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Growing Beyond What Nature Intended Part 3 – Steroid Synergy with GH, IGF-1, Insulin, and Thryoid
November 1, 1999 By Bryan Hypertrophy Leave a Comment
The Feasibility of Using GH, IGF-1, Insulin, and Thryoid to Enhance the Anabolic Effects of Androgens
Warning: The following information is intended only as a hypothetical consideration of ways in which human physiology may be altered, through pharmacological means, to achieve striking muscularity. The drugs discussed in this series of articles are, by and large, prescription drugs and should not be used without the supervision of a qualified physician. No attempt should be made to circumvent the laws in your area to obtain these drugs without a prescription. As always, Meso-Rx does not condone in any way the illegal acquisition and/or use of prescription drugs for purposes other than those approved by the FDA or other legally recognized regulatory bodies.
In the first installment of this series we discussed the mechanism by which human growth hormone (GH) exerts its anabolic effects in the body. We also discussed the important role of insulin-like growth factor-1 (IGF-1) in the anabolic properties of GH. In part two we discussed the role of androgens in GH secretion and sensitivity in a hypothetical pharmacological regimen aimed at dramatically increasing skeletal muscle growth. Based on research looking at the effects of androgens on GH secretion and IGF-1 sensitivity, it was deduced that the testosterone esters should provide the most potent anabolic stimulus compared to other androgens, especially those that do not aromatize. Now, in the final installment, we shall look at the feasibility of using GH, IGF-1, Insulin, and perhaps tri-iodothyronine (T3) to enhance the anabolic properties of androgens.
Growth hormone
What would an article about GH be without some useful discussion of GH! First let me quote a well known bodybuilding advisor named Daniel Duchaine;
To put it bluntly, studies involving GH and healthy young men show that although circulating IGF-1 is elevated with GH therapy there is little or no change in muscle protein synthesis rates (1,2,3). Deysigg (1) looked at the effect of recombinant GH on strength, body composition and endocrine parameters in power athletes. Subjects received in a double-blind manner either GH treatment (0.09IU/kg/day) or placebo for a period of six weeks. To avoid confounding factors such as concurrent us of steroids, urine specimens were tested at regular intervals for these substances. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated group. There was no effect of GH treatment on maximal strength or body composition.
Other studies have observed similar results. Yarasheski (2) conducted a 12 week study with sixteen men (21-34 yr) assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). Both groups trained all major muscle groups in an identical fashion while receiving 40 µg GH/kg/day or placebo. Fat-free mass (FFM) and total body water increased in both groups but more in the GH recipients. Whole body protein synthesis rate increased more, and whole body protein balance was greater in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis. The larger increase in FFM with GH treatment can simply be attributed to an increase in total body water. In this study as well as the previous one, resistance training supplemented with GH did not further enhance muscle growth or strength.
Later, Yarasheski performed a similar study but this time he used experienced weight lifters (3). Skeletal muscle protein synthesis and the whole body rate of protein breakdown were determined using labeled amino acids ([13C]leucine) in 7 young healthy experienced male weight lifters before and at the end of 14 days of subcutaneous GH administration (40 µg/kg/day). GH administration doubled fasting insulin-like growth factor-I levels, but did not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown. These findings confirm what others have found, namely that short-term GH treatment does not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown.
You may argue that in the real world, bodybuilders don’t use GH alone. It is generally combined with some form of anabolic steroid. Unfortunately I was unable to find a controlled study looking at the effectiveness of combining androgens and GH in healthy athletes for the purposes of building muscle. There is one study however that looked at the effects of combining both very high doses of androgens (up to 2.4 mg/kg/day) with or without concomitant GH use (4IU/day) (4). In all cases, using androgens with GH caused a significant decline in IGFBP3 levels. As you know, this dramatically decreases the half life of IGF-1 and thus the biological activity is attenuated. One other very enlightening finding of this study was that on a low calorie diet, it didn’t matter how much androgens or GH they were using, both IGF-1 and IGFBP-3 declined significantly. Clearly the effectiveness of any cycle using androgens with or without GH will be greatly diminished by lowering calories, and more importantly total protein. Still, the one question you may have, namely does high dose androgens make GH worth using, was not addresses by this study. The consensus generally is still no.
In HIV patients work is being done to determine if GH or androgens will prevent wasting. In these studies Deca Durablolin and other androgens have proven successful at preserving lean mass while GH has not proven to be effective (4). Concerning GH treatment in unhealthy populations, Michael Mooney, a well respected authority on HIV and muscle preservation, has challenged the claims made by at least one manufacturer of a GH product called Serostim. He wrote a letter to them challenging their claims that Serostim or any other brand of GH has true anabolic effects in this population.
MK-677?
But…keep your eye out for a new GH secretagogue called Merck-677 or simply MK-677. A secretagogue is a substance that isn’t GH itself, but instead causes the body to increase it’s natural GH release. One thing that is unique about MK-677 is that it works within the body’s natural GH secretion patterns, as opposed to simply causing bolus and sudden increases in circulating GH. As mentioned earlier, negative feedback has been one of the main problems with using GH for muscle growth in adults. MK-677 is orally active (no more needles), it isn’t a protein based hormone yet it mimics GHRH and increases GH levels in a pulsatile fashion. Early studies have already shown it to reverse diet induced muscle loss in healthy adults (5). In fact, a single oral 25 mg dose per day was all that was needed to reverse muscle wasting during caloric restriction (18Kcal/kg/day). Merck will be trying to find as many applications for this drug as possible. Very interesting. Yes,…very interesting.
IGF-1
IGF-1, or insulin-like growth factor-1, is known to be the mediator of GH anabolic effects so it is natural that it would also be investigated as an anabolic. As it turns out, IGF-1 is indeed anabolic. IGF-1’s anabolic effects are limited only by amino acid supply within muscle cells (6,7) . In essence, the more you eat, the more you grow with IGF-1. Unfortunately, simply elevating serum IGF-1 has not proven to be anabolic in healthy individuals (1,2,3). In addition, the side effects of using significant dosages make using pure IGF-1 prohibitive. IGF-I does not naturally exist in quantity free of its binding proteins, and limitations associated with administering free IGF-I (i.e. Long R3IGF-1) therapeutically have proven significant: acute insulin effects (e.g. hypoglycemia), suppression of growth hormone secretion, edema, hypotension, tachycardia, very short circulating half life, and limited and transient efficacy at safe dosage levels (8,9,10). LR3IGF-I has very low affinity for the IGF-binding proteins in the rat and hence is cleared from the circulation more quickly than is IGF-I. Yet because it stays free from binding proteins it is generally more potent unit per unit.
Keeping everything working, . . .or so we thought: Insulin & T3
Form the very onset let me say that I cannot in good conscience recommend that a body builder use insulin. This trend started a few years ago when some prominent people touted insulin as the mother of all anabolic hormones. Certainly if this were the case, type-II diabetics using huge amounts of insulin would not be bulging with fat, but instead bulging with muscles. Insulin is not anabolic in adult humans. Although extreme hyperinsulinemia has been shown to stimulate protein synthesis in isolated limb infusion experiments (13), these anabolic properties are ultimately the result of insulin binding to IGF-1 receptors. It was also used in a last ditch attempt to get GH to work, the rational being that maybe GH wasn’t working because of the concomitant insulin resistance. Unfortunately taking more and more insulin to combat GH induced insulin resistance leads to secondary negative side effects associated with hyperinsulinemia. Hyperinsulinemia causes the smooth muscles in your blood vessels to grow until the vessel openings become too small, predisposing yourself to a heart attack. By the way, the leading cause of death of type-II diabetics using insulin is from cardiovascular problems. In general, most bodybuilders are fooled by the tremendous increase in glycogen and water storage, making them feel “fuller”. The natural insulinogenic effect of carbohydrates combined with a fast protein like whey isolate is sufficiently anabolic in high quantities to induce dramatic glucose and amino acid uptake in muscle tissue. I can’t say as though I blame people though, when the gains stop coming and you’ve just taken out a second mortgage to pay for this GH, you find yourself willing to try anything. Nonetheless, throwing caution to the wind is not the answer.
Thyroid hormones, on the other hand, offer significant benefits when used cautiously and “properly”. They should not be used haphazardly as a fat loss agent however, instead they are valuable in correcting thyroid dysfunction brought on by androgen use. When done properly, T3 is used as “replacement therapy” and serves only to normalize decreased T3 levels. Research has shown that high dose androgens pushes T3 levels down (14,15). This is significant because the real value of optimal thyroid levels is not for fat loss, but instead for optimum anabolic activity. T3 has diverse facilitative anabolic effects including, increasing GH secretion(16,17), up-regulating GH receptors (18), up-regulating IGF-1 receptors (19,20), and other less well defined anabolic effects (21,22). Don’t get the wrong idea however, for T3 to facilitate anabolism, it must stay in the high normal range. A little too high or a little too low significantly changes the biological effects of thyroid hormones. Bringing T3 levels too high will undoubtedly backfire and lead to muscle, strength losses, and rebound fat gain.
You will need regular blood tests to determine the optimal dose of T3 (e.g. Cytomel) to bring you up to the optimum range. If you are unwilling, or do not have access to, regular blood work I would not recommend using T3. The old “take your morning temperature” recommendation is simply too inaccurate. Most people use way too much T3 and cause more problems than anything else. However, if you are willing to take care of yourself while optimizing muscle gains, have your free T3 checked before using any T3, yet during your full dose androgen regimen. Try to bring your free T3 levels up to ~7.0-7.4 pmol/L. Your doctor may use conventional units on your blood work which means it will read in “pg/dL”. If that’s the case bring your levels up to about 450-480 pg/dL. Doing this will allow optimal caloric intake while minimizing fat gain, as well as optimize the anabolic actions of the androgens you are using.
In summary, GH acting primarily through IGF-1 is a very powerful anabolic hormone. So powerful that the body has set in place complex systems to control the anabolic effects of both GH and IGF-1 in order to prevent unnatural muscle growth. These systems have thwarted our attempts at using bolus injections of GH and IGF-1 in their isolated forms to grow beyond what nature intended. Hope may be on the horizon however, as new ways of increasing GH levels (e.g. MK-677) that more closely matches naturally occurring secretion patterns show promise, as well as new forms of IGF-1 that are identical to naturally occurring forms (e.g. Somatokine) show more predictable anabolic properties with fewer side effects. Initial results are indeed promising and could lead to the emergence of a mandatory addition to our present androgen-based regimens.
References:
1. Deyssig, R., Frisch H., Blum WF., and Waldhor T. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Act Endocrinol. 128:313-318, 1998.
2. Yarasheski KE., Campbell JA., Smith K., et al: Effect of growth hormone and resistance exercise on muscle growth in young men. Am. J Physiol. 262 (Endocrinol. Metab. 25):E261-E267, 1992.
3. Yarasheski KE., Zachwieja JJ., Angelopolous TJ., and Bier DM. Short term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J. Appl. Physiol. 74:3073-3076, 1993.
4. Karila T., Koistinen H., Seppala M., Koisten R., & Seppala T. Growth hormone induced increases in serum IGFBP-3 levels is reversed by anabolic steroids in substance abusing power athletes. Clin. Endocrinol. 49:459-463, 1998
5. Sattler FR, Jaque SV, Schroeder ET, Olson C, Dube MP, Martinez C, Briggs W, Horton R, Azen S. Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus J Clin Endocrinol Metab. 84(4):1268-76, 1999
6. Murphy MG, Plunkett LM, Gertz BJ, He W, Wittreich J, Polvino WM, Clemmons DR. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. 83(2):320-5, 1998
7. Fryburg DA, Jahn LA, Hill SA, Oliveras DM, Barrett EJ. Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms. J Clin Invest. 96(4):1722-9, 1995
8. Fryburg DA. Insulin-like growth factor I exerts growth hormone- and insulin-like actions on human muscle protein metabolism. Am J Physiol. 267(2 Pt 1):E331-6, 1994
9. Ebeling PR, Jones JD, O’Fallon WM, Janes CH, Riggs BL. Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women. J Clin Endocrinol Metab 77(5):1384-7, 1993
10. Guler HP, Zapf J, Froesch ER. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med 317(3):137-40, 1987
11. Rennert NJ, Boulware SD, Kerr D, Caprio S, Tamborlane WV, Sherwin RS. Metabolic effects of rhIGF-1 in normal human subjects Adv Exp Med Biol. 343:311-8, 1993
12. Gregory R. Adams & Samuel A. McCue. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. J Appl Physiol 84(5): 1716-1722, 1998
13. Elisabeth R. Barton-Davis, Daria I. Shoturma, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A 22;95(26):15603-7, 1998
14. Hillier TA., David A. Fryburg, Linda A. Jahn, and Eugene J. Barrett. Extreme hyperinsulinemia unmasks insulin’s effect to stimulate protein synthesis in human forearm. Am. J. Physiol. 274 (Endocrinol. Metab. 37): E1067-E1074, 1998
15. Deyssig R., Weissel M. Ingestion of androgenic-anabolic steroids induces mild thyroidal impairment in male body builders. J Clin Endocrin Metab. 76(4): 1069-1071, 1992
16. Markku A., Rahkila P., Reinila M., & Vihko R. Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes. Am J Sports Med. 15(4):357-361, 1987
17. Wolf M, Ingbar SH, Moses AC Thyroid hormone and growth hormone interact to regulate insulin-like growth factor-I messenger ribonucleic acid and circulating levels in the rat. Endocrinology 125(6):2905-14, 1989
18. Harakawa S, Yamashita S, Tobinaga T, Matsuo K, Hirayu H, Izumi M, Nagataki S, Melmed S. In vivo regulation of hepatic insulin-like growth factor-1 messenger ribonucleic acids with thyroid hormone. Endocrinol Jpn 37(2):205-11, 1990
19. Hochberg Z, Bick T, Harel Z Alterations of human growth hormone binding by rat liver membranes during hypo- and hyperthyroidism. Endocrinology 126(1):325-9, 1990
20. Matsuo K, Yamashita S, Niwa M, Kurihara M, Harakawa S, Izumi M, Nagataki S, Melmed S Thyroid hormone regulates rat pituitary insulin-like growth factor-I receptors. Endocrinology 126(1):550-4, 1990
21. King RA, Smith RM, Meller DJ, Dahlenburg GW, Lineham JD. Effect of growth hormone on growth and myelination in the neonatal hypothyroid rat. J Endocrinol 119(1):117-25, 1988
22. Nanto-Salonen K, Muller HL, Hoffman AR, Vu TH, Rosenfeld RG. Mechanisms of thyroid hormone action on the insulin-like growth factor system: all thyroid hormone effects are not growth hormone mediated. Endocrinology 132(2):781-8, 1993
23. Burstein PJ, Draznin B, Johnson CJ, Schalch DS. The effect of hypothyroidism on growth, serum growth hormone, the growth hormone-dependent somatomedin, insulin-like growth factor, and its carrier protein in rats. Endocrinology 104(4):1107-11, 1979
November 1, 1999 By Bryan Hypertrophy Leave a Comment
The Feasibility of Using GH, IGF-1, Insulin, and Thryoid to Enhance the Anabolic Effects of Androgens
Warning: The following information is intended only as a hypothetical consideration of ways in which human physiology may be altered, through pharmacological means, to achieve striking muscularity. The drugs discussed in this series of articles are, by and large, prescription drugs and should not be used without the supervision of a qualified physician. No attempt should be made to circumvent the laws in your area to obtain these drugs without a prescription. As always, Meso-Rx does not condone in any way the illegal acquisition and/or use of prescription drugs for purposes other than those approved by the FDA or other legally recognized regulatory bodies.
In the first installment of this series we discussed the mechanism by which human growth hormone (GH) exerts its anabolic effects in the body. We also discussed the important role of insulin-like growth factor-1 (IGF-1) in the anabolic properties of GH. In part two we discussed the role of androgens in GH secretion and sensitivity in a hypothetical pharmacological regimen aimed at dramatically increasing skeletal muscle growth. Based on research looking at the effects of androgens on GH secretion and IGF-1 sensitivity, it was deduced that the testosterone esters should provide the most potent anabolic stimulus compared to other androgens, especially those that do not aromatize. Now, in the final installment, we shall look at the feasibility of using GH, IGF-1, Insulin, and perhaps tri-iodothyronine (T3) to enhance the anabolic properties of androgens.
Growth hormone
What would an article about GH be without some useful discussion of GH! First let me quote a well known bodybuilding advisor named Daniel Duchaine;
“Wow, is this great stuff! It is the best for permanent muscle gains….People who use it can expect to gain 30 to 40 pounds of muscle in ten weeks.”
(Duchaine D. Steroid Underground handbook for men and women. Venice, Ca: HLR Technical Books, 1982, p.8)
As many of you may know, GH has not lived up to Mr. Duchaine’s expectations or any body else’s. Mr. Duchaine later recanted his previous enthusiasm.(Duchaine D. Steroid Underground handbook for men and women. Venice, Ca: HLR Technical Books, 1982, p.8)
“I’d guess that almost 90% of all athletes taking STH [growth hormone] got no anabolic results from it (this includes at least two Mr. Olympia competitors). ”
(Ultimate muscle mass, edited by Dan Duchaine. Mile High Publishing, Golden Co., 1993, p.20)
So what happened? A lot of people have been trying to figure that out. Research on GH has exploded over the last 15 years. This has been possible in that, for the last decade or so, GH has been produced through less expensive and labor intensive recombinant technology. In fact, there are so many studies looking at GH that I could not possibly address them all. Instead, I will try to focus on those few studies involving healthy young subjects and some sort of exercise when possible.(Ultimate muscle mass, edited by Dan Duchaine. Mile High Publishing, Golden Co., 1993, p.20)
To put it bluntly, studies involving GH and healthy young men show that although circulating IGF-1 is elevated with GH therapy there is little or no change in muscle protein synthesis rates (1,2,3). Deysigg (1) looked at the effect of recombinant GH on strength, body composition and endocrine parameters in power athletes. Subjects received in a double-blind manner either GH treatment (0.09IU/kg/day) or placebo for a period of six weeks. To avoid confounding factors such as concurrent us of steroids, urine specimens were tested at regular intervals for these substances. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated group. There was no effect of GH treatment on maximal strength or body composition.
Other studies have observed similar results. Yarasheski (2) conducted a 12 week study with sixteen men (21-34 yr) assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). Both groups trained all major muscle groups in an identical fashion while receiving 40 µg GH/kg/day or placebo. Fat-free mass (FFM) and total body water increased in both groups but more in the GH recipients. Whole body protein synthesis rate increased more, and whole body protein balance was greater in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis. The larger increase in FFM with GH treatment can simply be attributed to an increase in total body water. In this study as well as the previous one, resistance training supplemented with GH did not further enhance muscle growth or strength.
Later, Yarasheski performed a similar study but this time he used experienced weight lifters (3). Skeletal muscle protein synthesis and the whole body rate of protein breakdown were determined using labeled amino acids ([13C]leucine) in 7 young healthy experienced male weight lifters before and at the end of 14 days of subcutaneous GH administration (40 µg/kg/day). GH administration doubled fasting insulin-like growth factor-I levels, but did not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown. These findings confirm what others have found, namely that short-term GH treatment does not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown.
You may argue that in the real world, bodybuilders don’t use GH alone. It is generally combined with some form of anabolic steroid. Unfortunately I was unable to find a controlled study looking at the effectiveness of combining androgens and GH in healthy athletes for the purposes of building muscle. There is one study however that looked at the effects of combining both very high doses of androgens (up to 2.4 mg/kg/day) with or without concomitant GH use (4IU/day) (4). In all cases, using androgens with GH caused a significant decline in IGFBP3 levels. As you know, this dramatically decreases the half life of IGF-1 and thus the biological activity is attenuated. One other very enlightening finding of this study was that on a low calorie diet, it didn’t matter how much androgens or GH they were using, both IGF-1 and IGFBP-3 declined significantly. Clearly the effectiveness of any cycle using androgens with or without GH will be greatly diminished by lowering calories, and more importantly total protein. Still, the one question you may have, namely does high dose androgens make GH worth using, was not addresses by this study. The consensus generally is still no.
In HIV patients work is being done to determine if GH or androgens will prevent wasting. In these studies Deca Durablolin and other androgens have proven successful at preserving lean mass while GH has not proven to be effective (4). Concerning GH treatment in unhealthy populations, Michael Mooney, a well respected authority on HIV and muscle preservation, has challenged the claims made by at least one manufacturer of a GH product called Serostim. He wrote a letter to them challenging their claims that Serostim or any other brand of GH has true anabolic effects in this population.
“I underline that the only study of Serostim that included a critical evaluation of changes in muscle tissue to date showed no change and muscle using MRI (magnetic resonance imaging). All other studies so far have used Bioelectric Impedance Analysis, which measures lean body mass (LBM), but can not accurately measure changes in muscle. At the Third International Conference on Nutrition and HIV Infection at Cannes, France, April, 1999, Donald Kotler, M.D., of St. Lukes-Roosevelt Medical Center in New York reported the results of an interim analysis of a 6-month open-label trial of Serostim growth hormone. Dr. Kotler’s data showed that 6 mg of Serostim per day did not promote a significant change in muscle tissue during the first 12 weeks in the 8 subjects for whom repeat MRI data were available. Several other studies with various HIV-negative populations have also shown no apparent improvement in muscle tissue.”
So even in unhealthy populations, GH treatment does not increase muscle tissue growth. The final word on current methods of using subcutaneous GH and muscle growth is that it does not enhance muscle growth beyond what is accomplished by resistance exercise in healthy individuals.
MK-677?
But…keep your eye out for a new GH secretagogue called Merck-677 or simply MK-677. A secretagogue is a substance that isn’t GH itself, but instead causes the body to increase it’s natural GH release. One thing that is unique about MK-677 is that it works within the body’s natural GH secretion patterns, as opposed to simply causing bolus and sudden increases in circulating GH. As mentioned earlier, negative feedback has been one of the main problems with using GH for muscle growth in adults. MK-677 is orally active (no more needles), it isn’t a protein based hormone yet it mimics GHRH and increases GH levels in a pulsatile fashion. Early studies have already shown it to reverse diet induced muscle loss in healthy adults (5). In fact, a single oral 25 mg dose per day was all that was needed to reverse muscle wasting during caloric restriction (18Kcal/kg/day). Merck will be trying to find as many applications for this drug as possible. Very interesting. Yes,…very interesting.
IGF-1
IGF-1, or insulin-like growth factor-1, is known to be the mediator of GH anabolic effects so it is natural that it would also be investigated as an anabolic. As it turns out, IGF-1 is indeed anabolic. IGF-1’s anabolic effects are limited only by amino acid supply within muscle cells (6,7) . In essence, the more you eat, the more you grow with IGF-1. Unfortunately, simply elevating serum IGF-1 has not proven to be anabolic in healthy individuals (1,2,3). In addition, the side effects of using significant dosages make using pure IGF-1 prohibitive. IGF-I does not naturally exist in quantity free of its binding proteins, and limitations associated with administering free IGF-I (i.e. Long R3IGF-1) therapeutically have proven significant: acute insulin effects (e.g. hypoglycemia), suppression of growth hormone secretion, edema, hypotension, tachycardia, very short circulating half life, and limited and transient efficacy at safe dosage levels (8,9,10). LR3IGF-I has very low affinity for the IGF-binding proteins in the rat and hence is cleared from the circulation more quickly than is IGF-I. Yet because it stays free from binding proteins it is generally more potent unit per unit.
Keeping everything working, . . .or so we thought: Insulin & T3
Form the very onset let me say that I cannot in good conscience recommend that a body builder use insulin. This trend started a few years ago when some prominent people touted insulin as the mother of all anabolic hormones. Certainly if this were the case, type-II diabetics using huge amounts of insulin would not be bulging with fat, but instead bulging with muscles. Insulin is not anabolic in adult humans. Although extreme hyperinsulinemia has been shown to stimulate protein synthesis in isolated limb infusion experiments (13), these anabolic properties are ultimately the result of insulin binding to IGF-1 receptors. It was also used in a last ditch attempt to get GH to work, the rational being that maybe GH wasn’t working because of the concomitant insulin resistance. Unfortunately taking more and more insulin to combat GH induced insulin resistance leads to secondary negative side effects associated with hyperinsulinemia. Hyperinsulinemia causes the smooth muscles in your blood vessels to grow until the vessel openings become too small, predisposing yourself to a heart attack. By the way, the leading cause of death of type-II diabetics using insulin is from cardiovascular problems. In general, most bodybuilders are fooled by the tremendous increase in glycogen and water storage, making them feel “fuller”. The natural insulinogenic effect of carbohydrates combined with a fast protein like whey isolate is sufficiently anabolic in high quantities to induce dramatic glucose and amino acid uptake in muscle tissue. I can’t say as though I blame people though, when the gains stop coming and you’ve just taken out a second mortgage to pay for this GH, you find yourself willing to try anything. Nonetheless, throwing caution to the wind is not the answer.
Thyroid hormones, on the other hand, offer significant benefits when used cautiously and “properly”. They should not be used haphazardly as a fat loss agent however, instead they are valuable in correcting thyroid dysfunction brought on by androgen use. When done properly, T3 is used as “replacement therapy” and serves only to normalize decreased T3 levels. Research has shown that high dose androgens pushes T3 levels down (14,15). This is significant because the real value of optimal thyroid levels is not for fat loss, but instead for optimum anabolic activity. T3 has diverse facilitative anabolic effects including, increasing GH secretion(16,17), up-regulating GH receptors (18), up-regulating IGF-1 receptors (19,20), and other less well defined anabolic effects (21,22). Don’t get the wrong idea however, for T3 to facilitate anabolism, it must stay in the high normal range. A little too high or a little too low significantly changes the biological effects of thyroid hormones. Bringing T3 levels too high will undoubtedly backfire and lead to muscle, strength losses, and rebound fat gain.
You will need regular blood tests to determine the optimal dose of T3 (e.g. Cytomel) to bring you up to the optimum range. If you are unwilling, or do not have access to, regular blood work I would not recommend using T3. The old “take your morning temperature” recommendation is simply too inaccurate. Most people use way too much T3 and cause more problems than anything else. However, if you are willing to take care of yourself while optimizing muscle gains, have your free T3 checked before using any T3, yet during your full dose androgen regimen. Try to bring your free T3 levels up to ~7.0-7.4 pmol/L. Your doctor may use conventional units on your blood work which means it will read in “pg/dL”. If that’s the case bring your levels up to about 450-480 pg/dL. Doing this will allow optimal caloric intake while minimizing fat gain, as well as optimize the anabolic actions of the androgens you are using.
In summary, GH acting primarily through IGF-1 is a very powerful anabolic hormone. So powerful that the body has set in place complex systems to control the anabolic effects of both GH and IGF-1 in order to prevent unnatural muscle growth. These systems have thwarted our attempts at using bolus injections of GH and IGF-1 in their isolated forms to grow beyond what nature intended. Hope may be on the horizon however, as new ways of increasing GH levels (e.g. MK-677) that more closely matches naturally occurring secretion patterns show promise, as well as new forms of IGF-1 that are identical to naturally occurring forms (e.g. Somatokine) show more predictable anabolic properties with fewer side effects. Initial results are indeed promising and could lead to the emergence of a mandatory addition to our present androgen-based regimens.
References:
1. Deyssig, R., Frisch H., Blum WF., and Waldhor T. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Act Endocrinol. 128:313-318, 1998.
2. Yarasheski KE., Campbell JA., Smith K., et al: Effect of growth hormone and resistance exercise on muscle growth in young men. Am. J Physiol. 262 (Endocrinol. Metab. 25):E261-E267, 1992.
3. Yarasheski KE., Zachwieja JJ., Angelopolous TJ., and Bier DM. Short term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J. Appl. Physiol. 74:3073-3076, 1993.
4. Karila T., Koistinen H., Seppala M., Koisten R., & Seppala T. Growth hormone induced increases in serum IGFBP-3 levels is reversed by anabolic steroids in substance abusing power athletes. Clin. Endocrinol. 49:459-463, 1998
5. Sattler FR, Jaque SV, Schroeder ET, Olson C, Dube MP, Martinez C, Briggs W, Horton R, Azen S. Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus J Clin Endocrinol Metab. 84(4):1268-76, 1999
6. Murphy MG, Plunkett LM, Gertz BJ, He W, Wittreich J, Polvino WM, Clemmons DR. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. 83(2):320-5, 1998
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