomach distension by promoting visceral fat storage (the fat stored inbetween vital organs). By stopping insulin resistance before it starts, the body is much less prone to store this type of aesthetics damaging fat.
Obviously, GW-501516 is ideally suited as a companion drug to GH, but its lipid altering effect also makes it a great match with methylated (oral) AAS. With methyls having an adverse effect on lipid metabolism, GW’s profound effect in this area can help minimize AAS induced arteriosclerosis (hardening of the arteries caused by cholesterol build-up). Unlike many cholesterol support supplements/drugs available today, GW has a dual effect on cholesterol levels, helping to increase HDL (good cholesterol) while simultaneously decreasing LDL (bad cholesterol). With damaged cardiovascular health (i.e. heart attack, stroke) at the forefront of modern bodybuilding health issues, anything we can do to help protect ourselves from this potentially life threatening side effect is of great value.
Aside from enhanced fat loss and improvements in metabolic-cardiovascular health, GW-501516 is well known to increase muscular endurance; the main reason why W.A.D.A. was so quick to have it added to the banned substance list for Olympic athletes. While this benefit doesn’t directly contribute to recovery or muscle growth, it indirectly improves growth potential by allowing one to train more intensely, particularly for those who tend to train with a lot of volume, take little rest time inbetween sets, or train in the higher rep range. This is especially true for leg training, which already places large demands on the body’s endurance capacity.
Because of its versatility, GW does not fit the description of either a pre-contest or off-season drug, but rather, is equally suited to both training phases. Furthermore, with a non-stimulatory nature, it is well-tolerated among all individuals. Whether your goal is increased fat loss, enhanced endurance, or improved metabolic-cardiovascular health, GW can be used as a complimentary or standalone agent to affect positive change in all of these areas.
Accelerated fat loss, increased muscular endurance, improved metabolic health; these are just a few of the ways in which GW-5015156 can benefit our bodybuilding progress. So, it wasn’t surprising when it became all the rage back when it was first released 5 or so years ago, but what was surprising was its relatively quick fall from grace. Despite possessing a list of benefits applicable to nearly every bodybuilding goal, its time in the limelight was cut short when W.A.D.A (World Anti-Doping Agency) announced that GW-501516 had been “withdrawn from research by the pharmaceutical company and terminated when serious toxicities were discovered in pre-clinical studies”.
Supposedly, GW-501516 was carcinogenic, causing tumors in rat test subjects. Initial reports revealed that tumor formation had occurred in numerous organs at all dosage levels, affecting the liver, bladder, stomach, skin, thyroid, tongue, testes, ovaries and womb. This really put a damper on its résumé and before long, warnings started popping up all over the place, admonishing prospective users to stay away. As one might expect, the kneejerk reaction was to stop using the stuff, which at the time seemed fairly reasonable. After all, if W.A.D.A thought it was dangerous enough to release an official statement warning athletes of its potential side effects, there was probably a good reason for it, or so it was assumed.
With the study results having been confirmed, GW’s popularity plummeted—the general consensus being that it was too risky to use, but was this conclusion premature? At the time, the decision to abstain was probably a wise one, at least until we found out a little bit more about the stuff. Since then, additional information has come to light. A more accurate interpretation of the study results, as well as a meta-analysis of the available anecdotal evidence, has helped shape a more favorable view of this S.A.R.M.
When evaluating the clinical trials, we need to understand that while animal studies can serve as a useful guide, alerting us to potential issues in human beings, we shouldn’t automatically assume that we will be affected in the same way. Extrapolation of this sort is never entertained by scientists, as animal physiology—in this case rat physiology—is often quite different from people.
Clenbuterol, a commonly used bodybuilding drug, is a great example. Not only are animals able to metabolize massive dosages (relative to humans) of clen without dying, but it imparts an extreme anabolic effect, increasing muscle mass up to 30% within a short period of time. Furthermore, these animals did not weight train, eat huge quantities of protein, or engage in any of the other practices typically employed by bodybuilders attempting to grow muscle tissue. They were simply given large doses of the drug and they grew like weeds.
By comparison, human tolerance is very low, allowing us to use just a tiny fraction of the doses administered in animals. Likewise, our anabolic response is comparatively poor, with little to no muscle gain occurring even when using large doses in the presence of beta blockers (beta blockers can be used to help us tolerate large doses of clenbuterol by preventing lethal heart rate acceleration). This difference in physiological response shows us very clearly that animal studies are often an unreliable indicator of human response. Of course, this does not mean we should automatically discount the results, but we cannot draw any conclusions from them.
Equally important are the variables of relative dose and duration of use. The rats in the study (there were actually two studies) were administered doses ranging from 5-80 mg/kg of bodyweight, per day With Wistar rats (the type of rat used in the study) usually weighing 1 pound or less, the following figures will be based on a rat weight of ½ kg (slightly over 1 lb). Using that figure, the rats were given a dose of GW ranging from 2.5-40 mg daily. Applying those same dosing guidelines to humans, an equivalent dose for a 100 kg male would be 500-8,000 mg per day. Most bodybuilders only use 5-20 mg/day, meaning the rat dose was 25-160X higher than what is normally used in humans.
Furthermore, this study lasted 104 weeks; exactly 2 years. With Wistar rats having a lifespan of 2-3 years, these rats were subjected to treatment for 66-100% of their lifetime. If we put this in human terms (a typical bottle of GW-501516 contains 30 servings of 10 mg each), it would be like giving a newborn baby 1.66-27 bottles of GW-501516 per day and continuing treatment through adulthood for all, or most of its life. With an average bodybuilding dose of 1/30th of a bottle per day for 30-60 days, only a moron would equate the two. Factor in cross-species differences in physiological response and any faith in extrapolation becomes incredibly difficult to sustain.
Given the seriousness of the accusations (that GW-501516 causes cancer), even though it has little to stand on, we still need to take it seriously. Fortunately, we are not left in the dark regarding the real-world use of this drug, as 1,000’s of bodybuilders and other athletes have now been using it for over a half-decade without experiencing any medical problems, let alone cancer. There is also independent research being conducted, with no signs of cancer in sight, even when exceeding the dosages used in the above referenced study.
When looking at the evidence as a whole, it seem as if the initial cancer scare was nothing more than that—a scare. Let’s not forget all the other chemicals/drugs which were shown to cause cancer in research animals under similar circumstances, but were subsequently approved by the FDA and have now been in use by the general public for decades. Artificial sweeteners, anyone? Although I hate to pull the honesty card here, let’s also not forget that Big Pharma isn’t known for being the most moral/honest entity around town. Self-interest is Big Pharma’s middle name, but I digress. At this point, although one cannot state definitively that GW-501516 is safe (the same can be said for many other commonly used bodybuilding drugs), it appears that the risk is minimal, especially when adhering to conventional cycling guidelines.
Questions of safety aside, what makes this such a great bodybuilding drug? Although it does not provide overly dramatic results in any single area (except for perhaps its positive effect on metabolic health), the totality of its effects are nothing short of impressive. One of its most desirable benefits is its ability to stimulate fat loss. While I am not going to get into the science of “how” this stuff works (there are already plenty of articles available on the subject), I do want to touch on what differentiates GW-501516 from its peers.
Unlike most of the fat loss drugs today, GW does not stimulate the nervous system. Personally, I find this to be a relief, as there are plenty of times I don’t feel like having to contend with the jitters, nervousness, anxiety, or post-use crash, all of which are common occurrences with drugs like clenbuterol, ephedrine, caffeine, and every other stimulant drug out there. Similar to growth hormone, the fat loss effects of GW are not rapid, but they are consistent and ongoing, allowing us to accelerate fat loss over the long haul without any of the typical side effects associated with nervous system stimulation. This alone makes it worthy of consideration.
It is also one of the few non-stimulant drugs which induces fat loss via an increased rate of oxidation (the use of fat for energy—fat burning). There are two primary steps involved in the fat loss process: oxidation and lipolysis. Lipolysis is a term used to describe the release of fatty acids from the fat cell into the bloodstream, making them more likely to be used by the body for energy. Oxidation describes the use/burning of fat for energy. Both of these steps must occur in order for fat loss to take place. If fat is not first released from the fat cell, it cannot be used for energy. In the same way, if newly released fat is not used for energy, it will simply be re-deposited into the fat cell.
If one of these processes begins to exceed the other, the slower process is said to be the rate-limiting factor. In other words, the rate of fat loss is limited by the weakest link. When it comes to fat loss, oxidation is usually the rate-limiting factor. This make GW-501516 an excellent stacker with growth hormone, as its ability to increase oxidation pairs well with GH’s lipolytic effect, increasing the rate of fat loss beyond what can be achieved with either one alone.
But this is not the only reason GW-501516 makes a good match with growth hormone. As many of you probably know, as awesome a drug as GH is, it has some pretty significant downsides, especially those related to metabolic health. When used at replacement doses, it is a strictly positive addition to one’s program, leading to improvements in metabolic health and overall functioning, but at the doses normally used by bodybuilders, its injurious effects are undeniable.
Most notably, GH causes a decrease in insulin sensitivity and has been shown to result in clinical insulin resistance at doses as low as 5 IU/day. This has a barrage of negative effects on the body, such as impaired glucose metabolism, diminished fat loss, and visceral fat build-up, to name a few. You may be wondering how decreased fat loss made the list, being that growth hormone is specifically known to increase the rate of fat loss. The explanation is simple. Growth hormone has a very potent lipolytic effect, which overpowers the negative effect that insulin resistance has on fat loss. It’s like taking 4 steps forward and 2 steps back. You will still end up in the green after all is said and done, but maximum results are not obtained.
PPARδ agonists, such as GW-501516, have also been show to reverse the effects of metabolic syndrome by increasing insulin sensitivity. By re-establishing a normal degree of insulin sensitivity, not only are we able to mitigate GH’s harmful effects on metabolic health, but its fat loss effect is optimized as well. As an added benefit, GW-501516 also helps prevent “GH gut”. Contrary to popular belief, organ growth is not the primary mechanism by which GH causes stomach distension. The real problem is insulin resistance. Insulin resistance causes stomach distension by promoting visceral fat storage (the fat stored inbetween vital organs). By stopping insulin resistance before it starts, the body is much less prone to store this type of aesthetics damaging fat.
Obviously, GW-501516 is ideally suited as a companion drug to GH, but its lipid altering effect also makes it a great match with methylated (oral) AAS. With methyls having an adverse effect on lipid metabolism, GW’s profound effect in this area can help minimize AAS induced arteriosclerosis (hardening of the arteries caused by cholesterol build-up). Unlike many cholesterol support supplements/drugs available today, GW has a dual effect on cholesterol levels, helping to increase HDL (good cholesterol) while simultaneously decreasing LDL (bad cholesterol). With damaged cardiovascular health (i.e. heart attack, stroke) at the forefront of modern bodybuilding health issues, anything we can do to help protect ourselves from this potentially life threatening side effect is of great value.
Aside from enhanced fat loss and improvements in metabolic-cardiovascular health, GW-501516 is well known to increase muscular endurance; the main reason why W.A.D.A. was so quick to have it added to the banned substance list for Olympic athletes. While this benefit doesn’t directly contribute to recovery or muscle growth, it indirectly improves growth potential by allowing one to train more intensely, particularly for those who tend to train with a lot of volume, take little rest time inbetween sets, or train in the higher rep range. This is especially true for leg training, which already places large demands on the body’s endurance capacity.
Because of its versatility, GW does not fit the description of either a pre-contest or off-season drug, but rather, is equally suited to both training phases. Furthermore, with a non-stimulatory nature, it is well-tolerated among all individuals. Whether your goal is increased fat loss, enhanced endurance, or improved metabolic-cardiovascular health, GW can be used as a complimentary or standalone agent to affect positive change in all of these areas.
