Question to SETH ROBERTS -any totally non AR mediated compounds out there?

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    Question to SETH ROBERTS -any totally non AR mediated compounds out there?


    Hi Seth,

    There was a discussion a long time ago where you debated in favor of Anabolic Receptor down-regulation. I know that most people on the internet argue that there is no AR down-regulation as a result of steroid use, but that is a different discussion and those who wish to debate that can look for that old thread and read the discussion.

    I personally agree that there is AR down-regulation and thus my question is:
    Are there any substances out there, that build muscle entirely through non AR mediated means, and thus would not produce any AR down-regulation at all?

    When I say "substances that build muscle entirely through non AR mediated means" I am referring to muscle building effects that are at least somewhat comparable to steroids. Someone can answer my question by saying "creatine" and that would not be a wrong answer, technically. However, I am looking for things that have a PROFOUND muscle building effect.

    Thanks, as always, for your input

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    Quote Originally Posted by Sub7 View Post
    Hi Seth,

    There was a discussion a long time ago where you debated in favor of Anabolic Receptor down-regulation. I know that most people on the internet argue that there is no AR down-regulation as a result of steroid use, but that is a different discussion and those who wish to debate that can look for that old thread and read the discussion.

    I personally agree that there is AR down-regulation and thus my question is:
    Are there any substances out there, that build muscle entirely through non AR mediated means, and thus would not produce any AR down-regulation at all?

    When I say "substances that build muscle entirely through non AR mediated means" I am referring to muscle building effects that are at least somewhat comparable to steroids. Someone can answer my question by saying "creatine" and that would not be a wrong answer, technically. However, I am looking for things that have a PROFOUND muscle building effect.

    Thanks, as always, for your input
    The problem is that androgen receptor downregulation (or upregulation) is really a red herring since there re other mechanisms in place that result in desensitization of muscle to androgens.

    You could argue that IGF-1 builds muscle through non AR mediated means even though a recent paper demonstrated some cross talk going on there. Also, since IGF-1 is a target of the androgen receptor it is still on the same pathway. GH also elicits any muscle growth effects through IGF-1. There are other parallel pathways and of course there is myostatin inhibition. They may not result in AR downegulation but would likely elicit some sort of desensitization at some point.

    I think the essence of your question might be, are there any AAS that elicit their effect through non-AR mediated means-- the answer there is no.

    One of the things I would like to focus on if i ever get my newsletter going is the other molecular targets of muscle growth. Everyone loves AAS becuase they are so varied and interesting. But, there are a lot of other interesting patways to explore.
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    You are the frrrrikkin MAN!!!

    Excellent feedback as always... It sounds like we can almost say: "Muscle simply become unwilling to grow after a while, regardless of what mechanism the growth was elicited through, because eventually all growth happens through the same basic new-protein-synthesis-apparatus"

    Now, keeping things simpler and asking this hypothetical question, I would be curious to know if you have an opinion on:

    Let's say that someone is shooting test prop or test suspension everyday (assume that he has enough pain tolerance and enough spots in his body to shoot these everyday). After around 3 weeks, he realizes that his response is seriously diminished and he does not really grow any more. He is not even walking around with a permanent pump in his muscles anymore. For how long would he have to discontinue these very short-acting drugs to reset his receptors/growth apparatus, so he would respond to them strongly again? Can we give a rough answer at all? Weeks or months?
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    Quote Originally Posted by Sub7 View Post
    You are the frrrrikkin MAN!!!

    Excellent feedback as always... It sounds like we can almost say: "Muscle simply become unwilling to grow after a while, regardless of what mechanism the growth was elicited through, because eventually all growth happens through the same basic new-protein-synthesis-apparatus"

    Now, keeping things simpler and asking this hypothetical question, I would be curious to know if you have an opinion on:

    Let's say that someone is shooting test prop or test suspension everyday (assume that he has enough pain tolerance and enough spots in his body to shoot these everyday). After around 3 weeks, he realizes that his response is seriously diminished and he does not really grow any more. He is not even walking around with a permanent pump in his muscles anymore. For how long would he have to discontinue these very short-acting drugs to reset his receptors/growth apparatus, so he would respond to them strongly again? Can we give a rough answer at all? Weeks or months?
    There is a problem: The perceived diminishment in response does not necessarily coincide with the actual diminishment of response. A lot of the initial weight gains from AAS come from water and glycogen loading. When this effect is maximized, people assume that they have maxed out on that cycle when in reality they are just primed to begin true muscle protein accretion which of course happens at a much slower rate than water and glycogen loading. How long it would take to "reset" after growth has truly stopped would likely depend on the degree of adrenal disruption and in my experience, the adrenals can take a good amount of time to normalize.
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    Quote Originally Posted by sethroberts View Post
    How long it would take to "reset" after growth has truly stopped would likely depend on the degree of adrenal disruption and in my experience, the adrenals can take a good amount of time to normalize.
    Now that's a surprise answer. Adrenal disruption? As in adrenalin, cortisol, aldesterone and so on? I don't think you're referring to testosterone production returning to normal, because in the hypothetical example my subject was going to get back on test prop or suspension.

    Can you briefly explain, if this isn't too rude to ask, which adrenal hormone would make it hard to gain more muscle after adrenal function is disrupted?

    This also raises an opportunity to ask another question I had. We know that certain steroids can severely disrupt either the binding of cortisol to receptors or diminish cortisol production. How would abnormally low cortisol levels impact muscle growth? When we look at the specific steroids that beat cortisol down, those are also some of the most potent growth promoting steroids around. In that case, the hypothetical question that comes up is: when using a steroid that does not reduce cortisol production/binding very much, can we improve the said steroid's effect even further by taking an anti-cortisol medication with it? (not that I am saying this would be safe or desirable; just a thought experiment)
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    Quote Originally Posted by Sub7 View Post
    Now that's a surprise answer. Adrenal disruption? As in adrenalin, cortisol, aldesterone and so on? I don't think you're referring to testosterone production returning to normal, because in the hypothetical example my subject was going to get back on test prop or suspension.

    Can you briefly explain, if this isn't too rude to ask, which adrenal hormone would make it hard to gain more muscle after adrenal function is disrupted?

    This also raises an opportunity to ask another question I had. We know that certain steroids can severely disrupt either the binding of cortisol to receptors or diminish cortisol production. How would abnormally low cortisol levels impact muscle growth? When we look at the specific steroids that beat cortisol down, those are also some of the most potent growth promoting steroids around. In that case, the hypothetical question that comes up is: when using a steroid that does not reduce cortisol production/binding very much, can we improve the said steroid's effect even further by taking an anti-cortisol medication with it? (not that I am saying this would be safe or desirable; just a thought experiment)

    Androgens disrupt adrenal function at multiple points such as 11b eta hydroxylase inhbiition, direct antagonism of glucocortiocid receptors, reduction in transcortin levels and direct competition for hormone response elements. You are correct, lower cortisol levels and decreased cortisol singalling are two potent mechanisms through which a lot of androgens elicit anticatabolic effects. However, the body compensates by either producing more cortisol or more glucocorticoid receptors, etc to overcome these effects. Most steroids have one if not all of these effects on cortisol signalling.
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    Quite possibly you have mentioned in your earlier writings what to do about the severe reduction in muscle growth after a few weeks of steroid use (just so the message board henchmen do not jump on me; it can be a few weeks with something like superdrol, but three months or more with injectable Test E...), but for the record, can you share your opinion on the following:

    1) what do you suggest one should do when he finds that his response to steroids has already severely diminished during the cycle? (other than keep increasing the dosages until you are taking enough steroids to supply an army)

    2) Are there anythings that can be done during or before the cycle to delay the reduction in dose-response relationship to steroids (other than using the lowest dose that will elicit the desired response)

    3) Finally, some people (they are in the minority but do exist) report extraordinary fatigue with superdrol/pheraplex to the extent where they wish to stay in bed all day long. If this is primarily due to cortisol reduction (or reduction of the existing cortisol's binding ability to receptors) -and I have been asking for literally years what else could be going on, with no one ever being able to produce a good answer- can it be dangerous? Would this potentially reach clinically significant "adrenal exhaustion" levels?


    Thank you very much Sir and my apologies for asking questions that may already have been covered in your book. I will buy it very soon but will need to get ovwer this difficult holiday season -financially- first.
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    Damn, almost forgot to ask one of the most important questions I had about cortisol; this is critical -perhaps not to many people here but for me it is for reasons I can explain later.

    As far as I know, acidosis increases testosterone production. I am talking about a whole body acidosis where you are constantly doing high rep squats for example (and I am aware that I am already slaughtering terms and science, as the blood PH cannot fluctuate much under any conditions whatsoever; so instead of a serious change in blood ph, which is impossible, I am referring to an increase in urinary PH as well as a situation where the body is trying to balance the acids with the production of carbonate and other mechanisms to actually keep blood ph stable).

    Can you please explain through what mechanism acidosis increases testosterone production and whether acidosis, through a similar mechanism, can also increase cortisol production.

    There was some published research that concluded drinking the juice of 2 lemons a day reduced belly fat by the way. I tried looking but could not find it right now, however I am wondering if the mechanism is as follows: lemon consumption counters acidosis by alkalizing urine (and maybe to a very small extent the blood) and this leads to lower cortisol production, and thus to less belly fat.
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    Quote Originally Posted by Sub7 View Post
    Damn, almost forgot to ask one of the most important questions I had about cortisol; this is critical -perhaps not to many people here but for me it is for reasons I can explain later.

    As far as I know, acidosis increases testosterone production. I am talking about a whole body acidosis where you are constantly doing high rep squats for example (and I am aware that I am already slaughtering terms and science, as the blood PH cannot fluctuate much under any conditions whatsoever; so instead of a serious change in blood ph, which is impossible, I am referring to an increase in urinary PH as well as a situation where the body is trying to balance the acids with the production of carbonate and other mechanisms to actually keep blood ph stable).

    Can you please explain through what mechanism acidosis increases testosterone production and whether acidosis, through a similar mechanism, can also increase cortisol production.

    There was some published research that concluded drinking the juice of 2 lemons a day reduced belly fat by the way. I tried looking but could not find it right now, however I am wondering if the mechanism is as follows: lemon consumption counters acidosis by alkalizing urine (and maybe to a very small extent the blood) and this leads to lower cortisol production, and thus to less belly fat.
    I don't recall seeing any literature inidicating what you are saying. However, i have seen papers showing a chronic low level acidosis to prevent skeletal muscle anabolism and when the diet was supplemented with base, the environment became more anabolic.
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    Quote Originally Posted by Sub7 View Post
    Quite possibly you have mentioned in your earlier writings what to do about the severe reduction in muscle growth after a few weeks of steroid use (just so the message board henchmen do not jump on me; it can be a few weeks with something like superdrol, but three months or more with injectable Test E...), but for the record, can you share your opinion on the following:

    1) what do you suggest one should do when he finds that his response to steroids has already severely diminished during the cycle? (other than keep increasing the dosages until you are taking enough steroids to supply an army)

    2) Are there anythings that can be done during or before the cycle to delay the reduction in dose-response relationship to steroids (other than using the lowest dose that will elicit the desired response)

    3) Finally, some people (they are in the minority but do exist) report extraordinary fatigue with superdrol/pheraplex to the extent where they wish to stay in bed all day long. If this is primarily due to cortisol reduction (or reduction of the existing cortisol's binding ability to receptors) -and I have been asking for literally years what else could be going on, with no one ever being able to produce a good answer- can it be dangerous? Would this potentially reach clinically significant "adrenal exhaustion" levels?


    Thank you very much Sir and my apologies for asking questions that may already have been covered in your book. I will buy it very soon but will need to get ovwer this difficult holiday season -financially- first.
    1). I think you may have missed the part in my previous response where I stated that the "slowdown" in growth that most people are talking about is not really a slowdown in growth but the peak in water and glycogen accumulation. So, my suggestion is to approach it more analytically. Ignore the fact that water weight gain has slowed down and look in the mirror and on the scale to see if gains are progressing even if they are not progressing as fast as the initial gain.

    2) Can't think of anything off the top of my head.

    3) I don't really know for certain what the causes the fatigue. There is always the potential, with an untested drug like superdrol, for there to be serious side effects in a subset of users.
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    Quote Originally Posted by sethroberts View Post
    However, i have seen papers showing a chronic low level acidosis to prevent skeletal muscle anabolism and when the diet was supplemented with base, the environment became more anabolic.
    Any ideas at all, Seth as well as the other valued members here, as to what would be an ideal base to supplement with for this purpose? For a long time I am researching this exact topic but have not settled on one substance yet. I have experimented with

    calcium citrate
    potassium citrate
    lemon juice
    vinegar
    tums (calcium carbonate)
    baking soda (sodium bicarbonate)

    and did have success with them to varying degrees
  

  
 

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