- Jun 25, 2006
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Interleukin-15The New Super-Anabolic?
It’s available for sale as a research chemical, but be ready to fork over as much as a few thousand dollars per milligram for it (yes, you read that correctly). It is Interleukin-15, a hormone belonging to a class of compounds referred to as pro-inflammatory cytokines. IL-15, which is natural to the human body, was only recently isolated and manufactured for research purposes, so it is a very new buzzword in the medical community. Combine the new mystique and high price with research suggesting muscle growth, and you can imagine why people are starting to whisper about it in the bodybuilding world. Some are calling it the “next big thing,” relaying vague stories about some guy in Europe who went from 185 pounds to a 250-pound show physique with the use of IL-15. Others swear it’s the secret to the winning physiques of many competitors right now; almost a necessity in the top ranks. But what do we really know for sure about this new drug? I thought it would be a good idea to cut through some of the rumor and rhetoric, and get to the heart of the real medical research being done on Interleukin-15. Several good studies have been conducted in the past few years, giving us a much better picture of what this new inflammatory cytokine may mean to the bodybuilding world than we had just a few years ago.
The In-Vitro Data
I believe the first study to really bring IL-15 to the attention of the bodybuilding community was one conducted at the Geriatric Research Education and Clinical Center in Tacoma, Washington, published in the journal Endocrinology in August, 1995.[1] This investigation involved the incubation (an in-vitro study) of IL-15 with mouse and bovine skeletal muscle cell preparations, in an effort to determine if it had a functional role in the growth of skeletal muscle. The results made note of very strong anabolic actions inherent in this hormone, with IL-15 increasing myosin heavy chain contractile protein content an incredible fivefold in the mouse cell culture, and 2.5 fold in the bovine cell culture. Further experiments comparing the anabolic effects of IGF-1 to IL-15 in the bovine culture yielded similar results with similar drug concentrations (IGF-1 and IL-15 were about equal at both the 10ng/ml and 100ng/ml dosage levels). Even an additive effect was noted when the two compounds were used together (increasing contractile proteins close to five-fold over baseline).About two years later another noteworthy in-vitro IL-15 study was published.[2] It was conducted in the same laboratory as the first, and was essentially a follow-up to look more closely at the underlying anabolic mechanisms of this hormone. One point of interest was that the first study failed to notice any difference in the proliferation and differentiation rates of muscle precursor cells known as myoblasts, which form into new adult muscle cells. This is quite different from IGF-1, which is known to exert most of its anabolic action via new cell proliferation (hyperplasia) instead of increases in existing cell size (hypertrophy).
The researchers were concerned that local IGF-1 concentrations in the cell preparations of the first study were masking the differentiating effects of IL-15, and believed that this hormone may indeed share similarities to IGF-1 here. To set the issue to rest, this time they used cell preparations that were engineered with strongly reduced sensitivity to IGF-1. When the study was conducted in this manner, IL-15 was finally shown to stimulate new muscle cell proliferation. The researchers, however, suggested that the cell proliferating effects of IL-15 might be most prominent when IGF-1 concentrations or bioactivity are actually low, such as in conditions of wasting or normal aging.
The In-Vivo Data
An in-vivo (live animal) study finally popped up in the British Journal of Cancer in August, 2000.[3] This investigation, as the previous in-vitro investigations had done, suggested activities in this hormone that would seem very attractive to the bodybuilder for the purpose of building muscle. Here, researchers specifically looked at the effects of IL-15 in tumor-bearing rats that were in a state of severe catabolism (a condition referred to as cancer cachexia). It’s estimated that approximately one third of all cancer deaths are actually due to the high protein breakdown and severe wasting associated with the disease,[4] so we can understand why effective anti-wasting treatments are extremely desirable in the medical community. In looking at IL-15 in this cancer model, the anti-catabolic effect of this drug turned out to be quite profound, lowering protein breakdown rates by an incredible eightfold. Protein catabolism actually dropped to levels lower than those that are typically noted in non-tumor-bearing animals, indicating a strong protective effect toward skeletal muscle tissue. IL-15 was starting to look like a possible alternative to some of the recently attempted, and often less than effective or desirable, wasting treatments such as GH or IGF-1.
Lackluster Results
Things really get interesting in 2001 though, when an in-vivo animal study was published that looked directly at both protein turnover and fat metabolism in response to IL-15 administration[5]. It was the first of the IL-15 studies conducted to look at protein turnover (both synthesis and degradation) in a normal (healthy) model, and was additionally the only investigation anywhere looking at lipolysis rates and changes in body fat disposition. Here, rats were given 100mcg/kg of IL-15, which was injected subcutaneously each day. The treatment period was 7 days, after which point the organs and muscles were weighed and compared to control animals. What was found was pretty startling, and in contrast to what we would probably have expected given all the previous in-vitro data. IL-15 suppressed the rates of both protein synthesis and degradation, such that there was no notable change in the rate of protein accumulation. Except the soleus muscle, which had a modest 7% increase in mass during the study, none of the muscles studied had any measurable increases in size at all. What did change though was the amount of white adipose tissue, which was reduced by a remarkable 33% in the treated animals. Even though the anabolic activity of IL-15 seemed less than dramatic in this study, a compound that could cut a third of your body fat in 7 days still has tremendous potential, no?
In Conclusion
So where do we stand on IL-15 now? Research is continuing on this hormone and its potential role as a muscle building/protecting agent, and we will learn more as it continues. With the effects of IL-15 on muscle mass in healthy rats turning out to be modest though, we do seem to have cause to question if whether it will prove useful as a true muscle-building anabolic for the bodybuilder (at least in the context of being the “next big thing”). From conversations with one of the scientists involved in the research, it appears the present line of thinking is that this hormone might play its most important role when the body is presented with intense (abnormally high) rates of protein breakdown. It would not be as significant as a tissue builder for someone with healthy (normal) protein turnover rates. It seems the researchers are mostly hoping that under severe catabolic conditions IL-15 can be effectively used to preserve lean body mass by restoring normal rates of protein breakdown, an activity well documented in the rat cancer cachexia model. If so, it may very well end up becoming a life-saving tool in the treatment of muscle wasting from cancer or AIDS, atrophy after severe injury and immobilization, or even muscle loss from aging (sarcopenia). Time will ultimately tell if IL-15 pans out as an anabolic in the bodybuilding world though (perhaps a cutting agent?), so for now I would suggest not cashing in that 401K.
References
[1] Interleukin-15: a novel anabolic cytokine for skeletal muscle. Quinn LS, Haugh KL, Grabstein KH. Endocrinol 1995 136 (8) 3669-72[2] Interkeukin-15 Stimulates Skeletal Myoblast Differentiation. LS Quinn, Haugk KL., Damon S. Biochem Biophys Res Comm 1997 239: 6-10
[3] Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Quinn LS, Carbo N, et al. Br J Cancer 2000 83(4):526-31
[4] Cachexia. Kotler DP. Ann Intern Med 2000 133:622-34
[5] Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control. Carbo N, Lopez-Soriano J, Quinn LS. Biochem Biophys Acta 2001 1526:17-24
Black Market Update
By William Llewellyn This month we’re going to take another look south of the border. More specifically, I’d like to discuss BratisLabs, the newest veterinary steroid manufacturer to pop up on the multi-million-dollar Mexican steroid market. BratisLabs first opened its doors a year or so ago, and were immediately looked upon with suspicion by the bodybuilding community. Things just didn’t seem to add up in the eyes of the general public. For one, the products were spreading all over Mexico, yet the lab was supposedly of Eastern European origin. This was an immediate standout characteristic, of course. The packaging was also very simplistic, with the line including only oral products sold in bottles of loose pills (the easiest type of fakes to produce) for quite some time. Everything seemed to suggest to the trained eye that an underground steroid marketer was actually responsible for the Bratis line, and not a legitimately licensed drug company. So the big question now is, were the skeptics right? Is Bratis stuff bunk? The answer, perhaps surprisingly, is no! Bratis does indeed appear to be a legitimately run veterinary drug company, and reportedly is now fully licensed by the Mexican government to operate. The European link, still displayed prominently on the company’s packaging, is said to be due to the fact that a partnership exists between principles of the company in both regions (Mexico and Europe). The feedback on the line has been pretty impressive in fact, with some bodybuilders now specifically seeking out the Bratis products because they feel they offer among the best value for the dollar. To date I have not substantiated any complaints concerning under-dosing or quality control issues, suggesting to me that Bratis is indeed a reliable operation. The line has been greatly expanded since the company first started operating, and now includes both oral and injectable products such as: Methandrol 10 (methandrostenolone 10mg x 500 tabs), Metabolan 25 (methenolone 25mg x 100 tabs), Oxandrol 10 (oxandrolone 10mg x 100 tab), Oxitron 50 (oxymetholone 50mg x 100 tabs), Stanol 10 (stanozolol 10mg X 250 tabs), Testron 4 250 (Sustanon clone 250mg/ml 10ml), Stanol 50 (stanozolol 50mg/ml 20ml) and Decatron 250 (nandrolone decanoate 250mg/ml 10ml).— WL
It’s available for sale as a research chemical, but be ready to fork over as much as a few thousand dollars per milligram for it (yes, you read that correctly). It is Interleukin-15, a hormone belonging to a class of compounds referred to as pro-inflammatory cytokines. IL-15, which is natural to the human body, was only recently isolated and manufactured for research purposes, so it is a very new buzzword in the medical community. Combine the new mystique and high price with research suggesting muscle growth, and you can imagine why people are starting to whisper about it in the bodybuilding world. Some are calling it the “next big thing,” relaying vague stories about some guy in Europe who went from 185 pounds to a 250-pound show physique with the use of IL-15. Others swear it’s the secret to the winning physiques of many competitors right now; almost a necessity in the top ranks. But what do we really know for sure about this new drug? I thought it would be a good idea to cut through some of the rumor and rhetoric, and get to the heart of the real medical research being done on Interleukin-15. Several good studies have been conducted in the past few years, giving us a much better picture of what this new inflammatory cytokine may mean to the bodybuilding world than we had just a few years ago.
The In-Vitro Data
I believe the first study to really bring IL-15 to the attention of the bodybuilding community was one conducted at the Geriatric Research Education and Clinical Center in Tacoma, Washington, published in the journal Endocrinology in August, 1995.[1] This investigation involved the incubation (an in-vitro study) of IL-15 with mouse and bovine skeletal muscle cell preparations, in an effort to determine if it had a functional role in the growth of skeletal muscle. The results made note of very strong anabolic actions inherent in this hormone, with IL-15 increasing myosin heavy chain contractile protein content an incredible fivefold in the mouse cell culture, and 2.5 fold in the bovine cell culture. Further experiments comparing the anabolic effects of IGF-1 to IL-15 in the bovine culture yielded similar results with similar drug concentrations (IGF-1 and IL-15 were about equal at both the 10ng/ml and 100ng/ml dosage levels). Even an additive effect was noted when the two compounds were used together (increasing contractile proteins close to five-fold over baseline).About two years later another noteworthy in-vitro IL-15 study was published.[2] It was conducted in the same laboratory as the first, and was essentially a follow-up to look more closely at the underlying anabolic mechanisms of this hormone. One point of interest was that the first study failed to notice any difference in the proliferation and differentiation rates of muscle precursor cells known as myoblasts, which form into new adult muscle cells. This is quite different from IGF-1, which is known to exert most of its anabolic action via new cell proliferation (hyperplasia) instead of increases in existing cell size (hypertrophy).
The researchers were concerned that local IGF-1 concentrations in the cell preparations of the first study were masking the differentiating effects of IL-15, and believed that this hormone may indeed share similarities to IGF-1 here. To set the issue to rest, this time they used cell preparations that were engineered with strongly reduced sensitivity to IGF-1. When the study was conducted in this manner, IL-15 was finally shown to stimulate new muscle cell proliferation. The researchers, however, suggested that the cell proliferating effects of IL-15 might be most prominent when IGF-1 concentrations or bioactivity are actually low, such as in conditions of wasting or normal aging.
The In-Vivo Data
An in-vivo (live animal) study finally popped up in the British Journal of Cancer in August, 2000.[3] This investigation, as the previous in-vitro investigations had done, suggested activities in this hormone that would seem very attractive to the bodybuilder for the purpose of building muscle. Here, researchers specifically looked at the effects of IL-15 in tumor-bearing rats that were in a state of severe catabolism (a condition referred to as cancer cachexia). It’s estimated that approximately one third of all cancer deaths are actually due to the high protein breakdown and severe wasting associated with the disease,[4] so we can understand why effective anti-wasting treatments are extremely desirable in the medical community. In looking at IL-15 in this cancer model, the anti-catabolic effect of this drug turned out to be quite profound, lowering protein breakdown rates by an incredible eightfold. Protein catabolism actually dropped to levels lower than those that are typically noted in non-tumor-bearing animals, indicating a strong protective effect toward skeletal muscle tissue. IL-15 was starting to look like a possible alternative to some of the recently attempted, and often less than effective or desirable, wasting treatments such as GH or IGF-1.
Lackluster Results
Things really get interesting in 2001 though, when an in-vivo animal study was published that looked directly at both protein turnover and fat metabolism in response to IL-15 administration[5]. It was the first of the IL-15 studies conducted to look at protein turnover (both synthesis and degradation) in a normal (healthy) model, and was additionally the only investigation anywhere looking at lipolysis rates and changes in body fat disposition. Here, rats were given 100mcg/kg of IL-15, which was injected subcutaneously each day. The treatment period was 7 days, after which point the organs and muscles were weighed and compared to control animals. What was found was pretty startling, and in contrast to what we would probably have expected given all the previous in-vitro data. IL-15 suppressed the rates of both protein synthesis and degradation, such that there was no notable change in the rate of protein accumulation. Except the soleus muscle, which had a modest 7% increase in mass during the study, none of the muscles studied had any measurable increases in size at all. What did change though was the amount of white adipose tissue, which was reduced by a remarkable 33% in the treated animals. Even though the anabolic activity of IL-15 seemed less than dramatic in this study, a compound that could cut a third of your body fat in 7 days still has tremendous potential, no?
In Conclusion
So where do we stand on IL-15 now? Research is continuing on this hormone and its potential role as a muscle building/protecting agent, and we will learn more as it continues. With the effects of IL-15 on muscle mass in healthy rats turning out to be modest though, we do seem to have cause to question if whether it will prove useful as a true muscle-building anabolic for the bodybuilder (at least in the context of being the “next big thing”). From conversations with one of the scientists involved in the research, it appears the present line of thinking is that this hormone might play its most important role when the body is presented with intense (abnormally high) rates of protein breakdown. It would not be as significant as a tissue builder for someone with healthy (normal) protein turnover rates. It seems the researchers are mostly hoping that under severe catabolic conditions IL-15 can be effectively used to preserve lean body mass by restoring normal rates of protein breakdown, an activity well documented in the rat cancer cachexia model. If so, it may very well end up becoming a life-saving tool in the treatment of muscle wasting from cancer or AIDS, atrophy after severe injury and immobilization, or even muscle loss from aging (sarcopenia). Time will ultimately tell if IL-15 pans out as an anabolic in the bodybuilding world though (perhaps a cutting agent?), so for now I would suggest not cashing in that 401K.
References
[1] Interleukin-15: a novel anabolic cytokine for skeletal muscle. Quinn LS, Haugh KL, Grabstein KH. Endocrinol 1995 136 (8) 3669-72[2] Interkeukin-15 Stimulates Skeletal Myoblast Differentiation. LS Quinn, Haugk KL., Damon S. Biochem Biophys Res Comm 1997 239: 6-10
[3] Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Quinn LS, Carbo N, et al. Br J Cancer 2000 83(4):526-31
[4] Cachexia. Kotler DP. Ann Intern Med 2000 133:622-34
[5] Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control. Carbo N, Lopez-Soriano J, Quinn LS. Biochem Biophys Acta 2001 1526:17-24
Black Market Update
By William Llewellyn This month we’re going to take another look south of the border. More specifically, I’d like to discuss BratisLabs, the newest veterinary steroid manufacturer to pop up on the multi-million-dollar Mexican steroid market. BratisLabs first opened its doors a year or so ago, and were immediately looked upon with suspicion by the bodybuilding community. Things just didn’t seem to add up in the eyes of the general public. For one, the products were spreading all over Mexico, yet the lab was supposedly of Eastern European origin. This was an immediate standout characteristic, of course. The packaging was also very simplistic, with the line including only oral products sold in bottles of loose pills (the easiest type of fakes to produce) for quite some time. Everything seemed to suggest to the trained eye that an underground steroid marketer was actually responsible for the Bratis line, and not a legitimately licensed drug company. So the big question now is, were the skeptics right? Is Bratis stuff bunk? The answer, perhaps surprisingly, is no! Bratis does indeed appear to be a legitimately run veterinary drug company, and reportedly is now fully licensed by the Mexican government to operate. The European link, still displayed prominently on the company’s packaging, is said to be due to the fact that a partnership exists between principles of the company in both regions (Mexico and Europe). The feedback on the line has been pretty impressive in fact, with some bodybuilders now specifically seeking out the Bratis products because they feel they offer among the best value for the dollar. To date I have not substantiated any complaints concerning under-dosing or quality control issues, suggesting to me that Bratis is indeed a reliable operation. The line has been greatly expanded since the company first started operating, and now includes both oral and injectable products such as: Methandrol 10 (methandrostenolone 10mg x 500 tabs), Metabolan 25 (methenolone 25mg x 100 tabs), Oxandrol 10 (oxandrolone 10mg x 100 tab), Oxitron 50 (oxymetholone 50mg x 100 tabs), Stanol 10 (stanozolol 10mg X 250 tabs), Testron 4 250 (Sustanon clone 250mg/ml 10ml), Stanol 50 (stanozolol 50mg/ml 20ml) and Decatron 250 (nandrolone decanoate 250mg/ml 10ml).— WL