From a practical perspective, can one of you describe the difference(s) (in effect) of DHEA (dehydroepiandrosterone) vs 7-oxo? I would like to try one transdermally, and I would apreciate your input. What are the pros and cons of each?
DHEA vs. 7-oxo-DHEA:
both are very interesting compunds. It was probobly about a year ago where I first said topical DHEA would make a good fat loss product now that we have potent aromatase inhibitors available OTC. So right from the get go I agree with one assesment he made but only in topical application with the inclusion of an aromatase inhibitor. But I do not agree that DHEA is superior to 7-oxo-DHEA. I would stipulate that they are simply different.
I think much of the flaws in this gentlemans analysis arise because he examined many in-vitro studies on fat cells. In-vitro research is wonderfull because it helps isolate mechanism. But mechanism does not euqal outcome.
First lets lay down what was not addressed about 7-oxo-DHEA.
1. Read par's article. he proposes a theory that 7-oxo-DHEA is an RXR agonist. I am not sure I completely agree with him but it does explain the thyroid potentiation in the liver and the adipogenic effects in SAT tissue.
2. my opnion is that by some mechanism (maybe RXR agonism, I have no made up my mind) 7-oxo-DHEA does potentiate thyroid activity and does produce a futile energy cycle in the liter at least.
3. The theory I proposed quite a while ago was that 7-oxo-DHEA inhibits localized cortisol formation bit competitive occupation of 11-Beta-HSD1. 7-oxo-DHEA fluxes back and forth to 7-OH-DHEA via 11-Beta-HSD1. 11-Beta-HSD1 is also what converts inactive cortisol metabolites back in to active cortisol in local tissue. thus by ocupying this enzyme with excess substrate we induce competitive inhibtion of LOCALIZED cortisol formation. This upregulation of 11-Beta-HSD1 is particularly a problem for VAT tissue development but also SAT tissue in the obese. It is thought that upregulation of this enzyme is responsible for the crazy high Leptin levels in the obese.
I think that his first mistake was in the asumption that VAT tissue is easily lost in all members of the population. Quite the contray. Allthough it is highly lipolytic and prone to apoptosis it also shows extreme resiliance in certain individuals. Mostly because of the renin-angiotensin-aldosterone-system.
secondly the idea that increased cortisol is advantageous on a diet. First, As I stated above I beleive 7-oxo-DHEA to be a competitive inhibitor of 11-Beta-HSD1. So that means it blocks cotisol only in tissues heavily ladden with 11-Beta-HSD1. This means your liver and adipose tissue primarily. I will get in to specifics in a bit but this is also one of the reason why I don't think its wise to use 7-oxo-DHEA orally.
Now directly the issue of excess cortisol being advantageous for fat loss. I would disagree. Again I think he is only looking at studies on fat cells. First and foremost he never mentioned how cortisol is lowered and in what tissue. So that should tell you something.
To understad why this is really flawed you need to understand what regulates the HPA. The PVN releases CRH -> CRH causes the pituitary to release ACTH -> ACTH causes the adrenals to produce cotisone and cotisol. Cortisol feeds back to the GR and McR receptors in the mid brain and limbic regions. Thus shuts off further CRH release. (Note for the purpose of symplification I am leaving out the RAS-aldosterone system here, even though it is vitally important. Look for an article about it from me in the near future).
The liver is a key point in this system as it largely determines the levels of plasma cortisol that are available to induce negative feedback. In the liver there are two enzymes that effects plasma cortisol levels. 11-Beta-HSD2 and 11-Beta-HSD1. As stated HSD1 activates inactive cortisol. HSD2 deactivates active cortisol.
So High HSD2 and low HSD1 creates a sort of cortisol sink. You liver just eats the stuff up so the negative feedback never gets back to the brain. Plasma levels stay about the same because the adrenals just pump our more to compensate but this has devistating effects on body compositon because of hyperactive CRH release. (see my leptin articles and my writings on avant labs about psychological conditions and metabolic regulation).
The other end of the spectrum is low HSD2 and high HSD1. This creates a super response system. In some individuals this results in down regulaton of the GR and all the terible stuff that acompanies that (anxiety, psychological disorders, etc..). In others it results in whats called hypo-HPA (where there is very little CRH release and very little ACTH or cortisol release. (such individuals are stress intollerant and just break down under even the slightes pressure. See research on PTSD).
So 7-oxo is a HSD1 inhibitor. This is why I don't think its optimal to use it orally. lowering HSD1 in the liver results in a mild cortisol sink phenomenon as described above. its better to use it topicaly in a product like absolved, PACT, or the now defunct FL-7 to avoid major interaction with the liver.
which just leaves us with supressed cortisol in local tissue namely adipose. So allready we are getting a selective reduction in cortisols activity. As big cat cited 7-oxo supports fat storage in-vitro (probobly through RXR agonism as par described) but and this is a big BUT this should be depot specific. In other words it would reduce VAT tissue at the expense of SAT tissue. The end result is a better physique because of it. if one is eating at a caloric deficet then this will simply cause VAT loss at the expense of SAT loss. If in a maintinance to surplus then this will cause redistrobution of VAT tissue to SAT tissue. The mistake being made is that effects in fat cells does not equal whole body effects. increased SAT cell fat trapping is actually quite advantageous for ones body composition. It promotes better nutrient partitioning through numerous systems. I can go in to them if you so desire.
Why not plain DHEA?
the main advantages that DHEA has over 7-oxo is its directly lipolytic and it inhibits PPAR-gamma. This is why I think a targeted delivery product of DHEA + aromatase inhibitor would be ideal for SAT loss. I started a thread on this very subject ages ago on avant.
But there are numerous problems with it as well. first DHEA is insulugenic. In other words it has been shown to increase basal plasma insulin levels. So just because DHEA is directly lipolytic does not mean the end result will be increased lipolysis. The increased insulin secretion might cancle out any benefit that the increased lipolytic signals offered.
problem two is that DHEA is EXTREMELY supressive of both 11-Beta-HSD enzymes in the liver and there for I think it should NEVER be used orally. studies in rats showed it reduced the content of 11-BETA-HSD mRNA by 75% at a very reasonable dosage. That can and will throw the normal HPA functioning out of whack.
Finally, Big Cat mentioned the psychoactive effects of DHEA. This is true but its not necesarily advantageous. neuronal DHEA increases AVP and CRH release. Those are not the neuropeptides you want increased. Both of which are stress neurochemicals and induce anxiety. I am sure anyone who has used DHEA in large doses can attest to this (particularly if stacked with an aromatase inhibitor).
There is also the problem that DHEA does effect normal sex hormone levels. So all in all I think now as I did a year ago. That a localized delivery product of DHEA + aromatase inhibitor might be of some advantage. though its total speculation as the other negative effects of DHEA might out weight the benefits. Any and all other uses of DHEA I think hold no real scientific basis.
Is anyone aware of a transdermal DHEA/AI recipe?
well from what I am told straight DHEA can turn into test or estrogen.7oxo is non hormonal just helps burn fat and may help build muscle by keeping corisitol low.Ill bet there going to put this on the new ban list and that will suck:FUfinger:
thanks for that info, one thing I know for sure its helping me lose fat and ethier gain or maintain muscleUmm, not true. 7-oxo is a metabolite of dhea and is absolutely a hormone. True, there are some studies that indicate it has little to no activity with the ar in the prostate, but we still don't know much about its binding potential elsewhere. There are also some studies that indicate that 7-oxo influences endogenous testosterone and estrogen levels, indicating that it does have some ar and er binding potential at least in the hypothalamous and pituitary.
From Supplement Watch:well from what I am told straight DHEA can turn into test or estrogen.7oxo is non hormonal just helps burn fat and may help build muscle by keeping corisitol low.Ill bet there going to put this on the new ban list and that will suck:FUfinger:
any ideas if 7oxo could cause gyno or itchy nips?:blink:Umm, not true. 7-oxo is a metabolite of dhea and is absolutely a hormone. True, there are some studies that indicate it has little to no activity with the ar in the prostate, but we still don't know much about its binding potential elsewhere. There are also some studies that indicate that 7-oxo influences endogenous testosterone and estrogen levels, indicating that it does have some ar and er binding potential at least in the hypothalamous and pituitary.