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#Post#: 1032--------------------------------------------------
Metformin & Human Growth Hormone Use
DIR By: Road2HardCoreIron
Date: September 2, 2022, 2:58 pm
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Over the last few years insulin sensitizers, and metformin in
particular, have become quite popular among bodybuilders due to
their many positive effects, one of which is the ability to
combat growth hormone/exogenous insulin induced insulin
resistance. While their physique and health enhancing benefits
are undeniable, many have begun utilizing these compounds
indiscriminately, adhering to a more is better philosophy in
terms of dose, frequency of use, and the number of compounds
employed. This may be advantageous with some drugs, but is it
true in this instance?
Insulin sensitizers are rather unique in that many of their
positive and negative effects are mediated through a single
pathway; an enzyme known as adenosine monophosphate-activated
protein kinase, or AMPK for short. Acting as a cellular energy
regulator, AMPK is responsible for maintaining cellular energy
homeostasis via the regulation of ATP levels. When the body is
exposed to stresses that deplete ATP, such as heat shock, or
much more commonly, low blood glucose and hypoxia as a result of
diet and exercise, this enzyme is activated. As a result,
processes which involve ATP consumption (fatty acid and
cholesterol synthesis) are turned off, while processes which
involve ATP production (fatty acid and glucose oxidation) are
turned on in an attempt to replenish cellular energy levels.
This has a number of beneficial effects. It improves insulin
sensitivity (via improved insulin receptor function and
increased Glut-4 translocation), increases glucose uptake into
muscle tissue, simulates fat loss, improves cholesterol values,
and results in an overall improvement in metabolic health. With
such a diverse number of benefits and with all of them directly
applicable to the goals/circumstances of a bodybuilder,
referring to these compounds solely as “insulin sensitizers”
undermines their full value. Nevertheless, it makes sense why so
many have chosen to include them in their programs.
Unfortunately, when it comes to bodybuilding, their negative
effects have the potential to outweigh the good. Of course,
rather than having undesirable effects in an area of minimal
significance, they hit us right where it hurts by blunting
protein synthesis, and often in more than one way. Protein
synthesis is a very energy consuming process, so naturally, it
makes sense that AMPK would work to limit it, which it does by
inhibiting the activity of a protein called mTOR (mammalian
target of rapamycin). As a critical player in the initiation of
protein synthesis, any decrease in mTOR signaling is technically
a bad thing for bodybuilders. You see, AMPK and mTOR are
oppositional in nature in the sense that when one is activated,
the other is typically suppressed, but this doesn’t mean that
it’s impossible to activate both at the same time. In fact,
there are several scenarios in which this can happen, making it
a regular occurrence for bodybuilders. This is possible because
AMPK doesn’t inhibit mTOR directly. Rather, it inhibits another
protein that increases mTOR, so by manipulating those aspects of
our physiology that interfere with this function, we can
minimize AMPK’s negative effect on protein synthesis while
continuing to receive its benefits.
Up to this point, I haven’t addressed metformin directly, but
have referred to sensitizers in general. Here’s where that
changes. While the majority of sensitizers (including metformin)
in use today work to increase insulin sensitivity via AMPK
activation, metformin has other negative effects on androgen
receptors which compound its negative effect on protein
synthesis, the most problematic of which is its ability to
reduce androgen receptor density. In other words, this stuff
doesn’t just have a suppressive effect on androgen receptor
function, it actually gets rid of them! Being that androgen
receptor signaling is the primary mechanism through which
testosterone and other steroids stimulate muscle growth,
anything which eliminates this critical mediator not only
reduces the rate of muscle growth, but total growth potential as
well.
Metformin has also been proven to reduce endogenous testosterone
production in both men and women—significantly. This may not
matter much to steroid using bodybuilders who are already
experiencing H.P.T.A. suppression, but to a natural bodybuilders
or those engaged in PCT, it is about the worst possible side
effect. In terms of non-protein synthesis related side effects,
metformin impairs thyroid function by inhibiting TSH (thyroid
stimulating hormone) production, thereby lowering T4 and T3
levels. I could list numerous other well known side effects
ranging from lactic acidosis to digestive upset, but I will stop
there. For all these reasons and more, and given the fact that
natural alternatives exist which have been clinically proven to
work just as well without these side effects, I can see no good
reason why a bodybuilder would continue using this drug once
informed of the risks.
When reviewing the various natural insulin sensitizers,
berberine appears to be the most potent (there are many other
useful sensitizers, as well), providing insulin sensitizing
effects equal to metformin when compared on a mg per mg basis.
However, berberine has not been shown to cause many of the more
serious side effects associated with metformin use, such as
decreased androgen receptor density. Neither does it appear to
lower testosterone levels. In fact, there is substantial
evidence to indicate that berberine may have a positive impact
on testosterone levels in both men and women, as has been
demonstrated in several in vitro clinical trials. THS levels
also remain unaffected and when it comes to digestive
compatibility, it is well tolerated. Berberine also has several
other benefits which positively affect whole-body health, such
as the ability to improve cholesterol levels, reduce
inflammation, and protect against oxidative damage. These are
only its clinically proven benefits. Researchers speculate that
there are still many others.
Despite this, many of you are probably wondering if even natural
alternatives like berberine should part of your program, given
the potentially negative effects of AMPK activation on protein
synthesis. Without the right information, the kneejerk reaction
might be to run the other way. After all, what could be more
important to a bodybuilder than protein synthesis? However, when
taking the bigger picture into consideration, it quickly becomes
apparent that these fears are unfounded. In reality, a little
AMPK activation isn’t going to have a noticeable impact on
muscle growth. We already activate AMPK whenever we do cardio,
yet cardiovascular exercise has proven to be a complement to our
mass-building efforts, not a detriment.
Still, if we are going to be activating AMPK to a greater degree
than normal, we should take steps to ensure mTOR continues
exerting its anabolic effects at maximum capacity/near maximum
capacity. Fortunately, mTOR can be activated in many different
ways, and with bodybuilders already taking advantage of many of
these on a continual basis, there is no danger of suppressing
growth rate to a significant degree. Factors such as training,
diet, drug use, and even the consumption of certain amino acids
are all capable of activating mTOR to various degrees. When
combined, they can provide a dramatic increase in mTOR that far
exceeds the inhibitory influence of any insulin sensitizer, not
to mention the positive effects that sensitizers themselves have
on recover and growth via improved insulin sensitivity,
increased Glut-4 expression, increased muscle glucose uptake,
etc. There really is no need for concern. Real-world results
confirm this, with innumerable bodybuilders having reaped the
benefits of these products without any report of hindered
growth.
Still, proper use should be dictated by one’s circumstances.
Obviously, off-season bodybuilders attempting to maximize muscle
growth shouldn’t load up on them 24/7. Rather, they should be
used on an as needed basis, such as with moderate-large carb
containing meals. On the other hand, pre-contest bodybuilders
prioritizing fat loss will benefit from utilizing them more
often. In conclusion, natural insulin sensitizers can be a
valuable addition to one’s program, whereas pharmaceutical
preparations like metformin just have too many negative side
effects to justify their use in bodybuilders, especially with
more suitable alternatives are available.
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