Sublingual Dbol

[OuchThatHurts]

Ouchthathurts, superdrol isn't only a methyl , it's an alkalated methyl?

ultrasdrol, boladrol, msten, dmz, phera all over the counter anabolic hormones from that era, about twelve years ago

Yeah, I remember.

 

[Soalian]

It is true that sublingual delivery through the oral mucosa avoids the first pass hepatic metabolism and absorption through the GI tract common to oral AAS, but it doesn't meaningfully reduce hepatic strain as first pass is mere "blip" for 17AA androgens. To quote Peter Bond: "The liver has a blood flow rate of roughly 1 liter a minute and the 17alpha-alkylated AAS have half-lives in the order of hours with a relatively low volume of distribution. The liver will be exposed for quite some time to high concentrations, regardless of the route of administration. As such, I doubt it's relevant for hepatotoxicity."

Please correct me if I'm wrong here, I am asking because I don't know much about the issue and am trying to understand thigns right:


about Dianabol in particular, I don't know the pharmacology of the compound very well (and other oral c17a-alkylated steroids), but oral or sublingual,

Dianabol is first metabolized into its metabolites, and notably 17a-methyl estradiol, in this case for example, the liver doesn't play a role in the "first-pass" metabolization of the compound,

since the conversion takes place by the Aromatase enzyme, that is found is many tissues,

so in this case of 17a-methyl estradiol, dianabol doesn't undergo the conversion in the liver in particular, since the liver only contains aromatase enzyme in smaller amounts?

Therefore the dianabol can first go through the liver unchanged, before returning to the liver once it's been converted to let's say 17a-methyl estradiol, mainly in other tissues?

so for first conversion, in this case into 17a-methyl estradiol, taking it sublingual could be more effective than oral (for increased estrogen), because the liver plays basically only a small dose in this conversion anyway?

Thanks for clearing up this issue for me if you can

 

[Type-IIx]

Please correct me if I'm wrong here, I am asking because I don't know much about the issue and am trying to understand thigns right:


about Dianabol in particular, I don't know the pharmacology of the compound very well (and other oral c17a-alkylated steroids), but oral or sublingual,

Dianabol is first metabolized into its metabolites, and notably 17a-methyl estradiol, in this case for example, the liver doesn't play a role in the "first-pass" metabolization of the compound,

since the conversion takes place by the Aromatase enzyme, that is found is many tissues,

so in this case of 17a-methyl estradiol, dianabol doesn't undergo the conversion in the liver in particular, since the liver only contains aromatase enzyme in smaller amounts?

Therefore the dianabol can first go through the liver unchanged, before returning to the liver once it's been converted to let's say 17a-methyl estradiol, mainly in other tissues?

so for first conversion, in this case into 17a-methyl estradiol, taking it sublingual could be more effective than oral (for increased estrogen), because the liver plays basically only a small dose in this conversion anyway?

Thanks for clearing up this issue for me if you can

Phase I (Cytochrome P450 enzymes, notably the CYP3A family, oxidize, reduce & hydroxylate the hydrophobic androgen to more polar metabolites) & Phase II (glucoronidation & sulfation reactions to deactivate and facilitate excretion thereof) metabolism both occur in the liver. All androgens and routes (INCLUDING INJECTABLE) are metabolized in the liver.

Aromatization of the parent steroid (reconfiguration from the C-19 3-keto-4-ene androgen moiety to a C-18 estrogen) occurs, as you describe, in various tissues (but mostly in adipose, testes, and brain tissues; with some variation in expression between individuals and compartments).

Aromatization as a process is not so discrete nor isolated as you imply (it's also not a single reaction; it is three). During aromatization the liver is simultaneously exposed to high concentrations of toxic 17AA androgen (the parent Dianabol) on a long time-course that it must deactivate and excrete (because androgen, even testosterone, is toxic). All of these reactions are occurring simultaneously during the activity of the Dianabol.

While A-ring metabolism occurs under the umbrella of Phase I metabolism to reduce the Δ4,5, here, with Dianabol (a 1,4-diene or 3-keto-androsta-1,4-diene androgen), this occurs relatively late in the metabolism of the A ring after 1,2-hydrogenation. Aromatization distinctly occurs outside of the liver and for Aromatase, the parent steroid is the substrate.

You seem to want to break down the process of 17AAs into a simple model where A->B->C but the human body can chew gum and walk through doors at the same time.

In no way does it follow that sublingual administration of any 17AA confers any advantage for aromatization/estrogenicity, because skipping phase I metabolism by sublingual dosing serves only to obviate CYP reactions in the liver to more polar compounds; it does not meaningfully reduce hepatotoxicity (because the liver is exposed to high concentrations [and on a long time-course] of Dianabol because of its 17α-methylation, regardless of administration technique) nor alter Aromatase (a CYP19A1 gene that is expressed in non-liver cells) activity (which occurs outside the liver).

 

[Soalian]

Phase I (Cytochrome P450 enzymes, notably the CYP3A family, oxidize, reduce & hydroxylate the hydrophobic androgen to more polar metabolites) & Phase II (glucoronidation & sulfation reactions to deactivate and facilitate excretion thereof) metabolism both occur in the liver. All androgens and routes (INCLUDING INJECTABLE) are metabolized in the liver.

Aromatization of the parent steroid (reconfiguration from the C-19 3-keto-4-ene androgen moiety to a C-18 estrogen) occurs, as you describe, in various tissues (but mostly in adipose, testes, and brain tissues; with some variation in expression between individuals and compartments).

Aromatization as a process is not so discrete nor isolated as you imply (it's also not a single reaction; it is three). During aromatization the liver is simultaneously exposed to high concentrations of toxic 17AA androgen (the parent Dianabol) on a long time-course that it must deactivate and excrete (because androgen, even testosterone, is toxic). All of these reactions are occurring simultaneously during the activity of the Dianabol.

While A-ring metabolism occurs under the umbrella of Phase I metabolism to reduce the Δ4,5, here, with Dianabol (a 1,4-diene or 3-keto-androsta-1,4-diene androgen), this occurs relatively late in the metabolism of the A ring after 1,2-hydrogenation. Aromatization distinctly occurs outside of the liver and for Aromatase, the parent steroid is the substrate.

You seem to want to break down the process of 17AAs into a simple model where A->B->C but the human body can chew gum and walk through doors at the same time.

In no way does it follow that sublingual administration of any 17AA confers any advantage for aromatization/estrogenicity, because skipping phase I metabolism by sublingual dosing serves only to obviate CYP reactions in the liver to more polar compounds; it does not meaningfully reduce hepatotoxicity (because the liver is exposed to high concentrations [and on a long time-course] of Dianabol because of its 17α-methylation, regardless of administration technique) nor alter Aromatase (a CYP19A1 gene that is expressed in non-liver cells) activity (which occurs outside the liver).

thank you for the detailed reply; it helps getting a better picture of what's going on from knowledgeable users.

Was thinking about this the other day, and I apologize if it sounds like a basic question, but in people who have been on AAS for some amount of time (without adjunct HCG), so that their usual gonadal function is basically shut down,

would the aromatase enzyme still be active and doing its job with aromatizing the aromatize-able exogenous androgens (for example, Test) in the gonads of basically hypo-gonadal AAS users?

Or do the aromatizing activities of the gonads also shut down when the HPG axis (pituitary gonadotropins, LH and FSH,...) is also shut down, when exogenous AAS are present?

Thanks man for clearing this up, I'm still new to Endocrinology knowledge honestly lol

 

[Soalian]

It is true that sublingual delivery through the oral mucosa avoids the first pass hepatic metabolism and absorption through the GI tract common to oral AAS, but it doesn't meaningfully reduce hepatic strain as first pass is mere "blip" for 17AA androgens. To quote Peter Bond: "The liver has a blood flow rate of roughly 1 liter a minute and the 17alpha-alkylated AAS have half-lives in the order of hours with a relatively low volume of distribution. The liver will be exposed for quite some time to high concentrations, regardless of the route of administration. As such, I doubt it's relevant for hepatotoxicity."

Yes, the rationale for avoiding liver first-pass (through sublingual/injectable ROA) would then mostly be about increased Dbol bioavailability ?

how much more could we say bioavailability through sublingual ROA may be VS orally? (like, dbol tablets crushed into powder, then dissolved under tongue with water for sublingual ROA).

Given the liver blood flow rate of about 1 liter/minute, IDK whether avoiding hepatic first pass would truly yield better bioavailibilty (to muscles, kidneys, brain,...),

what do you guys think about it, would sublingual really yield enough of an increase in Dbol bioavailability VS oral, to warrant the use of Dbol sublingually, instead of orally ?

Thanks.

 

[Soalian]

I'm trying to find out info on how much would Dianabol resist the degradation effects of GI tract upon oral administration (stomach acid, etc,...) (aka how orally bioavailable it is upon exposure to the stomach environment),

also need to find how much water-soluble Dianabol really is, see if that makes it worthwhile to dissolve it in water for sublingual use (goal is for most of it to be absorbed through oral/buccal/sublingual mucosa, so higher water solubility would help here),


because if it turns out Dbol is very resistant to degradation in the GI tract (high oral bioavailablity),

then slow hepatic metabolism (due to the c17a structure of the compound, so first hepatic first pass will leave the molecule quite intact before reaching circulation),

and finally depending on Dbol's water solubility,

all those three factors might make sublingual Dbol administration not that much worth it over oral (not much more dbol reaching the target organs and receptors,etc,...)

Thoughts? @Type-IIx don't wanna tag you but you know a bit on this, @OuchThatHurts , others ?


Thanks.

 

[Soalian]

the gap between dianabol (and other oral AAS) oral VS sublingual bioavailability can come down to:


- compound resistance to GI and intestinal breakdown

- water solubility, so that sublingual Dbol dissolved in water might at least be absorbed through the sublingual/buccal mucosa

- resistance to first-pass hepatic breakdown (c17-alkylated steroids are designed to be quite resistant to hepatic breakdown)

 

[OuchThatHurts]

I'm trying to find out info on how much would Dianabol resist the degradation effects of GI tract upon oral administration (stomach acid, etc,...) (aka how orally bioavailable it is upon exposure to the stomach environment),

also need to find how much water-soluble Dianabol really is, see if that makes it worthwhile to dissolve it in water for sublingual use (goal is for most of it to be absorbed through oral/buccal/sublingual mucosa, so higher water solubility would help here),


because if it turns out Dbol is very resistant to degradation in the GI tract (high oral bioavailablity),

then slow hepatic metabolism (due to the c17a structure of the compound, so first hepatic first pass will leave the molecule quite intact before reaching circulation),

and finally depending on Dbol's water solubility,

all those three factors might make sublingual Dbol administration not that much worth it over oral (not much more dbol reaching the target organs and receptors,etc,...)

Thoughts? @Type-IIx don't wanna tag you but you know a bit on this, @OuchThatHurts , others ?


Thanks.

It will reach the bloodstream intact because that's exactly what alkylation is designed to do. But whether injected or absorbed through various mucosa, it will make many passes through the liver. So you may bypass first pass through the portal vein to the liver but it will pass through your liver many many times until it's all fully metabolized. This is why it's not liver friendly. Not just first pass.

Hope that made things clearer.

 

[Soalian]

It will reach the bloodstream intact because that's exactly what alkylation is designed to do. But whether injected or absorbed through various mucosa, it will make many passes through the liver. So you may bypass first pass through the portal vein to the liver but it will pass through your liver many many times until it's all fully metabolized. This is why it's not liver friendly. Not just first pass.

Hope that made things clearer.

yes, liver first pass won't affect he overall biovaialbilit for the Dbol, I was thinking more in terms of the Dbol's GI breakdown before reaching the liver, and to what extent Dianabol is thus orally biovaialble after more or less resistance to GI breakdown.

In this case, alternatives like sublingual might still yield better bioavailability than oral, because it avoids going through the whole gastrointestinal tract (stomach acidity, possiblly presence of foods in the stomach,etc...),

becaus yes, once it reaches the liver for first-pass hepatic metabolism, and even second-pass, etc,..., the c17a structura makes it quite resistant to hepatic breakdown so even after fist liver bypass the Dbol will reach the bloodstream almost un-modified (pretty much the same as sublingual, only this ROA will allow for quicker absoption and avoiding GI tract as well).

 

[OuchThatHurts]

The enzymatic action of the gut could have some effect but remember there is absolute bioavailability and relative bioavailability, if you want to go the sublingual route go for it. Although the oral bioavailability of these is usually very good (>90%) while the IV route would obviously be 100% (absolute bioavailability). Some people have gastric distress from orals and sublingual or a nasal mist might do better. But sublingual or nasal, much of it is going to drain down the esophagus anyway. And the AUC will be close for all methods (effective bioavailability).

Just curious, it's a cheap medication. Why are we splitting hairs? Is this just an experiment? Or do you have a reason in mind?

 

[Type-IIx]

the gap between dianabol (and other oral AAS) oral VS sublingual bioavailability can come down to:


- compound resistance to GI and intestinal breakdown

- water solubility, so that sublingual Dbol dissolved in water might at least be absorbed through the sublingual/buccal mucosa

- resistance to first-pass hepatic breakdown (c17-alkylated steroids are designed to be quite resistant to hepatic breakdown)

Nobody has any interest in playing whack-a-mole with your justifications for liking sublingual administration of 17AAs. It's been variously addressed that oral 17AAs have essentially 100% bioavailability via the oral route (profoundly well absorbed), and because they are resistant to hepatic metabolism, first pass is a "mere blip" (irrelevant) to their activity/bioavailability. I have no interest in further addressing any novel justifications you might come up with.

 

[Type-IIx]

thank you for the detailed reply; it helps getting a better picture of what's going on from knowledgeable users.

Was thinking about this the other day, and I apologize if it sounds like a basic question, but in people who have been on AAS for some amount of time (without adjunct HCG), so that their usual gonadal function is basically shut down,

would the aromatase enzyme still be active and doing its job with aromatizing the aromatize-able exogenous androgens (for example, Test) in the gonads of basically hypo-gonadal AAS users?

Or do the aromatizing activities of the gonads also shut down when the HPG axis (pituitary gonadotropins, LH and FSH,...) is also shut down, when exogenous AAS are present?

Thanks man for clearing this up, I'm still new to Endocrinology knowledge honestly lol

I apologize I cannot get to all of your quotes/tags, there are too many, this is feeling like work.

Aromatase activity in testis accounts for ~20% (very little) of aromatization (E2 synthesis) in adult men at normal hypogonadal concentrations. Chronic supra-physiologic androgen decreases GnRH pulse frequency & LH pulse amplitude (central effects), but there is good evidence (postmortem) that androgen abusers also see local testis cell (Leydig & Sertoli) necrosis (cell/tissue death).

So there's likely some minimal decrease in (i.e., Leydig cell) testis aromatase activity, yet this is largely irrelevant, since aromatization occurs in other tissues writ large.

 

[Soalian]

Nobody has any interest in playing whack-a-mole with your justifications for liking sublingual administration of 17AAs. It's been variously addressed that oral 17AAs have essentially 100% bioavailability via the oral route (profoundly well absorbed), and because they are resistant to hepatic metabolism, first pass is a "mere blip" (irrelevant) to their activity/bioavailability. I have no interest in further addressing any novel justifications you might come up with.

Don't worry, I won't because your knowledge in the matter pretty much vastly outlasts mine anyway lol

 

[Soalian]

4. Recommendations
I strongly recommend TUDCA or UDCA to anybody considering a cycle containing oral androgens, for what should by now be obvious reasons. They are extremely potent at preventing or reversing 17aa-androgen-mediated liver damage. There's really no excuse not to take them, in my opinion, and I would advise you not to run a cycle if you can't afford them. Oral androgens can send you straight to the ER if the right precautions are not taken, & your health is much more important than a few more pounds of here-today-gone-tomorrow muscle.

Silymarin and silybin, the milk thistle extracts, are very strong antioxidants and free-radical scavengers in hepatic tissue. They impede hepatic lipid peroxidation, increase glutathione concentrations, and even have anti-inflammatory and tissue-regenerative properties... Other plant-extracted compounds, such as celastrol, have similar effects... But while these extracts are excellent to take for general liver health, they are weak protection and not an appropriate treatment for cholestasis, as they do not appear to impact bile acid secretion/metabolism at pharmacologically-relevant doses. Silymarin did increase bile secretion and improve bile acid metabolism in rats -- but that effect was primarily noticed at a dose of 100mg/kg, administered via i.p. injection (100% bioavailability), and therefore doesn't have much bearing on humans who take much smaller amounts orally (~10% bioavailability).
...But Primordial Performance's "Liver Juice" is silymarin/silybin attached to an excellent delivery complex, and should be quite effective if taken 3x/day. It is the best milk thistle supplement out there, in my opinion.

NAC is also a fine antioxidant and glutathione-booster, but it suffers from poor bioavailability & is usually very underdosed in commercially-available supplements... So I wouldn't bother with it.

Sanofi-Aventi (or is it just 'Sanofi' these days?) manufactures the popular phospholipid-complex product "Essentiale" and "Essentiale Forte". The phosphatidylcholine therein has been shown to help protect hepatic cell membranes against the damaging effects of chenodeoxycholic acid, can inhibit lipid peroxidation, and can induce cytochrome P450, which stimulates the metabolic clearance of bile acids... So there's a reason that it's the most popular OTC liver support in Europe and Asia... But "Essentiale" can be hard to find in the USA -- and, on its own, I don't believe that it is totally adequate protection for users of oral androgens.

Essentiale Forte is patented brand; PPC is also available (and may be cheaper per dose) from Life Extension's Hepatopro product.

If you allow me to add to this comprehensive list already, maybe SAM-E would be a nice addition to a liver protocol as well.

NAC can be dosed as the user sees fit, IMO, since most products come in capsules or powder.

 

[Type-IIx]

Don't worry, I won't because your knowledge in the matter pretty much vastly outlasts mine anyway lol

Thanks bro. I recognize we have an instinct to sort of want to justify to others what we want to be true about practices/rituals. I know that there were some YouTube expertz putting out scintillating videos on the potency of sublingual admin. But in reality, it just doesn't have any significant effect on 17AA bioavailability or potency. And you'll see good bros swear up and down injectable 17AAs are better than oral... cannot be, if anything, they're worse (unless you feel some thrill from poking yourself with needles unnecessarily and/or enjoy the rush of injectable winny's crippling PIP).

 

[VaginaBoob89]

Man, I know he has good intentions, but nearly everything VigorousSteve has said has been wrong in my real world experience. The only two things he was sorta right about when it came to my own experience was lantus and anavar. He's a good dude but I'm not sure I'd take his advice on anything related to hardcore bodybuilding; his advice is good for gym rats who want to get good body but that's about it. Solely because it's coming from him, I really doubt siblingual administration will result in less toxicity.

 

[Soalian]

I kind of disagree with Nac being ineffective, esp if taken at a gram or over, but I could be incorrect, I take 2400 mgs at times. Other stuff you ve written appears to be correct.

What benefits do you get from higher doses NAC? Do you take it for neurological and mental conditions, such as Bipolar, OCD, neuroinflammatory stress, etc...?
Thanks.

 

[OuchThatHurts]

What benefits do you get from higher doses NAC? Do you take it for neurological and mental conditions, such as Bipolar, OCD, neuroinflammatory stress, etc...?
Thanks.

That's a whole different thread. NAC-->Cysteine--> glutathione, glutamate regulation... it's all on the board here or a simple Google search will yield everything you need to know also. Or feel free to start a new thread.

 

[Soalian]

That's a whole different thread. NAC-->Cysteine--> glutathione, glutamate regulation... it's all on the board here or a simple Google search will yield everything you need to know also. Or feel free to start a new thread.

Thank you, am educating myself on nootropics forums