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    Default 7-Keto DHEA's effect on cortisol

    Would 7-Keto DHEA be a cortisol antagonist in the same way DHEA is?

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    Quote Originally Posted by j03 View Post
    Would 7-Keto DHEA be a cortisol antagonist in the same way DHEA is?
    I don't recall the mechanism or details of DHEA's effects on the HPA, but both are inhibitors of 11beta-HSD1, the enzyme which catalyzes the conversion of cortisone to cortisol intracellularly.

    So, at least in part, the answer is yes, though the term "cortisol antagonist" is not quite right.

    I would hesitate to use 7-keto-DHEA, however, as I do worry that strong 11beta-HSD1 inhibition could lead to some nasty long-term side effects. (To wit, I strongly suspect 7-keto-DHEA is one of a handful of compounds potentially able to induce long-term HPA dysregulation otherwise known as "adrenal fatigue" or "burnout".)

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    Quote Originally Posted by Ex Dubio View Post
    I don't recall the mechanism or details of DHEA's effects on the HPA, but both are inhibitors of 11beta-HSD1, the enzyme which catalyzes the conversion of cortisone to cortisol intracellularly.

    So, at least in part, the answer is yes, though the term "cortisol antagonist" is not quite right.

    I would hesitate to use 7-keto-DHEA, however, as I do worry that strong 11beta-HSD1 inhibition could lead to some nasty long-term side effects. (To wit, I strongly suspect 7-keto-DHEA is one of a handful of compounds potentially able to induce long-term HPA dysregulation otherwise known as "adrenal fatigue" or "burnout".)
    If 7-keto-DHEA and DHEA are both 11beta-HSD1 inhibitiors, then wouldn't both of them be implicated with the same side effects?

    Then wouldn't 7-keto-DHEA be the best choice seeing it doesn't convert to androgens or estrogens?

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    Quote Originally Posted by j03 View Post
    If 7-keto-DHEA and DHEA are both 11beta-HSD1 inhibitiors, then wouldn't both of them be implicated with the same side effects?

    Then wouldn't 7-keto-DHEA be the best choice seeing it doesn't convert to androgens or estrogens?
    I don't recall offhand if DHEA directly inhibits 11beta-HSD1 or if it only does so by conversion to 7-keto. At any rate, DHEA is much weaker in this regard mg for mg.

    Keep in mind, people do not take DHEA to suppress cortisol; if anything, cortisol suppression from DHEA is likely to be an adverse effect.

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    I had thought it'd been established on this board that7-keto-DHEA was just plain old bad business considering it signifigantly dropped T which does not return to baseline for a LONG time.

    Anyway,I vaguely recall selective inhibitors of 11beta-HSD1 as being touted as big time by Spook (he noted bezafibrate as one) and ChemicalPA (11-oxo is also a 11beta-HSD1 inhibitor.The basis for this being improved CNS function and fat loss without systematically beating cortisol levels into the ground.

    Do I have 11beta-HSD1 inhibitors mistaken for something else?

    I had thought selective 11beta-HSD1 inhibition would be the absolute tits, as far as staving off overtraining symptoms and such and not the other way around i.e. inducing feelings of over training,chronic fatigue/burnout and the like.I had these sorts of benefits when I ran 11-oxo stand alone,a few years back.

    Quote Originally Posted by Ex Dubio View Post
    I don't recall the mechanism or details of DHEA's effects on the HPA, but both are inhibitors of 11beta-HSD1, the enzyme which catalyzes the conversion of cortisone to cortisol intracellularly.

    So, at least in part, the answer is yes, though the term "cortisol antagonist" is not quite right.

    I would hesitate to use 7-keto-DHEA, however, as I do worry that strong 11beta-HSD1 inhibition could lead to some nasty long-term side effects. (To wit, I strongly suspect 7-keto-DHEA is one of a handful of compounds potentially able to induce long-term HPA dysregulation otherwise known as "adrenal fatigue" or "burnout".)



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    Quote Originally Posted by Colin View Post
    Do I have 11beta-HSD1 inhibitors mistaken for something else?

    I had thought selective 11beta-HSD1 inhibition would be the absolute tits, as far as staving off overtraining symptoms and such and not the other way around i.e. inducing feelings of over training,chronic fatigue/burnout and the like.I had these sorts of benefits when I ran 11-oxo stand alone,a few years back.
    Probably not. I was under the impression that the mechanism of action of 7-keto was mostly limited to 11beta-HSD1 inhibition, though I've not followed up on this in a long time.

    But I'll give you my perspective on it. 11beta-HSD1 inhibitors block the conversion of cortisone to cortisol intracellularly in tissues that express 11beta-HSD1. 11beta-HSD1 is expressed in the CNS, in adipose tissue, in the liver, and in a handful of other places. But, most importantly, 11beta-HSD1 is expressed in the hypothalamus.

    So here's what I would expect to happen, and there is some evidence to support this IIRC. You take an 11beta-HSD1 inhibitor. Initially, cortisol's effects are blunted in the liver, in adipose tissue, and in the CNS. Bluting cortisol in the former two might be good, but blunted cortisol in the CNS is not. But that's almost beside the point.

    Because cortisol activity is then blunted in the hypothalamus, the HPA detects a reduction in serum cortisol, and increases its activity to compensate. This means more CRH, more ACTH, and more cortisol output. This likely occurs until the effects of 11beta-HSD1 inhibition are nearly negated, as the system "wants" to return to homeostatsis.

    Now, between the balance of increased cortisol output and continued 11beta-HSD1 inhibition, the net effects of cortisol in the hypothalamus, liver, and adipose tissue are essentially back to where they started. That is, there's ore cortisol floating around, but its conversion is also being partially blocked, and these effects cancel out.

    But what about all the issues that don't express 11beta-HSD1, including parts of the CNS, [some] skeletal muscle, and so on? Well, they experience the full effects of elevated serum cortisol. As such, in the long-run, the net effect of 7-keto would likely be to expose many tissues to significantly elevated concentrations of cortisol, and this is going to be harmful, particularly in parts of the CNS.

    Now, I haven't seen a lot of study into this matter, so this is somewhat speculative, but unless you can find an 11beta-HSD1 inhibitor that doesn't pass through the BBB (and remember, all steroids are lipid-soluble and pass easily), then I don't see how to avoid this.

    As a side note, I'd argue elevated cortisol is more of a consequence of overtraining than a cause. If anything, I'd expect lowering cortisol levels to exacerbate overtraining.

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    Quote Originally Posted by Ex Dubio View Post
    [...]
    As a side note, I'd argue elevated cortisol is more of a consequence of overtraining than a cause. If anything, I'd expect lowering cortisol levels to exacerbate overtraining.
    100% agree your body releases cortisol to cope with stress and repair damage induced by (over-)training. blocking it is the last thing you want to do, if you want to avoid CFS
    visit my nutrition & exercise science blog!
    SuppVersity @ SuppVersity.blogspot.com

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