A group of well-intentioned people, mostly men, take human growth hormone (HGH) or an HGH promoter to stay young and fit and, they think, to live longer. They are wrong in one important respect: injection of HGH or use of a promoter of HGH, if anything, shortens lives. Very recent research indicates that inhibition of growth hormone may in fact be an approach to life extension. This blog reviews key past and current research related to growth hormone, its health effects and longevity/shortivity.
What is HGH?
“Growth hormone (GH) is a protein-based peptide hormone. It stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. Somatotropin refers to the growth hormone 1 produced naturally in animals, whereas the term somatropin refers to growth hormone produced by recombinant DNA technology, and is abbreviated “HGH” in humans. — Growth hormone is used as prescription drug in medicine to treat children’s growth disorders and adult growth hormone deficiency. In the United States, it is only available legally from pharmacies, by prescription from a doctor(ref).”
“In recent years in the United States, some doctors have started to prescribe growth hormone in GH-deficient older patients (but not on healthy people) to increase vitality. While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial. At this time, HGH is still considered a very complex hormone, and many of its functions are still unknown(ref).
”Starting back in the late 1990s a number of publications appeared suggesting that HGH treatment may produce a number of positive effects in individuals with GH deficiency and may even help with aging, such as the 1997 publication Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging. “These GH secretagogues may have a therapeutic role in short stature and adult GH deficiency. In addition, the use of GH secretagogues in normal aging merits investigation, as growth hormone may regulate body composition in older adults.” The results of those early studies are sometimes cited out of context today to help sell such secretagogues as anti-aging supplements.
Marketing of HGH and HGH promoters for anti-aging
Normal production of HGH, like many other hormones, declines precipitously with advancing age. Today HGH and HGH secretagogues are shamelessly marketed by many companies as anti-aging substances despite lack of supporting research evidence. “Claims for GH as an anti-aging treatment date back to 1990 when the New England Journal of Medicine published a study wherein GH was used to treat 12 men over 60 (Effects of human growth hormone in men over 60 years old). At the conclusion of the study, all the men showed statistically significant increases in lean body mass and bone mineral, while the control group did not. The authors of the study noted that these improvements were the opposite of the changes that would normally occur over a 10- to 20-year aging period. Despite the fact the authors at no time claimed that GH had reversed the aging process itself, their results were misinterpreted as indicating that GH is an effective anti-aging agent(ref)” This has led to organizations such as the controversial American Academy of Anti-Aging Medicine promoting the use of this hormone as an “anti-aging agent”.”
The 2008 report Systematic review: the safety and efficacy of growth hormone in the healthy elderly relates “The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.”
The 2007 article No proof that growth hormone therapy makes you live longer, study finds relates “Surveyors of anti-aging elixirs tout human growth hormone as a remedy for all things sagging-from skin to libidos – and claim it can even prevent or reverse aging. But researchers at the Stanford University School of Medicine say there’s no evidence to suggest that this purported fountain of youth has any more effect than a trickle of tap water when it comes to fending off Father Time. — “There is certainly no data out there to suggest that giving growth hormone to an otherwise healthy person will make him or her live longer,” said Hau Liu, MD, a research fellow in the division of endocrinology and in the Center for Primary Care and Outcomes Research, and first author of a review study to be published in the Jan. 16 issue of Annals of Internal Medicine. “We did find, however, that there was substantial potential for adverse side effects.” — Those negative side effects included joint swelling and pain, carpal tunnel syndrome and a trend toward increased new diagnoses of diabetes or pre-diabetes. “You’re paying a lot of money for a therapy that may have minimal or no benefit and yet has a potential for some serious side effects,” Liu said. “You’ve got to really think about what this drug is doing for you.” — Growth hormone is widely promoted on the Internet and its use as a purported anti-aging drug has caught the attention of the popular media, ranging from the “Today Show” to Business Week. — Between 20,000 and 30,000 people in the United States used growth hormone as an anti-aging therapy in 2004, a tenfold increase since the mid-1990s, according to the authors of an unrelated study published in the Journal of the American Medical Association in 2005. This increase comes despite both the high cost of such therapy – often more than $1,000 a month – and the illegality of distributing growth hormone for anti-aging therapy in this country. Those numbers prompted Liu and some colleagues to see if the medical literature provided any support for such therapy.”
The Quackwatch article Growth Hormone Schemes and Scams provides a history of how marketing has trumped science in promoting HGH as an anti-aging substance. “Human growth hormone (HGH) is a substance secreted by the pituitary gland that promotes growth during childhood and adolescence. Growth hormone acts on the liver and other tissues to stimulate production of insulin-like growth factor I (IGF-I), which is responsible for the growth-promoting effects of growth hormone and also reflects the amount produced. Blood levels of circulating IGF-I tend to decrease as people age or become obese . Many marketers would like you to believe that boosting HGH blood levels can reduce body fat; build muscle; improve sex life, sleep quality, vision and memory; restore hair growth and color; strengthen the immune system; normalize blood sugar; increase energy; and “turn back your body’s biological clock.” This article traces the history of these claims and why you should disregard them. — Marketing “Milestones” — The drive to popularize growth hormone began about 20 years ago with publication of the book Life Extension: A Practical Scientific Approach, by Durk Pearson and Sandy Shaw . The book’s central premise was large amounts of vitamins, minerals, amino acids, and other substances would cause people to add muscle, burn fat, and live much longer. Although their advice had no scientific basis [3,4], Pearson and Shaw made hundreds of talk-show appearances that boosted sales of the substances they recommended. — Soon after the book’s publication, many amino acid products were claimed to cause overnight weight loss by increasing the release of growth hormone. So called “growth-hormone releasers” were also marketed to bodybuilders with claims that they would help build muscle. Such claims are unfounded because amino acids taken by mouth do not stimulate growth hormone release. These formulations are based mainly on misinterpreted studies of intravenous arginine, which can increase HGH blood levels for an hour or so. Taking it by mouth has no such effect. The FTC [5-9], and the New York City Department of Consumer Affairs  attacked some companies making “growth-hormone release” claims, but these actions had very little effect on the overall marketplace. — In 1990, The New England Journal of Medicine published a study that attracted mainstream media attention. The study involved 12 men, aged 61 to 81, who were apparently healthy but had IGF-I levels below those found in normal young men. The 12 men were given growth hormone injections three times a week for six months and compared with 9 men who received no treatment. The treatment resulted in a decrease in adipose (fatty) tissue and increases in lean body (muscle) mass and lumbar spine density . An accompanying editorial warned that some of the subjects had experienced side effects and that the long-range effects of administering HGH to healthy adults were unknown. It also warned that the hormone shots were expensive and that the study had not examined whether the men who received the hormone had substantially improved their muscle strength, mobility, or quality of life . — Despite the warning, the study inspired many offbeat physicians to market themselves as “anti-aging specialists.” Many such physicians offer expensive tests that supposedly determine the patient’s “biological age,” which they promise to lower with expensive hormone shots and dietary supplements.”
Continuing the Quackwatch quote, “In 2001, NBC’s Dateline showed what happened when a 57-year-old woman visited a Cenegenics clinic in Las Vegas, Nevada, where she underwent $1,500 worth of tests and was offered a hormone and 40-pill-a-day supplement program that would cost $1,500 a month. She was told that although she tested at “age 54,”her hormone levels were “sub-optimal” and that optimal would be the level of a 30-year -old . — — The Internet has added another dimension to the HGH marketplace. Thousands of Web sites and spam e-mailers are hawking the actual hormone; alleged HGH releasers; alleged oral hormone products (which can’t work because any HGH would be digested); and/or “homeopathic HGH” products. – The bottom line: Although growth hormone levels decline with age, it has not been proven that trying to maintain the levels that exist in young persons is beneficial. Considering the high cost, significant side effects, and lack of proven effectiveness, HGH shots appear to be a very poor investment. So called “growth-hormone releasers,” oral “growth hormone,” and “homeopathic HGH” products are fakes.” (The writer might be going a bit too far here, in that while some products are fakes, HGH secretagogues may to some extent work.)
Substances marketed mainly to men for strength and sexual vitality include include testosterone and strength-promoting steroids in addition to HGH. See the recent well-researched three-part press exposition in the Star-Ledger , especially Part 3: Booming anti-aging business relies on risky mix of steroids, growth hormone.
Molecular biology of GH and aging
A number of publications point to the importance of IGF-1 axis signaling in regulating healthspan and lifespan, for example the 2008 publication Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth hormone administration normally stimulates IGF production in tissues whereas greater longevity is normally associated with downregulation of IGF activity. The 2004 article The GH/IGF-I axis and longevity reports “These and other results suggest that in mammals too, lifespan can be increased by continuous, long-term downregulation of IGF signaling. Since growth hormone administration normally stimulates IGF production in tissues, the question arises whether the beneficial effects of GH, as reported by others, could be IGF independent.” So, besides producing nasty side effects, giving HGH to healthy elderly people may in fact shorten their lives. As pointed out in the 2010 article [IGF and insulin signaling pathways in longevity]: “The role of the somatotropic hormone axis in mammalian longevity has been studied in diverse experimental models in vivo. This endocrine axis allows regulation of lifespan via metabolism modifications and oxidative stress defense mechanisms.” Interventions like rapamycin which affect this axis via suppression of the mTOR gene or promotion of SIRT1 activity via resveratrol which also impacts on this axis appear indeed to be life-extending. The evidence suggests that affecting this axis via exogenous GH administration could well produce the opposite effect and be life-shortening.
Inhibiting growth hormone and cancer
Starting in the mid-late 1990s, inhibition of growth hormone has been seen as a possible anti-cancer therapy. The 2001 paper Antagonists of GHRH Decrease Production of GH and IGF-I in MXT Mouse Mammary Cancers and Inhibit Tumor Growth. “The goal of our study was to investigate whether antagonists of GHRH can interfere with the effects of GH and IGF-I in MXT mouse mammary cancers. GHRH antagonists JV-1-36 and JV-1-38 inhibited growth of estrogen-independent MXT mouse mammary cancers in vivo, producing about 50% reduction in tumor volume (P < 0.05). This growth inhibition was associated with a decrease in cell proliferation and an increase in apoptosis in MXT cancers.– Our results demonstrate that GHRH antagonists decrease the local production of both GH and IGF-I in MXT mouse mammary cancers, the resulting growth inhibition being the consequence of reduced cell proliferation and increased apoptosis.”
Other publications on the anti-cancer effects of inhibiting growth hormone go as far back as 1997. They include Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160 inhibit the growth of the OV-1063 human epithelial ovarian cancer cell line xenografted into nude mice, Antagonists of growth hormone-releasing hormone inhibit the proliferation of experimental non-small cell lung carcinoma, Suppression of tumor growth by growth hormone-releasing hormone antagonist JV-1-36 does not involve the inhibition of autocrine production of insulin-like growth factor II in H-69 small cell lung carcinoma,
Inhibition of growth hormone may be an approach to life extension
A December 2010 research publication suggests that life extension could possibly result from the opposite of what the HGH hucksters are promoting: Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice. “Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 Î¼g/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity.”
I caution that the SAMP8 mice used in the experiment were relatively short-lived to start with and it is not clear that the same experiment applied to normal wild-type mice would also result in healthspan extension and lifespan extension. Nonetheless, the popular press has speculated that the research results probably apply to humans as well. According a press report that appeared in multiple publications “ Scientists found blocking growth hormone with a compound called MZ-5-156, might actually help people live longer and reverse signs of aging, contrary to current thinking. — The researchers say the study is important because many older adults use growth hormone, thinking it is the fountain of youth, when instead it may be just the opposite and hazardous. — The study, published online in the Proceedings of the National Academy of Sciences, showed that blocking growth hormone in mice with a compound called MZ-5-156 improved cognition and activity of telomerase that protects DNA from damage that could increase lifespan. — They also found decreased tumor activity in the mice that are genetically engineered for studying the aging process. John E. Morley, M.D., study co-investigator and director of the divisions of geriatric medicine and endocrinology at Saint Louis University School of Medicine says sometime people take growth hormone because they think it will be the fountain of youth. — MZ-5-156 that is a “growth hormone-releasing hormone (GHRH) antagonist”, inhibited a variety of cancers, including prostate, breast, brain and lung cancers.” The ability of many GHRH antagonists for curbing cancer has been noted in the past. — In the aging mice, MZ-5-156 improved short-term memory and reversed oxidative stress in the brain, in turn reversing memory loss. — William A. Banks, M.D., lead study author and professor of internal medicine and geriatrics at the University of Washington School of Medicine in Seattle, said the findings from the research team, “determine that antagonists of growth hormone-releasing hormone have beneficial effects on aging.” — Contrary to the popular belief that growth hormone may be the “fountain-of-youth”, the new findings show that blocking the effect of growth hormone with the growth hormone releasing compound MZ-5-156, reversed signs of aging in mice and inhibited several types of cancer.
As a personal note, I took an HGH secretagogue for a short period about 15 years ago and then stopped. As long-stated in my treatise “I do not take HGH or HGH promoters because they can have serious side effects – I tried once and got a serious case of arthritis.”
The central guiding principle of this blog is scientific integrity. For that reason I do not accept advertisements or commercial sponsorships and I do not associate myself with anti-aging practitioners who provide therapies based on faulty or misrepresented science.