Human Growth Hormone. Applications, and the aging process

Human Growth Hormone

Applications, and the aging process

Written by Joachim Bartoll, October 2016 and February 2017.
Classic Muscle Newsletter #31

Part 1

Perhaps no other hormone in the body is subject to more misconceptions than human growth hormone (GH). If you are to believe the many claims repeatedly made on numerous web sites and blogs, as well as that often voiced by various “anti-aging clinics,” GH is a miracle hormone that can set back the aging clock. Growth hormone is also attractive to bodybuilders and athletes because of its reputed anabolic properties. Again, some self-styled web “experts” often proclaim that GH is the most anabolic of all hormones. Most such people are often associated with steroid websites that just happen to sell GH and insulin-like growth factor-1 (IGF-1,) which is a product of GH produced both in the liver and in other organs and tissues, including muscle.
Since IGF-1 is a very expensive hormone (when it’s the real stuff,) the likelihood that you’re purchasing actual IGF-1 from some Internet site that works out of a post office box in Estonia is remote at best. But that’s another story for another article.

The primary attractions to GH usage are to either help build muscle and lose body fat, or to forestall the aging process and hopefully recapture some of the features of youth, such as thicker skin, less skin wrinkles, lower body fat levels, and more muscle mass. Bodybuilders are convinced that GH not only is a potent anabolic hormone, but also helps to dramatically lower body fat levels. I recall a story passed around in various Internet bodybuilding forums in the 90s about how you can consume as much as 10,000 calories a day and not gain any fat if you are also injecting GH (or GH in combination with insulin.)

The actual truth about GH for bodybuilding and athletic purposes is considerably less dramatic than the many rumors that abound this hormone.
In fact, using the word “hormone” in reference to GH is itself a mistake, since GH is actually a “family” of about 100 hormones varying slightly in size, referred to as isoforms. The main form that circulates in the blood, however, is one particular form that weighs in at 22 kilodaltons. The primary importance of knowing this is that scientists have tried to come up with a drug test for GH for the last 25 years or so, and thus far have come up empty. Much of this is related to the ephemeral nature of GH.

GH is produced in the pituitary gland in the brain, which is 8% GH by weight. But the primary impetus for GH production in the pituitary is the release of growth hormone-releasing hormone (GHRH) from the hypothalamus structure in the brain. Another protein produced in the brain and gut, somatostatin, works to oppose the release of GH. The primary reason why GH levels tend to decline with age is thought to result from an imbalance between GHRH and somatostatin, with somatostatin becoming dominant over GHRH.
Administration of the amino acid L-arginine can provoke a GH release by blocking the effects of somatostatin on GH release. In fact, years ago intravenous arginine was often used as a test to provoke GH release in those suspected of having a GH deficiency. If the arginine failed to produce a normal GH response, the person tested was considered lacking in GH. These days other tests are used to test for a GH deficiency, such as providing insulin. Insulin lowers blood glucose and may provoke a GH release, since one function of GH is to increase blood glucose levels. But the most common test for GH is to just check the blood levels of IGF-1. This is done because GH only lasts about 30 minutes in the blood after being released by the pituitary gland, and then is degraded in the liver. IGF-1 production is promoted by GH in the liver, but since IGF-1 circulates in the blood bound to proteins, with IGFBP-3 being the most common, it lasts far longer in the blood, about 12 to 24 hours, so is more easily tested. The level of circulating IGF-1 is considered a marker of GH release, although it’s not accurate for many older people in the sense that they can show a normal IGF-1 level, yet still be deficient in GH. One thing to note about both GH and IGF-1 is that they are not steroid hormones such as testosterone and estrogen, but rather are polypeptide hormones composed of long strings of amino acids in a specific sequence. Growth hormone consists of 191 amino acids. 
Because of this, GH and IGF-1 can only be provided in injected form. However, growth hormone secretagogues, which are short amino acid peptides, can promote GH release by bypassing the somatostatin barrier in the brain. Many of these GH secretagogues are based on Ghrelin, which can itself promote a GH release. Ghrelin is also the most potent appetite stimulating substance in the body and rises between meals to signal hunger.

How to stimulate GH release

A number of amino acids besides Arginine are known to promote the release of GH. But as with arginine, most of these amino acids work best in this regard when provided intravenously. The use of Arginine as a GH-releaser was popular years ago based on the rationale described earlier. However, what most supplement purveyors failed to disclose about arginine supplements for GH was that most of the studies showing a significant GH release from arginine involved an IV-administration of the amino acid. On the other hand, some studies do indicate that under the proper conditions, arginine can promote a GH release.

Other methods thought to boost GH release include sufficient sleep, since GH is maximally released during stage 4 sleep, occurring right before REM or dream sleep occurs about 90 minutes after falling asleep. As noted, since GH is a counterregulatory hormone to hypoglycemia or low blood glucose, having lower levels of both glucose and fat in the blood will provoke a GH release.

One sure way to significantly boost GH release is to go on an extended fast. Levels of GH increase by over 300% on a fast, and this is caused by GH helping to maintain blood glucose levels and mobilize fat stores for energy purposes.

High intensity exercise characterized by briefer rest between sets promotes a greater GH release. Ironically, ingesting arginine before a workout will blunt the usual increase in GH produced by exercise, but will boost it about an hour after the workout. Having lower body fat levels boosts GH release, since high levels of body fat are known to blunt GH release. Aging itself blunts GH release, with levels of GH gradually declining starting at about age 40. The levels of GH drop about 14% per decade after that. Some men have shown a 50% drop in GH every seven years as they age. With a GH deficiency, body fat levels increase by 10 to 50 percent, with a loss of lean mass in the range of 30 to 50 percent. Bone mass declines by about 3 percent a year with lack of GH.

Part 2:

Growth Hormone in bodybuilding

The use of Growth Hormone in bodybuilding is controversial. Contrary to what is often written on the Internet, there is little or no scientific evidence to show that GH, when provided solely alone, without any other anabolic hormones such as testosterone or anabolic steroids, helps to build muscle or increase strength. This applies to those who still produce normal levels of GH. The picture changes in those with clinically diagnosed GH deficiency. When GH is provided to those with naturally low GH levels, it does promote anabolic effects in muscle, along with a loss of body fat. The bodybuilding theory about GH is that used alone it will help to preserve muscle mass, but not provide much of an anabolic effect. This notion was most apparent during the only drug-tested Mr. Olympia contest in history, the 1990 event held in Chicago. Many of the top competitors that year confided to trusted sources that while they had stopped using anabolic steroids about two weeks to a month prior to the contest, they had continued to use Growth Hormone all the way up to the contest, since there was no test procedure available for GH (not back then or now.)
When asked what the GH did for them, the usual response was that it helped to maintain the muscle mass they had developed from their training and steroid use, but had not added any muscle mass. Since these men were all strictly dieting, they couldn’t tell how much influence their use of GH had on body composition, specifically fat loss. One critique of the studies that have suggested that GH is useless for bodybuilding purposes is that the doses used in such studies are often not comparable to real world use by bodybuilders and athletes. An example of this is the usual therapeutic dose of GH to treat a deficiency is about one unit. Some well-known bodybuilders are known to use 12 to 18 or more units of GH each day! Among amateurs, 4 to 8 units a day is very common. Among professionals, 12 to 16 is also quite common. Only a few go higher than that.

In fact, the only study featuring bodybuilders that showed a true anabolic effect from using GH alone involved bodybuilders who had stopped using all anabolic steroid drugs. When they used GH alone, they showed definite anabolic effects in their muscles. This was thought to be caused by a temporary deficit in IGF-1 production caused by the cessation of steroid use. When the men began injecting GH, the IGF-1 release was restored to previous levels, producing anabolic effects in their muscle tissue.
With that said, the most common athletic use of GH is not to build more muscle mass, but rather to protect and help heal connective tissue. Tendons and ligaments are largely made up of connective tissue and the primary protein in connective tissue is collagen. GH is known to potently promote collagen synthesis in the body. This aspect of GH is not controversial and is not disputed. It’s been shown numerous times that using GH after a connective tissue injury will readily speed the healing of such injuries because of the upgraded production of collagen induced by GH administration.

But even more controversial than the athletic or bodybuilding use of GH is its effects on the aging process. The notion that GH blunts the aging process has its origins in a 1990 study published in the prestigious New England Journal of Medicine. That study spawned an entire cottage industry of “anti-aging clinics” that center around hormonal therapy, mainly GH and testosterone. The primary advertising of such clinics is that “you don’t have to grow old,” and implies that the control of aging is in your hands. But another school of thought claims opposite effects of GH: that it will actually accelerate aging and even possibly promote cancer and degenerative diseases associated with aging. Let’s take a closer look behind this in the next part.

Part 3

Do Growth Hormone slow down the aging process?

You can bet that Andrzej Bartke, Ph.D will never be invited to speak at an anti-aging conference. The Polish-born Bartke is a professor in the department of physiology at Southern Illinois University. He studies mammalian aging, especially that related to growth hormone and IGF-1. The reason why Bartke arouses the ire of anti-aging proponents is that he has published dozens of medical studies suggesting that, contrary to popular belief, GH accelerates rather than slows the aging process. He often discusses in his articles about the folly of using GH as a means of blunting the aging process, since in reality it will produce opposite results. This is obviously a serious statement, since the majority of those who undergo GH replacement therapy are older people who want to stay young. The only actual approved medical condition for GH usage is to treat a type of dwarfism. The use of GH has never been approved to help halt the aging process, although enforcement of this off-use of GH is rare.

Bartke offers a lot of evidence to prove his contention that using GH will, if anything, speed aging rather than slow it down. The primary problem with Bartke’s evidence is the source. Bartke derives all of his evidence from certain types of lab animals. One type is a transgenic mouse, meaning that the genes of this rodent have been manipulated so that it produces higher than normal levels of GH. When humans mimic this scenario from birth, a condition called Giantism develops. This leads to unusual height produced by the larger secretion of GH in the growing years. The people who are listed in the Guinness Book of World Records as the tallest people on earth got that way from being born with small tumors on their pituitary glands (adenoma) that led to larger than normal production of GH throughout their lives, and subsequent great height.
As such, the transgenic mouse that produces large amounts of GH is not exactly a precise model of GH metabolism and effects in normal humans. But the point of producing such a Frankenstein rodent was to show what could happen if excess GH was produced. Of course, what happens in a mouse or rat isn’t always duplicated in a human, and this is another problem with Bartke’s contentions about the effects of GH. His other animal model to prove his thesis about the alleged dangers of long-term GH is a type of dwarf mouse. This particular mouse shows a resistance at the cell receptor level to IGF-1, which is the product of GH release. This mouse is tiny even for a mouse, but it also tends to live much longer than other mice – as much as 75% longer! The reasons for this will be discussed later.

But for now, it’s important to realize that all of professor Bartke’s contentions about the aging effects of GH are based entirely on animal models. He has zero human evidence.

This is not to say that there is no human evidence about the longevity effects or lack of longevity effects associated with GH and IGF-1. Most animals that show a natural resistance to IGF-1 at the receptor level do tend to live longer. Humans who live to over age 100 show a selective resistance to IGF-1, in that they still produce IGF-1, but some parts of their bodies show resistance to it. This is thought to explain why these people make to 100 and over. But the question arises: what is it about GH and IGF-1 that may interfere with longevity rather than promote it?

In the transgenic mouse that produces large amounts of GH, the feedback mechanism that involves a higher level of IGF-1 in the blood acting to blunt GH release from the pituitary gland isn’t operational. That is, there is nothing in this mouse that blocks a huge release of GH in their bodies. The mice show such signs of accelerated aging as loss of cognitive or thinking function; imbalance of brain neurotransmitters; hair loss, and increased incidence of cancer. Some of these same symptoms are often seen in a human disease, acromegaly, which again is caused by a tumor on the pituitary gland that leads to much larger than usual release of GH.
The tallest man on record, Robert P. Wadlow from Alton, Illinois, was a giant who stood 8 feet and 11.1 inches tall (2.72 m.) and weighed 439 lb (199 kg) at his death at age 22. Wadlow didn’t have a tumor on his pituitary gland, but rather was born with a hyperplasia (excessive number) of cells in the pituitary that overproduced GH throughout his life. When he graduated from high school, he was already 8 feet, 4 inches. Although he was lean at 439 pounds, he suffered from myopathy, or weak muscles, to the extent that he had to wear a brace on his legs to enable him to walk. Wadlow died at only 22 after he contracted a blister on his leg from wearing the leg brace that became infected. He died 11 days after getting infected. The peripheral leg muscle weakness that Wadlow experienced was caused by the massive amount of GH released in his body. Interestingly, Wadlow had fairly large, but weak muscles, again thought to be the result of his GH release.

The famous professional wrestler, Andre the Giant was an acromegalic giant. Andre died at age 46 from heart failure related to diabetes, which in turn was related to his higher-than-normal GH production. GH tends to promote insulin resistance, which is the forerunner of type-2 diabetes. Although Andre’s height was often listed as 7-feet-4, in fact he was just under 7 feet tall. Adding to Andre’s health problems was the fact that he was obese, which itself says a lot about the notion that having larger than normal amounts of GH in your body will “burn body fat.” Some stories circulating in bodybuilding circles are that many retired professional bodybuilders who used massive doses of GH during their competition years now have type-2 diabetes, and many of them must inject insulin to control it.

The point of Wadlow and Andre’s cases is that producing a far higher than normal level of GH for a lifetime can without a doubt lead to some serious medical consequences. Some studies find that people with acromegaly often show higher rates of high blood pressure and colon cancer. Bartke notes in his rodent studies that animals with higher production of GH and IGF-1 show greater rates of cancer than do normal rodents. In fact, the cancer connection between GH and IGF-1 is controversial, sort of a chicken before the egg scenario. IGF-1 promotes mitosis or cellular division and cancer is a disease (actually over 100 different diseases) that is characterized by uncontrolled cellular division. Some studies suggest that IGF-1 can promote certain types of cancer, especially breast, colon, and prostate cancers. But the actual evidence for this remains both scant and confusing. For one, tumors are able to locally produce IGF-1 and do so since IGF-1 blocks a process called apoptosis, involving a self-destruction of the cell. Normal cells initiate apoptosis when something amiss is detected in the cell, such as the mutation of cellular DNA. The cells do this to prevent tumors from forming. But tumors themselves have that ability to produce IGF-1, which blocks apoptosis, thus allowing the tumor cells to survive. As such, the controversy is whether the IGF-1 produced naturally in the body serves as a type of fuel source for tumors, or whether the upgraded IGF-1 that appears in tumors is produced by the tumors themselves. The question remains unresolved at this point. However, many doctors are hesitant to prescribe GH therapy even to those with a diagnosed GH deficiency because of fears of cancer promotion that could result from the upgraded IGF-1 production that results from GH therapy. In contrast to these fears, however, children who have been treated with GH for years for growth-related problems do not show any increased incidence of cancer. Years ago, some of these children did show higher rates of leukemia, but the notion that this was related to the GH they were provided was later shown to be unrelated. More recent studies of humans on long-term growth hormone replacement therapy (GHRT) show no evidence at all of increased cancer incidence. The cancers that occurred in Bartke’s lab rodents were likely more related to the much higher amount of GH and IGF-1 produced by these animals. The cancer controversy is still an open question, but does seem more related to using higher doses of GH for extended times. Athletes who use GH off and on for years may be at higher risk for cancer, which is mostly an age-related disease, as they age although there is no evidence for this as yet.

Part 4

Part 4: Life span and GH activity

So… Why do animals with a low GH activity seem to live a lot longer than other animals? Most of the evidence points to lower production of oxygen metabolic byproducts called free radicals. Free radicals are unpaired electrons (electrons usually come in pairs) that seek to attach themselves to other electrons, which causes cellular havoc. Excess production of free radicals has been linked to accelerated aging, cardiovascular disease onset, and cancer. On the other hand, recent research shows that free radicals, when produced in moderate amounts provide many beneficial health effects. For example, free radicals play a role in the production of thyroid hormones. They also appear to promote exercise adaptations, including those related to anabolic effects in muscle following training, as well as lowered insulin resistance after exercise. But when they are produced in excess, the benefits of free radicals are reversed, leading to many negative effects.

In the body, excess free radical activity damages fats and proteins, leading to aging effects. They also damage a portion of the cell called the mitochondria, where energy is produced as ATP and where fat is oxidized. The mitochondria are the site of the greatest production of free radicals in the body because of all the oxygen processing that occurs in mitochondrial metabolism. While the body has internal antioxidant safeguards that help to protect the mitochondria, these natural defenses tend to decline with age. As the mitochondria become damaged from the continued onslaught of free radical attacks, cells gradually die and this is one major theory of the root cause of aging. A lack of GH in animals appears to lower the free radical damage to mitochondria, explaining why the animals with a relative lack of GH/IGF-1 live longer. The animals also appear to have increased resistance to stress, especially cellular stress. They also show lower resting insulin levels, also associated with longevity. Much of the increased insulin sensitivity in the animals derives from upgraded production of adiponectin, a fat cell-produced protein that promotes increased insulin sensitivity. The GH-lacking animals also show lower visceral fat stores, or fat that lies deep in the gut. This type of fat is associated with the greater release of inflammatory cytokines, immune proteins that spark inflammation in the body.

Again, increased systemic inflammation is linked to faster aging and disease, as well as extensive muscle loss. Animals lacking in GH activity surprisingly show increased rates of fat oxidation, likely because of preserved mitochondrial function (low systemic inflammation). Much of the general effects of lack of GH and IGF-1 appear to mimic the health benefits associated with caloric restriction, the only established way to extend life in animals.

Larger animals tend to have shorter lives compared to smaller animals, but there are many exceptions to this rule. While a mouse life is short, about 2 years or so, an elephant can live up to 80 years or more. There are whales said to be over 200 years old. At the other end of the spectrum are dogs. Larger dogs usually die earlier than smaller dogs. A casual observation of people who make it to over 100 show that none of them are tall or heavy. Most of them are short, small, and fairly thin. Some researchers ascribe this to their lower activity of IGF-1, yet these people produce enough IGF-1 to maintain health.

So, while it appears that having a relative lack of GH/IGF-1 activity in animals may confer some longevity benefits, is this also the case with humans? As noted, all of Bartke’s evidence stems from animals either born lacking IGF-1 and GH activity or bred to overproduce GH. What happens in humans who lack GH, will this offer increased longevity?

What happens when humans lack GH and IGF-1?

Antagonist Pleiotropy (AP) refers to how a gene that can be beneficial when you’re young can have negative effects once you’re older. A good example of this is the P53 tumor suppressor gene. As the name implies, this gene works to suppress incipient tumor formation when you’re young and in doing so helps to prevent cancer. People born with a rare lack of this gene are highly prone to being afflicted with cancer. But another function of P53 has to do with the aging process. Telomeres are the ends of chromosomes that shorten every time a cell undergoes division in order to replicate. The telomeres gradually grow shorter with the passing years, and once they more or less disappear, the cell undergoes senescence, which basically means it no longer functions. P53 enters the picture because it is required for this shortening of telomeres to occur. What this means is that when you get older, P53 promotes the aging process in cells. That is something that most people would consider a negative effect. Curiously, a recent study found that elephants produce higher levels of P53, and for this reason rarely get cancer. Scientists are hard at work trying to figure out how elephants are able to do this.

In relation to growth hormone and IGF-1, both are absolutely required for growth in the younger years. But according to some scientists, such as Bartke, these same hormones that are beneficial to the young can prove deadly to the old. As such, they fit into the pattern of Antagonistic Pleiotropy. Specifically, GH and IGF-1 promote cell growth when you’re young that is conducted in an orderly fashion. But when you get older, the cell division-promoting effects of IGF-1 can promote cancer.
Some scientists speculate that the drop in hormones with age, including GH, IGF-1, testosterone, and estrogen is an inherent protective mechanism of the body to prevent cancer. The highest rates of cancer occur in older people. The reason for this has to do with an increase in cellular DNA mutations as you age. With each cell replication, the production of DNA gets a bit more messed up, not enough to cause cancer but enough to speed the aging or senescence of the cell. A recent study found that two-thirds of all cancers are caused by DNA damage. According to some researchers, the body reduces the production of hormones that could promote increased cell growth, and that includes the aforementioned hormones. Since IGF-1 is directly involved in cell mitosis process, or the actual dividing of cells, it’s considered the most potent of the potential cancer-promoting hormones. Estrogen has been directly implicated in the onset of cancers of the breast and endometrium in women, and some emerging evidence also suggests that it may play a role in the onset of prostate cancer. The picture for testosterone is far more debatable. While some physicians still think that testosterone can promote prostate cancer, more recent research shows that the men most prone to prostate cancer usually have a long-standing deficiency of the hormone, rather than an excess. Also, as noted earlier, the situation with IGF-1 and cancer is far from conclusive, and is based more on the known growth-promoting effects of IGF-1 rather than any direct evidence that it produces carcinogenic effects. But the notion is that, since GH and IGF-1 do influence cellular growth and division and since cancer is a disease characterized by uncontrolled growth and cellular division, GH and IGF-1 are potentially very dangerous for use by older people.

In truth, the doses of GH provided for hormonal replacement therapy are quite low, about 1/10 that provided to treat growth hormone deficiency. Some studies have shown that people who’ve been on GH anti-aging therapy for 20 years show no signs of cancer, and most of these people began using the hormone when they were past age 40. On the other hand, many athletes and bodybuilders inject themselves with massive doses of GH and IGF-1 and for them, the picture is entirely different. The reason for this is that the long-term effects of even intermittent high dose usage of GH and IGF-1 are not known. Thus far, not many cases of cancer related to athletic use of GH and IGF-1 have appeared in the medical literature. The likely reason for this is that athletes who use the drugs are still young and the innate body defenses against tumor formation are still active. Lyle Alzado, a professional football player, died of a type of brain tumor that could be stimulated by GH use. Shortly before his death, Alzado publicly admitted to using anabolic steroids for 26 years, and more recently had added GH to his drug regime. He suggested that it was the GH that promoted the brain tumor that eventually caused his death. While this is theoretically possible, there is no direct evidence to prove Alzado’s contention that his use of large doses of GH caused his disease. Also, since Alzado’s body never underwent an autopsy, his precise cause of death remains speculative.

The researchers who suggest that the gradual decline of GH and IGF-1 with age is a natural protective mechanism of the body seem to suggest that the problems that arise when you are deficient in these hormones should just be accepted as part of the natural aging process, a concept rejected by many. Following this line of thought, no man would use testosterone replacement therapy and no woman would ever consider estrogen replacement. This would mean increased rates of depression, loss of muscle mass, increase of fat mass, sexual impotency, and other problems that would lead to a low quality of life.
Studies show that men who lack testosterone not only have higher rates of prostate cancer, but also show higher mortality rates. A lack of GH and IGF-1 would lead to a number of adverse effects on body composition and muscle function, as well as the function of the heart and brain. This is evident when you supply GH to people who are shown to be clinically deficient in the hormone. When GH therapy is begun, these people show a gain in muscle mass and a loss of body fat, especially subcutaneous fat or fat just below the skin.

Some humans have a genetic disease called Laron syndrome that leads to dwarfism. They have a deletion of the gene that dictates GH production, and as such show low levels of both GH and IGF-1. Besides being very short, these people show premature wrinkled skin, along with increased insulin resistance and diabetes, yet they often live to 80 to 90 years old. Most interestingly, they appear nearly immune to cancer. One study of 222 Brazilian Laron dwarfs showed no signs of cancer, although 9 to 24% of their family members who were not dwarfs did get cancer. Even more interesting from a health point of view, the Laron dwarfs showed increased abdominal fat, elevated levels of LDL cholesterol, and elevated levels of C-reactive protein, an indicator of systemic inflammation. These are all risk factors for cardiovascular disease, yet the dwarfs showed no signs of heart problems, including atherosclerosis. As noted earlier, many people age 100 and over show mutations in the function of their IGF-1 cell receptors leading to cellular resistance to IGF-1. They are always short, but live a long time.

On the other hand, a study of some people in Ecuador showed GH cell receptor mutations, IGF-1 deficiency, and stunted growth. While they showed a lower incidence of diabetes and cancer, they showed no extended longevity. They had shorter than normal lifespans and many of them died before age 65. Another type of dwarf that shows a deletion of the GH gene leads to a GH deficiency that results in a shorter lifespan than family members without the gene defect.  Normal adults with an outright deficiency of GH also show shorter lifespans, contrary to what is seen in animal studies.

What is it about a lack of GH or IGF-1 that may increase human mortality? IGF-1 is absolutely required for the function and maintenance of neurons or brain cells. Without the presence of IGF-1 neurons undergo apoptosis and gradually die off. IGF-1 also promotes neurite growth, which involves the production of new neuron connections that can affect memory and intelligence, as well as take over from other neurons that have expired. IGF-1 in the brain also promotes increases blood circulation and prevents the accumulation of beta-amyloid, a protein associated with the onset of Alzheimer’s disease. IGF-1 works with insulin in the brain to promote the optimal use of glucose, the primary fuel of the brain. A lack of IGF-1 can induce memory deficits and play a role in the common minor memory problem known as “senior moments.” IGF-1 is produced locally in the brain, but is also able to cross the protective blood-brain barrier and thus readily enter the brain.

A lack of GH and IGF-1 leads to endothelial dysfunction, which involves negative changes in the lining of blood vessels that can lead to atherosclerosis and cardiovascular disease (CVD). A lack of GH/IGF-1 can reduce the flow of blood in the coronary arteries and lead to coronary artery disease.
The lack of GH and IGF-1 can also lead to congestive heart failure; heart attacks and strokes. The Laron dwarfs that lack GH activity show impaired function of the left ventricle, the pumping chamber of the heart, along with reduced cardiac output during exercise. If you provide them with supplemental IGF-1, these symptoms disappear. IGF-1 blocks atherosclerosis by lowering oxidation stress in blood vessels, which in turn starts the process that results in a narrowing of arteries or atherosclerosis.

Part 5

Following exercise, IGF-1 is heavily involved in the muscle repair and hypertrophy process. This is mainly from promoting the activity of satellite cells – muscle stem cells that play an integral role in muscle repair and growth. As noted earlier, GH also appears to protect and aid in the maintenance of connective tissue. For this reason, a lack of GH will show up in the skin as premature aging due to a breakdown of the supporting connective tissue in skin. Some bodybuilders consider IGF-1 to be the most anabolic hormone of all, although nearly all IGF-1 sold on Internet sites is fake.
Studies that involved providing IGF-1 as a form of gene therapy to mice showed dramatic increases in muscle mass in as little as two weeks. These mice underwent a type of resistance exercise program and after two months of gene therapy they could lift 30% more weight and doubled the amount of muscle mass compared to another group of mice who did the same program, but didn’t get the gene therapy. Just providing the gene therapy IGF-1 alone without any exercise still led to a 15% increase in muscular volume and strength. This will no doubt be a form of “sports anabolics” in the future.

One of the common side effects often mentioned in relation to GH usage is elevated blood glucose levels related to insulin insensitivity. This insulin insensitivity is considered the first stage of type-2 diabetes, and many researchers often warn that using GH continuously might lead to the development of diabetes. GH promotes the release of stored fat, mainly from the deep-lying abdominal fat known as visceral fat. This fat is considered the most dangerous type of fat because it’s constantly being released in the body. The fat then travels in the portal blood system in the gut to the liver, where the fat accumulates causing such problems as fatty liver, insulin insensitivity, diabetes, and cardiovascular disease. The subcutaneous fat stores, or the fat lying just below the skin, isn’t as affected by GH, which is bad news to bodybuilders who think that using GH will make their muscles appear more defined. The insulin resistance associated with GH is caused by the GH actions on promoting the release of free fatty acids stored in lipocytes or fat cells. This excessive amount of free fatty acids in the blood produced by GH interferes with glucose uptake into muscles, leading to insulin resistance. Many athletes and bodybuilders are aware of this common GH side effect and use insulin injections to counteract the elevated blood glucose levels that result from GH usage.

As noted earlier, if you lack sufficient GH and then start using supplemental GH, you will likely gain lean mass or muscle, especially if you also lift weights. This effect suggests that GH may be of use in treating sarcopenia, the loss of lean mass with age. However, while testosterone appears to work well in that regard, the problem with GH is that IGF-1 can promote cancer. Many physicians fear that long-term use of GH may induce cancer in older people who stay on it continuously. On the other hand, this has not happened thus far in men and women who’ve used smaller doses of GH for up to 20 years straight. Interestingly, bodybuilders often combine GH with testosterone and insulin. This combination is likely responsible for the massive physiques that have appeared in bodybuilding contests in recent years. While there is no scientific evidence to justify this athletic use of GH and testosterone, studies have been published that show combining GH with testosterone does lead to greater anabolic effects than either hormone alone. While this would appear to substantiate the athletic use of these hormones, the doses provided in the studies were far below that used by athletes, and the subjects involved were older men who were deficient in both GH and testosterone.

So, what can we make of all this? It appears that the fears of serious side effects linked to GH usage are more applicable to animals that are either provided with large doses of GH, or genetically manipulated to produce higher than normal amounts of GH. The negative effects of GH are apparent in humans who suffer from acromegaly, characterized by an excessive production of GH. Such people have a greater risk for both diabetes and cardiovascular disease, as well as colon cancer. They also don’t live very long. But to suggest that such effects would produce similar problems in those who use doses of GH small enough to treat a deficiency of the hormone is quite a bit of a stretch, with no real evidence thus far. We do know that a lack of GH and IGF-1 leads to serious problems in the brain, heart, muscles, and connective tissue. In short, without these hormones the body gradually falls apart. GH therapy may indeed forestall these problems in those who are deficient in GH and get on a GH replacement regime. The 1990 New England Journal study started the concept that GH will make you “younger.” That, however, is a bit of a false hope. Those who get on GH with the idea that it will revert them back to the way they looked 30 to 40 years earlier will be disappointed. But GH therapy will reverse some of the effects linked to both aging and a lack of GH, such as muscle mass loss, skin aging changes, and mental function. According to the critics of GH replacement therapy, people should just accept the aging process as it is. As such, those who do have a deficiency of GH and IGF-1 but don’t treat it can expect to eventually suffer from cardiovascular disease, dementia, weak connective tissue leading to constant injuries, and other maladies. In short, a very poor quality of life and a likely shorter life span.

What about those older people who make it to 100 and over, yet show relative resistance to the effects of GH and IGF-1? Note that they have a selective resistance to these hormones. What this means is that the hormones don’t function in some parts of their bodies, but does function in others, including the cardiovascular system and brain. This is not the same as having a total deficiency of GH and IGF-1, which most studies suggest will curtail the lifespan. But let’s assume that GH therapy does accelerate aging. You may die sooner, but you will die with your brain, body, and mind intact. Would you rather live longer with a bad heart, dementia, and being so weak that you cannot take care of yourself? My feelings are that the small doses of GH provided in GH replacement therapy will not promote the cancer process, which is the greatest fear of long-term GH usage. On the other hand, the same cannot be said for the massive doses typically used by many athletes and bodybuilders. They are in no man’s land from a medical point of view. Thus far, the most common side effect seen with larger doses of GH is Carpel Tunnel Syndrome, an impingement of nerves in the wrist caused by a GH-induced thickening of the connective tissue sheath that surrounds those nerves. In most cases, this requires surgery for correction. Several well-known bodybuilders have had this surgery. GH can also cause water retention and should not be used right up to the day of a contest, although many bodybuilders deal with this problem by using potent diuretic drugs to promote excess water excretion. It’s a balance act that might as well backfire.
The other common side effect of GH may or may not be an extended, bloated abdomen. This appearance was rarely seen in bodybuilders before GH use became common in the early 90s. While the gut area is rich in IGF-1 receptors and as such is subject to growth, there is as yet no definitive proof that the “bodybuilding bloat” appearance is caused by GH. It may be caused by a combination of GH and insulin – and simply by overfeeding, although again, no one had yet proved this. Another liable explanation is gut inflammation and poor digestive health, resulting in water retention around the abdominal wall.


To summarize, based on the existing research, GH replacement therapy may be a good option for those who are clinically deficient in GH or IGF-1. But using GH as a means of extending youth is not rational. The reasons for this include the high cost of GH therapy, which can be thousands of dollars per month. Once you start GH therapy, you need to stay on it for a long time for any changes induced by the hormone to remain. What is often overlooked about the famous 1990 study that started the GH therapy revolution is that when the men in the study got off GH, all the improvements they showed while on GH reverted back to the way it was before they used the hormone. If you are deficient in GH, using it will make you look and feel much better, but won’t make you look younger, despite what the anti-aging clinics lead people to believe. If you exercise, the combination of GH and exercise will help you lose fat and that may make a difference in how you look. But if you aren’t lacking the hormone, using it will have little or no effect on body composition.

In the final analysis, whether to use GH is a personal choice. It may not accelerate aging as it does in animals exposed to large doses, but whether it will provide a life extension effect to those not deficient in the hormone also seems unlikely. As of now, the only true way to maximize lifespan is through optimal nutrition that involves obtaining all essential nutrients from animal-based foods or animal-based supplements as needed.
Just the other day a new study showed that aerobic exercise slows the aging the heart. It does this by slowing down the loss of telomeres, those ends of chromosomes that determine how fast a cell age. Another new study found that exercise, particularly high intensity interval training, can improve mitochondrial density by 69% in those over 40. When you consider that a major cause of the loss of muscle mass with aging is the loss of functional mitochondria, the adage that exercise is the true fountain of youth becomes even more relevant.

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