by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
It’s common knowledge that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are some of the agents used by bodybuilders and athletes. These agents are banned from being used by athletes in most international sport federations, including the International Olympic Committee (IOC). Since about 1990, the use of these agents has increased tremendously because of their potential use in anti-aging therapies. Reports of gains in lean body mass and strength with concurrent loses in fat mass have created even more interest in the general public. Supplement companies, sensing the public demand for GH and IGF-1, have released all kinds of supplements that allegedly elevate these anabolic hormones. Unfortunately in most cases the claims are made while drawing the reader’s attention to studies on GH instead of research that involves the GH releasing products directly. In most cases supplements that are alleged to elevate GH and IGF-1 do not hold up to scientific scrutiny.
Growth Hormone and Insulin-Like Growth Factor-1
Human growth hormone (hGH) is a protein hormone secreted into the blood by the anterior pituitary gland. It is the major hormone responsible for growth in humans after birth. It acts on a variety of tissues including bone, cartilage and muscle. While most people know of its anabolic actions, many don’t know that it is also involved in carbohydrate and lipid metabolism through interactions with other hormones [1]. Primarily two hormones produced in the hypothalamus modulate the secretion of GH: Somatostatin, and growth hormone releasing hormone (GHRH). GH, in turn, stimulates the liver to produce IGF-1. This is referred to as the GH/IGF-1 Axis. The diagram below illustrates this process. What is not evident from the diagram is that GH and IGF-1 exert a negative feedback on their own future production. This means that as GH and/or IGF-1 levels increase, GHRH levels will decrease, resulting in less GH/IGF-1 being produced. This makes it very important to accurately measure GH/IGF-1 levels and use the appropriate diagnosing criteria to determine if GH/IGF-1 therapy is appropriate. Giving exogenous GH or IGF-1 to people with normal levels of these hormones will result in decreased endogenous production of these hormones.
A number of factors can stimulate GH, including exercise, deep sleep, hypoglycemia, fasting, a high protein meal, and the infusion of amino acids. Growth hormone was originally used in the treatment of growth hormone- deficient children. It was prepared by extraction from cadaver pituitaries and/or rhesus monkeys. High demand placed the agent in extremely short supply, so pharmaceutical companies searched out alternative methods of producing GH. Growth hormone is now produced by recombinant DNA techniques and referred to as recombinant human growth hormone (rhGH).
IGF-1 is a protein hormone produced by the liver in response to GH. Once produced it travels in the blood and can exert anabolic actions on a variety of tissues. It is also produced by various cells in the body and acts locally. At the local level, IGF-1 secreted by muscle cells (or other cells) can act on adjacent cells or on the cell secreting the IGF-1. It can stimulate protein synthesis resulting in an increase in cell size and/or cell number. Like GH, it can also be produced by recombinant techniques.
GH and IGF-1 Therapies
In 1990, a now classic study was published in the New England Journal of Medicine [2]. Realizing that GH and IGF-1 levels decline with age, the investigators hypothesized that rhGH therapy would increase IGF-1 levels, increase lean body mass, and decrease fat mass. To test this hypothesis, they studied 21 healthy men from 61 to 81 years old who had plasma IGF-I levels of less than 350 U (units) per liter during a six-month base-line period and a six-month treatment period that followed. During the treatment period, 12 men (Group 1) received approximately 0.03 mg of recombinant human growth hormone per kilogram of body weight (0.03 mg/kg rhGH) subcutaneously, three times each week, and 9 men (Group 2) received no treatment. Plasma IGF-I levels were measured monthly. At the end of each period, lean body mass, fat mass, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites were measured. In Group 1, the mean plasma IGF-I levels increased into the range of 500 to 1500 U per liter during treatment. In contrast, Group 2 remained below 350 U per liter. Human growth hormone administration for six months in Group 1 was accompanied by an 8.8% increase in lean body mass, a 14.4% decrease in fat mass, and a 1.6% increase in average lumbar vertebral bone density. Skin thickness increased 7.1%, but was just below the level of statistical significance. There was no significant change in the bone density of the radius or proximal femur. In Group 2, there was no significant change in lean body mass, fat mass, skin thickness, or bone density during treatment. This study supported the hypothesis that a diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the increase in fat mass, and the thinning of the skin that occurs in old age [2].
Prior to the Rudman study, it was also known that IGF-1 levels and/or IGF binding proteins are lower in obese people [3, 4]. IGF binding proteins bind to IGF-1 and act to control IGF-1 activity in the body. It seems that in addition to increasing IGF-1, GH may also decrease IGF binding proteins [5]. There is only a limited amount of information on IGF-1 therapy, but research indicates that IGF-1 exerts anabolic actions by increasing nitrogen retention [6].
Other Options To Elevate GH and IGF-1
Since GH and IGF-1 levels are decreased with aging, obesity, and various clinical conditions, such as HIV/AIDs, it would seem logical to try treatment with GH and/or IGF-1. However, these are downstream hormones, in that they are stimulated at the lower end of the GH/IGF-1 Axis. It is often speculated that treatment with upstream hormones in any given endocrine axis would provide less side effects. Applying this notion to the GH/IGF-1 Axis calls for the use of GHRH instead of GH or IGF-1. The logic being that if GH declines with aging or some clinical condition, might this be due to lower GHRH levels? Recent evidence indicates that there is a decline in the hypothalamic release of GHRH with aging [7]. In one study, non-obese men greater than 60 years of age were injected randomly with 0.5 mg or 1.0 mg of GHRH twice each day for 14 days [8]. The short-term treatment restored GH and IGF-1 levels to that of healthy young non-obese men with an average age of 26 years. This short-term study suggests that prolonged treatment could improve age-related alterations in body composition [8]. From these results one would expect that treatment protocols would use GHRH all the time. One reason why GHRH is not always used in treatment protocols is that some people do not respond to GHRH. This blunted response may be due to elevated insulin levels [9]. This can be circumvented by growth hormone-releasing peptide 6 (GHRP6) or hexarelin [10, 11]. Long-term studies on the effects of GHRH, GHRP-6, and hexarelin on body composition during aging and various clinical states are still needed to determine the safety and efficacy of these treatment approaches.
Exercise and the GH/IGF-1 Axis
Both resistance exercise and aerobic exercise can stimulate GH release in men and women. However, exercise induced GH release appears to decline with aging [12]. Older men and women can still improve their body composition by any type of exercise and improve their strength by resistance exercise, although their progress may be slower than younger individuals. Since both GH therapy and exercise result in favorable body composition alterations, perhaps a combination of GH and exercise may increase the benefits of exercise. Using athletic adult males, GH treatment (0.15 IU/kg x day) for 1 week increased serum GH and IGF-I levels over the same exercise protocol without GH treatment [13]. After GH withdrawal, the same exercise protocol resulted in a lower GH response. This study used younger men and may not apply to older men. One area of concern, though, is that the GH treatment protocol was only one week and that after discontinuing GH treatment, the exercise induced GH responses were blunted. This certainly does not make GH a viable option for normal healthy men with normal GH release patterns and levels.
One critique of GH therapy is that the gains in lean body mass rarely result in increased force production, indicating that it is doubtful that the increase is localized to skeletal muscle contractile proteins. When GH therapy was combined with resistance exercise using GH dosages ranging from 0.0125 mg/kg rhGH per day to 0.04 mg/kg rhGH per day, muscle strength was not any greater than placebo treated subjects [14-18]. Short-term GH treatments have resulted in elevated insulin levels, indicating that GH may decrease insulin sensitivity [19-21]. The long-term effects of GH therapy in adults with GH deficiency did not result in insulin resistance [22]. This indicates that there are differences in responses to exogenous GH or that chronic adaptations occur with long-term administration.
Anti-Aging Protocols
More and more physicians are now jumping on the longevity bandwagon. It provides a nice source of income for them (especially if they sell the GH) and allows them to work with higher functioning patients in an outpatient setting. This is still a relatively young area of medicine and unfortunately there are lots of inexperienced physicians practicing in this area. If you are searching for a longevity physician, find out how long the doc has been practicing and ask for references. Standardized guidelines for determining proper function of the GH/IGF-1 Axis should be followed, and hormone levels should be obtained prior to initiation of GH therapy. Ideally, GHRH levels should also be obtained. If GHRH is low, ask your physician to try GHRH, GHRP-6, and/or hexarelin first. These agents will stimulate endogenous GH and IGF-1 levels in some people, but not all. If these agents don’t work after 2-3 months of treatment, your physician should be able to determine their ineffectiveness and then will most likely proceed to using GH. Lift weights and follow a healthy diet, which includes 5 or more servings of fruits and vegetables each day. Follow-up visits should include assessment of body composition, blood glucose levels, and insulin levels to verify that insulin sensitivity is not declining.
alpha-Glycerylphosphorylcholine (Alpha-GPC)
Alpha-GPC is used in the treatment of amnesia and cognitive disorders. A 1000-milligram (mg) injection of Alpha-GPC elevated plasma choline levels for 15-30 minutes [23]. The plasma levels of choline remained elevated for up to 6 hours. From experiments on rats, researchers have shown that Alpha-GPC increases acetylcholine levels in the brain. An increase in this neurotransmitter serves to inhibit somatostatin. Somatostatin lowers GH levels. By decreasing somatostatin, Alpha-GPC could indirectly elevate GH. Another interesting property of Alpha-GPC is that it serves as a precursor for the synthesis of phosphatidylcholine. This has been speculated to lead to changes in the cell membranes of anterior pituitary cells that enhance the stimulatory effect of growth hormone releasing hormone (GHRH) on GH release.
In 1992, the effects of Alpha-GPC on younger and older subjects were studied [24]. Alpha-glycerylphosphorylcholine stimulated GH in both groups. GHRH also increased GH levels in both groups. However, when Alpha-GPC and GHRH were combined, the resulting increase in GH levels was even greater than either agent alone. Given this evidence, Alpha-GPC looks like a viable supplement to try. There are a few problem areas, though. The first is that the 1000 mg of Alpha-GPC was injected. By itself, Alpha-GPC did not increase GH levels very much. While injectable Alpha-GPC enhanced the effect of GHRH on stimulating GH, there are no published studies on oral Alpha-GPC and GH release. However, unpublished work on my own lab indicates that oral Alpha-GPC will not stimulate GH release unless taken prior to exercise or in conjunction with other supplements. This work will be published in the future.
Arginine
Arginine is popular as a GH releaser, primarily based off infusion studies. It is true that infusing up to 30 g of arginine into people will elevate GH. However, most of us are not going to walk around with i.v. drip bags all day long. If we look at some studies on oral arginine supplementation, we find that some show no effects on GH or IGF-1 levels [25-27], while others show an increase in GH and/or IGF-1 levels [26, 28-30]. There are many reasons why there are discrepancies in the results from the various research groups. These reasons include differences in dosages, delivery methods (ie capsules vs liquid drink), type of arginine (ie arginine hydrochloride vs. arginine aspartate), the subjects, (ie age or training status), and calorie intakes of the subjects. Most studies also used very small numbers of subjects, making it difficult to detect effects.
Regardless of all these study differences, if they could be organized into some type of order, the scientific literature might make more sense. In one study, weight-trained men ingested .1 grams (100 milligrams) of arginine hydrochloride per kilogram of body weight (g Arg/kg BW). No effect was found on changes in body composition or GH levels [27]. Since these 20-22 year old guys weighed around 80 kg, they were taking 8 g of Arg per day. They also followed a weight loss diet that consisted of ingesting liquid meals for the 10-day period.
In contrast, another study found that 250 mg/kg BW of arginine aspartate for one week increased peak GH levels at nighttime [28]. These were also young men ranging from 20-35 years of age. Arginine aspartate did not affect daytime GH levels, but it did increase prolactin levels slightly. Body weights were not given for these subjects, but if we assume an average weight of 70 kg (the reference male weight in research), then they were taking in about 17-18 g per day, in three divided doses. In another study using male runners, 15 g arginine-L-aspartate increased GH levels [29]. The dose was divided in half and one part was taken in the morning on an empty stomach and the other part was taken 1 hour before bed.
Since most people looking to boost GH and/or IGF-1 levels are older, it would make sense to see if there is an effect on GH/IGF-1 release for these subjects. Research using 30 elderly people, administered 17 g of free arginine (from arginine aspartate) and found that IGF-1 and nitrogen balance increased significantly over 15 people taking a placebo [30].
From the simple review above on arginine ingestion by itself, we can see that it appears dosages higher than 8 g of arginine per day and/or arginine aspartate may be the better choice than arginine hydrochloride. Recently, it was found that there are three types of GH responders to arginine [26]. The three types of responders were categorized as non-responders, low responders, and high responders. The researchers reported that GH responses were not related to dose, order of dose, age, body weight, or percent fat. However, there were only 8 subjects in the study, making detection of trends very difficult. If this classification of responders holds true with larger subject numbers, then people should be able to ingest some arginine and take GH measurements before ingestion and at 30, 60 and 90 minutes after ingestion. If GH levels increase significantly, then there is some justification for continuing to take the supplement.
GABA/GHB/GBL
Gamma aminobutyric acid (GABA) is a neurotransmitter within the central nervous system. GABA is known to stimulate the release of a variety of hormones within the brain. Gamma hydroxybutyrolactone (GBL) and gamma hydroxybutyric acid (GHB) are precursors to GABA. The body can convert GBL into GHB. GHB in turn can be converted into GABA.
A 5 g oral dose of GABA can increase GH levels in people [31, 32]. It can also stimulate prolactin [31], which is not what most men would want. Several studies have shown that GHB stimulates GH [33-40]. Despite all the evidence that both GABA and GHB can stimulate GH release, no studies have ever shown an increase in lean body mass or a decrease in fat mass due to GABA, GHB, or GBL. In fact, long-term administration of GHB did not affect muscular mass in alcoholics [41]. Of course, it is possible that years of alcohol abuse would have prevented an effect of GHB on increasing lean body mass.
Since no long-term studies have shown any effects of GABA, GHB, or GBL, and there are case reports of death, coma, shock, seizures, and other adverse health effects, it is probably wise to avoid these agents. Many of the case reports involved the mixing of GHB or GBL with other drugs, which may have contributed to the problems. However, animal data indicates that there may be some potential for these agents to cause seizures by themselves. It’s probably a smart idea not to take them until more is known.
Glutamine
Glutamine is one of those supplements that people take for a variety of different reasons. Since this article focuses on GH and IGF-1 release, I will limit my discussion of glutamine to this area. In one study, 9 subjects ingested 2 g of glutamine orally [42]. GH levels on average increased 4.3 times. That is a big increase. You might be tempted to use larger dosages, however, this may prompt the liver to remove more glutamine and less will be around to stimulate GH release. One overweight subject did not have an increase in GH, so while most people may get a nice increase in GH, some may not. If the data from this study holds true, then overweight and obese people may not get much GH stimulation from glutamine.
Since this study only examined the effects of 2 g of glutamine on 9 subjects, there are many questions that remain to be answered. The first is what impact will these GH elevations have on body composition and performance? It would certainly seem like there is potential for these high GH levels to decrease body fat. One concern many people will have is the issue of relative vs. absolute dosage. In other words, we know that many drugs are prescribed on the basis of body weight, and if that is the case for glutamine, then people may want to ingest 27 mg per kilogram of body weight. That is the average glutamine dose used and may be the best value we have right now. For a 100-kilogram person (220 pounds), this would mean a glutamine dose of 2700 mg or 2.7 g. The glutamine in this study was given 45 minutes after a light meal of toast, coffee, and orange juice. It was mixed into soda that contained 20 g of dextrose, a sugar. One interpretation of this paper is that glutamine may have some value as a GH enhancer. While I certainly agree that more research needs to be done to see if these GH levels translate into physical improvements, there is no harm in trying glutamine now. You may want to experiment with one dose first thing in the morning, another dose before training, and another at night before bed. Each dose should be about 2 grams or 27 mg per kg of BW.
Lysine
Various studies have shown that injections or infusions of the amino acid lysine can increase growth hormone levels. However, research on the effects of lysine administered orally is lacking. Only one study could be found that actually studied the effects of oral lysine by itself without being administered with other amino acids [43]. Twelve hundred mg of lysine hydrochloride elevated GH over 3 times baseline. However, the researchers only used 8 subjects and did not describe their statistical techniques. The data is simply listed as the mean (average) plus or minus the standard deviation. Interpretation of this information is difficult and by itself does not support the use of lysine as a GH stimulator.
Ornithine
Ornithine is an amino acid that can be synthesized in the body from the amino acids arginine or citrulline. It was popular as a dietary supplement because of claims that it could stimulate GH and/or insulin. Ornithine is often taken as a salt consisting of two molecules of ornithine and one molecule of alpha-ketoglutarate. This supplement is known as ornithine alpha-ketoglutarate (OKG). OKG has been successfully used in clinical settings to treat burn, trauma, malnourished, and surgical patients. In most cases, OKG was infused directly into the blood or into the GI tract. These same studies showed that OKG treatment decreased muscle protein catabolism, promoted wound healing, and/or increased muscle protein synthesis. One possible mechanism is that OKG increased GH levels in these patients [44]. Since data from clinical patients does not apply directly to healthy populations and infusions can have far different effects than oral supplementations, the obvious question is just what happens to healthier people orally ingesting ornithine? It seems that when ornithine is taken along with alpha ketoglutarate, the effects are different than when either component is taken by itself [45]. Only one study could be found that studied the effect of oral ornithine on GH separately from alpha keto glutarate [46]. There was no effect on GH levels.
Tryptophan and 5-Hydroxytryptophan
Remember tryptophan? Years ago it was pretty popular as a sleep aid. Then a contaminated batch came into the US and people developed eosinophilia-myalgia syndrome, a potentially fatal disorder and free-form tryptophan was pulled off the market in the US. Unlike most other amino acids though, tryptophan has been shown to elevate GH levels in healthy subjects [47] and neurologic patients [48]. In normal patients, a 10 g dose of tryptophan increased GH levels and glucose, insulin, and glucagon [49]. In neurologic patients without neuroendocrine disorders, tryptophan lowered luteinizing hormone (LH) slightly (the hormone which stimulates the production of testosterone in men or estradiol in women). Despite the decreased LH levels, no changes were noted in sexual motivation. Tryptophan also lowered cortisol levels, although the response was quite variable. Since tryptophan sales are prohibited in many countries, companies have since started selling a similar compound, 5-hyroxytryptophan (5-HTP). GH release research on the effects of oral doses of 5-HTP is lacking. Most studies are intravenous studies and indicate that 5-HTP can increase GH, as well as cortisol and prolactin. Taking 5-HTP for GH does not appear to be a prudent decision at this time.
Combinations of Amino Acids
Often times when one or more supplements can exert a physiological effect, supplement companies will combine them in an attempt to maximize these same effects. While synergism among different amino acids is possible in the case of GH release, there are many different biochemical pathways that amino acids can travel, so synergism is not guaranteed. Fortunately, there have been several studies on combinations of various amino acids. One of the first studies compared the effects of 1200 mg arginine-2-pyrrolidone-5-carboxylate plus 1200 mg lysine hydrochloride vs. each separately versus 2400 mg of arginine-2-pyrrolidone-5-carboxylate to stimulate GH release [55]. Fifteen male volunteers were used to compare the effects of oral ingestion of these amino acids. The results indicated 1200 mg arginine-2-pyrrolidone-5-carboxylate plus 1200 mg lysine hydrochloride was better than either amino acid separately or 2400 mg of arginine-2-pyrrolidone-5-carboxylate at stimulating GH [43]. This study failed to report the statistical methods used, so the value of the results is debatable. One point to consider is that they used a unique form of arginine, and not L-arginine (the free form version of the amino acid).
So far, very few studies reviewed in this article addressed the effects of amino acids on GH levels in healthy, physically active people. Research in this area however, reports fairly consistent findings. One study tested the effects of three commercially available oral GH releasing products [49]. Product A contained 2.4 g of L-arginine and L-lysine. Product B contained 1.1 g of L-ornithine, 750 mg of tyrosine, 750 mg of pyridoxine hydrochloride (Vitamin B6), and 125 mg of ascorbic acid (Vitamin C). Product C was 20 g of Bovril that contained 7.8 g of protein (438 mg arginine, 412 mg lysine, 362 mg leucine, 312 mg valine, 238 mg phenylalanine, 200 mg isoleucine) and 580 mg of carbohydrate. The results indicated that each supplement had a varied effect on the subjects. None of the supplements worked as well as GHRH, which was also used for comparison purposes and as evidence that each subject had a functional pituitary (relative to GH release). In competitive weightlifters, 1 g each of L-arginine, L-ornithine, and L-lysine taken once after lunch and again after dinner, did not affect GH levels [50]. In another study, 1,500 mg of L-arginine and 1,500 L-lysine stimulated an increase in GH release at rest. In these 16 weight-trained men, the same mixture did not further increase the elevations in GH due to exercise [51]. Other low dose studies using branched chain amino acids also found no effect on GH release [52, 53]. In contrast, 20 g of glutamate/arginine salts increased GH and lowered cortisol in highly trained cyclists [54]. Overall, the data points to variable effects of amino acid mixtures for raising GH levels in physically active people. Like with some of the individual amino acids, the trend appears to be that fairly high doses are needed to have an effect.
Athletes are not the only groups that researchers have studied using amino acid mixtures. Older men ingested 3 g of L-arginine plus 3 g of L-lysine or placebo capsules twice daily for 14 days [46]. The arginine/lysine combination did not significantly alter spontaneous or GHRH-stimulated GH levels, or serum IGF-I. This study suggests that oral arginine/lysine supplementation is not a practical method of increasing GH/IGF-1 levels in healthy older men.
Ascorbic acid - Vitamin C
Most people take vitamin C because it is a great antioxidant and required by our bodies. It is necessary for wounds to heal, teeth to form, maintenance capillaries, and is involved in the production of various enzymes and adrenal hormones. It may seem surprising that vitamin C has been touted to elevate GH/IGF-1. There is no direct evidence that this occurs in humans. In studies using cultured cells, vitamin C has been shown to act as a cofactor to suppress prolactin levels and elevate dopamine levels [55, 56]. Since dopamine can serve as an agent to stimulate GH release, some companies may have figured that adding some extra vitamin C to their mix will help. There doesn’t appear to be any negatives to having some vitamin C in the mix, it just seem that there is no support for it at this time. This means dosages, timing, and delivery are at best, a guess.
Choline
Choline is a commonly found nutrient in a variety of foods. It is required by the body to make phospholipids. Years ago it was shown that a choline deficiency leads to the formation of fat deposits in the liver. The term lipotropic was then coined to describe choline and other substances that prevented fat deposition in the liver. Unfortunately, supplement companies convinced the general public that lipotropic meant agents would accelerate fat loss. This is hardly the case.
Recently some companies have made claims that choline supplementation would increase acetylcholine production leading to elevated GH levels. Most research to date has focused on the use of choline supplementation in memory enhancement for various disease states. No research thus far has indicated that choline will increase GH levels in humans. Research using rats indicate that choline does increase acetylcholine levels and that this leads to increased prolactin levels [57]. Would this apply to humans, and more importantly, what were the effects on GH? Since GH was not measured, we don’t know if there were any effects on GH. However, in a study using real people, 14 grams (in four divided doses) of choline was given to see if it had any effects on acetylcholine levels. The results indicated that the effects of increased dietary choline were transient and had little impact [58]. So the bottom line is that choline is a useful supplement for normal healthy people.
Colostrum
The colostrum sold as a nutritional supplement is derived from cows’ milk. It contains predominantly casein and whey protein. The whey protein includes immunoglobulins IgG, IgA, and IgM, growth factors (IGF-1), lactoferrin, lysozyme, lactoperoxidase, serum albumin, alpha-lactalbumin and beta-lactoglobulin. The detection of IGF-1 and other growth factors led some to speculate that these agents may cross the GI barrier intact [59, 60]. In one study, colostrum was reported to increase IGF-1 levels in track athletes [61]. There were several flaws with this study and the increase in IGF-1 may have been due to other factors in the colostrum besides the IGF-1. Since IGF-1 is considered a banned drug in international sports, Professor Peter Sonksen, studying human growth hormone on behalf of the International Olympic Committee (IOC), indicated that IGF-1 is broken down and inactivated when ingested orally [62]. There is, therefore, no mechanism by which ingested IGF-1 could act on the body as a growth factor. This is consistent with abstracts that have been presented at various international conferences indicating that colostrum can increase performance, yet serum IGF-1 levels did not differ between colostrum and placebo groups [63, 64]. Despite the research in this area, the IOC has banned colostrum by virtue of the fact that it contains a prohibited substance (ie IGF-1).
Outside of Olympic competition, people in every day life don’t care if agents are banned or not. They simply want to know if they work. Colostrum is slowly building up evidence that it can increase lean body mass in athletes. The only disadvantage with colostrum so far is that the doses are about 60 grams per day. This may be cost prohibitive. There are a limited number of long-term research studies that have been published on colostrum use as a dietary supplement. Authorities in this area point to the fact that people have been drinking milk for years and use that as an indication of the safety of colostrum. This is not direct evidence, but combined with the additional observation that Australian and Italian athletes (specifically cyclists and track and field athletes) have been consuming colostrum in fairly high dosages for years, it would appear to be a safe product.
Homeopathic Growth Hormone
Homeopathic GH formulas are dilutions of growth hormone. There are at least two patents in this area [65, 66] and one scientific paper has been published on the effects of homeopathic GH [67]. One patent indicates that, “Homeopathic dilutions of growth factors are preferably administered orally.“ Since GH is a protein hormone, the investigators have to demonstrate that GH can cross the GI barrier intact. So far there is no research that shows this can happen. If we assume it does, then the next question is how can these companies sell GH over the counter when it is a prescription drug? The same people holding the patents on the homeopathic formula wrote the paper on homeopathic GH. The paper is actually a series of three studies. It utilized methods such as BIA for body composition when far better options are available for determining body composition in terms of accuracy and reliability. As might be expected, the study showed incredible improvements in the groups receiving the supplement. Despite a research publication showing that a homeopathic formula can work, anecdotal reports have claimed absolutely no effect. This is supported by research, which claims a clear dose response relationship between the amount of GH administered and the resulting effects on IGF-1 levels and metabolism [68]. The point here is that if more GH results in greater effects, how can homeopathic formulas offer any solution when they offer amounts so low as to be undetectable? Until more research comes along to validate this type of product, save your money.
Hypothalamic Extracts
In the early years of bodybuilding, glandular extracts were very popular. Vince Gironda and other big name trainers of the time would recommend that their clients take handfuls of glandular pills. At first, scientists thought this stuff couldn’t possibly work. They rationalized that the GI tract would destroy any bioactive ingredients. Years later, we know that some agents do survive digestion. We still don’t know if glandular extracts given orally stimulate GH, however. Some older studies indicate that injections of hypothalamic extracts given to rats do in fact stimulate GH release [69-72]. There are several products on the market right now that contain hypothalamic extracts. If these agents were administered orally and in a delivery method that would prevent destruction of the bioactive agents by the GI tract, then perhaps they would stimulate GH release in humans. We certainly need research to find out not only if this is true, but also what other hormones are stimulated by these extracts and how safe this is for chronic consumption. My lab is currently testing several products in this area.
Levodopa
L-dopa is a precursor to dopamine and norepinephrine. It has a strong ability to increase GH release in normal and diabetic people. 500 mg of L-dopa elevated GH levels up to 5 times baseline [73]. This study compared different stimuli on their ability to induce GH release. It was found that peak levels of GH were much higher after exercise than L-dopa. L-dopa, however, stimulated an increase in GH that was longer lasting. One could speculate that ingestion of L-dopa would elevate GH levels and lead to an increase of lean body mass and fat loss with time. In a long-term study using post-menopausal women with Parkinson’s disease, chronic ingestion of L-dopa did not increase bone mass or GH levels [74]. It is possible that the disease prevented any benefits of L-dopa due to a decreased responsiveness of the anterior pituitary. Other studies have indicated that long-term use of L-dopa may induce side effects in mice and rats. Overall, while L-dopa may have application as a short term GH booster, its use as a long-term agent appears disappointing.
Miscellaneous Agents
There are lots of agents that have been touted to increase GH levels with absolutely no proof this can occur in cells, animals, or people. Rather than discuss each supplement individually, I thought it would make more sense to say these agents have no evidence and then list them. Chromium polynicotinate, gingko biloba, inosine, kelp, licorice, Macuna pruriens, monosodium glutamate (MSG), Muira puama, naringenin, niacin, selenium, Shilajit, and Tribulus terrestris have all been touted as increasing GH levels with absolutely no direct evidence. What’s funny is that some of these agents may actually suppress GH release. Take for example, inosine. It stimulates insulin release and inhibits the breakdown of fat – definitely not things a hard training bodybuilder would want, nor is it a good ingredient for a GH releasing supplement. Licorice can lower testosterone levels in rats [75] and humans [76]. This is a bad choice for GH stimulation since it may decrease another major anabolic hormone. Muira puama contains L-dopa, and since L-dopa can increase GH levels, this has led some to speculate that it would as well. This certainly is within the realm of possibility, but we need to know how much L-dopa is in the product before we can determine what it will do.
Peptide GH-Releasing Factors
A number of peptides exist that can increase GH levels in humans. Many of these are being investigated for their possible use in combating GH deficiency in children and adults. These include GHRP-1, GHRP-2, GHRP-6, growth hormone releasing factor (GRF), and hexarelin. Orally ingested GHRP-1 stimulates GH release in a variety of animals as well as people [77]. It is a peptide five amino acids long and somehow survives digestion and crosses into the blood intact. Cell culture studies indicate that GHRP-1 inhibits thyroid hormone release [78]. This may make it less than ideal as a GH releasing agent. GHRP-2 is a potent GH stimulating agent, but also stimulates prolactin and cortisol [79]. It is known that most of the GH releasing peptides stimulate not only GH, but also prolactin and cortisol [79, 80]. While their clinical use appears warranted in cases of GH deficiency or disease, their use by healthy people may not be ideal since they elevate other hormones and may decrease thyroid release as well. Recent evidence also demonstrates that these agents can bind directly to various tissues of the body including heart, adrenal, ovary, testis, lung and skeletal muscle [80]. The significance of this is not clear at this point. These agents may exert favorable effects on some tissues and not so favorable effects on other tissues.
Sprays
There are tons of GH releasing sprays on the market. So far not a single company has published a scientific paper in a major peer-reviewed journal that proves their product can increase GH. Most products usually say <100 ng or <320 ng of GH or some other agent. This tells you nothing about how much the product actually contains, and in fact the product can contain zero ng and actually comply with the label claim. Claims have been made that the bioactive ingredients are “in a special polymer matrix, which allows it to be absorbed directly into the cells of the oral mucosa, avoiding inactivation in the digestive process.” Terms like “intra-oral delivery,” and charts for “comparing various delivery methods,” are often used. The flaw with these approaches is that the charts did not depict the delivery of GH, instead they depicted delivery of other molecules and we cannot assume that all molecules will have the same transport kinetics using the same delivery methods. Unpublished work done in my lab indicates that only one spray on the market actually raised GH levels in humans, however the increase was minimal. Until clear research is given showing a product works, hold off on the sprays.
St John’s Wort
Everyone seems to know that if you have mild forms of depression then taking St John’s Wort (SJW) may be helpful. What is not so well know is a recent study that shows that the herb can stimulate GH release [81]. The effects of a single dose of a methanolic extract of Hypericum perforatum (SJW) on plasma concentrations of GH, prolactin, and cortisol in 12 healthy male volunteers were reported. After STW ingestion, there was a significant increase in GH and a significant decrease in prolactin levels, while cortisol levels were unchanged. By combining these results with those of animal studies, it may be inferred that SJW may increase some aspects of brain dopamine function in humans [81]. We still don’t know much about when to take it and the long-term effects on the hypothalamus, but so far STW appears well tolerated.
A World of Potential
After looking at many studies on various agents that stimulate GH release, some clear points can be made to describe the ideal GH-releasing agent. First, it has to cross the GI tract intact or breakdown into bioactive components. The product needs to have a component that can stimulate GHRH, mildly increase acetylcholine levels, decrease somatostatin levels, and stimulate GH release. All this has to be done without increasing prolactin or cortisol or suppressing other important hormones like testosterone or thyroid hormones. So far, nothing on the market can accomplish this, but the near future looks very interesting.
References:
1. Adamson, U. and E. Cerasi, Acute effects of exogenous growth hormone in man: time- and dose-bound modification of glucose tolerance and glucose-induced insulin release. Acta Endocrinologica, 1975. 80(2): p. 247-261.
2. Rudman, D., et al., Effects of human growth hormone in men over 60 years old. New England Journal of Medicine, 1990. 323(1): p. 1-6.
3. Grzywa, M., Serum somatomedin activity and growth hormone level in obese men: dependence on degree of obesity and hyperlipidemia. Experimental & Clinical Endocrinology, 1986. 88(3): p. 325-333.
4. Tappy, L., C. Jan, and E. Temler, Plasma IGF-1 binding proteins in lean and obese non-diabetic subjects. International Journal of Obesity & Related Metabolic Disorders, 1993. 17(6): p. 355-357.
5. Norrelund, H., et al., Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP-1 levels. Experimental studies in normal, obese and GH-deficient adults. Growth Hormone & Igf Research, 1999. 9(1): p. 52-60.
6. Fouque, D., et al., Recombinant human insulin-like growth factor-1 induces an anabolic response in malnourished CAPD patients. Kidney International, 2000. 57(2): p. 646-654.
7. Russell-Aulet, M., et al., In vivo semiquantification of hypothalamic growth hormone-releasing hormone (GHRH) output in humans: evidence for relative GHRH deficiency in aging. Journal of Clinical Endocrinology & Metabolism, 1999. 84(10): p. 3490-3497.
8. Corpas, E., et al., Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Journal of Clinical Endocrinology & Metabolism, 1992. 75(2): p. 530-535.
9. Lanzi, R., et al., Elevated insulin levels contribute to the reduced growth hormone (GH) response to GH-releasing hormone in obese subjects. Metabolism: Clinical & Experimental, 1999. 48(9): p. 1152-6.
10. Micic, D., et al., Growth hormone (GH) response to GH-releasing peptide-6 and GH-releasing hormone in normal-weight and overweight patients with non-insulin-dependent diabetes mellitus. Metabolism: Clinical & Experimental, 1999. 48(4): p. 525-530.
11. Gasperi, M., et al., Low dose hexarelin and growth hormone (GH)-releasing hormone as a diagnostic tool for the diagnosis of GH deficiency in adults: comparison with insulin-induced hypoglycemia test. Journal of Clinical Endocrinology & Metabolism, 1999. 84(8): p. 2633-2737.
12. Hakkinen, K., et al., Acute hormone responses to heavy resistance lower and upper extremity exercise in young versus old men. European journal of applied physiology and occupational physiology, 1998. 77(4): p. 312-319.
13. Wallace, J.D., et al., Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: a potential test for GH abuse in sport. Journal of Clinical Endocrinology & Metabolism, 1999. 84(10): p. 3591-3601.
14. Zachwieja, J.J., et al., Resistance exercise and growth hormone administration in older men: effects on insulin sensitivity and secretion during a stable-label intravenous glucose tolerance test. Metabolism: Clinical & Experimental, 1996. 45(2): p. 254-260.
15. Yarasheski, K.E., J.A. Campbell, and W.M. Kohrt, Effect of resistance exercise and growth hormone on bone density in older men. Clinical Endocrinology, 1997. 47(2): p. 223-229.
16. Yarasheski, K.E., et al., Effect of growth hormone and resistance exercise on muscle growth and strength in older men. American Journal of Physiology, 1995. 268(2 Pt 1): p. E268-E276.
17. Yarasheski, K.E., et al., Effect of growth hormone and resistance exercise on muscle growth in young men. American Journal of Physiology, 1992. 262(3 Pt 1): p. E261-E267.
18. Taaffe, D.R., et al., Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. Journal of Clinical Endocrinology & Metabolism, 1994. 79(5): p. 1361-1366.
19. Moller, N., et al., Impact of 2 weeks high dose growth hormone treatment on basal and insulin stimulated substrate metabolism in humans. Clinical Endocrinology, 1993. 39(5): p. 577-581.
20. Fleming, R.Y., et al., Effect of recombinant human growth hormone on catabolic hormones and free fatty acids following thermal injury. Journal of Trauma-Injury Infection & Critical Care, 1992. 32(6): p. 698-702; discussion 702-3.
21. Zachwieja, J.J. and K.E. Yarasheski, Does growth hormone therapy in conjunction with resistance exercise increase muscle force production and muscle mass in men and women aged 60 years or older? Physical Therapy, 1999. 79(1): p. 76-82.
22. Johnston, D.G., et al., Long-term effects of growth hormone therapy on intermediary metabolism and insulin sensitivity in hypopituitary adults. Journal of Endocrinological Investigation, 1999. 22(5 Suppl): p. 37-40.
23. Gatti, G., et al., A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphoryl-choline and citicoline in normal volunteers. International Journal of Clinical Pharmacology, Therapy, & Toxicology, 1992. 30(9): p. 331-335.
24. Ceda, G., et al., alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Hormone & Metabolic Research, 1992. 24(3): p. 119-121.
25. Corpas, E., et al., Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men. Journal of Gerontology, 1993. 48(4): p. M128-M133.
26. Moore, T., et al., Growth hormone response to oral arginine supplementation. Medicine and Science in Sports and Exercise, 1998. 30(5): p. S18, Abstract 98.
27. Walberg-Rankin, J., The effect of oral arginine during energy restriction in male weight trainers. Journal of Strength and Conditioning Research, 1994. 8(3): p. 170-177.
28. Besset, A., et al., Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man. Acta Endocrinologica, 1982. 99(1): p. 18-23.
29. Colombani, P.C., et al., Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run. European Journal of Nutrition, 1999. 38(6): p. 263-270.
30. Hurson, M., et al., Metabolic effects of arginine in a healthy elderly population [published erratum appears in JPEN: Journal of Parenteral and Enteral Nutrition, 1995 Jul- Aug;19(4):329]. JPEN Journal of Parenteral and Enteral Nutrition, 1995. 19(3): p. 227-230.
31. Cavagnini, F., et al., Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone. Journal of Clinical Endocrinology & Metabolism, 1980. 51(4): p. 789-792.
32. Cavagnini, F., et al., Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. Acta Endocrinologica, 1980. 93(2): p. 149-154.
33. Gerra, G., et al., Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid. International Clinical Psychopharmacology, 1994. 9(3): p. 211-215.
34. Gerra, G., et al., Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid. International Clinical Psychopharmacology, 1995. 10(4): p. 245-250.
35. Takahara, J., et al., Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. Journal of Clinical Endocrinology & Metabolism, 1977. 44(5): p. 1014-1017.
36. Van Cauter, E., et al., Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men. Journal of Clinical Investigation, 1997. 100(3): p. 745-753.
37. Vescovi, P.P. and C. Di Gennaro, Failure of gammahydroxy butyric acid to stimulate growth hormone secretion in cocaine addicts. Neuropeptides, 1997. 31(5): p. 459-462.
38. Vescovi, P.P. and V. Coiro, Persistence of defective serotonergic and GABAergic controls of growth hormone secretion in long-term abstinent alcoholics. Alcohol & Alcoholism, 1997. 32(1): p. 85-90.
39. Volpi, R., et al., Different control mechanisms of growth hormone (GH) secretion between gamma-amino- and gamma-hydroxy-butyric acid: neuroendocrine evidence in Parkinson’s disease. Psychoneuroendocrinology, 1997. 22(7): p. 531-538.
40. Volpi, R., et al., Muscarinic cholinergic mediation of the GH response to gamma-hydroxybutyric acid: neuroendocrine evidence in normal and parkinsonian subjects. Psychoneuroendocrinology, 2000. 25(2): p. 179-185.
41. Addolorato, G., et al., Long-term administration of GHB does not affect muscular mass in alcoholics. Life Sciences, 1999. 65(14): p. L191-L196.
42. Welbourne, T.C., Increased plasma bicarbonate and growth hormone after an oral glutamine load. American Journal of Clinical Nutrition, 1995. 61(5): p. 1058-1061.
43. Isidori, A., A. Lo Monaco, and M. Cappa, A study of growth hormone release in man after oral administration of amino acids. Current Medical Research & Opinion, 1981. 7(7): p. 475-481.
44. Cynober, L., Ornithine alpha-ketoglutarate in nutritional support. Nutrition, 1991. 7(5): p. 313-322.
45. Cynober, L., et al., Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. J Am Coll Nutr, 1990. 9(1): p. 2-12.
46. Bucci, L., et al., Ornithine ingestion and growth hormone release in bodybuilders. Nutrition Research, 1990. 10: p. 239-245.
47. Hedo, J.A., M.L. Villanueva, and J. Marco, Elevation of plasma glucose and glucagon after tryptophan ingestion in man. Metabolism: Clinical & Experimental, 1977. 26(10): p. 1131-1144.
48. Hyyppa, M.T., et al., L-Tryptophan administration in man: effects on gonadotrophin, growth hormone and cortisol secretion and on sexual motivation. Monographs in Neural Sciences, 1976. 3: p. 102-108.
49. Lambert, M.I., et al., Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. International Journal of Sport Nutrition, 1993. 3(3): p. 298-305.
50. Fogelholm, G.M., et al., Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters. International Journal of Sport Nutrition, 1993. 3(3): p. 290-297.
51. Suminski, R.R., et al., Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. International Journal of Sport Nutrition, 1997. 7(1): p. 48-60.
52. Bigard, A.X., et al., Branched-chain amino acid supplementation during repeated prolonged skiing exercises at altitude. International Journal of Sport Nutrition, 1996. 6(3): p. 295-306.
53. Fry, A.C., et al., Endocrine and performance responses to high volume training and amino acid supplementation in elite junior weightlifters. International Journal of Sport Nutrition, 1993. 3(3): p. 306-322.
54. Eto, B., et al., Glutamate-arginine salts and hormonal responses to exercise. Archives of Physiology & Biochemistry, 1995. 103(2): p. 160-164.
55. Shin, S.H., et al., Dopamine requires ascorbic acid to be the prolactin release-inhibiting factor. American Journal of Physiology, 1997. 273(3 Pt 1): p. E593-8.
56. Shin, S.H. and R. Stirling, Ascorbic acid potentiates the inhibitory effect of dopamine on prolactin release in primary cultured rat pituitary cells. Journal of Endocrinology, 1988. 118(2): p. 287-94.
57. Gurun, M.S., et al., Centrally administered choline increases plasma prolactin levels in conscious rats. Neuroscience Letters, 1997. 232(2): p. 79-82.
58. Mohs, R.C. and K.L. Davis, Interaction of choline and scopolamine in human memory. Life Sciences, 1985. 37(2): p. 193-7.
59. Francis, G.L., et al., Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form. Biochem J, 1988. 251(1): p. 95-103.
60. Ginjala, V. and R. Pakkanen, Determination of transforming growth factor-beta 1 (TGF-beta 1) and insulin-like growth factor (IGF-1) in bovine colostrum samples. J Immunoassay, 1998. 19(2-3): p. 195-207.
61. Mero, A., et al., Effects of bovine colostrum supplementation on serum IGF-I, IgG, hormone, and saliva IgA during training. J Appl Physiol, 1997. 83(4): p. 1144-51.
62. Australian Sports Drug Agency, Drugs in Sport Update (Vol 2, Issue 3), 1998, ASDA Newsletters.
63. Buckley, J.D., et al. Oral supplementation with bovine colostrum (IntactÔ ) improves rowing performance in elite female rowers. in 5th IOC World Congress on Sport Sciences 1999. 1999. Sydney , Australia.
64. Buckley, J., et al. Effect of an oral bovine colostrum supplement (intact TM) on running performance - abstract. in Australian Conference of Science and Medicine in Sport,. 1998. Adelaide Convention Centre, Adelaide: Canberra, Sports Medicine Australia,.
65. Brewitt, B.A., Homeopathic dilutions of growth factors. 1997, Brewitt, B.: United States Patent.
66. Brewitt, B.A., Treatment methods using homeopathic preparations of growth factors. 2000, Brewitt, B.A.: United States Patent.
67. Brewitt, B., et al., Homeopathic human growth hormone for physiologic and psychologic health. Alternative and Complementary Therapies, 1999. 5(6): p. 373-385.
68. Tanaka, T., et al., Pharmacokinetics and metabolic effects of high-dose growth hormone administration in healthy adult men. Endocr J, 1999. 46(4): p. 605-12.
69. Ishida, Y., et al., In vivo depletion of pituitary growth hormone by hypothalamic extracts. Endocrinology, 1965. 77(4): p. 759-62.
70. Pecile, A., et al., Growth hormone-releasing activity of hypothalamic extracts at different ages. Endocrinology, 1965. 77(2): p. 241-6.
71. Stachura, M.E., A.P. Dhariwal, and L.A. Frohman, Inhibition and stimulation of rat growth hormone secretion in vitro by hypothalamic extracts. Endocrine Research Communications, 1974. 1(1): p. 35-51.
73. Sutton, J. and L. Lazarus, Growth hormone in exercise: comparison of physiological and pharmacological stimuli. Journal of Applied Physiology, 1976. 41(4): p. 523-7.
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