I have had many questions regarding injection time and splitting injections on HGH. I spent some time on the net tonight and found this article, I thought a few of you may appreciate it. It supports the morning and split injections (unless you are 60 or older) to avoid suppressing your own GH levels and says NOT to inject 1-4 hours before bed...
© 2002-2004 Colorado Futurescience, Inc.
HUMAN GROWTH HORMONE (HGH)
written by Jerry Emanuelson
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 little effects of aging, while the effects of aging are so obvious in a 60 year-old person?
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 14 percent per decade. 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 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.
By increasing the levels of HGH in our bodies, we can slow, or even reverse, many of the manifestations of aging. 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 aging 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.)
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 internal organs that have atrophied with age.
Increase bone density.
Strengthen the immune system.
What HGH cannot do:
It cannot eliminate the effects of oxidation damage, although it may alleviate some of it.
It cannot undo the effects of cardiovascular disease, although it sometimes reduces some of its effects. It can also slow its progression by improving one's cholesterol profile.
It 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.
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. 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. The natural production of somatostatin increases with age, and causes a corresponding decrease in HGH production by the pituitary.
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 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 hexarelin, 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.)
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 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, 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) option. But let's look at these three methods in greater detail:
There are a number of substances that increase the natural secretion of HGH. Most of them are amino acids. The most effective and economical way of causing this HGH release 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.
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 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 the standard test for the ability of the pituitary to release growth hormone. (It is generally believe that L-arginine promotes HGH release by inhibiting somatostatin). 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 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 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 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.
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 40's, and sometimes (but 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. For some people, it is not a very effective means of HGH release for any long period of time. For a few others, 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 Inner Power. Another advantage of using the Inner Power formulations 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 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 the 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.
Many products are currently be 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 most of the so-called "oral HGH sprays" is clearly fraudulent. I just received a bulk email ad for one of these products, and looked at its website. The website quotes data from a report on injectable HGH, a completely unrelated product. The website 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 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 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. At least one pharmaceutical company has developed a novel technology with the potential to enable the absorption of HGH through the membranes of the nose. The product is in phase 1 clinical trials by Nastech Pharmaceutical Company, Inc. If this product does make it to market, it won't be for several years, and it will be available only by prescription.
Growth Hormone Releasing Hormone [REMOVED MOST BUT LEFT ENOUGH FOR YOU TO SEE WHAT IT IS]
An injectable GHRH product has been produced with recombinant DNA technology, and it is available by prescription in the United States and many other countries. It is 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. The generic name of Geref is sermorelin.
Unfortunately, at adult doses, Geref currently costs more than injectable HGH, and it is more difficult to obtain. Also, it doesn'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 Geref with L-arginine may be superior to the use of HGH, but this varies from individual to individual. Geref looks very promising, but there is currently very little available experience with using Geref in anti-aging medicine.
Geref is a much smaller molecule than HGH, and research has been done on a Geref nasal spray. Only 3 to 5 percent of Geref is absorbed in the nasal spray form, however. This makes a Geref nasal spray far too expensive, so Geref is only available in injectable form. It is likely that the new Nastech technology could be used to make an effective Geref nasal spray, but work on such a product hasn't even started yet.
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 worked the best was MK-0677, which was very effective in restoring HGH release in middle-aged and "normally-aging" elderly individuals to the levels of much younger people. MK-0677 was an oral medicine that restored 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 target market. 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) has stopped all further development of MK-0677. Other effective oral HGH releasers developed by the pharmaceutical companies seem to be facing a similar fate.
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.
In a free market, MK-0677 would likely have had a revolutionary impact on the health of most people over 40. Since free market in pharmaceuticals does not exist, MK-0677 will remain a laboratory curiosity.
The one way to enhance your HGH levels regardless of age, or other factors, is to use injectable HGH. For most people past the age of 45 years or so, this is the only HGH option that really works well. The use of injectable HGH has been a subject shrouded in mystery for most people. The rest of this chapter will describe some of the details about what using injectable HGH is really like. The cost has come down to less than $300 a month for most anti-aging doses, and the process is as simple as getting a prescription from your doctor and getting the prescription filled at a drugstore.
What doctor should you go to, and what drugstore should you use?
Any licensed physician can prescribe HGH, but few are willing to do so. It is best to find a physician who is familiar with HGH, and who has other patients using it. As stated elsewhere in this manual, there are 3 excellent sources for locating an anti-aging physician, and these three sources are also the best for finding a physician to prescribe HGH therapy. Those lists of physicians are at the following web sites:
The American College for Advancement in Medicine
The Life Extension Foundation
The American Academy of Anti-Aging Medicine
Not all of the physicians on the above lists are familiar with HGH therapy, so ask before making an appointment.
Most of these physicians will want to do a comprehensive physical examination on your first visit. You will find that this initial consultation is well worth the money. Ask about cost first, though. With many anti-aging physicians, this initial exam will cost about $200 plus the costs of routine blood tests. The typical cost is somewhat higher in the coastal population centers, especially in New York, Florida and California. (A few "high-end" anti-aging clinics will charge $1,500 or more for an initial exam. The more expensive clinics may also want you to buy HGH directly from them for a highly inflated price -- 4 or 5 times the price you would pay at your local drugstore.)
I usually recommend the ACAM physicians as the most likely to offer excellent service at a very reasonable cost.
[removed some excess info. on what a dr. would do since most people don't go through a doctor]
It was once thought that the effects of HGH were due to only to IGF-1. We know that IGF-1 has important effects, but the advantages that one gains with HGH are often not proportional to the increase it causes in IGF-1 levels. Some people on HGH therapy have only a small increase in IGF-1 levels, yet have large positive results from using HGH.
Which brand of HGH? The sharp reduction in the price of HGH in the past few years has been due to the fact that there are several companies producing it. Since the beginning of 2004, however, prices at most pharmacies have jumped by about 20 percent. In the United States, injectable human growth hormone is available in the following brands:
Humatrope (from Eli Lilly). This was the first brand of HGH to become widely available. Recently, however, it has become the most expensive brand in the United States.
Genotropin (from Pharmacia/Upjohn).
Saizen (from Serono Laboratories).
Norditropin (from Novo Nordisk)
Nutropin (from Genentech)
All of these brands contain real high-quality injectable HGH made with recombinant DNA technology. Each of the brands is a little different in the packaging and mode of delivery, though. (Saizen and Genotropin seem to currently be the most popular for use in anti-aging medicine. Humatrope was the most popular until its recent large price increases.)
Originally, the HGH package consisted of two vials. One vial contained powdered freeze-dried HGH. The other vial contained sterile water with a bacteriostatic preservative. When the user was ready to begin using the contents of the package, a certain amount of the sterile water would be drawn out of the second vial (with a needle and syringe) and injected into the first vial to dissolve the powdered HGH. The solution would then be ready for injection. The unused portion would have to be kept refrigerated. The entire vial of dissolved HGH would have to be used within 2 or 3 weeks.
The HGH is dissolved by the patient because HGH powder is much more durable than dissolved HGH. The dissolved HGH is very susceptible to being attacked by bacteria and degraded by proteolytic enzymes. HGH is always normally refrigerated, but if HGH powder is is left at room temperature for a few hours, no harm is done as long as the room is not too warm. (Sterile powdered HGH can even be left in a cool room for days or weeks, but this is not a good idea.) After being dissolved in water, the un-refrigerated HGH solution loses its much of its potency after a few hours, and becomes completely unusable in a day or two, especially if the room is warm. The HGH solution must be kept refrigerated.
HGH is still sold with the HGH powder separate from the sterile water, but there are now several more convenient options for the mixing process.
I prefer the Genotropin Intra-Mix cartridge for several reasons. In the Genotropin Intra-Mix cartridge, the HGH powder and the sterile water are in separate compartments of the same cartridge. Turning a knob on the handle at one end of the cartridge (until it screws all the way in -- three turns) automatically mixes the HGH and the sterile water. Since there is no mixing needle exposed to the room air, better sterility is obtained, and the Intra-Mix cartridge is advertised to last 3 weeks after mixing. (Most other brands are advertised to last 2 weeks.) With careful refrigeration, I'm sure that the useful life of an Intra-Mix cartridge can be safely stretched to 4 weeks.
Another thing that I like about the Genotropin Intra-Mix cartridge is that it is very expensive to counterfeit. Counterfeit medicines are always a potential problem, and the conventional two-vial HGH package is very easy to counterfeit -- and very profitable for any counterfeiter. Counterfeit HGH has not been a big problem, but counterfeit HGH has appeared on the market on several occasions. The most recent counterfeiting problem has been with Nutropin.
Genotropin Intra-Mix cartridges also have the most concentrated solution of HGH. With the 5.8 mg. (17.4 unit) cartridge, one unit of HGH is only 0.06 cc. This is about two drops. (This can be a significant psychological advantage when you're first learning to inject HGH.)
Most HGH packages require you to inject the HGH using insulin syringes. (The same ones used by diabetics.) Usually, you will use the smallest size syringe. This is a 0.3 cc. syringe with an 8 mm. 30 gauge needle. This is a very short, thin needle.
Some HGH packages use a pen with a built-in needle. For those who wish to avoid needles completely, Saizen is available in the CoolClick cartridge which blasts the HGH through the skin in a very narrow jet. Buying Saizen with the CoolClick cartridge will increase the cost, though.
HGH is sometimes measured in international units, and sometimes measured in milligrams (mg).
3 International Units = 1 milligram
Different doctors have different recommendations for the amount of HGH you should inject. The dose may depend upon your age and overall health. It is often best to start with a low dose, such as one half unit per day, and work up from there. Most physicians recommend taking 1 unit per day, 4 or 5 days a week. Many people recommend taking two or three days a week off so that your pituitary gland doesn't forget how to make its own HGH. (You may want to use the amino acid HGH releasers on the off days.)
Adverse effects from injectable HGH therapy are very rare as long as the amount of HGH used averages 1 unit or less per day. Most anti-aging physicians believe that 1.5 units per day reaches the point of diminishing returns, and more than 2 units per day begins to put you at some risk of side effects. (The clinical studies that resulted in frequent side effects from HGH used much larger doses.)
When you increase or decrease your dosage, it is best to do it very slowly. Even at doses below 2 units per day, abrupt changes in dosage can cause temporary problems such as water retention and headache in some people.
Many people experience increases in blood glucose levels when starting HGH. This effect usually goes away with time, but there appears to be a definite advantage to taking the prescription medicine metformin along with HGH to keep glucose levels under control. (Also, there is evidence that metformin can slow the aging process at a more fundamental level than HGH.)
Since the largest natural HGH release in healthy young people occurs shortly after the onset of sleep, most doctors originally suggested that HGH be injected just before bedtime. Some people (especially those between 40 and 65 years old) report better results taking the HGH in the morning (or at some other time of the day), and letting their pituitary gland supply the nighttime HGH dose.
Most people over the age of 65 or 70 have a very small natural production of HGH after sleep onset, so injecting HGH just before bedtime is probably best for these older people.
There appears to be a definite advantage to dividing the HGH into a few smaller injections taken throughout the day. The advantage is usually not a large one, though, and most people find this far too inconvenient.
For most people, convenience outweighs the small advantages of one dosing schedule over another. Most people inject their growth hormone once a day at whatever time is the most convenient.
(It is probably best not to inject HGH during the period of 1 to 4 hours before bedtime. This may cause some inhibition of the natural HGH release during sleep.)
HGH requires a somewhat larger dose in women to achieve the same effectiveness as in men. Exactly why this is true is not well understood. It is known that taking oral estrogen cuts the effectiveness of HGH in half as compared with transdermal estrogen. Women taking oral estrogen should consider switching to patches or gels.
HGH can be purchased through almost any pharmacy. At your local pharmacy, though, the price is likely to be higher than necessary, and they probably don't keep it in stock. Most local pharmacies require take a day or two to obtain it. For these reasons, many people prefer to use a mail order pharmacy.
[I REMOVED THE PRICING PART]
For many people, the main problem with HGH is the difficulty in giving themselves a injection. When you see a physician for an HGH prescription, you will receive instruction on how to give yourself the HGH injection. Nearly everyone has some apprehension about it the first few times that they do it. If you are a needle phobic, it may seem out of the question. If you do have needle phobia, please see the Needle Phobia Page at this web site.
Needle phobia is a serious problem, but it is one that can be overcome. Needle phobia has always been a problem for me. Because I am on an experimental Life Extension program, I get a complete blood chemistry test every six months. I always have to take certain precautions (listed on the Needle Phobia Page) when getting blood drawn for these tests. I still pass out during a needle procedure once every few years.
After getting blood drawn for a baseline IGF-1 reading before starting HGH injections, I passed out because of carelessly standing up too fast afterward. As I was lying on the floor of the doctor's office returning to consciousness, I was thinking to myself that my plan for giving myself 5 injections a week was not getting off to a very good start. I did begin giving myself HGH injections two weeks later, though. Overcoming needle phobia is sometimes very difficult, but it can be done. For anyone on a Life Extension program, overcoming needle phobia has enormous benefits.
A few references:
The thymus gland: a target organ for growth hormone.
Savino W, Postel-Vinay MC, Smaniotto S, Dardenne M.
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro,
Scand J Immunol. 2002 May;55(5):442-52.
Age-associated loss of bone marrow hematopoietic cells is reversed by GH and accompanies thymic reconstitution.
French RA, Broussard SR, Meier WA, Minshall C, Arkins S, Zachary JF, Dantzer R, Kelley KW.
Laboratory of Immunophysiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Endocrinology. 2002 Feb;143(2):690-9.
An excellent technical book on HGH for scientists and health care professionals:
GROWTH HORMONE IN ADULTS: Physiological and Clinical Aspects, edited by Anders Juul and Jens O. L. Jorgensen. Cambridge University Press: 2000.
