Do noninjectable forms of Human Growth Hormone work?
Lead articles in financial magazines like this tend to draw much attention. A
great deal has been written in the medical literature about injectable Human
Growth Hormone (i HGH) during the last several years. As a result of the lay
press reporting on these medical studies, people with limited disposable income
and those on the antiaging bandwagon are looking for noninjectable HGH (nHGH)
products that may give them the same effects as the conventional
injectable---with the advantage of no injection, nearly one-tenth the price and
no prescription needed.
HGH and Its Effects
HGH, comprised of 191 amino acids linked in a specific sequence, is secreted in
pulses from the anterior pituitary gland. These pulses range from nine to 29
pulses per 24 hours and can be strengthened by exercise and other variables.
Once secreted by the pituitary gland, circulating levels of HGH stimulate
production of insulinlike Growth factor-1 (IGF-1) from the liver. Most of the
positive effects of HGH are mediated by the IGF-1 system, which also includes
specific binding proteins. This is a highly regulated system, and several
factors play a role in the pulsatile HGH secretion.
Injectable HGH is currently produced by recombinant DNA biotechnology methods.
Only a handful of pharmaceutical companies worldwide are capable of producing
injectable HGH. Studies show a host of beneficial effects using iHGH. The
positive effects have been reported on body composition (lean body mass, fat
mass, fluid volume), bone mineral density, muscle strength, exercise
performance, cardiovascular health, metabolism (energy expenditure as well as
protein, carbohydrate and lipid metabolism), skin, immune function,
psychological well-being and quality of life.1 All studies in the medical
literature showing the benefits of restoring HGH used the injectable form. This
is an important and often overlooked fact.
No published studies do a direct head-to-head comparison of injectable vs.
noninjectable HGH. Until this is done, the only available data are from
companies marketing and selling these noninjectable forms. Certainly, nHGH
products are available from many sources, but there is much concern about their
effectiveness. This article reviews various noninjectable HGH products' claims,
ingredient contents and overall efficacy.
Amino Acid Secretagogues
This category of n-HGH products uses amino acids as "secretagogues," which
stimulate pituitary gland production of HGH. Other proprietary agents are
usually part of the powder/tablet mix and give each product a presumed marketing
advantage. Although studies show certain amino acids in combination, such as
L-lysine and L-arginine, can stimulate pituitary HGH,2-5 no published studies
show evidence that these other proprietary factors provide additional pituitary
HGH secretion. Manufacturers no doubt believe added minerals act as cofactors in
some hormonal cascade, but there is little evidence of efficacy. Pharmaceutical
companies are investigating several biosynthetic hexa- and heptapeptides as well
as nonpeptide secretagogues,6-7 but these are considered drugs and are not
The claims and statements made by several companies advertising oral products
require careful reading. One HGH ad states: "Over 20 years of testing and
research in clinics and universities all over the world have proven the
effectiveness of Human Growth Hormone. It literally de-ages the body." The ad
then lists the many benefits shown from studies using injectable HGH. The ad
does not say that their specific formula has been tested and shown to have all
these benefits. The research they allude to has been conducted on the injectable
form of HGH. This is borrowed science, pure and simple.
The product in the ad consists of an amino acid "stack"---an effervescent amino
acid powder mixed with water and taken on an empty stomach. (Amino acids need to
be taken on an empty stomach for full absorption.) This delivery system is not
supported by HGH research and long-term use of oral amino acids presents a
compliance problem because they taste bad and can cause stomach discomfort.
Studies show at least two grams are needed to have any effect on pituitary HGH
stimulation, and while most products provide 315 g, this dose often results in
One company seems to have great faith in its amino acid formulas. They have
challenged at least two competitors to a "showdown on IGF-1 levels." IGF-1 serum
levels have been used to show if HGH products work. If the product increases
IGF-1 levels significantly, there is presumed effectiveness. Walter Essman,
M.D., Ph.D., at City University of New York, conducted the study for this
company and reported average IGF-1 levels increased by 25 percent, 46 percent
and 93 percent at 60, 120 and 180 days, respectively.5 Thirteen subjects (six
females and seven males), ages 4772, were each given 15-g packets (each
containing L-glutamine, L-lysine and L-arginine, plus sugars, citric acid and
natural flavoring) to be taken three times a day on an empty stomach for 180
days. Essman concluded that this amino acid formula is an effective HGH
secretagogue, and no adverse side effects were noted. The basis for calling this
formula effective was on the elevation of IGF-1 levels. However, there was no
control group, and other endpoints for judging effectiveness such as body
composition and metabolism were not reported. In addition, because the study has
not been published, no one has substantiated the data, which therefore become
Homeopathic Oral Sprays
The idea behind HGH oral sprays is to deliver the large HGH protein via the oral
mucosa into the systemic circulation instead of risking it being degraded by the
stomach and liver metabolism if taken orally. Unlike amino acid secretagogues,
HGH oral sprays contain HGH itself. All HGH oral sprays are deemed homeopathic
because this is the only way to sell oral HGH legally. There is considerable
controversy as to whether the large 191 amino acid HGH protein can be
effectively delivered through the oral mucosa and have systemic effects as the
According to Elmer Cranton, M.D., founder of alternative/complementary medical
clinics in Virginia and Washington, D.C., "A protein molecule that large cannot
penetrate intact into membranes to any significant degree. Most would be wasted
if it were used in a nasal spray or orally."8 However, according to a report by
Roy Dittman, O.M.D., using a patent-pending "macro-molecular complex," the HGH
protein can be delivered and absorbed through the oral mucous membranes.9
A "study" exists, now well circulated among the antiaging medical community,
examining the clinical effects of an oral HGH spray. The Waveland study tested
the effectiveness of an oral HGH spray (150 ng per day) on quality of life and
on IGF-1 levels in 18 healthy subjects, ages 30*65. They reported 13 out of 18
patients had a significant increase in IGF-1 levels; two subjects had little or
no change; and three subjects had lowered IGF-1 levels. Self-reported comments
on quality of life included increases in strength, endurance and sex drive as
well as deeper sleep, better complexion and weight loss.10 This study was not a
placebo-controlled, randomized trial, so it suffers from many biases.
Manufacturers seem to be racing to produce an oral spray with the greatest
amount of HGH in one bottle. One manufacturer has tested its brand and compared
it to nine other products in terms of actual HGH content. They report their
product has 672 ng/mL HGH vs. 36 ng/mL or less in the other products and
therefore claims to "beat the competition hands down." However, in homeopathy,
less is considered more---that is, the less concentrated a homeopathic is, the
stronger it is.11-12 If this company were producing a true homeopathic, they
shouldn't be trying to claim that a higher concentration is superior.
Oral sprays may contain recombinant Human Growth Hormone (r-HGH), but it is not
certain which manufacturers use this purer form. Some have used the bovine form
along with various peptides, Growth factors, amino acids, animal extracts,
minerals, ethanol and glycerin. The main ingredient, by volume, is water. The
pharmaceutical-grade rHGH is diluted to a desired (and legal) homeopathic
concentration. Some products claim to be "hand-succussed" and made according to
the Homeopathic Pharmacopoeia of the United States (HPUS). Hand-succussed has
nothing to do with absorption but only with the traditional way of making
homeopathics and transferring the "energetic" quality.
Another issue raised by some doctors is whether this HGH protein can be
stabilized in an aqueous (water) solution without degrading over time. For
example, Cranton states: "The HGH molecule loses potency very rapidly when
dissolved in solution. Only with efrigeration can biological activity be
maintained for up to two weeks. That's how fragile the molecule is."8
Apparently, Cranton is unaware of Genentech's iHGH product called Nutropin AQ, a
sterile liquid intended for subcutaneous administration. It has an HGH
concentration of 5 mg/mL, and is preserved only by sodium chloride (8.7 mg/mL),
phenol (2.5 mg/mL), polysorbate 20 (2 mg/mL) and sodium citrate (5 mM).13 This
liquid HGH has a shelf life of 18 months from date of manufacture.14
Ethanol is often used in these oral sprays to prevent bacterial Growth, but the
effect this alcohol has on the HGH protein structure may render it inactive,
especially with high concentrations of alcohol.14 Several products contain as
much as 47 percent alcohol.
Homeopathic Oral Tablets
The advertisement reads, "Clinically tested, homeopathically proven" and touts
"increased energy, lean body mass, improved physical appearance and reduced body
fat." Only one company to date has published a peer-reviewed study on a
homeopathic HGH oral tablet formula. Seattle-based Biomed Comm and Vitalabs,
based in Jonesboro, Ga., cosponsored three double-blind, placebo-controlled
The three studies used two different homeopathic HGH formulations (6X+12C and
6C+100C+200C) and were conducted in three separate areas of the United States.
In Seattle, the study lasted 30 days and involved 15 subjects. In Santa Fe N.M.,
46 subjects were part of a 21-day homeopathic proving study. In Boulder, Colo.,
101 subjects were in a crossover study lasting 42 days. The studies reported
significant increases in energy, weight loss and upper arm size; decreased hip
size; and relieved joint and knee swelling, compared with placebo. The authors
concluded with three major findings: 1) Homeopathic HGH produced a physiological
effect shown by reproducible increases in serum IGF-1 levels compared with
placebo; 2) Multiple beneficial effects of treatment were demonstrated, such as
increased lean mass, weight and fat loss, relieved fatigue and improved
psychological well-being; and 3) Subjects who received homeopathic HGH reported
relief from symptoms they had when they entered the studies, such as fatigue and
poor skin appearance.
Regarding homeopathic HGH increasing serum IGF-1 levels, the Santa Fe trial
showed an 18 percent increase in serum IGF-1 after only seven days. Subjects in
the Seattle group had 18 percent increases and the Boulder group had 21 percent
increases, all within 21 days of starting HGH. What this all means long-term
remains to be shown. Would levels continue to increase, return to baseline or
drop below baseline? Longer-duration studies with many more subjects are
required to fully assess the effects homeopathic oral HGH has on IGF-1 levels.
There are other limitations on any conclusions that might be drawn from these
studies. Primarily, the placebo effect in these studies was stronger than the
normally observed 30 to 40 percent. In each placebo group there were transient
12 percent increases in serum IGF-1, and placebo effects as high as 100 percent
in self-perceived quality-of-life topics. Some of the major placebo effects were
increased energy, enhanced physical endurance, relief from carpal tunnel
syndrome, reduced appetite, change in hair color, increased skin thickness,
fewer skin wrinkles, and relief from skin rashes. Still, the studies
demonstrated treatment trend effects beyond those of placebo in terms of serum
IGF-1 levels, increased lean body mass, increased physical strength, decreased
hip size, improved sleep quality and decreased blood pressure.
Another limitation is selection bias. Even though the study was double-blinded
and subjects did not know which they were getting, most of them knew the nature
of the substance being tested. In the Santa Fe trial, the small number of
subjects were "trained in a proving course" on how to journal symptoms and
subtle changes. The subject pools came from health professionals' patient bases
and were not adequately randomized. These facts make it difficult to control for
selection bias. Lastly, there were too many variables to adjust for, such as
age, gender and past Hormone use. The small number of subjects also limits the
statistical power of the study.
HGH Skin Creams
Is it possible for a skin cream to provide benefits that would mimic what
non-injectable HGH products claimed? One company believes so.15
One Florida-based company claims to have a "Growth Hormone potentiator and
releasing Hormone," available only by prescription. The company claims that
"multiple studies have shown 100 percent efficacy within 48 hours" and that
"within the first 36 hours of beginning the program, trained and conditioned
athletes reported an average increase of greater than 25 percent in their
muscular strength, endurance and recovery time." The marketing materials fail to
provide adequate studies to validate the claims made.
What's in it for the doctors? Six figures annually without an increase in
overhead. The product costs the doctor $65 for a small one-ounce bottle, which
he/she sells for $150. While this may be less expensive than injectable HGH,
there is no evidence for safety and effectiveness. I suggest physicians,
pharmacists and their patients steer clear of this marketing scheme.
The benefits of injectable HGH are primarily desirable changes in body
composition, from fat reduction to muscle mass increases. Most products being
marketed as dietary supplements or secretagogues have limited potential for
increasing HGH. While iHGH has shown a number of benefits, none of those
benefits as of yet have been objectively measured with oral tablets, capsules or
Noninjectable HGH Products And Their Ingredients
Michael L. Bennett, Pharm.D., is director of the Natural Hormone Research
Institute, a non-profit organization dedicated to the education, use and
clinical research of natural, bioidentical Hormones.
by Michael L. Bennett, Pharm.D.
1. Carroll P, et al. Growth Hormone deficiency in adulthood and the effects of
Growth Hormone replacement: a review. J Clin Endocrinol Metab 1998;83:382-92.
2. Isidori A, et al. A study of Growth Hormone release in man after oral
administration of amino acids. Curr Med Res Opin 1981;7:475-81.
3. Kasai K, et al. Stimulatory effect of glycine on Human Growth Hormone
secretion. Metabolism 1978;27:201-8.
4. Welbourne TC. Increased plasma bicarbonate and Growth Hormone after an oral
glutamine load. Am J Clin Nutr 1995;61:1058-61.
5. Essman WB. Clinical evaluation of a Human Growth Hormone secretagogue. Poster
Presentation for 6th International Congress on Anti-Aging and Biomedical
Technology, 1998 Dec 11-13, Las Vegas, Nev.
6. Laron Z. Growth Hormone secretagogues. Clinical experience and therapeutic
potential. Drugs 1995;50(4):595-601.
7. Chapman I, et al. Stimulation of the Growth Hormone (GH)-insulin-like Growth
factor I axis by daily oral administration of a GH secretagogue (MK677) in
healthy elderly subjects. J Clin Endocrinol Metab 1996;81:4249-57.
8. Cranton, E. HGH oral or nasal spray? I doubt it!
www.drcranton.com/hrt/hghspray.htm. Information as of 2000 May 12.
9. Dittman, R. Science fiction or science facts? Dispelling the Growth Hormone
absorption myth---recent research reviewed. www.antiaginginfo.net/myth.htm.
Information as of 2000 May 14.
10. Mizrock B. Oral GH spray: outcome-based research study. Waveland Wellness
Center, Chicago, Ill., 1998.
11. Davis HA. Feeling younger with homeopathic HGH. East Canaan (CT): Safe Goods
12. Brewitt B, et al. Homeopathic Human Growth Hormone for physiologic and
psychologic health. Alt Comp Therapies 1999;12:373-85.
13. Nutropin AQ Package Insert. 1997 March.
14. Genentech Product Information Specialist. Fax information on Nutropin AQ;
2000 May 12.
15. Health Care Resources. Trans-D-Tropin marketing material, 1999 July.
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