Human Growth Hormone (HGH)

Narkissos

Latest revision: May 17, 2010

Important Note: Many people come directly to this chapter from a search engine without realizing that it is one chapter of an online Life Extension Manual. If you are interested in this subject, please read the rest of the Manual as well, beginning with the important Preface to the Life Extension Manual.


The average person thinks of the damage of aging as an inevitable process of wear and tear. However, if wear and tear were the primary cause of aging in humans, a 60 year-old should have only twice the signs of aging as a 30 year-old.

Why do most 30-year-olds show few effects of aging, while the effects of aging are so obvious in a 60 year-old person? If wear and tear were the major cause of aging, a 90-year-old person would only have 3 times as much aging damage as a 30-year-old.

At the age of 30, people have spent most of their lives with fairly high levels of human growth hormone (HGH). HGH is responsible for growth during childhood -- and for the repair and regeneration of human tissue throughout our lives. By the time we reach the age of 30, our HGH levels are only about 20 percent of their peak levels during childhood, and after the age of 30, they continue to decline at about 12 to 15 percent per decade, and often much more. By the time most of us are 30 years old, our bodies no longer produce enough HGH to repair all of the damage that is occurring in our bodies. As our HGH levels continue to decline, the damage that we call aging continues to accelerate.

The decline in HGH is not the only cause of the manifestations of aging. Even if our HGH levels remained at the level of a 25 year-old, we would continue to experience the effects of aging, but those effects would be greatly reduced until we reached a very advanced age. HGH does not affect the root cause of aging, as measured by maximum lifespan, but it can certainly affect many of the manifestations of aging.

By increasing the levels of HGH in our bodies, we can slow, or even reverse, many of the manifestations of aging. It must be done carefully, though, and under medical supervision. Ideally, this HGH replacement should begin at about the age of 30 years, but HGH replacement can be beneficial at any age above 30. In fact, for older people, HGH therapy can reverse the manifestations of aging by 5 to 15 years or more. There is no other single therapy currently available that can have the impact on the aging body that HGH can have.



What HGH therapy can do:

• Reduce excess body fat, especially abdominal fat. (The reduction of abdominal fat is the single most profound effect of HGH replacement in many people.)
• Increase muscle mass (and physical strength if combined with moderate exercise).
• Reduce wrinkling of the skin and some other effects of skin aging.
• Re-grow certain internal organs that have atrophied with age.
• Increase bone density.
• Strengthen the immune system.
• Reverse cognitive decline.
• Stimulate production of the bone marrow cells that produce red blood cells.
• Reduce the probability that you will spend the last years of your life in a nursing home.
• HGH slows the progression of cardiovascular disease, and reduces the risk of death from cardiovascular disease, in individuals with natural growth hormone levels that are below average for the age of the individual. HGH can also slow the progression of cardiovascular disease by improving one's cholesterol profile. There is increasing evidence over the past year or two that maintaining healthy growth hormone levels results in a stronger heart. Individuals with low growth hormone levels have an overall increased risk of death due to cardiovascular disease. Low growth hormone levels cause a particularly large increase in the risk of stroke as compared with individuals receiving growth hormone replacement.

What HGH cannot do:

• It cannot eliminate the effects of oxidation damage, although it may alleviate some of it.
• HGH cannot eliminate the effects of the reduction of other hormones. In fact, a deficiency of certain other hormones will decrease the beneficial effects of HGH.
• It cannot significantly reverse the damage to human proteins caused by glucose, although it may reverse a little of this damage.
• Although it helps skin to look younger, it cannot eliminate all of the damage cause by sunlight and other ultraviolet sources.
• It cannot increase maximum lifespan. For many people with HGH or IGF-1 genetic defects, however, it can significantly extend life expectancy.

Note: As of this writing, there is a federal law in the United States that prohibits the use of human growth hormone for any purpose outside of a very narrow range of conditions. At the beginning of 2007, the federal government made some attempts to start enforcing this previously obscure law. This caused great human suffering and several deaths.

I can give a personal example of the health damage caused by the prohibition on the "off-label" use of HGH. I have a strong genetic tendency toward spinal osteoporosis, which the evidence strongly suggests is IFG-1 related. (IGF-1 is produced in response to growth hormone.) My father died very slowly of the effects of this disease as his spine crumbled away. The FDA does not recognize this condition, and federal law prohibits the use of HGH against osteoporosis unless damage to the pituitary gland can be demonstrated. As a result of FDA attempts to enforce this law, I spent 6 months without HGH. During this period, I lost 8 percent of the bone mineral density of my L1 vertebrae, more than 10 percent of my L2 vertebrae, and more than 21 percent of the density of my L3 vertebrae. During this same period, I crossed the threshold from spinal osteopenia to spinal osteoporosis. I am quite healthy otherwise. I subsequently obtained medical care outside of the United States in order to avoid further spinal deterioration. By taking control of my own medical care, I have been able to substantially regain much of my loss of spinal bone mineral density.
Many doctors in the United States simply ignore the law prohibiting the uses of HGH for conditions not specifically approved by the FDA. Any doctor who does so, however, is risking legal problems. Although it is almost impossible to actually convict any physician for prescribing HGH for any legitimate medical condition (because juries are more compassionate than government bureaucracies), the federal government has tried, and such attempts have been financially very costly for physicians.

HGH is produced by the pituitary gland. The ability of the pituitary gland to produce HGH declines very little with aging in most people. The decline with aging occurs one step back from the actual secretion of HGH by the pituitary. There are at least 3 substances which control HGH secretion:

• Growth hormone releasing hormone (GHRH), a substance which declines with age. Increasing levels of GHRH causes the pituitary to increase its output of HGH.
• Growth hormone releasing peptide (GHRP) is another substance that declines with age. Increasing levels of GHRP also causes the pituitary to increase its output of HGH.
• Somatostatin is a hormone that blocks the release of HGH by the pituitary gland. The natural production of somatostatin increases with age, and causes a corresponding decrease in HGH production by the pituitary gland.

The production of HGH is controlled by GHRH, GHRP, somatostatin, and other substances in the body. The degree to which changes in the levels of each of these substances is responsible for the decline in human growth hormone varies from individual to individual, and is somewhat gender-dependent.

The only naturally-occuring growth hormone releasing peptide appears to be ghrelin. Ghrelin is a hormone with many other effects, including being a powerful appetite stimulant. When given to laboratory animals, the animals eat huge amounts of food. The weight gain induced by overeating completely overwhelms the fat burning caused by the growth hormone release, and the animals become obese. Pharmaceutical companies have produced synthetic growth hormone releasing peptides, such as GHRP-6 and GHRP-2, which stimulate HGH in humans, but do not increase appetite significantly. These substances are not on the market yet, and probably won't be for many years, if ever.

Pharmaceutical companies have produced a number of other promising analogs of ghrelin that restore the normal pulsatile release of growth hormone without the other unwanted effects of ghrelin. These substances include:

• Hexarelin
• MK-0677 (ibutamoren mesylate, developed by Merck)
• Capromorelin (developed by Pfizer)
• Tabimorelin
• SM-130686 (Sumitomo Pharmaceuticals)
• Ipamorelin (Novo Nordisk)
• NN703 (Novo Nordisk. Similar to ipamorelin, but more selective)

Many of the above growth hormone releasing analogs of ghrelin are effective when taken orally. None of them are on the market anywhere in the world. Hexarelin is a peptide that is fairly easy to synthesize, and it is sometimes used outside of legitimate medical channels. The other substances on the above list are only available in rare clinical trials.
Even though the above compounds have all been researched and found effective, it is doubtful if the research will proceed much farther. Most of these compounds are mainly effective against age-related declines in growth hormone. The United States Food and Drug Administration (FDA) does not regard the age-related decline in growth hormone to be a disease, even when it results in serious disability and death. Because of the size of the U.S. market and the worldwide influence of the FDA, these valuable medicines will probably be forever blocked from the market. (Because of the effectiveness of MK-0677, however, there is some hope for it eventually being approved somewhere in the world for a condition other than age-related growth hormone decline.)

Three major analogs of growth hormone releasing hormone have been developed by pharmaceutical companies, and will be discussed later:

• Sermorelin (Geref, developed by Serono, withdrawn from the market)
• Tesamorelin (Theratechnologies)
• CJC-1295 (ConjuChem Biotechnologies)

The effects of HGH in the human body have been studied intensively for decades, but the factors that affect HGH production remain rather complex and mysterious. Part of the reason for this is that the quantities of these substances produced by the body are on the order of a milligram per day in adults. Most people only produce about a teaspoonful of these substances during their entire adult lives.

To make the HGH situation even more complex, HGH is normally released in pulses or bursts throughout the day. There are usually 10 to 20 surges of HGH release, with the largest release occurring shortly after you fall asleep. Is there any advantage to having HGH released in pulses? Or is this simply the body's most efficient way of producing HGH? Nobody knows the answer to this important question.

There are indications, however, that some of the ghrelin analogs or the GHRH analogs may be superior to ordinary HGH replacement. Ordinary HGH therapy does not increase insulin sensitivity or decrease glucose levels, although it logically should be expected to -- since it increases the level of IGF-1 (insulin-like growth factor number 1). IGF-1 decreases glucose levels, so there is something about the continuous presence of growth hormone that is offsetting this IGF-1 related decrease in blood glucose. When youthful pulsatile release of growth hormone is restored, often (most notably with Tesamorelin) the IGF-1 related decrease in blood glucose is seen, as would be expected.

There are three basic ways for increasing HGH:

• Taking a substance that increases the natural secretion of HGH by the pituitary gland.
• Using an injectable human growth hormone releasing hormone (GHRH).
• Using injectable human growth hormone.

With current technology and available substances, taking a substance that increases the natural secretion of HGH generally works best for those between the ages of roughly 30 to 45 years.

For most people over 45, injectable HGH is most effective -- and usually the only effective -- of the currently available options (although sermorelin works for some people). Tesamorelin looks like it will be very promising when it becomes available. But let's look at these three methods in greater detail.
There are a number of substances that increase the natural secretion of HGH. Some of them are amino acids. The relationship of certain amino acids to growth hormone is complex and varies greatly among different individuals and among individuals of different ages. All absolute and universal statements made about this subject are clearly false.

The most effective and economical way of causing this HGH release for many people seems to be taking 2 grams of the amino acid L-glutamine in the morning and taking 10 to 30 grams of the amino acid L-arginine before bedtime. Both of these amino acids must be taken on an empty stomach. Amino acids are generally not very effective in people over the age of about 40 to 45. In fact, for people over about the age of about 40 to 45, HGH increases due to amino acids may only be barely measurable on laboratory tests, and may have no real practical effect.

There has been only one scientific study showing that L-glutamine causes HGH release, but there is a large body of anecdotal evidence from anti-aging physicians and their patients that L-glutamine is actually effective in most persons under about age 45.

There is a large body of scientific study on the effects of L-arginine on growth hormone release. In fact, the administration of a large dose of L-arginine is a standard test for the ability of the pituitary to release growth hormone. (Another test using insulin is actually more effective, but it is not accepted as the standard test by the U.S. Food and Drug Administration.) Most scientists believe that L-arginine promotes HGH release by inhibiting somatostatin, and this has been demonstrated in at least one scientific study. L-arginine has many other benefits in addition to being a growth hormone releaser. See the chapter of this manual on Arginine for additional information about using arginine as a growth hormone releaser and for safety warnings about the use of arginine.

There are several problems with the use of arginine and other amino acids as HGH releasers. Their effectiveness generally diminishes with age, and with continued use. This has led some people to the opinion that amino acids such as L-arginine are weak or ineffective HGH releasers. This can be a dangerous assumption. In some young people, L-arginine may actually cause dangerously high levels of HGH release. Many young people use L-arginine, but it should not be used by anyone until at least 5 years after they have completed their long bone growth (unless they are under close medical supervision).

I personally know of one 19 year-old female who took L-arginine (about ten grams) before bedtime for one week. She stopped after one week because it was making her nauseous, which was an indication of an excessive level of HGH release. Even though she had not grown since she was 16, during the subsequent month, she grew an additional inch, and had a noticeable growth of her heel bones.

(Please note that this is an article about HGH replacement in adults. Please don't ask me questions about using HGH for gaining height. There are plenty of endocrinologists who specialize in that subject. As to whether L-arginine can be used to safely increase height in young people: The answer is that nobody knows.)

For most people, the doses of amino acids mentioned above (2 grams of L-glutamine and 10-30 grams of L-arginine) are about right for maintaining youthful levels of HGH beginning at about age 30, and continuing into the early 40s, and sometimes (but very rarely) beyond 50. In order to maintain its effectiveness, these amino acids should be used for about 6 weeks, then stopped for 2 or 3 weeks. The same 6-week ON, 2 or 3 weeks OFF cycle can be continued indefinitely. This cycling helps to maintain the effectiveness of the HGH release.

Unfortunately, the effectiveness of HGH release with amino acids is highly variable from individual to individual. (I cannot emphasize this individual variability enough!) For some people, it is not a very effective means of HGH release for any long period of time. For a few (very few) rare individuals, it maintains its effectiveness until the age of 60 and beyond.

For these amino acids to be effective, certain other substances must be present, and other substances must not be present.

In order to insure that you have the proper co-factors for these amino acids to produce HGH, it is best to take the L-arginine in one of the commercial products formulated by Durk Pearson and Sandy Shaw to optimize HGH release. Several companies listed in the Recommended Reading and Resources chapter sell these products under the brand names such as Innerpower™. Another advantage of using the Inner Power formulation is that L-arginine tastes awful, and you have to take too much of it to be able to take it in capsules. So the only practical way to take L-arginine is to take it, along with the necessary co-factors, in a specially formulated drink mix.

(Some other options for growth hormone release with arginine-based supplements were discussed in the chapter on Arginine.)

In order for your body to naturally produce HGH, or to produce HGH in response to certain amino acids, the following things must NOT be present:

• Anti-cholinergic medicines. This includes most medicines that make you drowsy or dehydrated. The most common of these medicines are the antihistamines that make you drowsy, including Benadryl (or any other brand of diphenhydramine), Sominex, Nytol, Tylenol-PM, and Zyrtec. (Claritin, Clarinex and Allegra probably do not affect the HGH-releasing effect of amino acids or natural HGH release.)
• Alcohol, in any appreciable quantity, blunts the HGH-releasing effect of amino acids and also suppresses natural HGH release. An ounce or less of alcohol two or three hours before taking a HGH releaser will have little effect on HGH release, but using alcohol to get to sleep can dramatically suppress your natural HGH release during sleep.
• Eating protein or carbohydrate within 3 hours before (or one hour after) taking an amino-acid HGH releaser will significantly blunt the growth hormone release induced by these amino acids.

There are many commercial products that are advertised to promote HGH release. Many of them are simply extremely expensive versions of the amino acids known to cause HGH release. Some of these products do work, but often at an extremely inflated price. Most of these products (especially the heavily advertised ones) are simply very expensive scams. (I get a lot of email from people asking about the latest of the many scams, and saying that surely this product must work because the advertising says that it does.) As the U.S. Food and Drug Administration has made it more difficult to obtain real human growth hormone, the number of HGH scams has grown by an incredible amount. If you search for information on HGH on the internet, you will find hundreds of these frauds and scams.

Many products are currently being advertised as Oral HGH sprays. I don't see how these products can possibly work. They don't contain enough HGH to have any biological effect, and all of the scientific evidence indicates that the HGH molecule is far too large to be absorbed through the membranes of the mouth. If HGH is swallowed, it is destroyed in the digestive tract before it can be absorbed into the blood stream.
The advertising for nearly all of the so-called "oral HGH sprays" is clearly fraudulent. Most people have received junk email advertising these products. I looked at the web site referred to by one of these bulk email ads. The web site quotes data from a report on injectable HGH, a completely unrelated product. The web site quotes data on oral absorption from the Physicians Desk Reference, but if you look at that page of the referenced edition of the Physicians Desk Reference, you see that the absorption data is for a completely unrelated multivitamin product made by another company.

Many "oral HGH" products advertise their HGH levels in nanograms. Keep in mind that the average daily injectable dose of HGH (one unit) is 333,333 nanograms, whereas the advertised amount of HGH in "oral HGH sprays" is 600 to 2000 nanograms per day. Also, without refrigeration, more than 90 percent of the HGH in an ordinary liquid solution is lost every 24 hours.

The technology for getting a molecule as large as HGH to be absorbed through the membranes of the mouth or nose is a technology potentially worth billions of dollars. No company that develops such an advanced technology is going to use it on an over-the-counter product.

The technology used to make an inhalable form of insulin was originally developed for use with human growth hormone. Genentech spent about $4 million on the use of this technology for an inhalable version of growth hormone between 1986 and 1989, but decided not to spend additional money to take the technology to market. Other companies have been sporadically working on an inhalable version of growth hormone, but it is a very technologically difficult project. Don't expect an inhalable growth hormone to be on the market for several years.

The internet is filled with fraudulent HGH products. Most of them use advertising tactics similar to those listed above. Some of the advertising is even more incredible. I found one Australian company openly advertising a pill that, according to the label, contained 8 milligrams of recombinant human growth hormone in each pill. A bottle of these pill was claimed to contain 2160 units of recombinant human growth hormone. They were selling the product for less than 35 Australian dollars per bottle. In almost any country in the world, 2160 units of recombinant human growth hormone would be about the same value as a very nice new automobile.

Growth Hormone Releasing Hormone
The information here on growth hormone releasing hormone (GHRH) will only be of academic interest to most people, since consistently effective medicines analogous to GHRH are not yet available. That situation may change in the future, though.

An injectable GHRH product has been produced with recombinant DNA technology, and was once commonly available by prescription in the United States and many other countries. It was sold under the brand name Geref by Serono Labs. GHRH is a protein consisting of a chain of 44 amino acids. Geref consists of only a 29 amino acid fragment of the GHRH molecule, but it appears to have the same effect as the full GHRH molecule (at least, for most people for a short period of time). The generic name of Geref is sermorelin.

Geref (sermorelin) was withdrawn from the market for general use in November, 2002. From 2002 until 2008, Geref was available only for diagnostic use and in clinical trials. In mid-2007, a few compounding pharmacies made sermorelin available available at a reasonable price for general use by prescription. This sermorelin is no longer available from compounding pharmacies, though. Much of the sermorelin sold in the United States in recent years reportedly came from biotech companies in China, and was not necessarily identical to Geref.

Geref was totally withdrawn from the market in 2008, with the last sales from Serono occurring on September 30, 2008.

Other than the exception noted above, at adult doses, the cost of Geref has always been more than injectable HGH, and it has always been more difficult to obtain. Also, it didn't work for everyone. Some studies indicate that GHRH seems to work better when used in conjunction with L-arginine. If the release of HGH in pulses is important, the use of sermorelin with L-arginine may be superior to the use of HGH, but this varies greatly from individual to individual. The use of sermorelin for anything other than diagnostic use has been generally disappointing.

One problem with sermorelin, as well as many other GHRH analogs, is that they have a very short lifetime in the body, usually with a half-life of only minutes. (It appears that this half-life problem can be solved for some of these GHRH analogs by chemically combining them with polyethylene glycol, among other methods.)

Sermorelin is a much smaller molecule than HGH, and research has been done on a sermorelin nasal spray. Only 3 to 5 percent of sermorelin is absorbed in the nasal spray form, however. This makes a sermorelin nasal spray far too expensive, so sermorelin was only available in injectable form.
Theratechnologies of Canada has developed what appears to be a much better form of GHRH. Tesamorelin contains the same number of amino acids (44) as natural growth hormone releasing hormone, but it has been modified to last longer in the human body. It avoids the short half-life problem of sermorelin, and tesamorelin appears to be much more effective. It is awaiting FDA approval in the United States for HIV-related fat accumulation. It is also currently under investigation for the reduction of abdominal fat in otherwise normal adults with reduced levels of growth hormone. The tentative plan is to sell Tesamorelin under the brand name Egrifta.

Tesamorelin has produced many encouraging results, including a small improvement in glucose levels. Human growth hormone often produces a temporary increase in insulin resistance when it is first started, especially in high doses. Tesamorelin seems to have the opposite effect. The manufacturer of Tesamorelin completed an agreement in October, 2008 with the pharmaceutical company Serono for marketing Tesamorelin in the United States, and an official New Drug Application was filed with the FDA on June 1, 2009. Tesamorelin is awaiting FDA approval. It is impossible to know what decision the FDA will make, since FDA decisions are not always based on science, but a response to the New Drug Application is expected in the second quarter of 2010. (The response is currently scheduled for May 27.) It is not known what legal and distribution restrictions that the FDA may place on the "off-label" use of Tesamorelin.

Another long-acting analog of GHRH that looks very promising is CJC-1295, but that product is at least 3 years away from approval by government agencies. CJC-1295 maintains a much longer half-life in the human body by partially binding to albumin, a important protein that is prevalent in the human bloodstream.

As stated earlier, pharmaceutical companies have produced growth hormone releasing agents that have been shown to be very effective in reversing the decline in HGH production with age. The one that has consistently worked the best is MK-0677 (ibutamoren mesylate), which is very effective in restoring HGH release in middle-aged and "normally-aging" elderly individuals to the levels of much younger people. MK-0677 is an oral medicine that restores the release of HGH in the pulsatile fashion characteristic of HGH release in young people. Unfortunately, it was not very effective in restoring HGH in the frail elderly, which was its original target market. It appears, in fact, that any form of HGH supplementation in the very frail elderly, and in the critically-ill elderly, is actually quite harmful. Restoring HGH in "normally-aging" people is not a function that the Food and Drug Administration (FDA) considers to be a legitimate function of a medicine; therefore, Merck (the pharmaceutical company) stopped all further development of MK-0677. Other effective oral HGH releasers developed by the pharmaceutical companies have faced a similar fate for similar reasons.

A considerable amount of research has been done on HGH releasers by the pharmaceutical companies, and some very promising substances have been developed, but there is no sign that any of them will be on the market anytime soon. MK-0677 (ibutamoren mesylate) is a substance, though, that seems to be too good to go away. It still appears in successful clinical trials from time to time. It recently completed another successful medical test in normally aging adults, and is currently undergoing clinical trials for use in fibromyalgia.

In a free market, MK-0677 (ibutamoren mesylate) would likely have had a revolutionary impact on the health of most people over 40. In fact, it is possible that MK-0677 could have revolutionized health care, prevented great human suffering, and literally saved trillions of dollars in health care. Since a free market in pharmaceuticals does not exist, MK-0677 will probably remain a laboratory curiosity more many years.


Read full article here: http://www.futurescience.com/hgh.html

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CYCLEON

excellent article!

CYCLEON

The interesting thing to me is first the growth of peptides as effective substitutes to RHGH and second the newer methodology of "pulsing", ie instead of a steady daily amount ramping up 2-3x per week or doses of 20 iu but spaced out - the idea being to pattern off of the body's natural growth spikes - which as a teenager comes in spurts usually

aXe

Cyc and Nark...what the fark? You guys are still around? Cool to see you guys I gotta start posting here again.

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