URI:
   DIR Return Create A Forum - Home
       ---------------------------------------------------------
       Road2HardCoreIron
  HTML https://road2hardcoreiron.createaforum.com
       ---------------------------------------------------------
       *****************************************************
   DIR Return to: HGH/ IGF1/ SLIN & Peptides
       *****************************************************
       #Post#: 1032--------------------------------------------------
       Metformin & Human Growth Hormone Use
   DIR By: Road2HardCoreIron
       Date: September 2, 2022, 2:58 pm
       ---------------------------------------------------------
       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.
       *****************************************************
       Page 1 of 1