Growth Hormone and Fat Loss
Written by Dan Gwartney, MD
09 April 2007
For bodybuilders, there is no questioning the ability of growth hormone to increase fat loss and improve both muscle growth and definition.1 However, despite the epidemic of obesity that's threatening the U.S. economy with a health care crisis, pharmaceutical companies seem unwilling to develop the hormone for this use. This is surprising, given the number of physiologic benefits growth hormone replacement has been shown to provide and the immense revenue stream it would generate.2
There appears to be a significant amount of support for such use within the medical community, though a majority of physicians still hold reservations. One group, the American Academy of Anti-Aging Medicine (A4M), serves a growing and influential demographic of the U.S. population. It administers hormone replacement and nutritional guidance to baby boomers who wish to stave off the deleterious effects of aging. Though the A4M criticizes performance drug use by athletes and was founded by the writers of the book Death in the Locker Room, a book that highly criticized steroid use, its mission closely mirrors the goal of many bodybuilders- to optimize health.3 Whereas the A4M focuses on staving off the debilitating effects of aging and prolonging life, bodybuilders seek to optimize performance and appearance throughout adulthood.
The Evolution of GH
Growth hormone has long been used to correct growth deficiencies in children.4 The original source of growth hormone was a rather crude extract from the pituitary (brain) of dead people. This cadaveric-derived growth hormone was effective, but carried the risk of a life-threatening infection called Creutzfeld-Jacob disease.5 C-J disease is the human form of "mad cow" disease. Due to the source and high risk of infection, cadaveric growth hormone was produced in limited supply and used only in the most severe cases.
An advanced technique of producing growth hormone in the lab was developed during the 1970s and 1980s, allowing for increased production with no risk of infection. The technique, called recombinant technology, involved placing the gene for the growth hormone protein into bacteria.6 Growth hormone could then be separated in highly concentrated quantities with guaranteed purity. With the availability of recombinant growth hormone (rGH), research into other possible benefits of rGH therapy soon followed.
It was known early on that growth hormone deficiency causes problems in adults as well as children, but until the advent of rGH, little could be done. Growth hormone deficient adults typically suffer from a myriad of symptoms, including obesity, heart failure, bone loss and a poor quality of life.6 Growth hormone replacement with rGH corrects these symptoms without causing negative side effects, when therapy is monitored by a physician.2
Growth hormone therapy has advanced considerably since the early days. Whereas the original material was derived from the pituitaries of cadavers, rGH is now produced in sterile labs. There are differences in the material beyond the source that need to be considered. Cadaveric GH consists of GH as it is produced by the body. It's composed of many different forms of GH. Some are heavier, others lighter, and many are joined as dimers (two GH molecules bonded together) or tetramers (four GH molecules bonded together).7 It's unknown if the more varied natural pattern of GH offers benefits beyond the 22-Kd form present in rGH. It's likely there are actions or benefits present in the natural forms that are not accounted for in rGH, but having uniform material makes dosing and treatment much easier and more predictable in practice. Thus far, no reports of identified deficiencies or syndromes have evolved from rGH use.
Comparing GH Efficiency
Recently, an excellent review on growth hormone therapy was published in the journal Growth Hormone & IGF Research.6 Revisiting the original days of growth hormone therapy, the review evaluated various treatment protocols and benefits ascribed to rGH treatment. The author of the review, Torben Laursen, explained how cadaveric GH was injected intramuscularly in physicians' clinics two to three times per week.
Comparing the pharmacokinetics (how quickly and efficiently a drug is delivered and cleared), Laursen demonstrated how, despite the improvement in growth rates, early treatment protocols were less than ideal. When injected into the muscle, GH enters the bloodstream quickly and has a short half-life.8 Despite delivering a higher peak concentration, IM-administered GH is cleared from the system as rapidly as 12 hours. This left patients devoid of GH benefits for 36-60 hours between treatments.
Improved pharmacokinetics are provided when the hormone is injected under the skin (subcutaneous, SC). SC-injected rGH reaches its peak concentration more slowly (four to six hours) but levels remain elevated for approximately 16 hours. Approximately 50-70 percent of an SC dose is absorbed.9 The pattern of release following SC injection more closely mimics the natural rhythm. Some additional benefits, such as higher IGF-1 levels, were noted when a second daily SC injection was added to the regimen, though some drawbacks also existed.10 Adding a second SC injection maintains high free fatty acids (FFA) in the blood, which interferes with insulin sensitivity. Also, IGF-1 can interfere with the ability of insulin to connect with receptors, a step that's vital for normal glucose entry into cells, particularly skeletal muscle. These effects may combine to cause the body to increase the baseline levels of insulin, which can lead to fat gain and may even progress into a pre-diabetic state known as glucose intolerance.
Laursen's review was of further value in reporting on the suitability of various sites for SC injections.6 The abdomen is the most common site for injections, but due to the frequency (daily or twice-daily) of injections, other sites are often used due to bruising, soreness or other reasons. Many patients use the thigh for injections, which delivers the drug as well as does the abdomen, so long as the injections are carefully placed in the SC space and do not penetrate into the underlying muscle. When injected into the muscle of the thigh, rGH enters and clears the system too quickly. This point is of particular relevance to bodybuilders, who typically are much leaner than average people.
Body Fat and Anabolic Effects
It's clear from published studies that rGH therapy reduces body fat and increases lean muscle in GH-deficient adults. It is further evident from the results obtained by today's professional bodybuilders that rGH can also dramatically reduce body fat in healthy, lean adults while maintaining muscle mass.
Growth hormone appears to have more than one mechanism of improving body composition, reducing body fat and increasing lean mass. The fat cells, particularly fat deposited on or within the abdomen, have GH receptors that cause free fatty acids (FFA) to be released when stimulated.11 These FFA circulate through the body and reduce the demand for protein to be broken down to form glucose during periods of starvation. If the metabolic demand is not high enough, these FFA are re-deposited as fat, but the amino acid pools in muscle and the liver are preserved. This is referred to as the lipolytic effect of GH.4
Bodybuilders also benefit from the anabolic effects of rGH. Receptors exist on muscle cells as well, which activate the production of certain proteins in muscle cells, including the formation of IGF-1. IGF-1 is a secondary messenger that acts throughout the body to promote tissue growth. While blood levels of IGF-1 are measured, this predominantly reflects IGF-1 produced in the liver.12 Determining circulating (blood) levels of GH and IGF-1 is useful for monitoring therapy, but the effects of both hormones are only relevant at the cellular level. When rGH stimulates GH-receptors on muscle cells, the IGF-1 produced only acts strongly on the cells and tissues immediately adjacent.
One matter that is not clearly discussed in Laursen's review is dosing. For treatment of GH-deficiency, dosing is an individual matter. A patient may be placed on a standard starting dose and followed weekly or monthly by monitoring blood levels of IGF-1, as well as any symptoms or complaints that initiated treatment.13 Once a normal IGF-1 level is reached, the dose is set unless there is an event that requires a change in treatment. This could include problems with blood glucose, carpal tunnel syndrome, etc.
For the bodybuilder, particularly without the benefit of physician monitoring, this is much more problematic; nearly all research done on humans involved GH-deficient people. It is impossible to predict from that group how rGH treatment may affect people with normal pituitary function (the site of GH production and release). It's clear that the high doses given to GH-deficient children are excessive for healthy adults. In fact, some bodybuilders have developed acromegaly (an overgrowth of bones and organs resulting in a freakish appearance) from the early days of rGH trial and error.
Close Monitoring Needed
Most of the benefits of rGH therapy are dose-dependent, meaning that greater benefits come with higher doses. However, nearly all the direct adverse effects of rGH are dose-dependent, as well.14 It is critical for healthy adults who are considering rGH use to monitor IGF-1 levels as well as blood glucose and insulin, while watching closely for any of the common side effects. It is also critical that users of rGH consider the risk of GH increasing the growth or malignancy of benign tumors or malignant cancers. Physicians who may be agreeable to the use of rGH for healthy adults typically start with low doses, gradually titrating the dose with slight increases until suitable results are obtained. Common starting doses may be as low as one to two International Units (IU) rGH per day for five days per week. Keeping doses low may prolong the time required to achieve the body composition changes desired, but the risk of side effects can be minimized. This was recently proven in a study published in the Journal of Clinical Endocrinology & Metabolism, sponsored in part by the pharmaceutical company Pfizer.15
It's likely that as the anti-aging movement grows, rGH therapy for middle-aged adults will become more prevalent. Whether this translates to medical supervision and direction of hormone therapy for athletes remains to be seen, though in the current political environment, it is unlikely.
References
1. Llewellyn W. Growth hormone. Anabolics 2004. Molecular Nutrition Press, Jupiter, Fl;2004:
2. American Academy of Anti-Aging Medicine Official Position Statement. Safety and Efficacy of Adult Human Growth Hormone Therapy. Issued Nov 12, 2002.
3. Goldman B, Bush P, Klatz R. Death in the Locker Room: Steroids, Cocaine & Sports. The Body Press, Tucson, AZ; 1987.
4. Raben MS, Hollenberg CH. Effects of growth hormone on plasma fatty acids. J Clin Invest, 1959;38:484-8.
5. Buchanan CR, Preece MA, et al. Mortality, neoplasia, and Creutzfeld-Jakob's disease in patients treated with human pituitary growth hormone in the United Kingdom. BMJ, 1991;302:824-8.
6. Laursen T. Clinical pharmacological aspects of growth hormone administration. Growth Hormone & IGF-1 Research, 2004;14:16-44.
7. Baumann G. Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins. Endocr Rev, 1991;12:424-49.
8. Ziesel HJ, von Petrykowski U, et al. Pharmacokinetics and short-term metabolic effects of mammalian cell-derived biosynthetic human growth hormone in man. Horm Res, 1992;37(Suppl 2):5-13.
9. Janssen YJ, Frolich M, et al. The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency. Br J Clin Pharmacol, 1999;47:273-8.
10. Laursen T, Jorgensen JOL, et al. Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults. Clin Endocrinol, 1994;41:337-43.
11. Spina LCD, Soares DV, et al. Glucose metabolism and visceral fat in GH deficient adults: 1 year of GH replacement. Growth Hormone & IGF-1 Research, 2004;14:45-51.
12. Sjogren K, Liu JL, et al. Liver-derived insulin-like growth factor (IGF-1) is the principal source of IGF-1 in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci, USA 1999;96:7088-92.
13. Johannsson G, Rosen T, et al. Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults. Clin Endocrinol Oxf, 1997;47:571-81.
14. Holmes SJ, Shalet SM. Which adults develop side-effects of growth hormone replacement? Clin Endocrinol Oxf, 1995;43:143-9.
15. Albert SG, Mooradian AD. Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Meta, 2004 Feb;89:695-701.
There appears to be a significant amount of support for such use within the medical community, though a majority of physicians still hold reservations. One group, the American Academy of Anti-Aging Medicine (A4M), serves a growing and influential demographic of the U.S. population. It administers hormone replacement and nutritional guidance to baby boomers who wish to stave off the deleterious effects of aging. Though the A4M criticizes performance drug use by athletes and was founded by the writers of the book Death in the Locker Room, a book that highly criticized steroid use, its mission closely mirrors the goal of many bodybuilders- to optimize health.3 Whereas the A4M focuses on staving off the debilitating effects of aging and prolonging life, bodybuilders seek to optimize performance and appearance throughout adulthood.
The Evolution of GH
Growth hormone has long been used to correct growth deficiencies in children.4 The original source of growth hormone was a rather crude extract from the pituitary (brain) of dead people. This cadaveric-derived growth hormone was effective, but carried the risk of a life-threatening infection called Creutzfeld-Jacob disease.5 C-J disease is the human form of "mad cow" disease. Due to the source and high risk of infection, cadaveric growth hormone was produced in limited supply and used only in the most severe cases.
An advanced technique of producing growth hormone in the lab was developed during the 1970s and 1980s, allowing for increased production with no risk of infection. The technique, called recombinant technology, involved placing the gene for the growth hormone protein into bacteria.6 Growth hormone could then be separated in highly concentrated quantities with guaranteed purity. With the availability of recombinant growth hormone (rGH), research into other possible benefits of rGH therapy soon followed.
It was known early on that growth hormone deficiency causes problems in adults as well as children, but until the advent of rGH, little could be done. Growth hormone deficient adults typically suffer from a myriad of symptoms, including obesity, heart failure, bone loss and a poor quality of life.6 Growth hormone replacement with rGH corrects these symptoms without causing negative side effects, when therapy is monitored by a physician.2
Growth hormone therapy has advanced considerably since the early days. Whereas the original material was derived from the pituitaries of cadavers, rGH is now produced in sterile labs. There are differences in the material beyond the source that need to be considered. Cadaveric GH consists of GH as it is produced by the body. It's composed of many different forms of GH. Some are heavier, others lighter, and many are joined as dimers (two GH molecules bonded together) or tetramers (four GH molecules bonded together).7 It's unknown if the more varied natural pattern of GH offers benefits beyond the 22-Kd form present in rGH. It's likely there are actions or benefits present in the natural forms that are not accounted for in rGH, but having uniform material makes dosing and treatment much easier and more predictable in practice. Thus far, no reports of identified deficiencies or syndromes have evolved from rGH use.
Comparing GH Efficiency
Recently, an excellent review on growth hormone therapy was published in the journal Growth Hormone & IGF Research.6 Revisiting the original days of growth hormone therapy, the review evaluated various treatment protocols and benefits ascribed to rGH treatment. The author of the review, Torben Laursen, explained how cadaveric GH was injected intramuscularly in physicians' clinics two to three times per week.
Comparing the pharmacokinetics (how quickly and efficiently a drug is delivered and cleared), Laursen demonstrated how, despite the improvement in growth rates, early treatment protocols were less than ideal. When injected into the muscle, GH enters the bloodstream quickly and has a short half-life.8 Despite delivering a higher peak concentration, IM-administered GH is cleared from the system as rapidly as 12 hours. This left patients devoid of GH benefits for 36-60 hours between treatments.
Improved pharmacokinetics are provided when the hormone is injected under the skin (subcutaneous, SC). SC-injected rGH reaches its peak concentration more slowly (four to six hours) but levels remain elevated for approximately 16 hours. Approximately 50-70 percent of an SC dose is absorbed.9 The pattern of release following SC injection more closely mimics the natural rhythm. Some additional benefits, such as higher IGF-1 levels, were noted when a second daily SC injection was added to the regimen, though some drawbacks also existed.10 Adding a second SC injection maintains high free fatty acids (FFA) in the blood, which interferes with insulin sensitivity. Also, IGF-1 can interfere with the ability of insulin to connect with receptors, a step that's vital for normal glucose entry into cells, particularly skeletal muscle. These effects may combine to cause the body to increase the baseline levels of insulin, which can lead to fat gain and may even progress into a pre-diabetic state known as glucose intolerance.
Laursen's review was of further value in reporting on the suitability of various sites for SC injections.6 The abdomen is the most common site for injections, but due to the frequency (daily or twice-daily) of injections, other sites are often used due to bruising, soreness or other reasons. Many patients use the thigh for injections, which delivers the drug as well as does the abdomen, so long as the injections are carefully placed in the SC space and do not penetrate into the underlying muscle. When injected into the muscle of the thigh, rGH enters and clears the system too quickly. This point is of particular relevance to bodybuilders, who typically are much leaner than average people.
Body Fat and Anabolic Effects
It's clear from published studies that rGH therapy reduces body fat and increases lean muscle in GH-deficient adults. It is further evident from the results obtained by today's professional bodybuilders that rGH can also dramatically reduce body fat in healthy, lean adults while maintaining muscle mass.
Growth hormone appears to have more than one mechanism of improving body composition, reducing body fat and increasing lean mass. The fat cells, particularly fat deposited on or within the abdomen, have GH receptors that cause free fatty acids (FFA) to be released when stimulated.11 These FFA circulate through the body and reduce the demand for protein to be broken down to form glucose during periods of starvation. If the metabolic demand is not high enough, these FFA are re-deposited as fat, but the amino acid pools in muscle and the liver are preserved. This is referred to as the lipolytic effect of GH.4
Bodybuilders also benefit from the anabolic effects of rGH. Receptors exist on muscle cells as well, which activate the production of certain proteins in muscle cells, including the formation of IGF-1. IGF-1 is a secondary messenger that acts throughout the body to promote tissue growth. While blood levels of IGF-1 are measured, this predominantly reflects IGF-1 produced in the liver.12 Determining circulating (blood) levels of GH and IGF-1 is useful for monitoring therapy, but the effects of both hormones are only relevant at the cellular level. When rGH stimulates GH-receptors on muscle cells, the IGF-1 produced only acts strongly on the cells and tissues immediately adjacent.
One matter that is not clearly discussed in Laursen's review is dosing. For treatment of GH-deficiency, dosing is an individual matter. A patient may be placed on a standard starting dose and followed weekly or monthly by monitoring blood levels of IGF-1, as well as any symptoms or complaints that initiated treatment.13 Once a normal IGF-1 level is reached, the dose is set unless there is an event that requires a change in treatment. This could include problems with blood glucose, carpal tunnel syndrome, etc.
For the bodybuilder, particularly without the benefit of physician monitoring, this is much more problematic; nearly all research done on humans involved GH-deficient people. It is impossible to predict from that group how rGH treatment may affect people with normal pituitary function (the site of GH production and release). It's clear that the high doses given to GH-deficient children are excessive for healthy adults. In fact, some bodybuilders have developed acromegaly (an overgrowth of bones and organs resulting in a freakish appearance) from the early days of rGH trial and error.
Close Monitoring Needed
Most of the benefits of rGH therapy are dose-dependent, meaning that greater benefits come with higher doses. However, nearly all the direct adverse effects of rGH are dose-dependent, as well.14 It is critical for healthy adults who are considering rGH use to monitor IGF-1 levels as well as blood glucose and insulin, while watching closely for any of the common side effects. It is also critical that users of rGH consider the risk of GH increasing the growth or malignancy of benign tumors or malignant cancers. Physicians who may be agreeable to the use of rGH for healthy adults typically start with low doses, gradually titrating the dose with slight increases until suitable results are obtained. Common starting doses may be as low as one to two International Units (IU) rGH per day for five days per week. Keeping doses low may prolong the time required to achieve the body composition changes desired, but the risk of side effects can be minimized. This was recently proven in a study published in the Journal of Clinical Endocrinology & Metabolism, sponsored in part by the pharmaceutical company Pfizer.15
It's likely that as the anti-aging movement grows, rGH therapy for middle-aged adults will become more prevalent. Whether this translates to medical supervision and direction of hormone therapy for athletes remains to be seen, though in the current political environment, it is unlikely.
References
1. Llewellyn W. Growth hormone. Anabolics 2004. Molecular Nutrition Press, Jupiter, Fl;2004:
2. American Academy of Anti-Aging Medicine Official Position Statement. Safety and Efficacy of Adult Human Growth Hormone Therapy. Issued Nov 12, 2002.
3. Goldman B, Bush P, Klatz R. Death in the Locker Room: Steroids, Cocaine & Sports. The Body Press, Tucson, AZ; 1987.
4. Raben MS, Hollenberg CH. Effects of growth hormone on plasma fatty acids. J Clin Invest, 1959;38:484-8.
5. Buchanan CR, Preece MA, et al. Mortality, neoplasia, and Creutzfeld-Jakob's disease in patients treated with human pituitary growth hormone in the United Kingdom. BMJ, 1991;302:824-8.
6. Laursen T. Clinical pharmacological aspects of growth hormone administration. Growth Hormone & IGF-1 Research, 2004;14:16-44.
7. Baumann G. Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins. Endocr Rev, 1991;12:424-49.
8. Ziesel HJ, von Petrykowski U, et al. Pharmacokinetics and short-term metabolic effects of mammalian cell-derived biosynthetic human growth hormone in man. Horm Res, 1992;37(Suppl 2):5-13.
9. Janssen YJ, Frolich M, et al. The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency. Br J Clin Pharmacol, 1999;47:273-8.
10. Laursen T, Jorgensen JOL, et al. Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults. Clin Endocrinol, 1994;41:337-43.
11. Spina LCD, Soares DV, et al. Glucose metabolism and visceral fat in GH deficient adults: 1 year of GH replacement. Growth Hormone & IGF-1 Research, 2004;14:45-51.
12. Sjogren K, Liu JL, et al. Liver-derived insulin-like growth factor (IGF-1) is the principal source of IGF-1 in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci, USA 1999;96:7088-92.
13. Johannsson G, Rosen T, et al. Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults. Clin Endocrinol Oxf, 1997;47:571-81.
14. Holmes SJ, Shalet SM. Which adults develop side-effects of growth hormone replacement? Clin Endocrinol Oxf, 1995;43:143-9.
15. Albert SG, Mooradian AD. Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Meta, 2004 Feb;89:695-701.