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Human Growth Hormone and Secretagogues



HGH DESCRIPTION
Human Growth Hormone (HGH) is a heterogenous mixture of polypeptides secreted by the anterior pituitary gland. The principal form of HGH is a polypeptide containing 191 amino acids with a molecular weight of 215,000 daltons. This form of HGH is produced by recombinant DNA technology and is marketed for the treatment of short stature in Growth Hormone (GH)-deficient children and adolescents. Recombinant HGH or somatropin is also used for the treatment of GH deficiency in adults, short stature in association with renal insufficiency, AIDS-related wasting and short stature associated with Turner's Syndrome. In all of these cases, GH must be administered parenterally since it has very poor oral bioavailability.

GH is the primary Hormone responsible for Growth in Humans, as well as other mammals, and it helps regulate such metabolic processes as anabolism and lipolysis. Normal Human aging is associated with decreased GH secretion. Mean GH level in those over the age of 60 is about half of that in young adults. The reduction in GH levels with aging is believed to contribute to age-related decreases in muscle mass and strength and decreased lipolysis.

The effects of GH are largely mediated via IGF-1 (insulin-like Growth factor 1). IGF-1 is a mitogen and may promote some cancers, including prostate, breast and colorectal cancers. Clearly, long-term safety studies, as well as efficacy studies, are essential to evaluate the role, if any, of GH replacement in the aging population.

The release of GH from somatotroph cells of the anterior pituitary gland is a complex process involving multiple regulators. The hypothalamic peptide GHRH (Growth Hormone-releasing Hormone) acts on the somatotrophs to release GH, while the inhibitory peptide somatostatin blocks GH release. In addition, GH release appears to be influenced by a third, separate mechanism, as well???a Growth Hormone secretagogue pathway. GH secretagogues, abbreviated GHSs, can be amino acids, such as L-arginine, small peptides and nonpeptides. Further, neurotransmitters, such as acetylcholine, dopamine and norepinephrine, and neuropeptides, such as opioid peptides, are also involved in the control of GH secretion.

Recently, HGH has entered the dietary supplement marketplace, as have IGF-1 (see Insulin-Growth Factor 1) and several so-called GH secretagogues or releasers. The substances being marketed as GH secretagogues or releasers include the amino acids L-arginine, L-glutamine, L-ornithine, glycine, L-dopa, as well as such substances as ornithine alpha-ketoglutarate (see Ornithine Alpha-Ketoglutarate) and the herbs Macuna pruriens and Tribulus terrestris.

TRADE NAMES
Recapture HGH (Transcend Marketing International), HGH 2000 (Global Nutrition), Eden GH1 (Nutribolics), Biogevity (Neways), Bioregenics GH (Oasis Wellness Network).

ACTIONS AND PHARMACOLOGY
ACTIONS
Supplemental HGH and secretagogues or releasers have putative anabolic and lipolytic activities, as well as putative "anti-aging" activity.

MECHANISM OF ACTION
The mechanism of the putative actions of supplemental HGH and secretagogues or releasers is unknown. The actions of endogenous GH and parenteral GH are thought to be mediated via the anabolic Hormone IGF-1 and by interaction with specific GH receptors that are widely distributed in body tissues.

PHARMACOKINETICS
Orally administered GH has very poor bioavailability. It is claimed that GH is significantly absorbed from the oral mucosa if delivered by a spray. There is no substantiation for this. It is likely that orally administered GH is digested in the small intestine to the amino acids thah comprise the molecule.

INDICATIONS AND USAGE
There are no indications for the non-pharmaceutical use of HGH in any form. Claims that it is an anti-aging substance, that it enhances athletic and sexual performance, that it promotes joint health, is a sleep aid and an immune enhancer, that it has antidiabetic and antiatherosclerotic effects, and is a neuroprotector, are unsupported by credible evidence. Injected HGH may reduce fat and increase lean body mass in some, but serious side effects may attend the use of HGH for this purpose. There is preliminary evidence that injected HGH may be of benefit in some with Crohn's disease and that it might be helpful in treating dilated cardiomyopathy. There is some fear that high doses of HGH might promote some cancers.

RESEARCH SUMMARY
Recombinant Human Growth Hormone, given parenterally to men aged 61 to 81, reportedly resulted in significant improvements in lean body mass, muscle tone, skin thickness and density of lumbar vertebrae. Significant loss of adipose tissue was also reported. The researchers concluded that "the effects of six months of Human Growth Hormone treatment on lean body mass and adipose tissue were equivalent in magnitude to the changes incurred during 10 to 20 years of aging."

Subsequent studies also demonstrated some positive effects of HGH replacement therapy on body composition in those over 60. Some serious side effects were also noted, however, including arthralgias of both small and large joints, insulin resistance leading to higher serum fasting glucose levels, fluid retention in the lower extremities, carpal tunnel syndrome, gynecomastia and headaches. Due to the prevalence of some of these side effects, the researchers who conducted the first Human trial reduced the dosage of HGH they had been using by half.


In a preliminary study, recombinant Human Growth Hormone, given parenterally for three months to patients with idiopathic dilated cardiomyopathy, was reported to increase myocardial mass and reduce the size of the left ventricular chamber. These changes were associated with improved clinical status.

Recently, in another preliminary study, injected HGH was said to be beneficial in some with Crohn's disease. Improvement was measured by scores on the Crohn's Disease Activity Index over a four-month period.

There is no credible evidence that oral HGH has any health benefit.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
(For information on the pharmaceutical use of somatropin, see Physicians' Desk Reference.)

CONTRAINDICATIONS
Supplemental Human Growth Hormone is contraindicated in those with any evidence of active malignancy. It is also contraindicated in those who are hypersensitive to any component of an HGH-containing product.

PRECAUTIONS
Pregnant women and nursing mothers should avoid the use of HGH-containing supplements.

Adolescents should avoid the use of supplemental HGH.

Those with diabetes should avoid the use of supplemental HGH.

Oral forms of HGH are not meant to be used parenterally and should never be used in such a manner.






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