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Growth hormone's link to starvation may be clue to increasing life span, researchers find 6-27-08
Researchers at UT Southwestern Medical Center have determined that starvation
blocks the effects of growth hormone via a mechanism that may have implications
in treating diabetes and extending life span.
"It's been well-established that growth is blunted during starvation. But our
work shows that this is not just from running out of energy. It's much more
sophisticated than that," said Dr. Steven Kliewer, professor of molecular
biology and senior author of a study available online and appearing in today's
issue of the journal Cell Metabolism.
Using genetically altered mice, the researchers found that during fasting, the
actions of growth hormone are blocked by a fat-burning hormone called FGF21.
"It's something that we hadn't anticipated," said Dr. Kliewer.
Growth hormone has many functions in the growth and reproduction of cells, such
as controlling the length of developing arm and leg bones in children.
Growth hormone has several other functions, however, even in adults. It promotes
the breakdown of fats, stimulates creation of protein and increases levels of
IGF-1 (insulin-like growth factor-1), a hormone that promotes growth. Too much
growth hormone can cause insulin resistance, resulting in diabetes, and lead to
other disorders.
In the current study, mice that were genetically altered to produce excess FGF21
grew to be much smaller than ordinary mice, even though they ate more and had
more fat in proportion to their size.
Paradoxically, and to the researchers' surprise, the altered, smaller mice
produced much greater amounts of growth hormone than normal.
Why didn't the altered mice grow larger than normal in response? The researchers
found that FGF21 does not block the production of growth hormone; rather, it
works to prevent growth hormone from activating the genes it normally controls.
Interfering with the actions of growth hormone has been shown to increase life
span in mice, Dr. Kliewer said.
"In addition, intermittent fasting – which increases FGF21 concentrations – also
extends life span in mice. This raises the intriguing possibility that FGF21
might be a longevity factor," Dr. Kliewer said.
"This is something that we're beginning to test in the lab," he said. "But our
genetically engineered mice have all the classic hallmarks of extended life
span: growth hormone resistance, low concentrations of IGF-1, increased insulin
sensitivity and small size."
FGF21 is already being tested in human clinical trials for treatment of obesity
and diabetes in adults, but the new findings linking FGF21 to interference with
growth hormone might indicate that caution is needed before using it in children
or teens, Dr. Kliewer said.
Comment:
If you are using IGF-1, homeopathic human growth hormone or secretagogues; they work best when used at times the body naturally secretes human growth hormone. These times are when (unfortunately) 1 hour after onset of deep sleep and during moderate exercise. Here is further information for athletes:
What many athletes and coaches have failed to understand, however, is that
athletes can employ specific training regimens and dietary strategies to
optimise their natural secretion of human growth hormone (hGH), so inducing
those very adaptations to training that others are cheating to achieve.
Human growth hormone is produced in the anterior portion of the pituitary gland,
a pea-sized organ suspended just below the brain, which produces no fewer than
nine different hormones. Between them these hormones regulate a number of
essential physiological functions, including water and energy balance,
reproductive activity and the workings of many other glands in the body.
As its name suggests, growth hormone has largely been associated with the
function of growth. For centuries scientists believed that puberty was a cut-off
point, with human growth hormone (hGH) playing no part in growth or any other
function after that. Recent evidence suggests, however, that human growth
hormone (hGH) is involved in many physiological processes throughout life,
including the turnover of muscle, bone and collagen, the regulation of fat
metabolism and the maintenance of a healthier body composition in later life.
A relatively recent discovery is the existence of growth hormone deficiency in
adults (GHDA), which has shed further light on the function of this busy little
hormone. People with GHDA have a relatively low muscle mass and high body fat,
creating a tendency to obesity, an increased risk of heart disease and a greatly
reduced exercise capacity. Treatment of this condition usually requires regular
injections of growth hormone.
In general, human growth hormone (hGH) secretion follows a circadian rhythm and
is secreted in 6-12 discrete pulses per day, with the largest pulse secreted
about an hour after the onset of night-time sleep (around midnight for most
people). The release and inhibition of human growth hormone (hGH) are governed
by two hypothalamic hormones: growth hormone releasing hormone (GHRH)) and
somatostatin. Growth hormone secretion can be triggered by a number of natural
stimuli, the most powerful of which are sleep and exercise.
The fact that exercise acts as a major stimulus for the natural secretion of
human growth hormone (hGH) is well known, but there is still little evidence to
suggest how this might happen. Various researchers have suggested that it could
be triggered by exercise-induced increases in adrenaline, nitric oxide, blood
lactate, acidity or nerve activity, either individually or together.
Today there is little doubt that optimising secretion of natural human growth
hormone (hGH) is beneficial to sportsmen and women, with none of the many risks
associated with hormone abuse, including joint pain, arthritis, abnormal heart
growth, muscle weakness, increased blood fats, impaired glucose regulation,
diabetes, impotence and, of course, the consequences of breaking the law!
Diet, exercise and sleep patterns all play a role in human growth hormone (hGH)
secretion. Since the largest human growth hormone (hGH) surge in a normal day
tends to occur around one hour after the onset of night-time sleep, it is vital
for athletes to get plenty of it. If the quality of sleep is inadequate there
will be a reduction in the volume of human growth hormone (hGH) secreted, with
negative consequences for health and fitness. Important preconditions for good
quality sleep and optimal human growth hormone (hGH) secretion during sleep
include a dark room and a balanced diet containing adequate protein(1). Of
course, an adequate quantity of sleep is also required for good health
generally, and for most people this means around eight hours.
As far as diet is concerned, athletes are normally advised to ensure it is high
in carbohydrate, which generally involves consuming foods with a higher glycemic
index (ie more sugary) immediately after exercise and the more starchy varieties
of carbohydrates at most other times. As far as fluid intake is concerned, the
standard advice is to drink carbohydrate-electrolyte (sports) drinks before,
during and after exercise.
High-carb diets may be appropriate in many situations but, since hyperglycemia
(elevated blood carbohydrate) tends to switch off human growth hormone (hGH)
secretion, this strategy may not be appropriate where optimal adaptation is the
priority. Fat taken before exercise has also been found to reduce human growth
hormone (hGH) secretion (2).
It is hard to argue against the use of carbohydrate immediately after training
in the few days leading up to a competition, when it is important to ensure that
carbohydrate stores in the muscles are fully repleted. However, this is not the
best strategy for maintaining the release of human growth hormone (hGH) after
exercise, particularly if the carbs have a high glycemic index, as these
(sugary) foods stimulate insulin secretion which, in turn, contributes to a
reduction in human growth hormone (hGH) (3).
It is also important to drink plenty of water during training, as dehydration
has been shown to significantly reduce the exercise-induced human growth hormone
(hGH) response (4).
As far as supplementation before exercise is concerned, it has been shown that
ingestion of 1.5g of arginine will increase human growth hormone (hGH) secretion
by blocking release of the hGH-inhibitor somatostatin, although some studies
have suggested this causes gastric disturbance(5). However, 2g of glutamine will
lead to elevation of human growth hormone (hGH) 90 minutes later without side
effects (6). It may also be a good idea to ingest some amino acids after
exercise, as this has been shown to enhance human growth hormone (hGH) secretion
too (7).
In terms of training, research has shown that to achieve an elevation of human
growth hormone (hGH) above baseline you need to spend at least 10 minutes
training at above lactate threshold intensity (8) This results in the biggest
volume of human growth hormone (hGH) secreted in response to a single exercise
bout, with levels of the hormone declining gradually over a period of an hour.
It is also known that multiple daily sessions can give rise to optimal human
growth hormone (hGH) secretion over a 24-hour period.
One study investigating the effects of three exercise sessions a day with either
1.5 or three-hour recovery periods between them found that the longer recoveries
led to the greatest volume of 24-hour human growth hormone (hGH) secretion (9).
Another showed an even larger human growth hormone (hGH) peak in response to
sprints on an exercise bike (10).
In the light of the above-mentioned research and current recommendations for
both diet and exercise, it might be a good idea to think about ‘periodising’
diet in a similar way to training. During periods of training, when we are
trying to increase muscle mass, minimize body fat and maximize the adaptive
response to training, it would seem logical to adopt an hGH-enhancing approach,
reverting to a high-carb diet before and during competition.
Exercise and dietary strategies
In summary, then, exercise above lactate threshold induces the secretion of
human growth hormone (hGH), promoting the use of fat as fuel. This, in turn,
spares muscle carbohydrate, keeps body fat down and muscle mass high and
enhances adaptation to specific exercise stimuli. The benefits are clear, but
simply switching to high intensity work for the whole year is not the answer;
rather, a periodised program, where the number of sprints or higher intensity
workouts alters according to the competitive program, is the best way forward.
A suggested exercise and dietary strategy for optimizing human growth hormone (hGH)
secretion is as follows:
* Exercise – three sessions per week, each involving at least 10 minutes’ work
above lactate threshold or a number of sprints, with a 1:3 work-rest ratio;
* Before exercise – no fat for 60 minutes before, 2g glutamine 60-90 minutes
before;
* During exercise – plenty of plain water (ie 200 ml every 10-15 minutes if
training in 18-21°C);
* After exercise – avoid sugar for two hours post exercise but take 25g protein
immediately afterwards in the form of either a protein shake, protein bar, lean
meat or eggs (although you should limit your consumption of eggs to avoid too
much cholesterol).