To answer the OP's original question. To the best of my knowledge, I've yet to see any literature indicating tachyphylaxis of metformin. To the lay-reader, tachyphylaxis is considered a diminishing response from a drug. Diet modifications are generally the cause and effect for lack-of efficacy with metformin. Not the drug itself.
Sure, in isolation metformin acts independently, antagonisticlly on mTOR, several citations have undeviatingly confirmed this. Conflicting as it may seem, this doesn't appear to be of concerns if an individual is loaded up on anabolics, GH, high protein intake, consumption of EAA's or the likes.
In contrast, unbeknownst too some, AMPK activation itself will increase glucose uptake and muscle protein synthesis as demonstrated by Douglas R. Bolster, et al, Published, JBC Papers in Press, May 7, 2002, DOI 10.1074/jbc.C200171200
"The results also further establish AMPK as a unique energy sensor that not only modulates glucose and fatty acid metabolism but also appears to regulate, in part, the anabolic functions of mRNA translation and mixed muscle protein synthesis"
To conclude:
"In conclusion, this research identifies a new cellular function for AMPK by its ability to modulate skeletal muscle protein synthesis and the phosphorylation state of translation initiation factors upon activation".
Also consider the following:
Unlike the former citation demonstrated on animal models. The following was observed in humans by Dennis C. Gore, MD, et al; Ann Surg. 2005 Feb; 241(2): 334–342.
"Metformin had a demonstrable anabolic effect on muscle protein metabolism. For example, patients treated with metformin had a significantly less negative net balance of alanine and phenylalanine across the leg (Table 6). Measurements of muscle protein kinetics using 3-compartment modeling demonstrated a trend toward increases in muscle protein synthesis (Fom; P = 0.074) for patients given metformin. Placebo- and metformin-treated patients were similar in Fmo (as an index of muscle protein breakdown), as were values of phenylalanine transport. Most notably, there was a significant increase in the fractional synthetic rate of muscle protein in those patients receiving metformin"
Conclusive enough. Eva C. Diaz, et al, also demonstrated the same end points.
Effects of Pharmacological Interventions on Muscle Protein Synthesis and Breakdown in Recovery from Burns
"Interestingly, despite decreased endogenous glucose production and increased glucose clearance and oxidation, metformin treatment did not decrease the rate of muscle protein breakdown. Certainly, it would be expected that a reduction in gluconeogenesis would lead to a decreased demand of substrate (amino acids) from skeletal muscle, and thus reduced protein breakdown rates. Similarly, a shift in the utilization of amino acids as fuel toward a greater oxidation of glucose should primarily decrease muscle protein breakdown. However, the improvement in net balance reported in the intervention group was mainly due to an elevation in the rate of protein synthesis and not to changes in protein breakdown. This suggests that the anabolic effect of metformin in burn patients is mediated by improving the state of insulin resistance associated with the stress response to burn injury. Indeed, the infusion of insulin after seven days of metformin treatment further increased the rate of muscle protein synthesis"
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I can comprehend yours (and other's) tunnel-sighted diversion upon the face-value on some spoken literature that may show consequent of hindering muscle growth on its own. Subsequently, many individuals that adjuvantlly use metformin alongside their AAS concoctions to achieve their maximal growth potential have yet to expres stunted growth, including myself.
What most on boards like here and alike lack to consider. One has to take into account the barrage of many other mTOR/TORC1 (supplements and lifestyle [epigenetic responses]) activators and inhibitors that interplay, thus potentially canceling or enhancing growth promoting pathways. Exercise in itself would more than likely create negligible responses on mTOR from the adjuvant use of metformin.
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Your question of why would one take metformin.
Well, supraphyiological doses of anabolics have been shown to set the stage for endothelial dysfunction and neurodegenerative diseases to name a few known morbidities. Metformin has been shown to improve endothelial function as well through AMPK expression have
"neuroprotective affects from increased formation of advanced glycosylation end products (AGEs)". Chung MM, et al.
Biochim Biophys Acta. 2015 May;1852(5):720-31. doi: 10.1016/j.bbadis.2015.01.006. Epub 2015 Jan 13.
Vitale C, et al. J Intern Med. 2005.
Why not potentially mitigate would be my question.
If your concerns are the focal point of inhibition on IGF-1, you may want to rethink using/consuming the following, as these have been shown to cause disruptive effects on IGF-1--- signaling pathways.
•caffeine
•alcohol consumption
•Curcumin
•Grapes, nuts, tomatoes, guava, watermelon, papaya, apricot, pink grapefruit, green tea, raisins, prunes and legumes.
•high carb intake
If one has undiagnosed or uncontrolled sleep apnea. There's a strong correlation of impaired pulsitile actions of GH, decreased IGF-1 levels. This goes without mentioning there's robust hypothesis's and animal models indicating inactivation/impared AMPK expression is correlated with systematic inflammation. I'm sure we can agree that the incorporated use of AAS can exasperate the presence of OSA. Uncontrolled sleep apnea in-of itself is a known biomarker for signalling inflammatory responses.
Coincidently, A. Mark Evens, et al; reported their findings as such: Biochem J. 2016 Sep 1; 473(17): 2561–2572.
Published online 2016 Aug 30. doi: 10.1042/BCJ20160002
"Our findings identify exciting new avenues for the treatment of sleep disordered breathing, because drugs that mimic AMPK activation could restore normal breathing patterns in people suffering from this disease"
It appears AMPK expression may play a pivotal role in lessening AHI's associated with OAS. If my OSA wasn't controlled, I'd definitely be reaching for metformin. As well, a CPAP.
I'm not here to sway your opinion one-way or the other. Yet, if your concerns are of that soley of IGF-1 and or MPS. I truly believe you're missing the boat.
Have a goodnight. I'm exhausted talking about metformin.
.gif "IP Gear")
