Interesting DHEA Study

[DmitryWI]

I have original bottle of t-gel, just never get to use it, but Nutraplanet has penetrate on sale now you can use it instead of t-gel, DHEA powder I got from Custom.
I have 3 jobs as of today, so I've been a little busy, but I think I'll keep the log and update it once or twice a week.
I've been nutty for 3 months now and wanted to do SD cycle first, but went to physical today for my job and still have blood pressure issues, so Rxt+DHEA is a good alternative for now.

 

[CROWLER]

Thanks for the info.




CROWLER

 

[mass_builder]

7-keto and 7-hydroxy forms are tailored to offer the anti-cortisol effects with minimal androgenicity. It won't restore libido like DHEA, but has it's place, especially in the first few weeks of PCT stacked with creatine or P.Serine. The 1fast stuff is a good deal, you could cap it or put it in a pro shake. BAC isn't bad either, they both assay pretty pure, but 1fast was a little stronger. I'm in my early 30's and only use DHEA for PCT, but after 40 or 50 may take it daily, if I've given up the juice. But that's not to say it would help on cycle, I just don't employee it that way usually. I've never tried it trans because it seems to be relatively well absorbed from the gut, but you can get at least 3.5% in 190 proof alcohol, so it's a viable option. I suspect you could get up to 10% in absolute ethanol.

DHEA is better anti-cortisol than 7-keto DHEA

from big cat article:

This is however the most utterly stupid thing I have ever heard. 7-oxo-DHEA is quite poor at aiding fat loss, and may actually inhibit it, while the much cheaper and more readily available DHEA is an excellent and often overlooked diet aid. One study (1) that directly compares the effects of DHEA to 7-oxo-DHEA clearly demonstrates this: cells treated with DHEA had significantly reduced levels fatty acid content, where as cells treated with 7-oxo had significantly increased levels of fatty acids.

This correlated well with the level of expression of stearoyl coA desaturase (SCD1), and may be mediated by changes in this enzyme, as DHEA treated cells had a much lower expression of SCD1, and cells treated with 7-oxo had considerably elevated levels of SCD1. DHEA also inhibited differentiation of pre-adipocytes into adipocytes, probably through a reduction in the proliferation and differentiation factor PPARgamma (3), and the study also demonstrated that DHEA had a thermogenic effect in already differentiating cells, whereas 7-oxo promoted differentiation with no effect on thermogenesis at all.

This is corroborated in another study (2) that shows that DHEA increases expression of UCP1 and UCP3 in fat cells. Since every fat cell expressing UCP1 is by definition a brown fat cell, we can conclude that next to inhibiting the differentiation of pre-adipocytes into new fat cells, it also turns differentiating and differentiated fat cells into brown fat cells.

Brown fat cells are thermogenically active and contribute to the process of burning calories. Thanks to their expression of UCP1 they also manage to uncouple this process from energy production. A brown fat cell produces more heat than energy, meaning more calories are burned for the same amount of energy produced. So not only does DHEA prevent the formation of new fat cells, those that are formed are metabolically active, while 7-oXo has no such effects at all and invariably leads to a higher level of fat in the cell.

One the supposed benefits touted for 7-oxo by supplement manufacturers is its ability to inhibit cortisol formation (4) more so than DHEA. This very thing is its major downside. Cortisol is only adipogenic in visceral fat. When on a diet, visceral fat is the easiest and fastest to be mobilized. A correct diet will not allow for visceral fat gain at all. Cortisol is highly lipolytic in all other tissues however, meaning you lose a considerable ally in the war on fat.

This suppression of cortisol is most likely why 7-oxo treated cells have a much higher fat content and why it doesn't inhibit differentiation. Furthermore DHEA also has distinct roles in enhancing beta-adrenergic mediated fat loss (5) and as a neuro-active steroid it lowers food intake (6).

The combination of all these effects make fat loss probably the best supported and documented role for DHEA, more so than any other purpose it was previously marketed for, while its analog 7-oxo-DHEA is currently marketed for that very purpose, while it actually decreases fat loss through several different pathways.

References


Gomez FE, Miyazaki M, Kim YC, Marwah P, Lardy HA, Ntambi JM, Fox BG. Molecular differences caused by differentiation of 3T3-L1 preadipocytes in the presence of either dehydroepiandrosterone (DHEA) or 7-oxo-DHEA. Biochemistry. 2002 Apr 30;41(17):5473-82.
Ryu JW, Kim MS, Kim CH, Song KH, Park JY, Lee JD, Kim JB, Lee KU. DHEA administration increases brown fat uncoupling protein 1 levels in obese OLETF rats. Biochem Biophys Res Commun. 2003 Apr 4;303(2):726-31.
Kajita K, Ishizuka T, Mune T, Miura A, Ishizawa M, Kanoh Y, Kawai Y, Natsume Y, Yasuda K. Dehydroepiandrosterone down-regulates the expression of peroxisome proliferator-activated receptor gamma in adipocytes. Endocrinology. 2003 Jan;144(1):253-9.
Hampl R, Lapcik O, Hill M, Klak J, Kasal A, Novacek A, Sterzl I, Sterzl J, Starka L. 7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy? Physiol Res. 2000;49 Suppl 1:S107-12.
Tagliaferro AR, Ronan AM, Payne J, Meeker LD, Tse S. Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats. Am J Physiol. 1995 Jun;268(6 Pt 2):R1374-80.
Wright BE, Svec F, Porter JR. Central effects of dehydroepiandrosterone in Zucker rats. Int J Obes Relat Metab Disord. 1995 Dec;19(12):887-92.

 

[DR.D]

Nice post MB! I agree.

 

[Alpha Dog]

Nice post MB! I agree.

That article from Big Cat created quite a debate at bb.com

Both DHEA and 7-oxo-dhea have their place.

http://forum.bodybuilding.com/showthread.php?t=257404&highlight=dhea

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.