SARMs Ban Update 2018 August 30
> agree with everything except for receptor competition. that’s just a myth.
> It's not a bloody myth, it's pharmacology, specifically pharmacodynamics, it's entirely true, to the point there is a science dedicated to it. You should genuinely reassess your beliefs about this!
This sparked an old debate the forum used to have in regards to whether or not SARMs should (or could) be stacked.
I am including my response here so this post can be used as a ground for discussion. This wasn't meant to be uber in depth, but I can reference more sources in a few days if people want.
> Merely "term-dropping" to sound smart is not an argument. You have not explained in any way that receptor competition would be an issue with stacking SARMs.
> Let me break it down for you. Two main factors control competition for the same receptor by two different ligands. 1) The dissociation constant between receptor and ligand; ie: how strongly they associate noncovalently 2) The concentration of ligand / receptor (whether or not it’s saturated)
> Testosterone levels in healthy males is 300-1000ng/dL, and those running cycles go for around 3000-5000ng/dL. LGD4033, for example, this study shows PEAK plasma concentrations of 9.916ng/mL, or 0.099ng/dL at day 21 of 1mg LGD4033/day. SARMs are not binding so strongly to the AR that they are forcing out other androgens. (most studies show K_I comparable to test) Even if they were perfect superagonists, the AR receptor saturation is SO LOW that they would not be fighting each other.
> If you think 0.09ng/dL of LGD4033 (or even 0.9 ng/dL @ 10mg/day) is going to cause AR saturation issues, then 300ng/dL of testosterone to 3000ng/dL on a blast would absolutely be too much for the receptors to handle. This is not the case.
> Oh, and I think you "should genuinely reassess your beliefs about this!"
> I recall when I frequented these forums that there were assumptions based on science like this, which is awesome, but often it did not translate so to muscle gains.
> From the logs I used to read, people experienced barely any more muscle gain stacking SARMs.
> Do you have any evidence of it building more mass over an equal period of time with the same efficiency?
> I’m not advocating to stack SARMs. It increases suppression to levels higher than either compound alone, something i’ve mentioned before. If you have a test base, sure go for it. I don’t think it’s worth it at that point but you do you; SARMs on a blast are good for lowering SHBG and (some) for antagonizing the prostate AR. Their androgenic benefits are much less obvious (and more expensive) than just adding another compound, or running more test.
> But, drugs have therapeutic windows and their dose–response relationship is USUALLY sigmoidal. The issue here really comes down to that. Compounds are stacked all of the time for AAS cycles, with contest preps running test, DHB, NPP, orals, etc. all at once, all at much higher plasma concentrations. Each compound has unique profiles with diminishing returns. But if the compounds produce unique enough results, it is obvious that the stack is beneficial.
> Also, there’s not going to be any data on the topic because it’s such a niche thing. Everything we do is based on word of mouth and people’s opinions. One guy might say 10mg LGD gave him the best gains of his life with no sides, another might say 5mg a day LGD had them lethargic by week 4. Concluding anything really from conflicting reports is hard.
> Relying on user input, unfortunately, is unlikely to support either case. The burden of proof in this situation falls on the science behind cellular signaling.