Science Behind Product X

[Seth Roberts]

This thread is for the discussion of the science behind product X. I wanted to start a new thread so that people didn't have to wade through 300 posts by Pat Arnold et al. attacking us and our products. If you want to discuss the science or ask a question, fine, but if you are here to attack us I will ask to have your post removed from the thread. If you ask a question and I answer it then it is done. If you disagree, that is fine, say you disagree and end it.

[Slated]

hey guys, thanks for the great supps and science. I ordered a bottle of each right when they became avaliable. I'm curious though, to achieve best results, what dose would be best for a 'cycle'. I plan to use it as a bridge after my 1ad/4ad cycle or at least some of the 8 week bridge. Thanks again

[Slated]

in short, how many bottles do I need of each to give it the full Marine Corps try.

[Seth Roberts]

Here is a summary:

Local reduction in glucocorticoid (cortisol) signalling will result in an anti-catabolic effect. It is very well accepted that glucocorticoid signalling is catabolic in skeletal muscle. It has been shown that inhibition of 11 beta hydroxysteroid dehydrogenase type 1 (11BHSD1) results in reduced local levels of cortisol. 3,7-D5-BCA is a selective inhibitor of 11BHSD1 and would therefore reduce local levels of cortisol resulting in an anticatabolic effect.

As for beta-sitosterol, it has been shown to inhibit conversion of testosterone to DHT. For those that are not aware, DHT is not active in skeletal muscle because it is deactivated by 3-alpha hydroxysteroid dehydrognase and rapidly bound by albumin. You do not see anabolic effects from DHT unless you exceed the capacity of this enzyme or you use an a-ring protected DHT derivative (like dromostanaolone). In any case, the inclusion of beta sitosterol is to increase circulating levels of test by preventing one route of metabolism (to DHT) and by decreasing DHT's suppressive effect on LH pulse frequency.

Glycyrrhetinic hydrogen succinate (GHS) is a promiscuous inhibitor of 11BHSD1 and 2 that has been shown to increase insulin sensittivity.

I will post more when I have a chance.
Seth

[acecombact1]

ok i have a question, you claim that ecdy and methoxy in product X are more bioavilable and effective, because they are delivered transdermally.

yet many of the animal research on these two substances are via oral administration, and yet with the substances low bioavibility they were anabolic.

now in humans, many people had tried orally with no results even at high doses. there is a thread on here were some one took 1-2 g of ecdy for couple of months with no effects whatsoever.

so clearly. the 2 compounds has different effects on animals than humans, and the low bioavibility is no issue. if they work in low-bioavilability in animals why dont they work in humans?

so based on did conclude that transdermal delivery of methoxy and ecdy would be anabolic, or beneficial in any sort of way?!

[dio]

As for beta-sitosterol, it has been shown to inhibit conversion of testosterone to DHT. For those that are not aware, DHT is not active in skeletal muscle because it is deactivated by 3-alpha hydroxysteroid dehydrognase and rapidly bound by albumin. You do not see anabolic effects from DHT unless you exceed the capacity of this enzyme or you use an a-ring protected DHT derivative (like dromostanaolone). In any case, the inclusion of beta sitosterol is to increase circulating levels of test by preventing one route of metabolism (to DHT) and by decreasing DHT's suppressive effect on LH pulse frequency.

Seth

OK, here's what I posted in response to this on the avant board:

Seth,

I will save you the trouble of relocating my post and address your defense.

1. As I noted before (when Eric posted it) your reasoning here is weak. Inhibiting DHT conversion systemically (which beta-sistoral HAS NOT been proven to do) does not have ANY anabolic/anti-catabolic action. If this were the case, then everyone using propecia would be jacked.

2. Your understanding of deactivation of DHT in muscle is inadequate. DHT and 3 alpha are converted back and forth by the 3 aHSD enzyme. It isn't automatically bound. Unless you have a way to influence the balance of this conversion, addressing this enzyme guarantees nothing.

3. It's highly unlikely that using beta-sistoral will increase circulating test. Even if it did, it would be meaningless. Finasteride increases circulating test by inhibiting 5ar -- producing zero results.

4. Regular physiological levels of DHT do not suppress testosterone. Estrogen is a much stronger negative control.

5. Please show some support for all (any?) statements that you have made.

[acecombact1]

Here is a summary:

Local reduction in glucocorticoid (cortisol) signalling will result in an anti-catabolic effect. It is very well accepted that glucocorticoid signalling is catabolic in skeletal muscle. It has been shown that inhibition of 11 beta hydroxysteroid dehydrogenase type 1 (11BHSD1) results in reduced local levels of cortisol. 3,7-D5-BCA is a selective inhibitor of 11BHSD1 and would therefore reduce local levels of cortisol resulting in an anticatabolic effect.

As for beta-sitosterol, it has been shown to inhibit conversion of testosterone to DHT. For those that are not aware, DHT is not active in skeletal muscle because it is deactivated by 3-alpha hydroxysteroid dehydrognase and rapidly bound by albumin. You do not see anabolic effects from DHT unless you exceed the capacity of this enzyme or you use an a-ring protected DHT derivative (like dromostanaolone). In any case, the inclusion of beta sitosterol is to increase circulating levels of test by preventing one route of metabolism (to DHT) and by decreasing DHT's suppressive effect on LH pulse frequency.

Glycyrrhetinic hydrogen succinate (GHS) is a promiscuous inhibitor of 11BHSD1 and 2 that has been shown to increase insulin sensittivity.

I will post more when I have a chance.
Seth

so let me get this strate.....cortisol and glucosteroids are ctabolic, i already know that. inhibiting cortisol would be anti-catabolic, but not anabolic i.e it dosent increase protein synthasis.

so only anabolic mechnisim in product X, is using an aromatase inhibitors that work on the negative feedback of HTPA axis and increase testostrone (temporary) similar to 6-oxo. which can be anabolic for shot amount of time.

beta-sitosterol inhibits convertion of test to DHT, so more testsoterone can be utilized in anabolic process?!

but if DHT is not anabolic why do people take DHT derivative steroids like winny and masterone and yet gain muscle mass. what about M5aa its suppoesed to convert to methyl DHT. are they worthless.

is that how product X work?

PS:so if i want to mimic product X i would use 6-oxo aromatase inhibitor, oral spironolactone for DHT, and PS for cortisol?!

[Seth Roberts]

Ace,
There can be very big differences in oral bioavailability from one species to another (even from rat to mouse let alone from rodent to human). There were also quite a few studies done where ecdysteroids were given by injection to rodents. If a person is taking 1 to 2 grams per day of ecdy and there is only a 4% oral bioavialabiltiy, then that person is only getting 40 to 80 mg of ecdy. That is a hypothetical percentage because noone knows the exact amount.

[Seth Roberts]

Here is a paper that explains what happens to DHT in skeletal muscle.

1: Can J Biochem. 1977 Sep;55(9):995-1000. Related Articles, Links


Apparent saturability of a 4S dihydrotestosterone-binding protein in rat muscle cytosol: role of 3 alpha-hydroxysteroid dehydrogenase and albumin.

Dionne FT, Dube JY, Tremblay RR.

In our studies of the binding of steroids in rat skeletal muscles, we have shown the existence of a saturable '4S' dihydrotestosterone-binding protein of low affinity (Kd = 1.16 X 10(-6) M). Competition studies led us to believe that the binding of dihydrotesterone (DHT) was due to 3 alpha-hydroxysteroid dehydrogenase (3 alpha-OHSD) enzyme responsible for the conversion of DHT to androstanediol (Adiol). Indeed, both the binding and the enzymatic activity are inhibited by various 3-keto steroids. In addition, the dissociation constant (Kd) and the Michaelis constant (Km) of the enzyme are similar. However, experiments with ammonium sulfate fractions of the cytosol have shown a partial separation of the binding and of the enzymatic activity. On the other hand, we have established that DHT (3 micrometer) is almost completely metabolized to Adiol during a 2-h incubation of 0 degrees C even in the absence of added coenzymes. Furthermore the '4S' protein binds Adiol more strongly than DHT and this binding is not saturable. Finally the binding behaviour of both DHT and Adiol with either muscle cytosol or rat albumin is similar when subjected to ammonium sulfate fractionation and sucrose density gradient centrifugation. In conclusion, the skeletal muscle 3 alpha-OHSD rapidly metabolizes DHT into Adiol which then binds strongly to a nonspecific binding protein, presumably rat serum albumin. Thus it can be said that the observed saturability of DHT binding is only apparent.

PMID: 907903 [PubMed - indexed for MEDLINE]


The same process occurs in the liver as a pathway for degradation of DHT from circulation.

You can not look at this in a vacuum. Yes, by itself, suppression of 5AR is not singificantly anabolic. But, combined with aromatase inhibition it should produce a nice increase in testosterone production with no additional conversion to DHT as well as less androgenic feedback to the hypothalamus as well as greater AR stimulation in the skeletal muscle.

[Seth Roberts]

Decreasing the catabolic state will tip the scales towards the anabolic state. These two processes are always taking place but are usually in balance. If you decrease catabolism, you will generally increase anabolism. Also, if you accept that ecdy and methoxy are anabolic, then there is another anabolic stimulus. If you do not accept this, then you still should have a reasonable increase in endogenous testosterone which will be anabolic.

Winstrol (stanozolol) and masteron (dromostanolone) are A-ring substituted DHT derivatives which protects them from 3-alpha HSD.

Oral spironolactone is an androgen receptor antagonist -- so that would not be a good idea. And, as I told you before, PS decreases SYSTEMIC cortisol levels temporarily which is quickly followed by a significant rebound in cortisol production. Not a good thing.
Seth

[1fast400]

What defense is planned should the government come in and say your transdermal formula is systemic and therefor illegal?

[Seth Roberts]

Mike,
That is not a scientific qestion. Please remove it or I will ask a mod to. You can repost it in the other thread if you are so inclined.
Seth

[1fast400]

That is not a scientific qestion. Please remove it or I will ask a mod to. You can repost it in the other thread if you are so inclined.

Yes it is. You will have to justify your creation should the government step in. Trust me, this is a very real threat and I've wondered myself how I would/will deal with it when the time comes. I'm just curious what your plan is? Are you saying this product isn't illegal to make?

[iamthewalrus15]

I still gotta say, with these ingredients I am skeptical.. However, I really hope it works as well as the reports.. If it does you've got one hot product! Look forward to seeing what happens, and appreciate all your efforts to bring something new to the market!

[BiggJohn]

Should one take Product X will on Procepia?

[dio]

Here is a paper that explains what happens to DHT in skeletal muscle.

1: Can J Biochem. 1977 Sep;55(9):995-1000. Related Articles, Links


Apparent saturability of a 4S dihydrotestosterone-binding protein in rat muscle cytosol: role of 3 alpha-hydroxysteroid dehydrogenase and albumin.

Dionne FT, Dube JY, Tremblay RR.

In our studies of the binding of steroids in rat skeletal muscles, we have shown the existence of a saturable '4S' dihydrotestosterone-binding protein of low affinity (Kd = 1.16 X 10(-6) M). Competition studies led us to believe that the binding of dihydrotesterone (DHT) was due to 3 alpha-hydroxysteroid dehydrogenase (3 alpha-OHSD) enzyme responsible for the conversion of DHT to androstanediol (Adiol). Indeed, both the binding and the enzymatic activity are inhibited by various 3-keto steroids. In addition, the dissociation constant (Kd) and the Michaelis constant (Km) of the enzyme are similar. However, experiments with ammonium sulfate fractions of the cytosol have shown a partial separation of the binding and of the enzymatic activity. On the other hand, we have established that DHT (3 micrometer) is almost completely metabolized to Adiol during a 2-h incubation of 0 degrees C even in the absence of added coenzymes. Furthermore the '4S' protein binds Adiol more strongly than DHT and this binding is not saturable. Finally the binding behaviour of both DHT and Adiol with either muscle cytosol or rat albumin is similar when subjected to ammonium sulfate fractionation and sucrose density gradient centrifugation. In conclusion, the skeletal muscle 3 alpha-OHSD rapidly metabolizes DHT into Adiol which then binds strongly to a nonspecific binding protein, presumably rat serum albumin. Thus it can be said that the observed saturability of DHT binding is only apparent.

PMID: 907903 [PubMed - indexed for MEDLINE]


The same process occurs in the liver as a pathway for degradation of DHT from circulation.

You can not look at this in a vacuum. Yes, by itself, suppression of 5AR is not singificantly anabolic. But, combined with aromatase inhibition it should produce a nice increase in testosterone production with no additional conversion to DHT as well as less androgenic feedback to the hypothalamus as well as greater AR stimulation in the skeletal muscle.

Hey Seth,

Thanks for the response. That's only the second real reference I've seen supporting the DHT deactivated stance (the first is a brief mention in Vida). Anyway, I'll see if I can pull the full paper later. I've posted a reference supporting intraconversion below. You'll note that it does not deal directly with muscle but both studies reference the 3 aHSD enzyme as being the prime mover.

Onward: You still have not established how:

1. Inhibiting 5ar would increase DHT concentrations in muscle (I should have mentioned this the first time, but that DHT deactivation statement has always bugged me.) Id this was a valid theory (and I don't think it is) then we still would have seen something from all the people currently using them

2. Physiological levels of DHT suppress testosterone production

3.Is there an aromatase inhibtor in this product? You mention one above, but I don't recall seeing one in the ingredients list.

4. Are you relying on the Alternative Medicine journal to support the properties you attribute to betasistoral?

There's more but the above is a good place to start.


I have some others that deal specifically with the 3a HSD enzyme if you're interested.

J Steroid Biochem. 1990 Apr;35(5):611-6. Related Articles, Links
3 alpha-hydroxysteroid dehydrogenase in the cytosol of rat submandibular gland.

Furuyama M, Koshika S, Amaki A, Hosaka M.

Department of Biochemistry, Kanagawa Dental College, Yokosuka, Japan.

We examined the in vitro shuttle metabolism between dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) by 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD, E.C. 1.1.1.50) in rat submandibular gland (SMG) and ventral prostate (VP). The protein having molecular weight of 30 kDa, which was revealed by Sephacryl S-200 column chromatography, had 3 alpha-HSD activity to produce 3 alpha-diol from DHT, and also showed an oxidative 3 alpha-HSD (3 alpha-HSDO) ability to produce DHT from 3 alpha-diol. From the kinetic studies, the apparent Km and Vmax values of 3 alpha-HSD for DHT and NADPH were 6.4 microM, 1429 pmol/mg protein per min and 33.0 microM, 1205 pmol in SMG, and 9.3 microM, 377 pmol and 34.0 microM, 192 pmol in VP. The corresponding values of 3 alpha-HSDO for 3 alpha-diol and NADP+ were 18.0 microM, 714 pmol and 14.0 microM, 445 pmol in SMG, and 14.0 microM, 417 pmol and 36.0 microM, 77 pmol in VP. The affinities for DHT and 3 alpha-diol and the cosubstrate requirements of this enzyme in SMG were similar to those in VP. However, higher capacities of 3 alpha-HSD and 3 alpha-HSDO in SMG than in VP were shown. This suggests that there may be more 3 alpha-HSD in the SMG.

PMID: 2355736 [PubMed - indexed for MEDLINE]

[w_llewellyn]

2. Your understanding of deactivation of DHT in muscle is inadequate. DHT and 3 alpha are converted back and forth by the 3 aHSD enzyme. It isn't automatically bound. Unless you have a way to influence the balance of this conversion, addressing this enzyme guarantees nothing.

Not to take sides, as I have not spent time investigating many of the ingredients in this product, but I will point out this statement is incorrect. 3ahsd is largely preferential towads its inactivation of DHT to 3-alpha-diol. It is really not a back and fourth enzyme. This is the key reason why DHT is not anabolic; its levels are effectively blunted in skeletal muscle.

That said, DHT also has anabolic value outside of its AR/Muscle-tissue mitigated effects. I do not believe that diminishing systemic DHT coversion in of itself has any anabolic effect.. If anything it can interfere with them by diminishing some of DHT's positive effects on the neuromuscular system.

Inhibiting DHT breakdown specifically in muscle tissue would seem of interest, however it was also be a great scientific feat.

[acecombact1]

Ace,
There can be very big differences in oral bioavailability from one species to another (even from rat to mouse let alone from rodent to human). There were also quite a few studies done where ecdysteroids were given by injection to rodents. If a person is taking 1 to 2 grams per day of ecdy and there is only a 4% oral bioavialabiltiy, then that person is only getting 40 to 80 mg of ecdy. That is a hypothetical percentage because noone knows the exact amount.

i agree with you there could be a difference in bioavailability from one species to another, and that mean there can be a big difference of effects of methoxy and ecdy from one speicies to another, is there a study that says methoxy or ecdy are anabolic in humans!!. i dont think so...... Clen is found to be very anabolic in cows and mice, but in humans it has no anabolic effect, maybe anti-catabolic, but we cant prove that either.

in scientific research we observe, then suggest a hypotheses, then we try to disapprove the hypothesis if we can by conducting experiments. if we cant disapprove the Hypothesis then that prove the Hypothesis is true.

now you predict methoxy and ecdy are anabolic in humans, i can disprove it in many ways:

1- there is no data or research on the two compounds done by humans
2- many people had tried without no results
3- you dont know the oral bioavibility of methoxy and ecdy in humans, and thatt means dermal delivery can and maybe cant enhance bioavibility.
4- your tester results are not accurate, and could be results of other compounds in product or simply placebo.

im just curious as every one else to know if the 2 compounds work, one way to know if these compounds work, is to choose two testers give them 2 bottles one contain methoxy and ecdy, and the other palcebo. then we put the two testers under same training routine, diet and resting time. then observe the results.

[juanca]

yup, this will prob be taken out of this thread, but....

all the testers didnt really report anything major out of this
they all looked the same, most of there strength was the same, and its expensive also..

none the less, i am going to try X transdermal...

[acecombact1]

As for beta-sitosterol, it has been shown to inhibit conversion of testosterone to DHT. For those that are not aware, DHT is not active in skeletal muscle because it is deactivated by 3-alpha hydroxysteroid dehydrognase and rapidly bound by albumin. You do not see anabolic effects from DHT unless you exceed the capacity of this enzyme or you use an a-ring protected DHT derivative (like dromostanaolone). In any case, the inclusion of beta sitosterol is to increase circulating levels of test by preventing one route of metabolism (to DHT) and by decreasing DHT's suppressive effect on LH pulse frequency.

DHT doesn't stay active at the AR very much, often being drawn to SHBG, albumin, aromatase or 3bHSD, but still adds distinct hardness and boosts strength to some degree.

you messed an imporatant fact here, DHT-compounds blocks the aromatase enzyme, which forms estrogen, now decreasing DHT levels will decrease the DHT binding to aromatase enzymes. which mean DHT could increase Test levels like any aromatse inhibitor. just look at proviron, there is tons of studies that indicated it increases free test levels in the body, and from bb users feedback proviron gives a great libido boast on cycle.

so inhibiting the convertion of testosterone to DHT is useless since DHT can raise tetosterone levels byt its self and that can be utilized in anabolic actions also!!!

no show how can you respond to this.

[Seth Roberts]

DIO, noone said inhibiting 5AR would increase DHT in skeletal muscle. It is clear that 5Ar inhibition alone is not very anabolic (from those using finasteride) but again beta sitosterol is not being given alone, it is being given in combination with several other ingredients. Physiologic levels of estrogen and DHT are the feedback stimulus at the hypothalamus and pituitary that lead to suppression of LH release. In the physiologic state, these are all in balance. If you decrease eother estrogen or DHT stimulation in the hypothalamus/pituitary, you decrease this suppression of LH which results in increased endogenous test production. It is generally accepted that Androgens regulate LH pulse frequency while estrogens regulate pulse amplitude (but it is likely that there is some overlap here). One of the mechanisms of methoxyisoflavone is through either aromatase inhibition or estrogen receptor antagonism or both. As Bill stated, 3alpha HSD is considered to be unidirectional -- yes, it can be bidirectional in in vitor sysems, but in vivo, it is biased towards reductase activity.

Hey Seth,

Thanks for the response. That's only the second real reference I've seen supporting the DHT deactivated stance (the first is a brief mention in Vida). Anyway, I'll see if I can pull the full paper later. I've posted a reference supporting intraconversion below. You'll note that it does not deal directly with muscle but both studies reference the 3 aHSD enzyme as being the prime mover.

Onward: You still have not established how:

1. Inhibiting 5ar would increase DHT concentrations in muscle (I should have mentioned this the first time, but that DHT deactivation statement has always bugged me.) Id this was a valid theory (and I don't think it is) then we still would have seen something from all the people currently using them

2. Physiological levels of DHT suppress testosterone production

3.Is there an aromatase inhibtor in this product? You mention one above, but I don't recall seeing one in the ingredients list.

4. Are you relying on the Alternative Medicine journal to support the properties you attribute to betasistoral?

There's more but the above is a good place to start.


I have some others that deal specifically with the 3a HSD enzyme if you're interested.

J Steroid Biochem. 1990 Apr;35(5):611-6. Related Articles, Links
3 alpha-hydroxysteroid dehydrogenase in the cytosol of rat submandibular gland.

Furuyama M, Koshika S, Amaki A, Hosaka M.

Department of Biochemistry, Kanagawa Dental College, Yokosuka, Japan.

We examined the in vitro shuttle metabolism between dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) by 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD, E.C. 1.1.1.50) in rat submandibular gland (SMG) and ventral prostate (VP). The protein having molecular weight of 30 kDa, which was revealed by Sephacryl S-200 column chromatography, had 3 alpha-HSD activity to produce 3 alpha-diol from DHT, and also showed an oxidative 3 alpha-HSD (3 alpha-HSDO) ability to produce DHT from 3 alpha-diol. From the kinetic studies, the apparent Km and Vmax values of 3 alpha-HSD for DHT and NADPH were 6.4 microM, 1429 pmol/mg protein per min and 33.0 microM, 1205 pmol in SMG, and 9.3 microM, 377 pmol and 34.0 microM, 192 pmol in VP. The corresponding values of 3 alpha-HSDO for 3 alpha-diol and NADP+ were 18.0 microM, 714 pmol and 14.0 microM, 445 pmol in SMG, and 14.0 microM, 417 pmol and 36.0 microM, 77 pmol in VP. The affinities for DHT and 3 alpha-diol and the cosubstrate requirements of this enzyme in SMG were similar to those in VP. However, higher capacities of 3 alpha-HSD and 3 alpha-HSDO in SMG than in VP were shown. This suggests that there may be more 3 alpha-HSD in the SMG.

PMID: 2355736 [PubMed - indexed for MEDLINE]

[Seth Roberts]

Your inquiries are starting to csound less scientific and more accusatory. No, aside from the russian studies, there are no direct studies on ecdy and methoxy being anabolic in humans. Before creatine and 4-ad came on the market, there were no studies on them being anabolic either. Clen is anticatabolic in humans and I have explained to you that anticatabolism generally equates to increased anabolism -- but you seem to be ignoring what I say. If you disagree, that is fine, but you have stated your disagreement and that is that.

i agree with you there could be a difference in bioavailability from one species to another, and that mean there can be a big difference of effects of methoxy and ecdy from one speicies to another, is there a study that says methoxy or ecdy are anabolic in humans!!. i dont think so...... Clen is found to be very anabolic in cows and mice, but in humans it has no anabolic effect, maybe anti-catabolic, but we cant prove that either.

in scientific research we observe, then suggest a hypotheses, then we try to disapprove the hypothesis if we can by conducting experiments. if we cant disapprove the Hypothesis then that prove the Hypothesis is true.

now you predict methoxy and ecdy are anabolic in humans, i can disprove it in many ways:

1- there is no data or research on the two compounds done by humans
2- many people had tried without no results
3- you dont know the oral bioavibility of methoxy and ecdy in humans, and thatt means dermal delivery can and maybe cant enhance bioavibility.
4- your tester results are not accurate, and could be results of other compounds in product or simply placebo.

im just curious as every one else to know if the 2 compounds work, one way to know if these compounds work, is to choose two testers give them 2 bottles one contain methoxy and ecdy, and the other palcebo. then we put the two testers under same training routine, diet and resting time. then observe the results.

[Seth Roberts]

Ace,
You are incorrect, DHT has a considerably longer half-life of binding (residence time) at the receptor than does testosterone. Your statement that it adds "hardness" is an anecdotal observation that is unquantifiable. DHT compounds may block aromatase, but we are talking about DHT here which proabably has little antiaromatase activity in vivo because it circulates at very low levels. DHT does not increase test levels but instead is a direct feedback stimulus for the suppression of LH release and therefore the suppression of testosterone -- see my response to DIO. Proviron increases free test by virtue of its very strong binding to SHBG -- it displaces bound test (and also estrogen by the way) from DHT -- this eventually results in feedback inhibition of testosterone release. You can not compare exogenous administration of synthetic derivateives od DHT to endogenous DHT. You argument is fundamentally flawed, It goes against everything that is known about basic endocrinology of androgens.

DHT doesn't stay active at the AR very much, often being drawn to SHBG, albumin, aromatase or 3bHSD, but still adds distinct hardness and boosts strength to some degree.

you messed an imporatant fact here, DHT-compounds blocks the aromatase enzyme, which forms estrogen, now decreasing DHT levels will decrease the DHT binding to aromatase enzymes. which mean DHT could increase Test levels like any aromatse inhibitor. just look at proviron, there is tons of studies that indicated it increases free test levels in the body, and from bb users feedback proviron gives a great libido boast on cycle.

so inhibiting the convertion of testosterone to DHT is useless since DHT can raise tetosterone levels byt its self and that can be utilized in anabolic actions also!!!

no show how can you respond to this.

[Footballstar]

If i used a transdermal of methoxy at 200 mg per 2ml and took 200 mg everyday for 30 days research says it will produce "better results then some steroids." If you finally made methoxy able to be readily absorbed by the body like you say it can be done transdermally this above statement should be true correct or close to the truth . Right ?

[Seth Roberts]

Show me the study where this is stated. We have never stated that these products will be better than illegal steroids. We have stated that they will replace prohormones and in most cases (except methyl-1-test) produce better results than PH's.
Seth

[acecombact1]

Ace,
You are incorrect, DHT has a considerably longer half-life of binding (residence time) at the receptor than does testosterone. .

Endocrinology. 1984 Jun;114(6):2100-6. Related Articles, Links


Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin.

Saartok T, Dahlberg E, Gustafsson JA.

It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [ RBAs relative to that of MT: MT greater than 19-nortestosterone ( NorT ; nandrolone) greater than methenolone (17 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3-one) greater than testosterone (T) greater than 1 alpha-methyl-DHT]. In other cases, AR binding was weak (RBA values less than 0.05): stanozolol (17 alpha-methyl-5 alpha- androstano [3,2-c]pyrazol-17 beta-ol), methanedienone (17 beta-hydroxy-17 alpha-methyl-1,4-androstadien-3-one), and fluoxymesterolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one) and ethylestrenol (17 alpha-ethyl-4- estren -17 beta-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5 alpha-androstane-3 alpha, 17 beta-diol and its 3 beta-isomer (3 alpha- and 3 beta-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (1 alpha-methyl-DHT much greater than DHT greater than T greater than 3 beta-adiol greater than 3 alpha-adiol = 17 alpha-methyl-T greater than methenolone greater than methanedienone greater than stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases.(ABSTRACT TRUNCATED AT 400 WORDS)


read the study DHT has stronger and more avid binding afinity to globulin (SHBG), and weak binding affinity to the AR.

[acecombact1]

yha i have another question, how effective is beta-sitosterol to finasteride in blocking DHT. is beta-sitosterol supposed to be site specific in its action?

[Seth Roberts]

What is your point, everyone knows that Dht binds more strongly to SHBG than testosterone. But, when bound, DHT stays bound to the receptor for a longer period of time than when testosterone is bound.

Beta sitosterol is a weaker inhibitor of 5 alpha reductase than finasteride. Beta sitosterol is a natural products whereas finasteride is a pharmaceutical which has been designed to be as strong of an inhibitor as possible. No, beta sitosterol is not site specific.

[dio]

Not to take sides, as I have not spent time investigating many of the ingredients in this product, but I will point out this statement is incorrect. 3ahsd is largely preferential towads its inactivation of DHT to 3-alpha-diol. It is really not a back and fourth enzyme. This is the key reason why DHT is not anabolic; its levels are effectively blunted in skeletal muscle.

That said, DHT also has anabolic value outside of its AR/Muscle-tissue mitigated effects. I do not believe that diminishing systemic DHT coversion in of itself has any anabolic effect.. If anything it can interfere with them by diminishing some of DHT's positive effects on the neuromuscular system.

Inhibiting DHT breakdown specifically in muscle tissue would seem of interest, however it was also be a great scientific feat.

I'm pretty sure I have a paper dealing with conversion in liver that says otherwise. I'll check next time I fire up my machine at home.

[dio]

DIO, noone said inhibiting 5AR would increase DHT in skeletal muscle. It is clear that 5Ar inhibition alone is not very anabolic (from those using finasteride) but again beta sitosterol is not being given alone, it is being given in combination with several other ingredients. Physiologic levels of estrogen and DHT are the feedback stimulus at the hypothalamus and pituitary that lead to suppression of LH release. In the physiologic state, these are all in balance. If you decrease eother estrogen or DHT stimulation in the hypothalamus/pituitary, you decrease this suppression of LH which results in increased endogenous test production. It is generally accepted that Androgens regulate LH pulse frequency while estrogens regulate pulse amplitude (but it is likely that there is some overlap here). One of the mechanisms of methoxyisoflavone is through either aromatase inhibition or estrogen receptor antagonism or both. As Bill stated, 3alpha HSD is considered to be unidirectional -- yes, it can be bidirectional in in vitor sysems, but in vivo, it is biased towards reductase activity.

I'll check to see if I have something countering Bill's view later, but it's largely irrelevant here anyway.

I agree with you on the estrogen levels regulating HPTA at physiological levels, but not with the DHT. Also, keep in mind that with estrogen antagonism any increases in T are a wash (excepting those with suppressed levels) due to the subsequent increase SHBG.

I don't see where you're getting the idea that decreasing physiological levels of DHT is going to do anything to increase test levels. The minor increases that come from 5ar inhibitors are a result of less T being metabolised to DHT, not increased test output. On top of that, there's no strong evidence showing that BS inhibits 5ar systemically.

The hardening effect of methoxy might at first seem to have something to do with estrogen, but I think that's not really the case. Otherwise, it would produce increases from T or at least protection from estrogen sides from a cycle. I've never seen any indication that it does either -- much less any research supporting this. I believe Spook had a theory that dealt with calcium retention.

In conclusion, I'm really at a loss why BS was included in this product at all.