Interesting article's on IGF-1 and hypertrophy.

[hackskii]

http://anabolicminds.com/forum/igf-1...ht=acetic+acid taken from this board and there are many articles here.
I wonder if I should post them all here?

J Appl Physiol. 2004 Mar;96(3):1097-104. Related Articles, Links


Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats.

Lee S, Barton ER, Sweeney HL, Farrar RP.

Department of Kinesiology, University of Texas, Austin 78712, USA.

Muscle hypertrophy is the product of increased drive through protein synthetic pathways and the incorporation of newly divided satellite cells. Gains in muscle mass and strength can be achieved through exercise regimens that include resistance training. Increased insulin-like growth factor-I (IGF-I) can also promote hypertrophy through increased protein synthesis and satellite cell proliferation. However, it is not known whether the combined effect of IGF-I and resistance training results in an additive hypertrophic response. Therefore, rats in which viral administration of IGF-I was directed to one limb were subjected to ladder climbing to test the interaction of each intervention on muscle mass and strength. After 8 wk of resistance training, a 23.3% increase in muscle mass and a 14.4% increase in peak tetanic tension (P(o)) were observed in the flexor hallucis longus (FHL). Viral expression of IGF-I without resistance training produced a 14.8% increase in mass and a 16.6% increase in P(o) in the FHL. The combined interventions produced a 31.8% increase in muscle mass and a 28.3% increase in P(o) in the FHL. Therefore, the combination of resistance training and overexpression of IGF-I induced greater hypertrophy than either treatment alone. The effect of increased IGF-I expression on the loss of muscle mass associated with detraining was also addressed. FHL muscles treated with IGF-I lost only 4.8% after detraining, whereas the untreated FHL lost 8.3% muscle mass. These results suggest that a combination of resistance training and overexpression of IGF-I could be an effective measure for attenuating the loss of training-induced adaptations.


FASEB J. 2003 Jan;17(1):59-60. Related Articles, Links


Persistent IGF-I overexpression in skeletal muscle transiently enhances DNA accretion and growth.

Fiorotto ML, Schwartz RJ, Delaughter MC

Adult transgenic mice with muscle-specific overexpression of insulin-like growth factor (IGF)-I have enlarged skeletal muscles. In this study, we; 1) characterized the development of muscle hypertrophy with respect to fiber type, age, and sex; 2) determined the primary anabolic process responsible for development of hypertrophy; and 3) identified secondary effects of muscle hypertrophy on body composition. Transgene expression increased with age and was present only in fibers expressing type IIB fast myosin heavy chain. Muscle masses were greater by 5 wk of age, and by 10 wk of age the differences were maximal despite continued transgene expression. Total DNA and RNA contents of the gastrocnemius muscle were greater for transgenic mice than for nontransgenic littermates. The differences were maximal by 5 wk of age and preceded the increase in protein mass. The accelerated protein deposition ceased when the protein/DNA ratio attained the same value as in nontransgenic controls. Despite localization of IGF-I expression to muscle without changes in plasma IGF-I concentrations, genotype also modified the normal age and sex effects on fat deposition and organ growth. Thus, enhanced DNA accretion by IGF-I was primarily responsible for stimulating muscle growth. In turn, secondary effects on body composition were incurred that likely reflect the impact of muscle mass on whole body metabolism.

J Physiol. 2004 Feb 15;555(Pt 1):231-40. Epub 2003 Oct 17. Related Articles, Links


The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.

Hameed M, Lange KH, Andersen JL, Schjerling P, Kjaer M, Harridge superdrol, Goldspink G.

Department of Surgery, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. m.hameed@rfc.ucl.ac.uk

The expression of two isoforms of insulin-like growth factor-I (IGF-I): mechano growth factor (MGF) and IGF-IEa were studied in muscle in response to growth hormone (GH) administration with and without resistance training in healthy elderly men. A third isoform, IGF-IEb was also investigated in response to resistance training only. The subjects (age 74 +/- 1 years, mean +/- S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline, after 5 and 12 weeks in the three groups. GH administration did not change MGF mRNA at 5 weeks, but significantly increased IGF-IEa mRNA (237%). After 12 weeks, MGF mRNA was significantly increased (80%) compared to baseline. Five weeks of resistance training significantly increased the mRNA expression of MGF (163%), IGF-IEa (68%) and IGF-IEb (75%). No further changes were observed after 12 weeks. However, after 5 weeks of training combined with GH treatment, MGF mRNA increased significantly (456%) and IGF-IEa mRNA by (167%). No further significant changes were noted at 12 weeks. The data suggest that when mechanical loading in the form of resistance training is combined with GH, MGF mRNA levels are enhanced. This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing.

J Physiol. 2003 Feb 15;547(Pt 1):247-54. Epub 2002 Dec 20. Related Articles, Links


Comment in:
J Physiol. 2003 Feb 15;547(Pt 1):2.

Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise.

Hameed M, Orrell RW, Cobbold M, Goldspink G, Harridge superdrol.

Department of Physiology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.

The mRNA expression of two splice variants of the insulin-like growth factor-I (IGF-I) gene, IGF-IEa and mechano growth factor (MGF), were studied in human skeletal muscle. Subjects (eight young, aged 25-36 years, and seven elderly, aged 70-82 years) completed 10 sets of six repetitions of single legged knee extensor exercise at 80 % of their one repetition maximum. Muscle biopsy samples were obtained from the quadriceps muscle of both the control and exercised legs 2.5 h after completion of the exercise bout. Expression levels of the IGF-I mRNA transcripts were determined using real-time quantitative RT-PCR with specific primers. The resting levels of MGF were significantly (approximately 100-fold) lower than those of the IGF-IEa isoform. No difference was observed between the resting levels of the two isoforms between the two subject groups. High resistance exercise resulted in a significant increase in MGF mRNA in the young, but not in the elderly subjects. No changes in IGF-IEa mRNA levels were observed as a result of exercise in either group. The mRNA levels of the transcription factor MyoD were greater at rest in the older subjects (P < 0.05), but there was no significant effect of the exercise bout. Electrophoretic separation of myosin heavy chain (MHC) isoforms showed the older subjects to have a lower (P < 0.05) percentage of MHC-II isoforms than the young subjects. However, no association was observed between the composition of the muscle and changes in the IGF-I isoforms with exercise. The data from this study show an attenuated MGF response to high resistance exercise in the older subjects, indicative of age-related desensitivity to mechanical loading. The data in young subjects indicate that the MGF and IGF-IEa isoforms are differentially regulated in human skeletal muscle.


Nat Genet. 2001 Feb;27(2):195-200. Related Articles, Links


Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.

Musaro A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N.

Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown, Massachusetts, USA.

Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.
*** This paper has a good diagram of the different exons used for the splice variants

J Cell Biol. 2002 Feb 18;156(4):751-60. Epub 2002 Feb 11. Related Articles, Links


Different modes of hypertrophy in skeletal muscle fibers.

Paul AC, Rosenthal N.

Mouse Biology Program, European Molecular Biology Laboratory, 00016 Monterotondo-Scalo, Rome, Italy.

Skeletal muscles display a remarkable diversity in their arrangement of fibers into fascicles and in their patterns of innervation, depending on functional requirements and species differences. Most human muscle fascicles, despite their great length, consist of fibers that extend continuously from one tendon to the other with a single nerve endplate band. Other mammalian muscles have multiple endplate bands and fibers that do not insert into both tendons but terminate intrafascicularly. We investigated whether these alternate structural features may dictate different modes of cell hypertrophy in two mouse gracilis muscles, in response to expression of a muscle-specific insulin-like growth factor (IGF)-1 transgene (mIGF-1) or to chronic exercise. Both hypertrophic stimuli independently activated GATA-2 expression and increased muscle cross-sectional area in both muscle types, with additive effects in exercising myosin light chain/mIGF transgenic mice, but without increasing fiber number. In singly innervated gracilis posterior muscle, hypertrophy was characterized by a greater average diameter of individual fibers, and centralized nuclei. In contrast, hypertrophic gracilis anterior muscle, which is multiply innervated, contained longer muscle fibers, with no increase in average diameter, or in centralized nuclei. Different modes of muscle hypertrophy in domestic and laboratory animals have important implications for building appropriate models of human neuromuscular disease

Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15603-7. Related Articles, Links


Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function.

Barton-Davis ER, Shoturma DI, Musaro A, Rosenthal N, Sweeney HL.

Department of Physiology, A700 Richards Building, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.

During the aging process, mammals lose up to a third of their skeletal muscle mass and strength. Although the mechanisms underlying this loss are not entirely understood, we attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers. We demonstrate that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice, and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles. Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. We propose that these effects are primarily due to stimulation of muscle regeneration via the activation of satellite cells by IGF-I. This supports the hypothesis that the primary cause of aging-related impairment of muscle function is a cumulative failure to repair damage sustained during muscle utilization. Our results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.

Acta Physiol Scand. 1999 Dec;167(4):301-5. Related Articles, Links


Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle.

Barton-Davis ER, Shoturma DI, Sweeney HL.

Department of Physiology, A700 Richards Bldg., University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.

Insulin-like growth factor I (IGF-I) is critical in promoting growth of skeletal muscle. When IGF-I is introduced into mouse hindlimb muscles by viral-mediated gene transfer, local overexpression of IGF-I produces significant increases in muscle mass and strength compared with untreated controls (Barton-Davis et al. 1998). We have proposed that this functional hypertrophy is primarily owing to the activation of satellite cells which leads to increased muscle regeneration. In order to test if satellite cells are essential in mediating the hypertrophic effects of IGF-I, we used gamma radiation to destroy the proliferative capacity of satellite cells. The right hindlimbs of adult C57BL/6 male mice were subjected to one of the following treatments: (1) 2,500 rad gamma radiation only, (2) viral-mediated gene transfer of IGF-I only, (3) 2,500 rad gamma radiation plus viral-mediated gene transfer of IGF-I, or (4) no intervention as a control. Approximately 4 months after treatment, the extensor digitorum longus muscles (EDL) from both hindlimbs were removed for mechanical and morphological measurements. Treatment with gamma radiation significantly prevented normal growth of the muscle. When combined with IGF-I treatment, approximately half of the IGF-I effect was prevented by gamma radiation treatment. This suggests that the remaining half of IGF-I induced hypertrophy is owing to paracrine/autocrine effects on the adult myofibres. Thus, these data are consistent with a mechanism by which IGF-I induced muscle hypertrophy via a combination of satellite cell activation and increasing protein synthesis in differentiated myofibres

[hackskii]

Passages taken from "Grow Young With HGH" by Ronald Klatz, MD, president of the Academy of Anti-Aging Medicine.

The most abundant hormone made by the pituitary gland is human growth hormone, also called somatotrophin. Growth hormone production hits its peak during adolescence. Most HGH is secreted into the bloodstream in brief bursts, and most HGH secretion takes place during the early hours of REM (deep) sleep.

Once in the bloodstream, human growth hormone stays there for only a short time, only a few minutes, just long enough to stimulate its uptake into the liver, where it is then converted into growth factors. The most important of these growth factors is called IGF-1, short for Insulin-like Growth Factor-1. IGF-1 is also known as somatomedin C.

Growth hormone exerts its actions either directly or indirectly through its intermediary insulin growth factors (IGF-1) to every organ system of the body. Almost nothing escapes its magic touch. In the same ways that it grows the bones of young children, it increases the size of most organs and tissue. Even the brain is affected. The latest studies in animals show that it can regenerate damaged brain tissue.

It is IGF-1, rather than growth hormone itself, which can vary widely through the day, that is used as a measurement of how much growth hormone is being secreted by the body. IGF-1 is directly responsible for most of the benefits and actions associated with HGH. IGF-1 is 10 times more potent than human growth hormone and is now under investigation as a separate drug for many of the same indications of human growth hormone. Phil Micans of International Aging Systems in London believes that IGF-1 will be the hormone of choice in a few years.

HGH and IGF-1 Get at the Blueprint of Aging

"The blueprint of aging is in the DNA under the hood of the telomere", the "clock" at the end of every chromosome that is shortened with each cell division, says noted plastic surgeon and antiaging researcher, Vincent Giampapa, MD, director of clinical research at the Longevity Institute International in Montclair, New Jersey. To actually reverse aging at the cellular level, we will need a substance that will restore telomere length and like a genie turn old cells into young ones. That is not yet available, although Giampapa believes it will be in less than a decade. Until then, growth hormone and its attendant hormone IGF-1 can do the next best thing, help keep the cell in as healthy a state as possible.

The cell's ability to function depends on the genetic material, the DNA, in the nucleus of the cell which codes for all the proteins, hormones, and enzymes that make the cell run. The DNA is like an army under constant attack from oxygen free-radicals, ultraviolet light, the heat of the body, and other damaging factors. Although the DNA has the ability to repair itself, it falls down on the job with age, a victim of the same aging process that affects the cell. At the same time, damage is accumulating in the energy center of the cell, the mitochondria, which has its own DNA. Up until now, one of the few ways we could limit the damage to the DNA was to take antioxidant supplements such as vitamin C and E to bolster our own defenses.

But, according to Dr. Giampapa and Thierry Hertoghe, MD, a physician specializing in hormone replacement therapy in Brussels, the latest European research shows that human growth hormone and IGF-1 can go further than antioxidants and can do what antioxidants cannot. Human growth hormone and IGF-1 act like carriers to bring the cell the raw materials it needs for renovation and repair. IGF-1 launches the delivery of the nucleic acids, DNA and RNA, right into the cell nucleus, where the DNA resides. The nucleic acids are used to repair damage to the DNA and stimulate cell division. Growth hormone initiates the transport of amino acids, the building blocks of protein, and nucleic acids into the cytoplasm of the cell, the area outside the nucleus. This includes the cell membranes and intracellular organelles, such as the mitochondria. In this way, human growth hormone and IGF-1 don't just minimize the damage to the DNA and cellar structures, they help heal the cell and the DNA. These two hormones actually treat the blueprints of aging.

Information on IGF-1

IGF-1 is the other end of the growth hormone chain, the downstream player that actually exerts most of the effects we associate with human growth hormone. IGF-1 is causing a great deal of excitement among two groups, researchers who are exploring its vast potential and bodybuilders who are already using it and claiming eyepopping gains in muscle.

IGF-1 More Potent Than Human Growth Hormone

Human growth hormone exerts most of its effects through IGF-1. Therefore, it is not surprising that IGF-1 injections will do for you what human growth hormone does--and then some, according to its proponents. It increases lean body mass, reduces fat, builds bone, muscle, and nerves. By taking it directly, you bypass the pituitary gland, which may be "burnt out" with aging.

IGF-1 appears to be even more potent than growth hormone in its anti-aging action. According to Keith Kelly, Ph.D., who did the work showing that growth hormone reversed the shrinking of the thymus, when he does his experiments on cells in culture, only IGF-1--and not growth hormone-- works. But both IGF-1 and growth hormone work in the living animal. "I know that both growth hormone and IGF-1 are substantially elevated in the old animals treated with growth hormone," he says, "but my prediction is that the main player is going to be IGF-1."

IGF-1 and It's Potentials

IGF-1 Preventing Brain Aging and Disease
One of the spectacularly exciting uses of growth hormone and IGF-1 may be to prevent and treat the effects of brain aging. In an experiment that has momentous implications for brain injury, stroke, aging, and neurodegenerative disease, a team of scientists in New Zealand showed that IGF-1 can stop the death of cells in the brain. Barbara Johnston, Peter Gluckman, and their colleagues at the University of Auckland found that injections of IGF-1 given 2 hours after brain injury in fetal lambs rescued the damaged neurons and salvaged cells that would otherwise have died during apoptosis, which is the programmed cell death that is believed to cause the loss of brain cells for up to 3 days after the original injury. The treatment was effective in stopping the cell death throughout the brain, including the hippocampus, the cortex, the areas associated with thinking and memory. The treatment was also effective in the striatum, the part of the brain that plays a role in Parkinson's disease in humans. IGF-1 replacement was also found to reduce seizures in animals with brain damage.

These researchers also suggest that IGF-1 might be used to inhibit the effects of neonatal hypoxia during birth (lack of oxygen to the brain) which can leave a baby with permanent brain damage. If IGF-1 can stop the programmed death of cells, then this opens up a world of undreamed-of-possibilities. For instance, the programmed death of cardiac cells after a heart attack leaves the victim with a heart full of dead tissue that before could not be repaired. Brain tissue is destroyed due to a stroke (CVA), and this cell death many times leaves the victim unable to walk, talk, or think clearly. It may also play a role in other neurodegenerative diseases such as Alzheimer's disease, muscular dystrophy, and multiple sclerosis. For the first time we may have a weapon against death at the cellular level.


IGF-1 Improving Glucose Metabolism
As its name indicates IGF-1, or insulin-like growth factor-1, has similar properties to insulin, and it has been shown to improve blood sugar profiles in type 2 diabetic patients. High doses of growth hormone have been shown to increase insulin resistance, but IGF-1 administration actually normalized the insulin resistance in a group of healthy volunteers.

In the latter study, Nelly Mauras and Bernard Beaufrere of the Nemours Children's Clinic in Jacksonville, Florida, were looking at several different things: the effect of IGF-1 on protein metabolism; its ability to stop the protein-wasting caused by glucocorticosteroid drugs like prednisone, and its effect on insulin and glucose metabolism. They divided the volunteers into three groups who got one of the following: IGF-1 alone, IGF-1 plus prednisone, and prednisone alone. The study found that IGF-1 at 100 micrograms per kilogram of body weight given twice daily enhanced the body's protein metabolism in the same way as growth hormone. Like growth hormone, it markedly decreased the protein breakdown in the volunteers who were taking prednisone. But whereas growth hormone in an earlier study caused carbohydrate intolerance and insulin resistance when given in combination with prednisone, IGF-1 did not cause these diabetes-like effects. Instead, those subjects who received IGF-1 along with prednisone had normal glucose metabolism. This was remarkable, say the researchers, in light of the fact that glucocorticoids are known to suppress circulating insulin and decrease insulin sensitivity. As a result of this and previous studies, the researchers believe that IGF-1 offers promise in the treatment of protein catabolic states, such as patients who require IV feedings after surgery.


IGF-1 Helping Diabetes
Two 1997 double-blind clinical studies showed that recombinant IGF-1 injections can markedly reduce the need for insulin by up to 45% in patients with insulin-dependent diabetes mellitus. One study involved 8 adults between ages 24 and 49 and the other 43 children and adolescents between the ages of 8 and 17. In the adult trial, IGF-1 also lowered the total cholesterol and triglycerides after only four days of treatment.

While these were short term trials lasting nineteen days and four weeks, respectively, that fact that the insulin requirement dropped markedly and there were no serious side effects make IGF-1 a promising drug for the treatment of diabetes. While it does not do away with the need for insulin, it improved the control of blood sugar and thus may help prevent the dire complications of diabetes, including heart disease, blindness, and peripheral nerve damage that can lead to amputation.


IGF-1 Regenerating Nerves
Another exciting potential use of IGF-1 is in the repair of peripheral nerve tissue that has been damaged by injury or illness. If a nerve is torn in the arm or leg, it means that the connection to the muscle may be impaired, and as a result there is loss of movement and the muscle atrophies. While peripheral nerves can regenerate to some extent, severe tears of more than a few millimeters may result in permanent injury. Now IGF-1 has repaired and reconnected severed nerve endings of up to a distance of 6 millimeters, a feat previously unheard of.

Swedish scientist Hans-Arne Hansson of the Institute of Neurobiology at the University of Goteborg found that IGF-1 in combination with other growth factors could stimulate even more dramatic regeneration. "IGF-1 by itself and in combination with other growth factors is likely to be of importance in promoting healing and repair processes in clinical practice within a few years," he writes.

In studies of cells in culture and in animals, IGF-1 has been shown to have remarkable effects on the spinal cord motor neurons. It increased motor neuron activity in spinal cord cultures by 150 to 270 percent. And it significantly decreased programmed cell death in developing chick embryos. In animal studies, it enhanced the sprouting of axons of the spinal cord motor neurons. And it increased intramuscular nerve sprouting a whopping ten fold when it was given to normal adult rats. In fact, according to a group of researchers at Cephalon, Inc., in West Chester, Pennsylvania, IGF-1 may be the "long-sought endogenous motor neuron sprouting factor."

The implications of this work for helping people is nothing short of mind-boggling. If IGF-1 can regenerate spinal cord motor neurons, it may be useful in treating amyotrophic lateral sclerosis (ALS), a devastating disease in which the loss of spinal cord and cortical motor neurons results in complete paralysis and death. It may also be useful for peripheral neuropathies, such as Charcot-Marie-Tooth syndrome.

John Wittig, MD, of UCLA has been using IGF-1 to prevent AIDS wasting in HIV infected patients. IGF-1 may allow more aggressive chemotherapy of certain cancers, since drugs like vincristine and cisplatin can cause peripheral neuropathies at higher doses.


The Growth Factor Army
IGF-1 is only one of the body's many growth factors that are now being identified, isolated, and cloned using genetic engineering technology for use as drugs. As growth factor researcher Eric Dupont, Ph.D., says, "Growth hormone is the general and growth factors are the foot soldiers." Growth factors function like hormones, hooking onto the receptors of cells and sending a biochemical signal across the cell's interior. Whereas hormones usually send long distance messages, growth factors for the most part do local calls.


IGF-1, The Bodybuilder's Dream
A number of world-class bodybuilders are using IGF-1 and reporting massive muscle magnification of up to 20 pounds. An article in Muscle Mass 2000 trumpets IGF-1 as "Possibly the Most Potent Bodybuilding Drug Ever!" According to author T.C. Luoma, "IGF-1 is out there on the streets of America right now; it's being sold out of the trunks of cars in Venice and brown paper packages containing it are being discreetly handed out at Southern California gyms." While there are no controlled studies supporting the musclemen's claims, the anecdotal evidence is building up. "Bodybuilders are claiming they are experiencing drops of 5% body fat in a month, while increases in lean body mass and strength are 'incredible.' Statements like, 'It's the most wonderful stuff in the world, and 'I couldn't believe it man' are the norm."

There are skeptics, such as Mauro Di Pasquale, MD, an expert in performance-enhancing compounds, but there is a rationale for the belief that HGH taken with IGF-1 will work better. There is a feedback mechanism between the human growth hormone in the pituitary gland and the IGF-1 in the liver. The human growth hormone stimulates the release of IGF-1, but when the levels of IGF-1 rise to a certain point in the circulation, it signals the shutdown of growth hormone. But there is a lag time in all of this, which means that growth hormone levels increase at night and IGF-1 levels increase during the day. Bodybuilders hope that taking the two together will have a double-fisted effect on protein synthesis