Growth hormone, produced in the pituitary gland, is one of the body’s
three major anabolic hormones. The others are testosterone and insulin.
A peptide hormone, meaning that it’s composed of a long chain of amino
acids in a specific sequence, supplemental growth hormone must be
administered by injection. As noted in a previous installment of this
column, GH use by athletes and bodybuilders is rampant, mainly because
it
remains undetectable by current drug-testing methods. Whether using
GH alone provides any true anabolic effects to athletes remains a matter
of conjecture, although numerous anecdotes testify that it does.
Bodybuilders rarely, if ever, use GH alone; it’s part of the anabolic
hormone triumvirate, with testosterone and insulin.
The other population interested in GH is older. GH drops about 14
percent per decade, and some antiaging researchers suggest that the loss
of GH and insulinlike growth factor 1 may be responsible for the loss
of both physical and mental function common in older people. IGF-1 is
produced in the liver under the stimulation of GH release. It’s also
produced locally in muscle, where it’s involved in muscle repair and
growth. Both hormones maintain muscle and connective tissue, and their
lack may be involved in the loss of lean mass seen in the aged.
Some studies, notably a 2007 study published by researchers from
Stanford University, examined the use of GH therapy in the aged and
concluded that the risks outweighed any potential benefits. It was a
meta-analysis, or compilation, of previous GH studies, most of which
used excessive doses and produced such side effects as peripheral edema,
which is water retention in the extremities, joint pain, muscle pain,
glucose intolerance and loss of insulin sensitivity. The latter two
effects can set people up for diabetes if they have the genetics for the
disease. Although it wasn’t mentioned in the Stanford analysis,
numerous recent studies show that much lower doses produce the benefits
of GH minus the side effects.
Still, the fact that GH must be injected presents problems for many
people. Injections don’t duplicate the hormone’s natural release
pattern, which could be related to side effects. GH is normally released
in small bursts, or pulses, several times a day, with the major pulse
released during the initial 90 minutes of sleep, during stage-4, deep
sleep. Because of the problem, researchers have sought other ways to
boost sagging GH. Since GH is nothing more than a complex protein,
though, taking it orally means it would just be broken down in the gut.
As research into the mysteries of GH continued, scientists discovered
GH receptors in the body and that much smaller amino acid peptides
could interact with them to stimulate GH. Those peptides are called
secretagogues and usually consist of about six amino acids linked
together. Researchers also discovered ghrelin, another natural GH
secretagogue. With that information scientists developed drugs such as
MK-677 that mimic the effects of ghrelin and other GH secretagogues in
the body.
Secretagogue drugs offer considerable potential advantages over GH
injections. For one, they can be taken orally with no loss of activity.
They boost the natural pulsatile release of the body’s own GH. Although
older people often have less GH, the pituitary continues to synthesize
it throughout life. The problem is that other substances, such as
somatostatin, that inhibit GH release also rise with age. GH release
itself is governed by a balance between growth-hormone-releasing hormone
and somatostatin. For unknown reasons, the body makes more somatostatin
with age, while GHRH remains stable—an imbalance that favors
somatostatin dominance and less GH release.
Oral GH secretagogues such as MK-677 bypass the somatostatin barrier
by interacting directly with GH receptors, thus producing GH release.
Since GH is quite expensive, an effective oral drug could replace GH
injections and even eliminate most current GH-related side effects. The
question is, Do the oral GH-releasing drugs work in the real world as
well as they do on paper or in the lab?
A few studies show that GH secreatagogues such as MK-677 increase the
body’s GH production in both the young and the old. In the most recent
study that examined the effects of MK-677, 65 healthy people aged 60 to
81 received either 25 milligrams of MK-677 or a placebo for two years.
1
During the first year some subjects got MK-677, while others got a
placebo. After the first year those who had taken the placebo took
actual MK-677, while those who had been taking the MK-677 either
continued using the drug or were assigned to a placebo group. That’s
known as a placebo-controlled, randomized, crossover double-blind study
and is considered the highest quality study available.
As expected, the drug produced GH in amounts typical of young adults
in the older people who used it, to the extent that 20 percent of lost
lean mass was regained. Bodyfat increased on their arms and legs, which
was surprising considering that GH is always linked to less bodyfat.
While GH injections have been shown to decrease dangerous visceral
bodyfat, MK-677 had no effect on that particular fat-storage area.
Fasting blood glucose rose, while insulin sensitivity declined, which is
common with GH injections. The most common side effect, however, was an
increase in appetite that subsided in a few months. That’s no surprise,
since MK-677 mimics the effects of ghrelin, which has a potent
appetite-stimulating effect. Some subjects also experienced a mild
lower-body edema and muscle pain. On the other hand, low-density
lipoprotein declined in those on MK-677, an effect not produced by GH
injections. A high count of LDL is linked to cardiovascular disease.
The authors note that MK-677 likely works because it mimics ghrelin
in activating the body’s GH receptors. That system has a built-in safety
factor because as GH rises, so does IGF-1. The increased IGF-1 signals
the pituitary gland that the body has reached its optimal GH point. The
pituitary responds by ceasing GH release. The increased fat stores in
those on MK-677 reflect the ghrelin-like activity of the drug. While GH
promotes fat oxidation, ghrelin promotes fat accretion. Although that
doesn’t sound good, consider that many older people lose their appetite,
which adds to the loss of muscle that frequently occurs. Unfortunately,
MK-677 didn’t have any discernible effect on strength, function or
quality of life in this study.
GH injections don’t increase strength in older people, however, or in
younger people not deficient in the hormone. Only one study found an
increase in strength in older men on GH, and they were also using
testosterone. In this study, though, MK-677 did counteract three common
factors related to muscle loss with age: reduced GH secretion, loss of
fat-free mass and inadequate food intake.
Could GH secretagogues benefit those who are younger? Some
preliminary studies show that giving MK-677 to young men boosts GH
release and even encourages gains in lean mass. Secretagogues bypass the
body’s usual limitations on GH release. On the other hand, using a drug
that mimics ghrelin, such as MK-677, could reverse the effect of GH by
causing hunger—and a considerable gain in bodyfat. I doubt that few
bodybuilders would consider that an advantage.
GH secretagogues not based on ghrelin may be effective GH boosters
without the negative body composition changes linked to a ghrelin-based
drug. The primary advantage of such drugs, however, is to restore
GH-releasing ability in older people at far less expense and in a more
natural manner than in present GH replacement therapy.
GH Effects in Athletes:
Real or Imagined?
Published research linking ergogenic effects to growth hormone use is
scant. Yet its prevalence in bodybuilding and athletics cannot be
denied. Surely GH does something to boost athletic prowess or muscle
size and strength gains. Indeed, anecdotal evidence indicates that a
combination of GH, testosterone and insulin is largely responsible for
the noticeable difference in muscle mass between today’s bodybuilding
competitors and those in the past. GH by itself isn’t very anabolic, but
when it’s taken in that combination, the three hormones appear to offer
a synergistic anabolic effect that hasn’t yet been explored or defined
by mainstream science sources.
A recent study suggests that any gains made from using GH are entirely due to the placebo effect.
2
Sixty-four noncompetitive recreational athletes were randomly assigned
to either a placebo or GH group, the latter getting two milligrams a day
of GH. The athletes didn’t know which group they were in. Physical
performance was measured by various tests that examined endurance,
strength, power and sprint capacity. More men than women believed they
were receiving GH—81 percent vs. 31 percent. The men who thought they
were taking GH improved both perceived and measured physical
performance, even though they were in the placebo group. The authors
suggest that many of the favorable effects ascribed to GH occur because
athletes believe they will.
That isn’t unprecedented. More than 25 years ago a study was
published in which powerlifters were told that they were getting
injections of an anabolic steroid called Deca-Durabolin. About nine out
of the 12 lifters reached their best lifts during the study. All the
lifters had received placebo injections—which just goes to show that you
can never discount the power of the placebo.
References
1 Nass, R., et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults.
Ann Inter Med. 149:601-611.
2 Meinhardt, U., et al. (2008). The power of the mind: An
evaluation of the placebo effect in a study of GH on physical
performance.
GH IGF-1 Res. 18(Supp): S34.
Editing errata: In the February ’09 installment of this column,
“Testosterone and Rapid Weight Loss,” the statement, “The more SHBG your
body has, the less testosterone you have in your blood,” should have
read, “The more SHBG your body has, the less active testosterone you
have in your blood.” Also, the statement, “In addition, the carbohydrate
and fat may have spurred an increased release of growth hormone,”
should have read, “In addition, the reduced carbohydrate and fat may
have spurred an increased release of growth hormone.”
©,2015 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited
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