On July 5th 1990, America's most prestigious medical journal, the New England Journal of Medicine, published a human clinical study that changed the world of anti-aging medicine forever.
Daniel Rudman, MD and colleagues reported the results of their 6-month trial of synthetic human growth hormone (HGH) with 12 elderly men, aged 61 to 81. Astoundingly, without any change in diet, exercise, lifestyle, smoking etc., the 12 men gained muscle, lost fat, increased their bone density, thickened their skin and expanded their livers and spleens almost 20%.
In effect, HGH reversed the biological age of the subjects by 10 to 20 years!
Prior to Rudman's landmark study, hGH use had been restricted to two classes of people: young children, whose growth was severely stunted due to serious hGH deficiency and adults whose pituitary glands had been damaged or destroyed by injury, illness or radiation.
Prior to 1985, HGH was in extremely short supply. It was painstakingly extracted from the pituitary glands of human cadavers.
Human use of HGH began in 1958 when endocrinologist Maurice Raben injected HGH into a dwarf child. The child began to grow normally and over the next 30 years thousands of children were injected with cadaver derived HGH.
By 1985 the company that pioneered recombinant DNA technology, Genetech, had produced the first synthetic HGH, opening the way to mass production of hGH.
HGH is an extremely large and complex hormone, consisting of 191 specific amino acids linked in a 3 dimensional structure. Because it is a complex protein, HGH cannot survive digestion and must be taken by injection.
Genetech's product, Protropin, differed from natural HGH by one amino acid, but this did not affect its performance in the human body. The following year, the Drug Company Eli Lilly succeeded in making a 191 amino acid HGH that was 100% physically, chemically and biologically identical to HGH produced by the human pituitary gland.
Lilly's Humatrope was also approved by the USA FDA for both research and medical use and became what many clinicians now consider the "gold standard" of recombinant DNA produced hGH. Finally in 1996, thanks to the pioneering medical and legal work of Dr. Edmund Chein, the FDA lifted its ban on the use of HGH for adult patients.
From 1994 through 1996, over 800 people were treated with HGH at Dr. Chein's clinic. In 1995, Chein began his collaboration with Dr. L. Cass Terry. Terry used his skills as an academic researcher to help Chein turn the mass of clinical data gathered from his patients, into a meaningful statistical profile of results. These results would demonstrate to both scientists and the public, the safety and efficacy of HGH in improving a broad array of human health parameters in adults.
Chein and Terry's data were published for the first time in Dr. Ronald Klatz's 1997 book Grow young with HGH.
HGH is secreted by the pituitary gland, a tiny gland at the base of the brain. It is normally secreted in pulsatile bursts, with the largest daily amount being secreted in the first few hours of deep, slow wave sleep.
For reasons of convenience, Dr. Rudman in his 1990 study had given his 12 elderly men only 3 injections of HGH per week, at a high dose of 16 IU.
In a study published in 1996, Dr. Maxine Papadakis of UCSF reported mixed results with the identical high dose, low frequency protocol of HGH injections. Although both Rudman and Papadakis found significant multiple benefits, especially on the body composition of the subjects, they also reported some unpleasant side effects. These included carpal tunnel syndrome (wrist pain), gynecomastia (enlarged breasts), pains in both large and small joints and edema (excess fluid) in the legs.
Papadakis' team also noted, however, that the side effects disappeared or decreased markedly within 2 weeks after the HGH dose was lowered by 25 to 50%.
Chein and Terry chose to adopt an injection regimen, which more closely approximated the natural rhythms of normal HGH secretion. Their clinic patients were taught to self administer HGH injections subcutaneously (just below the skin), just before bedtime and upon arising 6 days per week. A weekly day of rest from injections was taken to prevent the patient's pituitary glands from getting "lazy" and ceasing whatever HGH secretion their gland was still releasing.
A dose of 0.3 to 0.7 IU of HGH was given twice daily, for a weekly total of about 4 to 8 IU HGH. Thus, Chein and Terry's weekly dose was only about one quarter to one half of the dose Rudman and Papadakis gave their patients 3 times weekly.
Chein and Terry have not found any major side effects among their 800 patients. Minor joint aches and pains and slight fluid retention are the only side effects they have found, and these generally disappear in the first month or two of treatment.
Chein and Terry believe their lower dose; natural rhythm HGH protocol is responsible for the minimal incidence of severity of side effects in their patients.
Based on the results of randomly selected questionnaires from 202 patients, aged 39 to 74 (15% women), Chein and Terry reported many outstanding benefits of their low dose, high frequency HGH program.
Over 80% improved, while 72% noted significant fat loss. 60 to 70% found improvement in skin texture, thickness, elasticity and wrinkle disappearance, while 38% reported new hair growth. 55 to 71% found improved healing capacity and healing of injuries, while 73% reported increased resistance to common illness.
A high incidence of improvement in sexual functioning and menstrual/ menopausal health was noted.
Also 62 to 84% of subjects enjoyed increases in energy levels, emotional stability, positive attitude and memory.
To fully understand the significance of the positive results reported by Rudman, Papadakis, Chein and Terry (as well as many others too numerous to mention in this short article), it is necessary to understand the basics of the biology of HGH.
HGH is one of many hormones secreted by the pituitary gland. Hormones are chemical messengers that help guide, direct and control the complex integration between (and physiologic functions of) our organs, tissues and cells.
Just as there is a hierarchy of control in an army, with generals directing colonels, who direct majors and captains, with orders eventually directing the corporals and privates to action, so the human glandular system is ordered and functions hierarchically.
The general of the hierarchy is the human brain, which affects the connecting link between the nervous system and the glandular system- the hypothalamus. The hypothalamus portion of the brain, activated by nerve signals from elsewhere in the brain, secretes releasing hormones, which in turn cause the pituitary to release its hormones.
Pituitary hormones, such as ACTH, thyrotropin and luteinizing hormone (LH), trigger other glands to release their hormones.
ACTH triggers the adrenals to secrete cortisol, thyrotropin causes thyroid hormone release and LH activates the sex glands to release their hormones.
Finally, these primary action hormones affect their target tissues- e.g. the sex hormones control the reproductive organs, thyroid hormone activates brain, liver, heart and muscles, while cortisol alters immune, brain and fat tissue, etc.
Out of all the various pituitary hormones, HGH has the most universal action, ultimately affecting every cell of the body. Unfortunately, HGH shows the greatest and most precipitous drop with age.
According to data from the April 1995 Journal of NIH Research, a healthy 10-year-old might secrete 2000mcg HGH per day. By age 20 hGH secretion has already dropped to 700mcg per day (a 75% drop!). 400mcg is secreted on average by 30, while from 40 to 80 hGH drops from about 325mcg to 225mcg per day.
Yet ironically, research has shown that the somatotrophs (HGH producing cells within the pituitary) of elderly people are frequently making as much HGH as young people! The problem then lies with defective HGH release and not manufacture.
Many factors (possibly including some nutrients) enhance HGH release; many all too common factors also inhibit HGH release.
Intense exercise, adrenaline mediated stress, emotional excitement, fasting and calorie restricted diets enhance growth hormone release.
While the "state of siege" stress hormone- cortisol, insulin excess and insulin resistance, obesity (especially abdominal obesity) and high blood levels of free fatty acids, all inhibit hGH release and at the same time that our cells are becoming less sensitive to HGH's effects.
When the pituitary in response to hypothalamic releasing factors secretes HGH, it only remains in the bloodstream for minutes. During this brief flare of activity, HGH induces the liver to produce various growth factors, especially Insulin like Growth Factor One (IGF-1). While HGH has some direct benefit on the health, metabolism and structure of our trillions of cells, much of HGH's benefit is mediated through IGF-1 and other growth factors HGH induces. Between them, HGH and IGF-1 help deliver to our cells the raw materials needed for repair and renovation.
According to Doctors Thierry Hertaghe and Vince Giampapa the latest European research indicates hGH and IGF-1 can go beyond the current antioxidant based anti-aging remedies in slowing, preventing and reversing aging at the cellular level.
Grace Wong of Genetech has shown that as we age cell proteins, as well as the DNA and RNA that provide the blueprint for making protein and other needed cell constituents, suffer ever accumulating damage.
A major cause of this age related cellular degradation is the ever-increasing incidence of free radicals released during normal cellular activity. These free radicals activate protease's, destructive enzymes that damage and degrade essential cell proteins and structures.
Antioxidants, such as vitamins C and E, SOD, etc., can reduce cellular levels of free radicals and thus reduce activation of the damaging proteases.
But HGH can actually activate a cellular defense force of protease inhibitors. Thus, even if high levels of free radicals can't be avoided, the protease inhibitors prevent the free radicals from triggering cell destructive proteases.
Thus Hertoghe and Giampapa note that HGH and IGF-1 can do what antioxidants cannot. Antioxidants can only reduce damage to already existing cell proteins and structures. HGH and IGF-1 help pull into the cell the nutrients needed to repair renovate and rebuild cellular structures. IGF-1 can even deliver nucleic acids (the building blocks of the genes) right into the protected citadel of the cell nucleus, where the DNA and genes, which direct our cellular architecture, reside.
Thus unlike antioxidants, HGH and IGF-1 don't just reduce cellular damage, they actively promote the healing and regeneration of aging cells.
As recently as the early 1980's, many medical texts focused on HGH's role primarily as the hormone necessary to achieve normal height and bone development. Yet the clinical human researches, as well as the basic research on HGH of the past 20 years, has now shown that hGH/ IGF-1 affects every aspect of human biology.
One of the many systems that weakens as we age is our immune system. Infectious ailments that might barely bother a healthy 20-year-old may be fatal to a typically immune compromised elderly person.
A key biomarker of aging is the "involution" or disappearance of the thymus gland. The thymus gland is the director and activator of the immune system. It secretes hormones such as thymosin and thymoietin, which regulate the immune system.
The thymus also transforms immature T-cells into programmed germ killing warriors. Researchers have been able to reverse the thymic atrophy of old rats through HGH, so that their thymus glands became as large and robust as the thymus glands of healthy young rats.
It is now known that the activity of all major immune cell types, such as T-cells, B-cells, natural killer (NK) cells and macrophages, can be beneficially altered by hGH/ IGF-1. Greg Fahey of the Naval Medical Research Institute, Bethesda MD, has noted that immune restoration has multiple benefits. These include improved ability to make DNA, have normal cell division, normal insulin sensitivity, normal thyroid hormone levels and more normal brain chemistry.
HGH's ability to normalize age impaired insulin sensitivity is an exciting area of current research. Clinical studies with HGH routinely show reductions in human body fat with simultaneous increases in lean body mass (muscle and organ tissue).
For example, in 6 months of HGH treatment at Sahlgrenska Hospital in Sweden, HGH deficient adults lost 20% of their body fat. Most of this fat loss occurred in abdominal fat, reduced by 30%, compared with a 13% reduction in peripheral (e.g. arm and leg) fat.
It is increased abdominal fat that is strongly correlated with increased incidence of heart attacks, hypertension and diabetes.
In a short term 1994 study with 9 obese women, just 5 weeks of HGH treatment was sufficient to show significant fat loss and lean tissue gain. In this double blind crossover study, the women lost an average of 4.6 pounds of body fat (mostly abdominal), while their lean body mass increased 6.6 pounds.
HGH induced losses of abdominal fat take on added significance from the viewpoint of endogenous (body produced) HGH release. Obese men make 25% less growth hormone daily and have a pulsatile GH release that is only 25% as much as a normal weight men! It is the interaction of insulin with hGH/ IGF-1 that seems to be responsible for HGH's anti-fat pro-muscle benefits.
As people age, their cells become more insulin resistant, frequently accompanied by increased blood insulin levels at the same time. Yet as we age, not all cells become equally insulin resistant. Unfortunately, it is the lean body mass cells (muscle and organ tissue) that primarily become insulin resistant. Fat cells may even increase their insulin sensitivity! Since insulin helps fats, sugars and amino acids from the blood enter cells, this means that our cardiac, nerve and muscle cells are being starved as we age, meanwhile our fat cells are being gorged. But insulin doesn't just help food enter our fat cells, it also directs them to turn that bonanza into body fat!
When HGH levels become adequate once again, however, it seems to reverse the situation. It directs the action of insulin toward feeding our precious heart, brain, muscle and other organ cells, while minimizing insulin's direction of food into fat cells. Also, fat cells have HGH membrane receptors and when adequate HGH activates these receptors it triggers a process called "lipolysis," breaking down existing fat.
In a very real sense, HGH puts fat cells on a diet and on fat burning "exercise programs" at the cellular level!
HGH has also been shown to benefit the brain and mind in many ways. Scientists have discovered HGH receptors in different parts of the brain, yet it seemed that the giant HGH molecule could not pass through the blood brain barrier. Research then discovered how HGH injections could influence the brain.
When HGH was injected into the leg, there was a 10-fold increase in HGH levels in the cerebrospinal fluid that bathes the brain. Researchers also discovered that hGH seems to rebalance neurotransmitter levels, increasing mood elevating levels of beta-endorphin, one of the brain's chief "feel good" biochemicals, while simultaneously lowering excessive dopamine levels.
Excessive dopamine produces feelings of agitation, irritability and quarrelsomeness- the "grumpy old men" syndrome.
Also, research with both pituitary damaged HGH deficient adults as well as age related HGH deficient adults, has consistently shown an antidepressant, mood elevating HGH effect. Many of the pituitary damaged (or removed) adults studied in Sweden became withdrawn, depressed, socially isolated, passive and pessimistic. After HGH treatment, many of these adults once aging became sociable, friendly, outgoing, zestful people.
The patients treated by Drs. Chein and Terry also noted improved stress resilience, more positive outlook, more joy and peace in life.
Neuroscientists have also found evidence in both humans and animals that HGH may actually reverse the typical brain shrinkage that occurs with age. While some brain cells die over the course of a lifetime, it is even more the myriad of dendritic connections between neurons that disappear with age. It is this ever changing, even renewing (if we're healthy and active) neuronal web that forms the basis for all learning and memory.
HGH/ IGF-1 seems to protect brain cells from death under non-ideal conditions. HGH also stimulates various nerve growth factors in the brain, which in turn cause new dendrites to sprout.
The 1990's have brought the human race- for the first time in history- the technology to reverse the generally inevitable and debilitating decline in HGH secretion. HGH research over 30 years has demonstrated with a wealth of detail, (way beyond what can even be hinted at in this short article), that HGH is the hormone of human rejuvenation and regeneration.
Even the elderly can attain HGH assisted recovery of lost strength, health and vigor of body and mind.
It is just in time, for the diet and lifestyles of late 20th century Westerners are almost perfect for producing catastrophic HGH decline.
Even in late youth and middle age, our carbohydrate, fat and calorie rich diet promotes insulin excess and high blood fats, combined with abdominal obesity, which reduces HGH secretion and effect. Our "couch potato" lifestyle fails to provide the intense exercise stimulus needed to produce pituitary HGH release. Our quietly desperate, stressful lives which we can neither flee from nor fight, causes chronic cortisol excess in many, inhibiting hGH release and promoting hGH stultifying obesity. Our modern self indulgence and lack of discipline makes it hard for most people to benefit from the cheapest and most researched method of increasing both pituitary hGH secretion, as well as cellular sensitivity to hGH- systematic under-eating, also known as long term caloric food reduction.
Thus HGH injections may provide the "jump start" our lives need, both to reverse (some of) our accumulated aging, as well as increase our own HGH production and release, with consequent rejuvenation and regeneration.
Those wishing more detail on HGH, as well as an excellent technical HGH bibliography, are referred to the excellent book: Grow Young With HGH by Ronald Klatz and Carol Khan (San Francisco, Harpers 1997).
HGH, IAS comments
The above book that James South MA refers to is available directly from the American Academy of Antiaging Medicine, of which Dr. Ronald Klatz is a founder. To order a copy telephone (USA) 773 528 1000. Of course we advocate all our pharmaceutical products to be used under the guidance of a physician, and this is particularly true of HGH. Apart from the fact that the product is injected, age, body weight and current blood levels (often monitored as IGF-1) set the doses. Long term administration can then be reduced when blood levels of younger persons are reached (normally considered around 25 years of age).