Stimulating Growth Hormone: A Life-Extension Approach

Free radical and crosslinking damage play a very important role in both age related diseases such as cardiovascular disease and cancer, and in aging itself. The damage done by these mechanisms is not the only deleterious change that takes place during aging, however.

By 1976, we had become convinced that the age related degradation of immune system function, loss of lean body mass and strength, and impaired healing also had to be dealt with in a comprehensive life extension program. On the basis of the scientific literature that we had read, we suspected that an endocrine system change - the age related reduction in GH (growth hormone) releases - played a major role in these problems. We further hypothesized that if one could restore GH release in an older person to resemble that of a healthy person in their early twenties, that these problems could be substantially ameliorated.

In 1976, we sent a written research proposal on aging, GH, and GH releasers to a private biomedical research foundation. They sent the proposal to one of the world's greatest experts on the molecular biology of human growth hormone for a critique; he told the foundation that our idea was plausible and had merit, and recommended funding it, which they did.

We started to use GH releasers on a regular basis in 1979, and have been using them ever since. This special Life Extension Newsletter issue on GH and GH Releasers describes some Of the most important things that we have learned over the past 16 years, from the scientific literature, from our own experiences, and from those of many of our friends and experimental subjects.

Growth Hormone Treatment of Frailty in Men Over 60

"The findings in this study are consistent with the hypothesis that the decrease in lean body mass, the increase in adipose-tissue mass, and the thinning of the skin that occur in older men are caused in part by reduced activity of the growth hormone-IGF-I axis, and can be restored in part by the administration of human growth hormone. The effects of six months of human growth hormone on lean body mass and adipose-tissue mass were equivalent in magnitude to the changes incurred during 10 to 20 years of aging." Rudman, Feller, Negraj, et al., New England Journal of Medicine (5 July 1990)

The researchers of the above study noted the decline of growth hormone release, both in overall amount and in pulse sizes, with aging, beginning at about the age 30, just as we wrote in Life Extension, A Practical Scientific Approach back in 1982. The results of the new growth hormone study were similar to those reported in earlier studies of growth hormone treatments in obese persons and in growth hormone deficient adults that we have described in this newsletter and elsewhere. An earlier study (Copeland 1990) reported a negative correlation between indices of adiposity (fatness) and IGF-I in male humans, but not in females, although both males and females experienced declining GH secretion with age. In females, however, decline in estrogen output after menopause causes a loss of body fat, adding additional complexity to analysis of changes in body fat with age.

The researchers chose to study elderly men between 61 and 81 years of age who were in the lowest 30% of that population in their plasma content of IGF-I (insulin-like growth factor, sometimes called somatomedin C). We have mentioned IGF-I as somatomedin C before; it is a substance produced and released by the liver in response to growth hormone. Since growth hormone is released in pulses and disappears very rapidly from the bloodstream, it is difficult to measure its bloodborne concentration because you have to take very frequent samples over 24 hours. IGF-I, however, has a nearly constant daily plasma concentration and is a good indicator of total daily growth hormone release (although it does not give you detailed information on growth hormone pulse sizes).

The 12 healthy elderly male subjects who received the growth hormone injections began with IGF-I plasma levels that were below 350 U per liter, which were raised up into the 500 to 1500 U per liter of healthy young adults throughout the study. The 9 men who served as controls had no changes in their IGF-I levels during the study.

The GH-treated group had a significant increase in lean body mass of 8.8%, adipose (fat) tissue mass decrease of 14.4%, skin thickness increase of 7.1%, and average density of lumbar vertebrae increased by 1.6%. Overall weight did not change. The differences in skin thickness and of adipose tissue mass between the groups did not quite reach statistical significance. (P=0.10 and 0.13 respectively; it is harder to see differences in a very small sample size due to the greater average variation seen in small samples.)

The study concluded that "Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age." The authors also note that the results indicate the liver's production of IGF-I in response to growth hormone is not impaired with aging and that the decline in plasma IGF-I is due to growth hormone deficiency rather than loss of efficacy of growth hormone (GH resistance).

Side effects noted in the GH-treated elderly men included small increases in the mean systolic blood pressure and fasting plasma glucose concentration.

D&S Comments: It's hard to believe that anybody could have missed the headlines last July 5th. A new study of growth hormone treatment in elderly frail men produced such dramatic results that they were splashed on the front page of almost every newspaper. The authors chose to publicize their findings through the media the very same day as their study appeared in the New England Journal of Medicine, an unusual action. We are sure these researchers were, by that means, appealing to the public to be sure this research would continue and be expanded to a larger study (this one involved 21 elderly men).

Since treatments with growth hormone itself would cost about $14,000 per year, we surmise that the powers-that-be at Medicare are likely to become very worried that the approximately 25,000,000 frail elderly might want this treatment, and will soon be trying to obstruct further such work, criticize these new findings, and otherwise interfere with people knowing about them. When the bureaucrats fail to scientifically discredit GH therapy for the frail elderly, they will attempt to prevent FDA approval of GH for this purpose, since FDA approval for this specific use would be required before Medicare/Medicaid/VA would have to pay for it.

When GH is finally approved for treatment of the "frail" elderly, the bureaucrats will try to define "frail" in a manner which severely limits the number of people who qualify. Perhaps GH will eventually force the government to publicly admit that a finite supply of taxes cannot pay for a near infinite demand for "free" medical care, and that tax supported medical care must eventually be limited to very basic services.

Finally, we agree that there is no evidence that increasing growth hormone levels (either by growth hormone itself or by the use of growth hormone releasers) to young adult levels can extend lifespan. However, there is increasing evidence that this can significantly improve the quality of life. The two of us have been taking arginine, choline, and vitamin B-5 supplements since 1979.

Rudman, Feller, Nagraj, et al, "Effects of Human Growth Hormone in Men Over 60 Years Old," New Engl J Med 323(1):1-6 (July 5, 1990)

Copeland, Colletti, Devlin, McAuliffe, "The Relationship Between Insulin-Like Growth Factor-I, Adiposity, and Aging," Metabolism 39(6):584-587 (June 1990)

Jorgensen et al., "Beneficial Effects of Growth Hormone Treatment in GH-Deficient Adults," The Lancet pp. 1221-1225, June 3, 1989.

Growth Hormone Releasers: An Update Review

Introduction

Some people can put on muscle much more easily than others. Every body builder over 30 years old wishes that he or she still had their teenage physiology which made the payoff from exercise so much greater. It is possible to regain that teenage ability to rapidly put on muscle with exercise -and you can do it legally, even if you compete in the Olympics, the AAU, or the IFBB where the use of performance-enhancing drugs is prohibited. You can do it with the right amounts of the right nutrient supplements. But first, let's consider what goes wrong with your ability to build muscle as you age.

Muscle Mass Changes with Aging

In the Special Report on Aging 1980, a booklet published and distributed by the National Institute on Aging, the following important research on exercise and muscle building was reported:

"Physically active adult men in the Baltimore Longitudinal Study of Aging exhibited no greater muscle mass than their age-matched peers who were not physically active! This was true for both men and women." (The Baltimore Longitudinal Study of Aging is an ongoing study of over 800 healthy persons who are periodically very extensively tested for biomedical and sociobehavioral changes as they age.)

Why have these healthy adults lost their ability to build muscle? When a teenager is physically active, he or she builds muscle with the help of the exercise induced release of their body's natural non-steroid anabolic, growth hormone. The exercise induced release of their body's growth hormone begins to vanish after the twenties, although growth hormone secretion continues in declining amounts in response to other stimuli, such as sleep and injury. "The weight loss and leaner appearance attributable to exercise in middle and old age is due to fat loss alone and not to increase in muscle mass," according to gerontology researcher Stephen P. Tzankoff. (This paper refers to ordinary exercise; Dr. Tzankoff was not studying the high intensity workouts used by bodybuilders. See also Bazzarre, 1975; Prinz, 1976; and Zadek, 1985.)

Loss of Lean Body Mass on Low Calorie Diets

A recent study found that obese persons on a low calorie diet did not lose lean body mass when they were treated with growth hormone (Clemmons, 1987). This is very important! Many people do not realize that if they go on a low calorie diet and do not exercise while dieting, 25% of the weight they lose will be lean body mass. Even with heavy exercise, 5% of the lost weight is still lean body mass (Brownell, 1983). Since it is very difficult for adults older than their twenties to replace lost lean body mass, it is important not to lose it in the first place.

Growth hormone itself should not be used without the guidance of a doctor since it is a powerful hormone and too much would be toxic. A very serious disease called acromegaly occurs when the pituitary gland chronically releases much too much growth hormone. Remember, nothing is perfectly safe, even oxygen and pure water can be lethal in excess! The natural nutrient amino acids arginine or ornithine can be used to stimulate the brain's release of growth hormone and are safer than using injections of human GH because the brain has a natural control system built in for the entry of nutrients into the brain and for the manufacture and release of pituitary hormones.

Loss of Lean Body Mass During Prolonged Exercise

Recent studies show that during long, vigorous exercise, a surprising amount of lean body mass, as much as 25% of total calories consumed, is used as fuel. (Dohm, 1982) There was an induction of enzymes necessary for utilizing amino acids for energy production in heavily exercised rats. Muscles in the animals that had exercised the hardest were actually less developed than those who had not worked so hard, presumably because they had used up more protein (for fuel) and had less available for muscle growth. One study found that after running a 100 km run, athletes had only 30% of pre-race serum amino acid levels and some of the essential amino acids did not return to normal until 3 days after the race. (Decombaz, 1979) This is one reason that athletes do need to consume more protein. Growth hormone releasers should also be very helpful in limiting protein losses.

Muscle and Bone Loss in Hospitals and Outer Space

The 24 rats aboard the shuttle Challenger in April 1985 had dramatic reductions of growth hormone secretion from their pituitary glands, a problem that has also affected astronauts and results in severe deconditioning (due to the small amount of muscular activity required under weightless conditions) of all muscles, including the heart. This has also been a serious problem for hospitalized patients. Arginine has recently been used in elderly patients recovering from major abdominal cancer surgery to help to quickly overcome the negative nitrogen balance (loss of lean body mass) and immune system suppression that takes place in such surgically severely stressed patients. (Daly, 1988)

We suggest growth hormone releasers as an inexpensive, safe potential solution for deconditioning in space travelers, too. You may not be a space traveler, but there will certainly be times when you cannot exercise, such as if you are injured in an accident. An arginine GH releaser will help to prevent muscle loss during your convalescence; in adequate doses, it can actually double to quadruple your bone healing rate.

Aging Loss of Pulses of Growth Hormone

There is another important change in growth hormone function with aging: a loss of the normal pulsatile release pattern. Important hormones, such as growth hormone, insulin, gonadotropins (sex hormone releasing hormones), testosterone, and many others, are released in normal young persons in pulses, rather than continuously. But in older animals and humans, those pulses are generally of a much smaller amplitude or may even be lost entirely. The hormones maybe dribbled out more or less continuously in reduced quantities. These changes may involve damage to receptors in cells or to receptors in certain parts of the brain. Continuous release of normally pulsatile hormones does not produce the normal response to that hormone. Continuous release of insulin, for example, results in a reduced sensitivity (downregulation) of cellular receptors to insulin. This does not happen with insulin released in pulses. (Paolisso, 1988)

These changes have important implications for people who are older than their twenties who want to increase their muscle mass. Exercise induced increases in muscle and loss of fat are due to a very substantial extent to the responses in your brain to that exercise; growth hormone release is an important response that declines with age. The difficulty that older bodybuilders have in increasing muscle mass is one reason they often turn to anabolic steroids, which perform similar anabolic functions with much greater potential risks. The bottom line is to take your nutrient GH releaser in a big pulse; don't mix it with a food that might slow its absorption from your gut or interfere with its passage across your blood-brain barrier membrane. (More on that later.)

No Pain, No Gain

"No pain, no gain." You've heard it many times, almost always from athletes and body builders who are over 20 years old. Sandy may have figured out what it means. An older bodybuilder, whose brain no longer releases growth hormone in response to exercise, will still release GH in response to injury. Perhaps people who have to experience pain to increase their muscle mass are doing so by injuring themselves. Unfortunately, much of that increase d mass by injury is just scar tissue. It looks good, but doesn't make you stronger. In fact, scar tissue is more likely to tear than real muscle.

The New Era of Growth Hormone Releasers

We began studying growth hormone in the mid-1970's because we had read about the age-related decline of growth hormone release and how this contributed to the process of aging and age-related diseases, including the age-related impairment of immune function. Growth hormone is manufactured and released from the pituitary gland in the brain in response to sleep (the old wives' tale about children having stunted growth when they don't sleep well is probably true), injury, exercise (in persons up to somewhere in their 20's), certain nutrients (such as arginine, ornithine, and to a lesser extent, niacin), and severe hypoglycemia. Recently, growth hormone has been reported to be released in response to saunas (hyperthermia). (Leppaluoto, 1986)

Immune System, Healing Enhanced by Growth Hormone

Growth hormone has other functions besides increasing the muscle to fat ratio of your body. It also stimulates your immune system, as does arginine itself. (Barbul 1986, 1990) Less growth hormone may mean more susceptibility to bacterial and viral diseases and cancer. Growth hormone is also important to healing (Barbul, 1977) and less of it leads to the much slower healing of middle and old age. Evel Knevel said in a recent interview that the reason he stopped doing daredevil stunts was because he couldn't heal up rapidly anymore and was spending most of his time in the hospital. We had begun investigating nutrients, such as the amino acid arginine (found in many foods, such as chicken and turkey meat) that can, in adequate quantities, stimulate the brain's pituitary gland to release growth hormone. We found many studies in which arginine had been used to speed healing and even increase resistance to injections of cancer cells in experimental animals.

In fact, a recent paper in Science (Edwards, 1988) reported that growth hormone activates macrophages, immune system cells that seek out and kill disease-causing microbes and cancer cells, by increasing their production of superoxide radicals. The latter is a type of active oxygen which, with singlet oxygen and hydroxyl radicals, are the weapons made by the macrophages to kill the bacteria. Normal tissues are protected from being damaged by superoxide radicals by antioxidants such as vitamins E, C, beta carotene, the amino acid cysteine, the selenium-containing enzyme glutathione peroxidase, and the copper and zinc containing enzyme superoxide dismutase.

Athletes and body builders seeking increased anabolic effects can obtain them with the help of GH releasers or anabolic steroids. Arginine will generally improve the function of your immune system. Anabolic steroids, however, may suppress immune system function. (Duda, 1988) When you travel to a contest, you will be exposed to lots of new bacteria and viruses, and your susceptibility to infection may be increased by stress, exhaustion, and jet-lag. If your immune system isn't capable of providing you with adequate protection, you are more likely to get sick, and sick contestants are not likely to be winners.

The Immune System and Exercise

A number of human studies have shown that exercise has complex effects on immune function. (Salit, 1988) Immediately after short-term strenuous exercise, untrained individuals had increased numbers of immune system cells (T and B lymphocytes) in the bloodstream, but these cells did not seem to function as well as those taken during rest. The responses of these cells to certain activators (mitogens, which test one's ability to produce more immune cells of the type needed to meet a challenge such as an infection) and the production of immunoglobulin antibodies by B cells was suppressed after intense exercise. In long term conditioning programs of moderate intensity, there doesn't seem to be much effect on immune function. However, individuals enduring very strenuous exercise showed transiently reduced response to mitogenic activation and increases in circulation of certain types of immune cells (neutrophils, killer cells) and cortisol. Chronic training also raises resting blood levels o f IL-2, a pyrogen (fever producing substance) above untrained, base levels and even higher levels result when untrained individuals do acute exercise. IL-2 amplifies inflammatory responses produced by white blood cells (macrophages) and thus can promote tissue damage. Free radical and activated oxygen scavenging nutrients such as vitamins C, E, and beta carotene can help to reduce this damage, and GH releases can improve both immune system function and tissue damage repair ability.

Sandy's Lucky Break

We were at the Gordon Research Conference on the Biology of Aging in 1979. Sandy was careless jumping up to get something from a high shelf of our room's closet and came down hard with an ominously loud "crack." That was a great place to hurt yourself, if you had to do that at all, because there were dozens of eminent physicians there. In fact, the originator of the free radical theory of aging, Dr. Denham Harman, suggested Sandy have her foot X-rayed. It was broken.

Arginine Releases Growth Hormone

Having a broken foot is extremely inconvenient and sometimes dangerous. Just try going up or down stairs on crutches! We had been about to start arginine supplementation experiments on ourselves for immunostimulation, when Sandy's broken foot provided us with a golden opportunity. We had read Scientific reports of arginine stimulating the healing of broken bones in experimental animals, and Sandy decided to take it.

At this time, Sandy was 35 years old, and far over the hill in terms of exercise induced GH release. She took 10 grams of arginine a day in a single dose on an empty stomach. (One might be able to ingest that amount daily in a very high protein diet heavy in chicken or turkey. Sandy was also taking about 2 grams of choline and 2 grams of vitamin B-5 per day.) About 45 minutes to one hour after taking the arginine, Sandy did bench presses for about 3 minutes, once daily, on her back, so there was no stress on the broken foot. After six weeks on this regimen, she had lost about 25 pounds of fat and had put on about 5 pounds of muscle! We were amazed. We thought that amount of arginine might be enough to stimulate the release of growth hormone. We knew that growth hormone increased the ratio of muscle to fat. (Christy, 1979; Murad, 1980) But we didn't realize how dramatic the effect could be in an essentially sedentary middle aged research scientist. Arnold Schwarzenegger in his Bodybuil ding for Men said that putting on 5 pounds of muscle would be difficult for an adult man working out every day for a year!

Other nutrients have been shown to cause growth hormone release, including niacin (200mg is a mild GH releaser) (Irie, 1967, 1970), tyrosine (nutrient amino acid - releases a small amount of GH in a small percentage of subjects with 40 gram intravenous doses), and methionine (nutrient amino acid - releases GH but can cause atherosclerosis under certain conditions). The nutrient amino acid arginine (and ornithine, another amino acid) are both relatively strong GH releasers. Arginine and ornithine can release enough GH to equal that found in a heavily exercising teenager.

Arginine and ornithine cause growth hormone release via your brain's cholinergic nervous system. (Casanueva, 1984) This is the system that uses acetylcholine - made in the brain from the nutrient choline with the help of the cofactor vitamin B-5 - to transmit information between the nerve cells. Without adequate amounts of acetylcholine, neither arginine nor ornithine can cause growth hormone release, though we know of no evidence that choline or vitamin B-5 alone can cause GH release. This is why we recommend the use of a choline + B-5 supplement in conjunction with arginine or ornithine GH releasers. Note that many antihistamines, cold pills, and the non-prescription sedative diphenhydramine are anticholingergics. These drugs will block the GH releasing effects of arginine and ornithine.

Contrary to what some people believe (and some fraudulent products claim), you can't develop winning muscle mass without exercise, even if you take a growth hormone releaser like arginine. But arginine is very effective at helping you maintain muscle mass you already have, even if you are not exercising. We are two 47 year old research scientists and almost completely sedentary, but we regularly take arginine supplements, as described below, and maintain the well muscled bodies we had twenty years ago. You may have seen 5'3" Sandy bend steel horseshoes on television.

In 1982, after we reported our ideas and experiences regarding the use of growth hormone releasers such as arginine in our first book, Life Extension, a Practical Scientific Approach there was a worldwide shortage of arginine for several months, and a worldwide shortage of ornithine for about a year! Their main prior use had been as ingredients in culture media.

Arginine Supplementation

We personally use arginine in either one of two different ways: we take 12-23 grams 45 minutes to one hour before exercise (to enhance the effects of the exercise) or just before bedtime (to enhance both sex and the natural pulse of growth hormone released shortly after one falls asleep). We generally recommend the following total daily quantities of arginine (free base) for healthy male adults: Weight 100 to 140 pounds, 12 grams; 140 to 200 pounds, 18 grams; over 200 pounds, 24 grams. For healthy female non-pregnant, non-lactating adults: under 120 pounds, 6 grams; 120 to 180 pounds, 12 grams; over 180 pounds, 18 grams. Women are usually more sensitive to GH releasing effects of arginine and ornithine than men. (Merimee, 1969) Start with about 25% of your target quantity, and increase it gradually over a period of a few days to minimize the occurrence of minor side effects such as nausea. If you prefer ornithine, use half of these amounts. The dose figures given in the literature usually refer to the amount of amino acid free base used, such as arginine. Many commercial products contain an acid addition salt such as arginine hydrochloride rather than the free base arginine. Some of the product labels give the amount of the contents as the free base, others as the hydrochloride. Unless the amount of the amino acid is given as the free base (e.g. 6 grams arginine), you will need to take about 20% more since the hydrochloride adds about 20% to the weight without contributing to the GH r eleasing activity.

Don't assume that more is always better. It is unlikely that a 60 gram dose would cause significantly more GH release than a 24 gram dose. A 30 gram injection of arginine is used to test pituitary function; this dose has been chosen to be high enough to completely saturate this GH release mechanism. (See the Cautions at the end of this article for side effects and precautions.)

It is important not to ingest certain other amino acids, either as a supplement or in foods, at the same time or shortly before taking the arginine. Some of these other amino acids, including lysine, compete with the arginine to enter the brain (where the action takes place). You can take your protein supplement or high protein low glycemic index carbohydrate meal after your workout.

Growth Hormone, Insulin and the Glycemic Index

Insulin is a natural hormone that, in some ways, opposes the actions of growth hormone. Growth hormone resembles insulin in certain respects; both help move amino acids into muscle. Insulin is also a fat storage hormone and a hunger promoting hormone, whereas GH works against fat storage, and tends to suppress hunger. Large snacks of carbohydrates that cause a large increase in blood sugar will tend to counteract the effect of the growth hormone by stimulating the release of a lot of insulin. A large insulin release can counteract the anti-fat storage effect of GH. Indeed, this is one of the problems with the amino acid lysine; lysine is more of an insulin releaser than a GH releaser. The ratio of GH to insulin is thought to play a major role in determining one's ratio of lean body mass to body fat. (Bray, 1983; Ratzmann, 1978) Relatively high ratios of GH to insulin are usually associated with a lean muscular build, while low ratios of GH to insulin are often associated with obesity, at least in non-diabetics. (Asimacopoulos-Jeannet, 1976; El-Khodary, 1972; Quabbe, 1971; Irie, 1970)

Insulin is a muscle building factor, however, so some - but not too much - is needed if you are going to be exercising. How do you get the right amount of insulin release?

We have written extensively about which carbohydrates (sugars and starches) increase blood sugar a lot, and hence release a lot of insulin, and those which increase it low to moderately, in our Life Extension Weight Loss Program. This is important because, as we noted above, insulin can oppose some of the actions of growth hormone. Also, large releases of insulin are more likely to cause reactive hypoglycemia and weakness by driving down blood sugar levels.

A standard measure of a carbohydrate's increase of blood sugar is the glycemic index. (Jenkins, 1981) The increase in blood sugar from eating a standard amount of a food is compared to that resulting from eating the same amount of glucose, or grape sugar. The ratio is called the glycemic index. Some complex carbohydrates have surprisingly high glycemic indexes (such as baked Russet potatoes, which increase blood sugar levels over 1.5 times as much as the same amount of pure sucrose), while others have relatively low glycemic indexes (such as pasta).

One simple sugar that increases blood sugar very little is natural fruit sugar, fructose. Fructose has a glycemic index of only 20 which is less than milk at 31. A recent study showed an increased time to exhaustion in trained men given fructose before endurance exercise compared to a similar group of men who received only a sweet placebo. (Okano, 1987) Note, however, that "high fructose corn syrup" may contain varying amounts of fructose. The usual high fructose corn syrup used to sweeten soft drinks, for example, is only 42% fructose, with the rest being mainly glucose, which has a glycemic index of 100. (Sucrose, cane or beet sugar, has a glycemic index of 59.)

For Best Results, Take Choline and B-5, Too

As we mentioned before, arginine works in the brain via the cholinergic nervous system. These brain cells use acetylcholine, a neurotransmitter, to communicate with each other. The normal brain can use the nutrient choline with the help of cofactor vitamin B-5 (pantothenic acid or calcium pantothenate) to make acetylcholine. Thus, we recommend that, if you are taking arginine supplements, you also take one to three grams of choline and one-half gram to two grams of vitamin B-5. Arginine causes the hypothalamus gland in the brain to release GHRF (growth hormone releasing factor) via a cholinergic mechanism. The GHRF in turn causes the pituitary to release GH. (See the Cautions at the end of this article for side effects and precautions.)

GH Releasers and Boron: Is Boron Really an Anabolic?

Do boron supplements really have anabolic effects? Can a boron supplement be used with GH releasers? Yes, boron supplements substantially increase the testosterone levels of experimental animals, both male and female, and it also worked in a clinical study on female humans. (Nielsen, 1987) A reasonable dose for a healthy human adult is about 3 milligrams of boron per day. You can get about this amount of boron in a diet that is high in green, leafy vegetables, fruit, legumes, and nuts.

Testosterone alone does not produce nearly the increase in muscle mass as the same amount of testosterone combined with a GH releaser that produces similar levels of GH to that of an exercising teenager. Note: According to the scientists at the U.S. Department of Agriculture who did the boron research, a variety of vitamin and mineral deficiencies can interfere with boron's testosterone increasing effects. We recommend taking a good multivitamin and mineral supplement.

Getting Off of Anabolic Steroids with GH Releasers

Anabolic steroids are so seductive. At first, relatively small doses help you to gain muscle faster. But these same steroids tell your brain to order your gonads to make less natural anabolic testosterone, so soon you have to take more. These larger doses tell your brain to really shut down your gonads. Indeed, anabolic steroids usually eventually cause loss of libido and testicular atrophy, which may be irreversible. Continued use of the necessarily increasing doses of the anabolic steroid causes downregulation of your testosterone receptors. Testosterone and anabolic steroids cause their anabolic effects via special receptors on cells. High levels of these steroids cause a reduction in receptor number, which means that you have to take even higher levels of the steroids just to keep getting the same effect, in a vicious cycle. These high doses will eventually seriously damage your gonads, liver, kidneys, and cardiovascular system, and may cause psychiatric problems, such as "roid ra ge."

But once on anabolic steroids, it is very hard to quit. The steroids have shut down your normal testosterone production, and they have reduced the number of testosterone receptors. This means that when you stop taking the steroids, you will have a far more difficult time building and maintaining muscle than if you had never started taking them. We have observed that the use of arginine as a GH releaser can help a bodybuilder get off of steroids without any loss of muscle mass!

Here is a case history: We were at a Florida health talk show radio station promoting our third book, when we received an on-the-air phone call from an adult body builder. He told us that he had been using Dianabol® heavily for a few years, and that it had damaged his health to such an extent that he finally believed his doctor who had told him that he was slowly killing himself with the black market steroids. He said that he went cold turkey on the steroid and had expected to lose about 30 pounds of muscle over the next few months. He had read about Sandy's use of arginine as a GH releaser in our Life Extension, A Practical Scientific Approach, so he started taking about 20 grams of arginine per day. Over the next three months, he actually gained five pounds of muscle, as measured by underwater weighing, and his tape measurements. He credited our GH releaser program for saving both his health and his physique. It is a lot easier to get off of anabolic steroids when you know that you can do so without losing muscle mass!

Running Out of Growth Hormone?

Some people have feared that the pituitary's growth hormone could be exhausted by frequent use of growth hormone releasers. Both arginine and ornithine cause pituitary GH release by stimulating the release of growth hormone releasing hormone from the hypothalamus. A study in which growth hormone releasing hormone was continuously infused for two weeks did not find any evidence of pituitary desensitization or depletion of growth hormone. (Vance, 1989) The pituitary contains a lot of GH; an exercising teenage size GH pulse will use only roughly 1% of that present.

We do not recommend that growth hormone releasers be used continuously; they should be used to enhance growth hormone release at the normal times of its pulsatile release. Continuous GH release would probably lead to a reduced effect of GH on its receptors, just as continuous insulin release causes loss of insulin receptor sensitivity. We recommend that growth hormone releasers be used either before exercise or just before sleep to enhance or restore natural releases at those times to levels typical of a teenager or young adult. Huge amounts of growth hormone, such as those associated with pituitary tumors, or which could be obtained by GH injections, can cause gigantism when it occurs in those who have not achieved their complete adult height, or acromegaly if it occurs later in life.

Growth Hormone Scandal

Sandy predicted in our 1982 best-seller Life Extension, A Practical Scientific Approach that there would eventually be a growth hormone scandal among Olympic athletes. Sure enough, in the recent past and continuing into the present there has been a scandal about the use of growth hormone. However, many growth hormone releasers are nutrients. These nutrients, such as arginine and niacin, are perfectly legal for Olympics, IFBB, NCAA, AAU, NFL, and NBA athletes to use. Do not take medically unsupervised GH injections; they can cause serious medical problems. Moreover, the currently available human GH preparations differ by one amino acid from the natural human GH, so tests for it will probably soon be developed.

Future Research on Growth Hormone

There are some authoritarians (such as certain Congressmen) who believe that medicinal substances should only be used to treat disease and never for the improvement of quality of life. Such a person is Rep. Henry Waxman of California, who now proposes that human growth hormone, available in large quantities now due to new recombinant DNA technology, be placed in the Controlled Substances List along with narcotics because it might be used by athletes, obese persons, or by parents to increase a child's height. Unfortunately, any substance on this List is, for all practical purposes, impossible to use in any research for purposes not already approved by the FDA. Thus, the many new potential uses for human growth hormone (beyond the treatment of hypopituitary dwarfs) (Kolata, 1986) could never be investigated legally. Fortunately, arginine is a nutrient amino acid, not a drug, and is not under the control of Rep. Waxman and his ilk in Congress. Moreover, the Proxmire Amendment requires th at the Food and Drug Administration (FDA) regulate it as a nutrient rather than as a drug, so long as "drug-like" claims are not made for the product.

Caveat Emptor - Let the Buyer Beware

Many GH releasers contain arginine and/or ornithine, but the amounts are often too small to do much.

There is one scientific paper which claims to show that a combination of one gram of arginine + one gram of ornithine causes GH release. Our statistical analysis of the data presented in that paper shows no significant difference between the purported GH releaser and a placebo.

We have reviewed the one scientific paper on a low dose arginine + lysine combination, and have concluded from the time course of the GH release that the scientists were measuring a needle-stick injury-induced release of GH in their teenage experimental subjects. Significant amounts of arginine + lysine could not have been absorbed from the gut in the short period of time before the observed GH peak. See the 50 page long chapter on GH releasers in our Life Extension Weight Loss Program for further data.

In our opinion, much of the black market "human growth hormone" is a worthless fraud. It is much easier to counterfeit a bottle and label than to counterfeit a $100 bill, and the GH counterfeiter is much less likely to get caught. Many arginine and/or ornithine "GH releaser" supplements are far too low in potency to be effective but you are a lot less likely to be harmed or ripped off with an arginine and/or ornithine GH releaser than if you buy a hypodermic syringe and a bottle of "human growth hormone." GH cannot be heat sterilized before injection. If that GH bottle is counterfeit, do you really think that the counterfeiter has the equipment and knowledge to manufacture a rigorously sterile fake? If it isn't sterile, and you shoot up on it, common household bacteria in that bottle could infect your heart, causing crippling rheumatic heart disease - or perhaps even kill you. Far more junkies die from injection infections than from the heroin itself. Think about that before sticking a needle into yourself....

Cautions

Because growth hormone opposes the actions of insulin, diabetics and borderline diabetics must NOT use growth hormone or growth hormone releasers except under a physician's order and supervision. A certain subset of adult onset diabetics seems to have abnormally slow GH metabolism, and the use of GH releasers in these people might contribute to diabetic reinopathy, which can gradually cause blindness. Since about half of the people who have diabetes don't know it, we very strongly recommend a complete physical exam with the usual clinical laboratory blood tests before using GH releasers.

Persons who have not completed their long bone growth (children and teenagers) should NOT use growth hormone or growth hormone releasers except under a physician's supervision. (This also applies to pregnant or lactating women.) It may seem like a great idea to increase one's growth and become taller but without the guidance of an experienced endocrinologist, you might use too much and become an 8 foot freak with disastrous joint and foot problems. Once one's long bone growth is completed, growth hormone or growth hormone releasers will not make you grow taller. Huge excesses of growth hormone, as occur in certain pituitary tumors, result in irreversible joint diameter enlargement, vocal cord thickening, or even acromegaly, with a pathologic growth of connective tissue.

Arginine and ornithine sometimes reactivate latent herpes virus infections, so persons who have ever had ocular or brain herpes must not use either of these as GH releasers.

Certain psychotics may experience worsened symptoms if they take arginine or ornithine supplements.

A 200 milligram dose of niacin (but not niacinamide) will cause a mild GH release - about as much as a non-exercising teenager. (Irie, 1967, 1970) Do not use more than 800 milligrams of niacin per day without having your liver function checked by a physician because, in some people, liver damage may occur at higher doses. 800 milligrams of niacin per day may help a little to reduce the elevated levels of VLDL and LDL cholesterol and triglycerides caused by anabolic steroids.

We do NOT recommend the use of methionine as a GH releaser. Even at doses which produce only mild and unreliable GH release, methionine may cause liver toxicity, atherosclerosis (especially with vitamin B-6 deficiency), or depression.

Saunas do cause substantial GH release, but do NOT go from a hot sauna into a cold shower or pool. This can cause your blood pressure to go up as high as 800mm. Hg. (140mm. Hg. is normally considered high blood pressure), which could result in a stroke or heart failure. If you take more than one sauna per day, you may develop tolerance to the sauna's GH releasing effect.

Arginine Side Effects: Most men and some women report increased libido with arginine supplements. There may also be increased irritability. A large release of GH can also cause nausea. Remember how Arnold Schwarzenegger used to keep a barf bucket next to his workout station when he was a teenager? He said that if he wasn't working out hard enough to throw up, he wasn't working out hard enough to win. In his twenties, this no longer happened because the exercise no longer caused such a big GH release. You are less likely to have annoying side effects if you start out with a small amount, and gradually increase your dose over a period of a couple of weeks.

Ornithine Side Effects: Arginine, but not ornithine, is found in ordinary food protein. Arginine has been given to medically monitored subjects at up to 60 grams per day without reports of serious problems. Much less is known about the safety of the regular use of large amounts of ornithine. Since about half of the arginine that you ingest is normally converted to ornithine in your body, it isn't surprising that the reported side effects of ornithine are similar to those of arginine. It takes about half as much ornithine as arginine to release a given amount of GH, but ornithine costs twice as much. We generally use arginine, considering it to be more medically conservative. The immunostimulant and wound healing stimulant effects of arginine are far better established, too. Moreover, arginine, but not ornithine, increases sperm count.

Choline Side Effects: Too much choline and/or vitamin B-5 can cause the production of too much acetylcholine. Since acetylcholine is what makes your muscles contract, this can cause excessive muscle tone. The most common symptoms of cholinergic excess is a stiff neck, a tension headache, or gut cramps, diarrhea, or constipation. You are less likely to have annoying side effects if you start out with a small amount, and gradually increase your dose over a period of a couple of weeks. Do not use choline bitartrate; in effective doses, there is so much bitartrate in this form of choline that diarrhea is almost inevitable, chronic diarrhea isn't just annoying; potassium loss can be so large that it may cause heart failure by ventricular fibrillation.

Niacin Side Effects: 200 milligrams of niacin will almost certainly cause transitory skin flushing and a sensation of heat, burning, or itching, though this is not dangerous. Do not take more than 800 milligrams of niacin per day without medical supervision, since the livers of some individuals cannot tolerate higher doses.

Boron Side Effects: People have died from accidental overdoses of boron, so do NOT try megadosing on it. One hundred times the normal dose of vitamin C per day is more likely to improve your health than hurt it. One hundred times the normal dose of boron per day might kill you. At the daily 3 milligram dose of boron that we have mentioned, you may experience an increase in libido, and perhaps even develop a few teenage pimples, whether you are a man or a woman. Some women may notice a bit more facial hair growth, but this isn't likely to be a big problem. In women, a considerable amount of the additional testosterone is naturally converted to estrogen (unlike with anabolic steroid drugs) which helps to counteract the masculinizing effect of the doubled testosterone levels. Indeed, some scientists are now suggesting the use of increased dietary boron by postmenopausal women for protection from osteoporosis.

Although the growth hormone releasing effects of arginine and ornithine have been stressed in this article, we do not wish to imply that all of the anabolic, wound healing, and immunostimulating effects of arginine and ornithine are due to their GH releasing activity. Arginine and ornithine also act as precursors to polyamines such as spermine and spermidine, which are growth stimulating substances, and these two amino acids have many other uses within the body, too. Nevertheless, the anabolic, wound healing, and immunostimulant effects of growth hormone itself are so similar to those of arginine and ornithine that we do not think that an exploration of this distinction would be of much interest to body builders and athletes.

Bibliography

See the extensive 50 page how-to text, extensive bibliography (94 references), and safety appendix about the use of growth hormone releasers in our book, The Life Extension Weight Loss Program (Doubleday Books, 1986).

Assimacopoulos-Jeanett, et al., "The Hormonal and Metabolic Basis of Experimental Obesity," in Albrink, editor, Clinics in Endocrinology and Metabolism, Vol. 5, pp. 337-365, Philadelphia: Saunders (1976).

Bazzarre, et al, "Human Growth Hormone Changes with Age," Proc. 3rd Int. Symp. on Growth Hormone, (Milan), North Holland: Amsterdam (1975).

Barbul et al., "Arginine: A Thymotropic and Wound-Healing Promoting Agent," Surgical Forum 28:101-103 (1977).

Barbul, "Arginine: Biochemistry, Physiology, and Therapeutic Implications," Journal of Parenteral and Enteral Nutrition 10(2):227-238 (1986).

Barbul, A., "Arginine and Immune Function," Nutrition 6(1):53-60, (Update on Immunonutrition Symposium Supplement: Jan/ Feb 1990).

Bray, "Diet and Exercise as Treatment for Obesity," in Conn, Jr. et al., editors Health and Obesity, New York: Raven Press (1983).

Brownell and Wadden, "Behaviorial and Self-Help Treatments," in Obesity, edited by M.R.C. Greenwood, New York: Churchill Livingstone (1983).

Casanueva, Villanueva, Cabranes, Cabezas-Cerrato, Fernandez-Cruz, "Cholinergic Mediation of Growth Hormone Secretion Elicited by Arginine, Clonidine, and Physical Exercise in Man," J. Clin. Endocr. Metab. 59(3):526-530 (1984).

Christy, "Anterior Pituitary Function in Normal Subjects and in Patients with Systemic Diseases," in Beeson, et al., editors Cecil Textbook of Medicine, 15th ed., pp. 2085-2091, Philadelphia: Saunders (1979).

Clemmons et al., "Growth Hormone Administration Conserves Lean Body Mass During Dietary Restriction in Obese Subjects," J. Clin Endocrinol Metab 64(5):878-83 (1987).

Daly, et al. "Immune and Metabolic Effects of Arginine in the Surgical Patient," Ann Surg 208(4):512-522 (1988).

Decombaz et al., "Biochemical Changes in a 100 Km Run: Free Amino Acids, Urea, and Creatinine," Eur J Appl Physiol 41:61-72 (1979).

Dohm, Williams, Kasperek, van Rij, "Increased Excretion of Urea and N-methylhistidine by Rats and Humans After a Bout of Exercise," J Appl Physiol 52(1):27-33 (1982).

Duda, M., "Study: Steroids Lower Immunity, Lipids," Phys Sportsmed 16(2):56 (1988).

Edwards, Ghiasuddin, Schepper, Yunger, Kelley, "A Newly Defined Property of Somatotropin: Priming of Macrophages for Production of Superoxide Anion," Science 239:769-771 (1988).

El-Khodary, et al., "Insulin Secretion and Body Composition in Obesity," Metabolism 21:641-655 (1972).

Irie, et al., "Effect of Nicotinic Acid Administration on Plasma Growth Hormone Concentrations," Proc Soc Exptl Biol Med 126:708 (1967).

Irie, et al., "Effect of Nicotinic Acid Administration on Plasma HGH, FFA, and Glucose in Obese Subjects and in Hypopituitary Patients," Metabolism 19:972-979 (1970).

Jenkins et al., "Glycemic Index of Foods: a Physiological Basis for Carbohydrate Exchange," American Journal of Clinical Nutrition 34:362-66 (1981).

Kolata, "Research News: New Growth Industry in Human Growth Hormone?" Science 234:22-24 (1986).

Leppaluoto et al., "Endocrine Effects of Repeated Sauna Bathing," Acta Physiol Scand 128:467-70 (1986).

Merimee, et al., "Arginine Initiated Release of Growth Hormone: Factors Modifying the Response in Normal Men," New Eng J Med 280(26):1434-1438 (1969).

Murad and Haynes, "Adenohypophyseal Hormones and Related Substances," in Gilman, Goodman, Gilman editors Goodman and Gilman's Pharmacological Basis of Therapeutics 6th ed, pp. 1369-1396, New York: MacMillan (1980).

Nielsen, Hunt, Mullen, Hunt, "Effect of Dietary Boron on Mineral, Estrogen, and Testosterone Metabolism in Postmenopausal Women," FASEB J. 1:394-397 (1987); Agricultural Research (Nov./Dec. 1987).

Okano et al., "Effect of Pre-exercise Fructose Ingestion on Endurance Performance in Fed Men," Medicine and Science in Sports and Exercise 20(2):105-109 (1987).

Paolisso et al., "Advantageous Metabolic Effects of Pulsatile Insulin Delivery in Non-Insulin Dependent Diabetic Patients," J Clin Endocrinol Metab 67(5):1005-10 (1988).

Prinz, et al., "Growth Hormone Levels During Sleep in Elderly Males," presented at the 29th Annual Gerontology Society Conference (Oct. 13, 1976).

Quabbe, et al., "Nocturnal Growth Hormone Secretion: Correlation with Sleeping EEG in Adult and Pattern in Children and Adolescents with Non-Pituitary Dwarfism, Overgrowth, and Obesity," Acta Endoctrinologica 67:767-783 (1971).

Ratzmann and Gottschling, "Abnormal Growth Hormone Response in Obesity with Normal Carbohydrate Tolerance and Normal Thyroid Function," Endokrinologie Band 72, Heft 2: 149-154 (1978).

Salit, M., "Exercise and Immunity," in Thomas, J., editor, Drugs, Athletes, and Physical Performance, pp. 169-179, Plenum Medical Book Company, New York (1988).

Vance et al., "Lack of in Vivo Somatotroph Desensitization or Depletion After 14 Days of Continuous Growth Hormone (GH)-Releasing Hormone Administration in Normal Men and a GH Deficient Boy," J. Clin Endocrin Metab 68:22-28 (1989).

Zadik et al., "The Influence of Age on the 24 Hour Integrated Concentration of Growth Hormone in Normal Individuals," J Clin Endocrinol Metab 60(3):513-516 (1985).

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By Durk Pearson and Sandy Shaw

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