Part 2 of a Series on Human Growth Hormone
By Dónal P. O’Mathúna, PhD
Interest in Human Growth Hormone (HGH) therapy has recently shifted away from its use by athletes to enhance performance to its use by baby boomers to prevent and even reverse the effects of aging.1
A huge marketing campaign is promoting HGH therapy as the latest Fountain of Youth. Barrages of e-mail claim HGH will "stop aging" and "turn back your body’s biological time clock 10-20 years." HGH is alleged to help you "lose weight while you sleep," "reduce body fat (without working out)," "increase energy levels," "restore youthful skin," "improve sleep," and "improve sexual potency."
Sound too good to be true? One advertisement urges, "Don’t believe the hype, read the science." The promoters claim "over 20,000 studies, abstracts and reports have documented these wonderful benefits."2 Little wonder, then, that they claim, "Anyone over 35 who wants to have good health and longevity will need to be on an HGH program."2
Many of your patients will have encountered these advertisements. Some will be tempted to try oral supplements, but since they don’t contain HGH, many will waste their time and money. They may even avoid good nutrition and healthy exercise in the misguided belief that these supplements are effective. They may neglect high-quality medical care in the belief that these supplements will cure all their ailments. However, interest in these products—and in prescription HGH injections—provides a useful opportunity to educate patients on how to examine claims made for therapies and remedies.
Background
Part 1 of this article described the role of HGH in human physiology.1 The amount of hormone produced by the body decreases with age, and has thus been associated with the effects of aging. Increased recognition of adult-onset forms of growth hormone deficiency (GHD) also have brought attention to this area.3
Many GHD symptoms resemble aging, and are reversed by HGH. These findings are used to claim that normal, older people can use HGH to overcome age-related changes such as reduced fat-free body mass, increased adipose tissue mass, irregular sleep cycles, and reduced bone density. Clinical studies with injectable HGH generally are positive for symptomatic relief and physiological changes. Although these results do not mean that aging has been stopped, these changes in body composition are highly desired by those attracted to anti-aging medicine.
Commercial Claims: HGH
Advertisements for commercial products claim that thousands of scientific studies support HGH’s anti-aging and "youthing" effects. The 24-page brochure for one product specifies nine studies it claims "prove HGH’s youthing effect."2 Of the nine, four studies had nothing to do with HGH or aging (two were for herbal remedies, one for Ayurvedic medicine, and one for testosterone). Four "studies" were reviews of HGH treatment that uniformly concluded that it was premature to recommend HGH administration to adults except in clinical trials4 or for those with demonstrated GHD.3 One study did find that HGH produced beneficial changes in body composition and is reviewed below.5
Such misrepresentation of study results should lead to skepticism about the rest of the claims made throughout any advertisement. In addition, the citations of five of the nine articles above contained at least one error. Such inattention to detail, quickly revealed by a MEDLINE search, also should heighten suspicion about the accuracy of the remainder of the brochure.
Commercial Claims: Oral Supplements
Popular HGH products are marketed as oral supplements, even though the polypeptide hormone is not active orally. These oral formulations do not actually contain HGH. Therefore, studies involving injectable, prescription-only, FDA-approved HGH are irrelevant to the efficacy of these oral products.
These oral HGH products contain various combinations of amino acids said to boost endogenous HGH levels. These oral products are sometimes called "HGH secretagogues," which should not be confused with pharmaceutical HGH secretagogues currently being developed to overcome muscle wasting conditions associated with various diseases.6
Clinical Studies: HGH
The first study to examine the anti-aging effects of injectable, prescription HGH involved 21 healthy men ages 61-81.5 Twelve men were randomly assigned to receive HGH (0.03 mg/kg subcutaneous three days/week) and the other nine men received no treatment. After six months, the treatment group had 8.8% more lean body mass, 14.4% less adipose tissue mass, and a 1.6% increase in lumbar vertebral bone density (all P < 0.05). No significant changes occurred in the control group.
Changes in body fat were examined in a double-blind, randomized study involving 110 healthy men and women (ages 65-88 years) given HGH (six months at 20 mcg/kg self-injected three times/week) with or without sex steroids.7 In women, neither HGH, hormone replacement therapy, nor both altered abdominal fat distribution. In men, subcutaneous fat but not visceral fat was reduced significantly compared to placebo after HGH (14%, P = 0.05) and HGH plus testosterone (16%, P = 0.0005).
A similar study examined the effects of HGH (0.02 mg/kg subcutaneous three times/week) with or without sex steroids on bone metabolism in 125 healthy men and women (> 65 years).8 Biochemical markers of bone metabolism had beneficial changes in women given HGH, but not in those given HGH plus hormone replacement therapy. In men, these markers showed small improvements with HGH and much larger ones with HGH plus testosterone. Bone mineral density did not increase in men or women given HGH alone.
A complex study divided 31 healthy men (ages 73-75 years) into four groups.9 The interventions were: HGH alone, HGH plus resistance training, placebo plus resistance training, or placebo alone. HGH alone had no significant effect on muscle strength, size, power, or fiber size, but did produce changes in myosin heavy chain composition consistent with more youthful muscle. Resistance training produced significant muscular gains that HGH did not augment, just as was found with younger athletes.1 HGH alone also significantly reduced fat mass and increased fat-free mass, but did not change bone mineral content.
It’s important to note that improvements in body composition do not mean that aging has been stopped or reversed.
Clinical Studies: Oral Supplements
Oral supplements to boost endogenous HGH production date back to a 1981 study using lysine and arginine. Ingestion of several amino acids, especially arginine, lysine, and ornithine, can elevate HGH levels, making this a popular practice with some athletes.10 However, the response is transient and highly variable, and reduced with aging.11 Among athletes, the increased HGH levels after oral amino acid intake did not lead to improved muscle mass or strength or any other beneficial changes in body composition.10 A search of MEDLINE produced only one study involving older people and the administration of oral amino acids (3 g arginine plus 3 g lysine PO bid).12 This double-blind, randomized study involved 16 men (mean, 68 years), and after 14 days no significant differences in HGH levels were observed between the amino acid group and those taking placebo.
Adverse Effects
Much remains unknown about the connections between HGH and aging. Animal studies consistently find that mice with genetically impaired growth hormone production are smaller, frail, and less fertile; however, they also tend to live longer.13 Also, higher than normal HGH levels are associated with reduced life expectancy in mice and humans; acromegaly is characterized by this complex.14 Adverse effects from subcutaneous HGH include carpal tunnel compression, arthralgia, fluid retention, and reduced HDL-cholesterol levels.1 In one study reviewed here, 12 of the 15 subjects taking HGH reported such adverse effects.9
There is concern about the safety of HGH obtained from glandular or organ material derived from animals. In the early 1980s, several cases of Creutzfeldt-Jakob disease developed because of contaminated cadaveric HGH.15 Although HGH commercially available in the United States is made via recombinant DNA technology, some countries still produce cadaveric HGH of questionable quality which may be available through illegitimate outlets.
Regarding oral supplements, no adverse effects were reported in the study involving older men taking 6 g amino acids bid.12 Higher doses (20-30 g amino acids/d) are sometimes recommended, and can lead to dyspepsia, nausea, or diarrhea.12
Formulation
Numerous formulations are available. The most popular ones are capsules containing 2-3 g of amino acids, usually arginine, lysine, and glutamine. Other herbs and glandular extracts often are included in these preparations. A month’s supply costs from $50 to $200. Injectable HGH is legally available only by prescription, but a black market makes it available, especially among certain athletes.
Conclusion
Although clinical studies have shown that some amino acid supplements, taken orally, will increase endogenous HGH levels, the results are inconsistent and the clinical significance unknown. Results with athletes show none of the desired benefits. The few studies with the elderly have not found HGH-boosting effects and instead suggest that the physiological impact of oral amino acid supplements diminishes with aging.
A small number of studies of subcutaneous HGH injections administered to elderly people do reveal, however, some beneficial changes in body composition. Although this is not evidence that any formulation of HGH stops or reverses aging, they are changes that are highly attractive and may provide protection against certain diseases.
The promotional campaigns for HGH oral supplements are based completely on studies that are irrelevant for the products being marketed. Even if the subcutaneous HGH studies were relevant, the changes in body composition do not support claims that HGH stops aging or causes "youthing." These advertisements may generate interest in HGH injections, but there is no evidence to support their use as anti-aging products.16
Recommendation
Physicians should take advantage of patient interest in these products to point out how these advertisements deceptively misuse scientific studies. Taking time to educate patients will help them avoid both wasting money on ineffective products and placing hope in false promises.
At the same time, HGH injections may produce beneficial changes in some older people’s body composition. A trial period may be appropriate, but HGH should always be prescribed under the careful supervision of physicians. Adverse effects are relatively common, and there are theoretical concerns that higher than normal levels of HGH may shorten lifespan. Patients should be reminded that the best ways to increase their chances of living a longer, healthier life are to adhere to well-established advice on nutrition, exercise, and smoking. Some patients also may need help in coming to accept that aging currently cannot be prevented.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing, Columbus, OH.
References
1. O’Mathúna DP. Human growth hormone and athletic performance. Altern Med Alert 2002;5:65-68.
2. Willix Jr., RD. Health care hoax. Advertisement received in the mail.
3. Meling TR, Nylen ES. Growth hormone deficiency in adults: A review. Am J Med Sci 1996;311:153-166.
4. Riedel M, et al. Growth hormone therapy in adults: Rationales, results, and perspectives. Exp Clin Endocrinol 1994;102:273-283.
5. Rudman D, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990;323:1-6.
6. Lamberts SWJ, et al. The endocrinology of aging. Science 1997;278:419-424.
7. Münzer T, et al. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab 2001;86:3604-3610.
8. Christmas C, et al. Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men. J Gerontol Ser A Biol Sci Med Sci 2002;57:M12-M18.
9. Lange KH, et al. GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly. J Clin Endocrinol Metab 2002;87: 513-523.
10. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 2002; 18:657-661.
11. Tanaka K, et al. Age-related decreases in plasma growth hormone: Response to growth hormone-releasing hormone, arginine, and L-dopa in obesity. Metabolism 1991;40:1257-1262.
12. Corpas E, et al. Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men. J Gerontol 1993;48:M128-M133.
13. Bartke A, et al. Genes that prolong life: Relationships of growth hormone and growth to aging and life span. J Gerontol Ser A Biol Sci Med Sci 2001;56:B340-B349.
14. Takala J, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999;341:785-792.
15. Williamson K. Creutzfeldt-Jakob disease: Another avenue? Br J Hosp Med 1994;51:7-8.
16. Olshansky SJ, et al. Position statement on human aging. Sci Aging Knowl Environ June 2002. Available at http://sageke.sciencemag.org/cgi/content/full/sageke;2002/24/pe9. Accessed July 5, 2002.
O'Mathuna DP. Human growth hormone to prevent key physiological effects of aging. Altern Med Alert 2002;5(9):104-107.
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