Commentary

Dear Mr. Morgenthaler,

Thank you for the “Health & Wellness Update.” I look forward to each issue, and the solid information it provides.

Praise for
Smart Publications
Health & Wellness Update

"Wealth of information for anyone that chooses alternative healing methods. It's an education in itself just to read one of these newsletters! Every time I get one I read it from cover to cover! Easy to understand and easy to decipher when looking for products. Well done! It's a joy to read."

Growth Hormone . . .
Is It All Hype?

Yes . . . But With Some Caveats Growth Hormone: what is it?

Growth hormone (GH) is a hormone secreted by the pituitary gland which is located in the center of the brain. A normal pituitary gland stores about 10 milligrams of growth hormone which is usually released in a series of pulses into the bloodstream throughout the day and night.

What does it do?

Why should you consider taking a GH supplement?

Adult Growth Hormone Deficiency
Years ago it was thought that growth hormone deficiency was something you were born with, or resulted from head injuries later in life that affected the release of growth hormone from the pituitary gland. It was well known that GH levels declined dramatically after early adulthood, but even older adults had detectable levels of GH.

When growth hormone and the tests that measured blood levels of GH became widely available in 1985, scientists and doctors finally recognized that some adults develop a severe deficiency of GH far beyond what is seen in normal aging. This new endocrine condition was termed Adult Growth Hormone Deficiency (AGHD).1

Symptoms of Adult GH Deficiency include increased body fat, decreased muscle mass and impaired exercise capacity, depression, abnormal blood lipids, and cardiovascular problems.

You are probably thinking that the symptoms of AGHD sound a lot like normal aging, and in a sense you are right. GH levels drop dramatically as we age … but people with medically recognized AGHD experience an even more severe version of the GH drop all of us experience. The first studies using GH in people with AGHD resulted in dramatic effects, including: decreased body fat, increased muscle mass, improved exercise capacity, improved mental outlook, increased bone mass, and decreased cardiovascular risk factors.2 In other words, AGHD patients given growth hormone had many of their premature symptoms of aging reversed within a matter of months. Over the last decade, AGHD has become a widely recognized syndrome that is easily and safely treatable with GH replacement, with dramatic positive effects on health and quality of life.3

The # 1 caveat you need to be aware of

It's important to realize that all of the studies about GH supplementation that are commonly quoted are based on GH injections. The previous study2, which reverses premature aging in a matter of months, is a good example. Regardless of what the manufacturer or supplement company claims, you can not expect this rapid response with an oral GH releaser. Most marketing claims will quote the fast acting results of GH given as an injection. But oral GH releasers are generally not as strong and it may take longer for users to notice the desired benefit.

If you want a significant rise in your GH, and if you don't mind the cost and the needle pokes, then please go find some GH from an open minded doctor or from an overseas pharmacy (see our web site, www.smart-publications.com). Otherwise, take what we consider the next best thing—a GH supplement that contains APG/Lysine.

GH and aging
It is well established that GH benefits children who are deficient in it, and adults who have abnormally low or undetectable GH levels. But the effect of GH on normal aging adults is still a subject of intense scientific scrutiny. This mostly stems from the fact that deficiencies in the GH/IGF system in animals often result in very long life spans compared to normal animals.4 Additionally, animals that have been genetically modified to produce extra amounts of GH have reduced life spans.5

This may seem surprising, in light of the popular belief that extra GH extends life span. However, we also know that individuals who don't produce GH and are not given any GH replacement during their entire life have a dramatically shorter life span than normal people, living only about 40 years.6 So, there seems to be some optimum amount of GH needed to maximize life span and health. Too little or too much GH both adversely affect health and life span … while maintaining a proper amount of GH as we age can dramatically improve our number of healthy years.

GH and cardiovascular health
People with a GH deficiency generally have numerous cardiovascular risk factors and increased death from heart disease. On the other hand, GH replacement therapy has been shown to help lower blood pressure, increase HDL (good) cholesterol, and decrease C-reactive protein.7

While we are all familiar with the benefits of raising HDL cholesterol and decreasing blood pressure, the improvement in C-reactive protein is also very significant. C-reactive protein is a newly recognized cardiovascular risk factor related to inflammation in the circulatory system.8 In fact, even if you have normal blood pressure and lipid levels, your risk for heart disease increases dramatically if you have elevated C-reactive protein levels.

The combination of improving HDL cholesterol, blood pressure, and C-reactive protein has dramatic cardiovascular health benefits. The good news is that researchers have also measured the thickness of the carotid artery in the neck as a marker of atherosclerosis and found that GH replacement actually caused a reduction in the thickness of the carotid artery, which is evidence of an actual reversal of artery disease.8

Does GH help you grow taller?
As discussed in "The historical use of GH supplementation" (see side bar), the first use of synthetic growth hormone was as a replacement for growth hormone derived from human pituitary glands obtained from cadavers. With the new availability of synthesized growth hormone, it wasn't long before scientific debate began about which children would benefit from growth hormone therapy. Before 1985, most children who were given growth hormone therapy had what is called idiopathic growth hormone deficiency. But only a small percentage of short children actually have this condition. In fact, the growth hormone system is very complex and involves hormones that release growth hormone itself, and receptors on cells that growth hormone activates.9 Additionally, one of the major effects on the body of growth hormone is to increase levels of another hormone complex named Insulin-Like Growth Factors (IGFs).10 Many of the effects of GH are mediated by the IGFs released by GH.

So as you can see, the GH/IGF hormone system is quite complicated, and a failure to grow normally can involve defects in one or more parts of this system. Because of this, extra growth hormone will not always result in increased growth. Despite these pitfalls, many short children with normal GH functioning continue to be treated with growth hormone in an attempt to increase their adult height.

Growth Hormone can have two kinds of effects:

Direct effects are the result of growth hormone binding its receptor on target cells. Fat cells (adipocytes), for example, have growth hormone receptors, and growth hormone stimulates them to break down triglyceride and supress their ability to take up and accumulate circulating lipids.

Indirect effects are mediated primarily by an insulin-like growth factor-1 (IGF-1), a hormone that is secreted from the liver and other tissues in response to growth hormone. A majority of the cell health and maintenance effects of growth hormone is actually due to IGF-1 acting on its target cells.

How is Growth Hormone released?

Nutritional GH releasers
Nutritional supplements that are used to stimulate GH release in humans became popular in the early 1980s. These early supplements were boldly advertised as "the fountain of youth" which slowed down—if not reversed—the aging process. Even with the advent of synthetic GH in 1985, the idea of releasing GH using nutritional supplements is still attractive, because pharmaceutical GH is very expensive and must be taken by injection, very few people choose to take advantage of it. (GH itself is not effective when taken orally.)

Now here's where we want to differentiate the popular GH supplements that claim to reverse aging from the GH supplements that have been clinically shown to stimulate the release of GH.

Amino acids that stimulate release of GH
Arginine is the most effective amino acid found to induce GH release. But the GH release from oral arginine is extremely variable, and most people end up with gastrointestinal complaints because of the large dose that is required. In fact, most of the nutritional compounds that release GH only work reliably when they are injected in large doses. These include arginine, lysine, ornithine, tyrosine, and tryptophan.15 To complicate matters, most of the products that are marketed as oral "growth hormone releasers" contain insufficient quantities of the nutrients needed to release GH, so consumers end up wasting their money in the hopes of finding an anti-aging elixir.

The combination of arginine pyroglutamate and lysine makes a very effective GH releaser.
A study published in 1981 used a special form of arginine (arginine pyroglutamate), in combination with lysine (another amino acid), to induce a significant GH release when taken orally in relatively small amounts. Fifteen healthy male subjects, aged 15 to 20 years old, were given 1,200 mg of arginine pyroglutamate combined with 1,200 mg of L-lysine hydrochloride. The results of this specific combination were spectacular, causing a large GH release that was sustained for several hours.16

This breakthrough paper has often been misquoted and discounted, as several other researchers failed to replicate the results.17-20

Unfortunately, these subsequent researchers used arginine hydrochloride and NOT arginine pyroglutamate, which was used with great results in the original study in 1981. This is disappointing, as it had been known since 1977 that the specific chelate of arginine and pyroglutamic acid (arginine pyroglutamate) had effects on the body that are not shared by arginine or pyroglutamic acid when taken individually or together.21

No nutritional supplement has shown equivalent results to the combination of arginine pyroglutamate and lysine for releasing significant amounts of biologically active GH when taken orally in small doses. Interestingly, when both arginine pyroglutamate and lysine are taken individually, even in large doses, they are not effective.16 It is the specific combination of arginine pyroglutamate and lysine, taken in the proper ratio, which makes a very effective GH releaser.

Because of these promising initial results, the combination of APG/Lysine was developed as a pharmaceutical in Italy. Further research showed that it could enhance immune function dramatically both in healthy elderly people, and in cancer patients.22-24 Notably, this combination of APG/Lysine was shown to improve immune function by increasing thymus hormone levels. This is an effect you would expect from growth hormone release, as growth hormone is known to enhance functioning of the thymus—the master gland of immunity.25-27

People get better results by using GH less often than every day, or just two or three times a week.

If you decide to take a GH releaser
Too much of a good thing can be as bad for you as not enough, and this holds true for GH. Like most hormones, it is the proper dose and timing that gives the most beneficial results. In the case of GH, research has shown that there are significant differences in the effects of GH depending on how often you take it and/or how often it is released.

It's best NOT to take a GH supplement every day. Here's why:
A decade ago, it was discovered that many children who were given GH replacement to enhance their growth suffered from a GH tolerance and withdrawal syndrome that resembles the tolerance one develops when he or she takes hormones like cortisone and testosterone.28 Specifically, when children stop getting GH supplementation, they stop growing, which becomes even more of an issue than the short stature they dealt with before they started taking GH. Initially, scientists thought this was a result of the GH injections suppressing the body's normal production of GH.

Similar hormone suppression is often seen with cortisone and testosterone therapy, where it often takes months for the body to begin normal production of its own hormones after stopping the cortisone or testosterone. Surprisingly, this was not found to be true for GH. After stopping GH injections, the body rapidly resumes its normal production of GH. Yet, the tissue's response to the normal GH levels was found to be markedly diminished.28 Scientists now believe that this is because the body becomes tolerant to GH from the daily supraphysiological levels of GH caused by the GH injections.

Obviously, this is a huge drawback to using GH replacement therapy. Because as soon as we stopped taking the GH supplement, we would be in even worse shape because we would be resistant to our own GH. Luckily, research has shown that the key to preventing these problems is to not use GH on a daily basis.

In research on short children receiving GH, it was shown that by using GH every other day rather than every day the tolerance and dependence syndrome could be completely prevented.29 It seems that allowing the body a one day break in between GH use allows the tissues to remain sensitive to both its own GH and the GH supplementation. Interestingly, the same is known to be true for cortisone which is often given in an "every other day regimen" to prevent tolerance and dependence. What is troubling, though, is that many short, but otherwise normal children are given GH replacement therapy in the hope that they will grow taller, and many of them are receiving GH every day which in the long term is likely counterproductive.

In research on adults, using GH two or three times a week has proven to be as effective as using GH every day.30 This makes the rationale of using GH daily questionable—because it is much more likely to not give optimal long term results. Typically, the companies that market pharmaceutical GH and GH releasing supplements don't inform doctors or consumers of this fact because obviously they would sell much less product. This is in spite of the research showing that people will get better and safer results by using GH less often than every day.31

Uridine and Growth Hormone?

Is GH supplementation safe?

There are no contraindications with other drugs or supplements. And if you decide to stop taking growth hormone releaser after you start, proper dosing will assure you will not experience any negative effects. Your pituitary gland will most likely, however, start producing the amount of growth hormone it did before you took it … and if you are a senior, that means it will produce very little.

How much should you take?

Conclusion

References

1. Jorgensen JO, Muller J, Moller J, et al. Adult growth hormone deficiency. Horm Res. 1994;42(4-5):235-41.
   Abstract
   
   
2. Cook DM, Ludlam WH, Cook MB. The adult growth hormone deficiency syndrome. Adv Intern Med. 2000;45:297-315.
   Abstract
   
   
3. Hoffman AR. Treatment of the adult growth hormone deficiency syndrome: Directions for future research. Growth Horm IGF Res. 2005 Jul;15 Suppl A:48-52.
   Abstract
   
   
4. Bartke A. Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology. 2005 Sep;146(9):3718-23.
   Abstract
   
   
5. Yamaza H, Komatsu T, Chiba T, et al. A transgenic dwarf rat model as a tool for the study of calorie restriction and aging. Exp Gerontol. 2004 Feb;39(2):269-72.
   Abstract
   
   
6. Besson A, Salemi S, Gallati S, et al. Reduced longevity in untreated patients with isolated growth hormone deficiency. J Clin Endocrinol Metab. 2003 Aug;88(8):3664-7.
   Abstract
   .
7. Colao A, Di Somma C, Rota F, Short-term effects of growth hormone (GH) treatment or deprivation on cardiovascular risk parameters and intima-media thickness at carotid arteries in patients with severe GH deficiency. J Clin Endocrinol Metab. 2005 Apr;90(4):2056-62.
   Abstract
   
   
8. Koenig W. Predicting risk and treatment benefit in atherosclerosis: the role of C-reactive protein. Int J Cardiol. 2005 Feb 15;98(2):199-206.
   Abstract
   
   
9. Woelfle J, Chia DJ, Massart-Schlesinger MB, et al. Molecular physiology, pathology, and regulation of the growth hormone/insulin-like growth factor-I system. Pediatr Nephrol. 2005 Mar;20(3):295-302.
   Abstract
   
   
10. Frystyk J. Free insulin-like growth factors—measurements and relationships to growth hormone secretion and glucose homeostasis. Growth Horm IGF Res. 2004 Oct;14(5):337-75.
    Abstract
    
    
11. Greenspan FS, Li CH, et al. Bioassay of hypophyseal growth hormone; the tibia test. Endocrinology. 1949 Nov;45(5):455-63.
    Abstract
    
    
12. de Jongh SE, Paesi FJ, van Wieringen G. The influence of growth hormone on the growth of the skeleton and soft tissues of the body. Arch Int Pharmacodyn Ther. 1950 Apr 15;82(2):148-54.
    Abstract
    
    
13. Lewis RA, Klein R, Wilkins L. The effect of pituitary growth hormone in dwarfism with osseous retardation and hypoglycemia and in a cretin treated with thyroid. J Clin Invest. 1950 Apr;29(4):460-4.
    Abstract
    
    
14. Cronin MJ. Pioneering recombinant growth hormone manufacturing: pounds produced per mile of height. J Pediatr. 1997 Jul;131(1 Pt 2):S5.
    Abstract
    
    
15. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition. 2002 Jul-Aug;18(7-8):657-61.
    Abstract
    
    
16. Isidori A, Lo Monaco A, Cappa M. A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin. 1981;7(7):475-81.
    Abstract
    
    
17. Suminski RR, Robertson RJ, Goss, FL, et al. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr. 1997 Mar;7(1):48-60.
    Abstract
    
    
18. Lambert MI, Hefer JA, Millar RP, et al. Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. Int J Sport Nutr. 1993 Sep;3(3):298-305.
    Abstract
    
    
19. Fogelholm GH, Naveri HK, Kiilavuori KT, et al. Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters. Int J Sport Nutr. 1993 Sep;3(3):290-7.
    Abstract
    
    
20. Corpas E, Blackman MR, Roberson R, et al. Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men. J Gerontol. 1993 Jul;48(4):M128-33.
    Abstract
    
    
21. Provenzano PM, Brucato A, GianguzzaS, et al. Chemistry and pharmacology of arginine pyroglutamate. Analysis of its effects on the CNS. Arzneimittelforschung. 1977;27(8):1553-7.
    Abstract
    .
22. Mocchegiani E, Cacciatore L, Talarico M, et al. Recovery of low thymic hormone levels in cancer patients by lysine-arginine combination. Int J Immunopharmacol. 1990;12(4):365-71.
    Abstract
    
    
23. Fabris N, Mocchegiani E. Arginine-containing compounds and thymic endocrine activity. Thymus. 1992;19 Suppl 1:S21-30.
    Abstract
    
    
24. Fabris N, Mocchegiani E, Muzzioli M, et al. Recovery of age-related decline of thymic endocrine activity and PHA response by lysin-arginine combination. Int J Immunopharmacol. 1986;8(7):677-85.
    Abstract
    
    
25. Mocchegiani E, Paolucci P, Balsamo A, et al. Influence of growth hormone on thymic endocrine activity in humans. Horm Res. 1990;33(6):248-55.
    Abstract
    
    
26. Fahy GM. Apparent induction of partial thymic regeneration in a normal human subject: a case report. J Anti Aging Med. 2003;6(3):219-27.
    Abstract
    
    
27. Savino W, Postel-Vinay MC, Smaniotto S, et al. The thymus gland: a target organ for growth hormone. Scand J Immunol. 2002 May;55(5):442-52.
    Abstract
    
    
28. Lampit M, Lorber A, Vilkas DL, et al. GH dependence and GH withdrawal syndrome in GH treatment of short normal children: evidence from growth and cardiac output. Eur J Endocrinol. 1998 Apr;138(4):401-7.
    Abstract
    
    
29. Lampit M, Hochberb Z. Prevention of Growth Deceleration after withdrawal of growth hormone therapy in idiopathic short stature. J Clin Endocrinol Metab. 2002 Aug;87(8):3573-7.
    Abstract
    
    
30. Pincelli AI, Bragato R, Scacchi M, et al. Three weekly injections (TWI) of low-dose growth hormone (GH) restore low normal circulating IGF-I concentrations and reverse cardiac abnormalities associated with adult onset GH deficiency (GHD). J Endocrinol Invest. 2003 May;26(5):420-8.
    Abstract
    
    
31. Amato G, Mazziotti G, Di Somma C, et al. Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections. J Clin Endocrinol Metab. 2000 Oct;85(10):3720-5.
    Abstract
    
    
32. Micic D, Casabiell X, Gualillo O, Pombo M, Dieguez C, Casanueva FF. Growth hormone secretagogues: the clinical future. Horm Res. 1999;51 Suppl 3:29-33.
    Abstract
    
    
33. Giusti M, Marini G, Sessarego P, Peluffo F, Valenti S, et al. Effect of cholinergic tone on growth hormone-releasing hormone-induced secretion of growth hormone in normal aging. Aging (Milano). 1992;4(3):231-7.
    Abstract
    
    
34. eda GP, Ceresini G, Denti L, Marzani G, Piovani E, et al. alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Horm Metab Res. 1992;24(3):119-21.
    Abstract
    
    
35. Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45.
    Abstract