Scott Stevenson on Anadrol science

[qbkilla]

Yes, too catabolic, and specifically it catabolizes hypertrophied muscle preferentially. I like clen as a recomp agent (it's truly an anabolic agent first and foremost, with lipolytic properties and performance-enhancing properties), I like DNP from a theoretical standpoint but it's the equivalent of taking an AK-47 to a nail for most. I like ECA as a mild lipolytic agent. I believe in a place for rhGH with the right compounds (including androgens, several of which have unique features contributing to a decrease in fat). For some, albuterol and caffeine may be superior to clen. There are a lot of options, and frankly, the thyroid hormones like T3 are the only fat-loss or recomp agents in popular use that I see no rational use for in healthy (euthyroid) bodybuilders.

Can you elaborate more on Albuterol vs clean. Does it raise metabolism more?

 

[nothuman]

I really don't recommend T3 at all (unless hypothyroid and seeking a euthyroid state, i.e., dose <= 25 mcg daily).

Just to be clear, if someone is slightly hypothyroid and wants to reach a normal state, 25mcg or less of T3 is ideal to feel better (resolve symptoms) you think?

I was thrown off when you said "euthyroid" since I understand that as high reverse T3 due to lack of T4 to T3 conversion. I don't know why one would seek that.

I actually struggle with this personally and hear all kinds of different opinions. I find 25-375mcg of T3 makes me feel better than 50mcg even though my blood tests look better on the higher dose. Go figure.

 

[Cabron]

I find 25-375mcg of T3 makes me feel better than 50mcg even though my blood tests look better on the higher dose. Go figure.

u dropped this "."

 

[Type-IIx]

Just to be clear, if someone is slightly hypothyroid and wants to reach a normal state, 25mcg or less of T3 is ideal to feel better (resolve symptoms) you think?

I was thrown off when you said "euthyroid" since I understand that as high reverse T3 due to lack of T4 to T3 conversion. I don't know why one would seek that.

I actually struggle with this personally and hear all kinds of different opinions. I find 25-375mcg of T3 makes me feel better than 50mcg even though my blood tests look better on the higher dose. Go figure.

Euthyroid just means "true" or "good" thyroid (literally) or normal/healthy thyroid function.

25 mcg is replacement T3, so yes, some dose at replacement or less just to bring up a decrement to thyroid function. Excessive diet can impact thyroid function, so a small dose of T3 could help someone that has reduced free T3 by dieting.

 

[PYGMY]

I like T3. All the times I’ve ever been the leanest I’ve ever been was while on T3. IMO 37.5-50mcg is plenty. I know 25mcg is just a replacement dose but when I worked with Shelby Starnes years and years ago he started me out at only 12.5mcg. Over 16 weeks he topped me out at only 37.5 and I was lean as shit. I did not notice any muscle loss at all. I was running Test, Mast, Tren and Var along with it.

 

[Cabron]

I like T3. All the times I’ve ever been the leanest I’ve ever been was while on T3. IMO 37.5-50mcg is plenty. I know 25mcg is just a replacement dose but when I worked with Shelby Starnes years and years ago he started me out at only 12.5mcg. Over 16 weeks he topped me out at only 37.5 and I was lean as shit. I did not notice any muscle loss at all. I was running Test, Mast, Tren and Var along with it.

nonsense

Shelby prescribes T3 and clen by the ounce, and dnp by the kilo


Bostin and Leo said so

 

[Fa Seeshus]

I just want to pound my 100mg Anadrol ed.
And hope of some increase in hemoglobin, since EQ does nothing for that.

Your Crit didn't go up at all on EQ? How long did you wait for the bloods?

 

[nothuman]

Euthyroid just means "true" or "good" thyroid (literally) or normal/healthy thyroid function.

25 mcg is replacement T3, so yes, some dose at replacement or less just to bring up a decrement to thyroid function. Excessive diet can impact thyroid function, so a small dose of T3 could help someone that has reduced free T3 by dieting.

Copy that re: euthyroidism definition

I'm glad you said that because that's been my experience. I read in other places that it's too low to resolve anything but my experience shows it is enough.

I was severely symptomatic but a small dose of T3 helped me and I tried increasing slowly until I reached 50mcg and then the symptoms came back with a vengeance. 25-37.5mcg seems to be my sweet spot as far as how I feel goes.

 

[PYGMY]

nonsense

Shelby prescribes T3 and clen by the ounce, and dnp by the kilo


Bostin and Leo said so

Ok, guy lol. Believe it or don’t. Really don’t give a fuck. I worked with him about 10 years ago and that’s the program he laid out for me.

And LMFAO @ because Bostin and Leo said so.

 

[275bills]

Ok, guy lol. Believe it or don’t. Really don’t give a fuck. I worked with him about 10 years ago and that’s the program he laid out for me.

And LMFAO @ because Bostin and Leo said so.

Pretty sure he was just joking

 

[PYGMY]

Pretty sure he was just joking

Whoopsy. My bad. My apologies if that’s the case. The sarcasm completely escaped me if that was indeed his intention.

 

[Cabron]

Pretty sure he was just joking

i was initially going to say t3 and clen by the gram


but went with pound, because i figured 'gram' wouldnt have been obvious enough despite being an order of magnitude higher than dosage range used lol

 

[Cabron]

Whoopsy. My bad. My apologies if that’s the case. The sarcasm completely escaped me if that was indeed his intention.

all good fam

 

[homonunculus]

I thought it was just OK with respect to the Anadrol portion. Not sure why he entertained MPMD's claim without analysis of any supporting literature. Sure, maybe (if even true that an Anadrol-only cycle increases serum estrogens; I'm willing to test this myself) oxymetholone decreases clearance and/or excretion of estrogens (by competitive glycolysation and/or conjugation?) but it's not particularly compelling, mostly because I doubt the claim that increased estrogens are attributable to oxymetholone to start.

Potential mAR binding: maybe, but that wouldn't result in pronounced anabolism, if anything mAR actions tend to attenuate rather than potentiate classical AR action (that's the prevailing hypothesis). These actions via mAR are transient, typified by GPCR nongenomic (rapid) action.

Very little discussion of metabolites and the Schanzer view that oxymetholone likely acts as a prohormone. My modeling data on 17α-methyl-5α-androstane-3α-17β-diol supports this. I posted this here: https://www.professionalmuscle.com/forums/index.php?threads/can’t-use-nolva…-what-is-next-best.171373/post-3099138

He's clearly a fountain of knowledge but I feel he didn't do any homework on the Anadrol topic and was somewhat unprepared. I liked his discussion of protein requirements, protein leveraging, glucagon and appetite, J. Antonio, et al. I wished that he had explained the fact that T3 (Cytomel) increases net protein breakdown (particularly, type IIB atrophy, i.e., selective catabolism of hypertrophied muscle) at moderate - high doses. But everything he said was correct, he just did not present the converse possibility (the risks/tradeoffs) if doses go beyond optimal (bringing the individual to a euthyroid state).

Hey IIx,

Thanks for your input! You, too, provide a massive amount of info. to the board here (and perhaps fall prey now n' again to the fact the some folks don't know WTF you're talking about... LOL! ) I've got limited parameters in terms of time and background knowledge of the listeners to work within. (My co-host does a good job of rapidly steering me to another topic either directly or in that I can see from subtle facial expressions it's time to abandon ship, though... )

I'd have to go back to listen to what I said, but I addressed MPMD's best guess b/c it was part of the question asked. (Only a very small % of oxymetholone makes its way to the urine as a glycosylated metabolite, it seems however. https://eje.bioscientifica.com/view/journals/eje/67/4/acta_67_4_009.xml As I type this, I can imagine eyes glazing over... LOL)

Yes, there are so many possibilities here. We know that 5α-androstane-3α-17β-diol binds ERbeta and that this 17 alpha methyl counterpart is a metabolite (https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.1407), but I certainly didn't run it through ligand binding modeling software. (Do you have a platform you recommend?... )

As far as membrane receptors, there's also the possibility of binding to membrane ER's, too that could be contributing (on a background of other factors) toward a propensity for gyno. https://academic.oup.com/endo/article/146/2/624/2878140

You're right, I only have so much time (in this case, it was one of the Q's that came across an hour or two before the podcast, I think). Even with a month to dig in and give my best, most detailed answer, I've come to recognize it wouldn't make sense for most podcast questions, as there are so many times when I've dug in on rabbit holes only to find / know that it's not appropriate for that audience. (This is why I might write an article, for instance.) I wonder sometimes if my co-host intentionally doesn't give me time to do that, so I'll have to be limited by "off the top of my head" thoughts... (Who's the smart one here?...)

-S

 

[PYGMY]

all good fam

Sorry again man.

 

[Type-IIx]

Hey IIx,

Thanks for your input! You, too, provide a massive amount of info. to the board here (and perhaps fall prey now n' again to the fact the some folks don't know WTF you're talking about... LOL! ) I've got limited parameters in terms of time and background knowledge of the listeners to work within. (My co-host does a good job of rapidly steering me to another topic either directly or in that I can see from subtle facial expressions it's time to abandon ship, though... )

I'd have to go back to listen to what I said, but I addressed MPMD's best guess b/c it was part of the question asked. (Only a very small % of oxymetholone makes its way to the urine as a glycosylated metabolite, it seems however. https://eje.bioscientifica.com/view/journals/eje/67/4/acta_67_4_009.xml As I type this, I can imagine eyes glazing over... LOL)

Yes, there are so many possibilities here. We know that 5α-androstane-3α-17β-diol binds ERbeta and that this 17 alpha methyl counterpart is a metabolite (https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.1407), but I certainly didn't run it through ligand binding modeling software. (Do you have a platform you recommend?... )

As far as membrane receptors, there's also the possibility of binding to membrane ER's, too that could be contributing (on a background of other factors) toward a propensity for gyno. https://academic.oup.com/endo/article/146/2/624/2878140

You're right, I only have so much time (in this case, it was one of the Q's that came across an hour or two before the podcast, I think). Even with a month to dig in and give my best, most detailed answer, I've come to recognize it wouldn't make sense for most podcast questions, as there are so many times when I've dug in on rabbit holes only to find / know that it's not appropriate for that audience. (This is why I might write an article, for instance.) I wonder sometimes if my co-host intentionally doesn't give me time to do that, so I'll have to be limited by "off the top of my head" thoughts... (Who's the smart one here?...)

-S

It's great to hear from you! You should know that I tremendously value your wealth of knowledge on androgens generally as well as expertise and personal successes in bodybuilding. The podcast that you did with Joe Jeffrey was an excellent brain dump on inter-individual variation in androgen response that aligned with the bulk of my notes on the topic and taught me some new facts as well (e.g., I hadn't fully appreciated the role of megalin, was unaware of bioavailability consequences of PDE7B isozymes). And now that you mention it, yes, the host has a massive influence on your ability to hone in on particular aspects of a subject and he truly only gave you the ability to skim the topic: quite understandable from both of your perspectives. In many ways it hearkens to the power of editorial review that guys like Chuck Poliquin and Christian Thibadeau have had to contend with - though more perniciously perhaps - writing for T-Nation.

With respect to the data on oxymetholone and phase II metabolism, I'll take a look, this isn't something I've investigated at all. It's interesting, worth a closer look.

On 5α-androstane-3α-17β-diol: this is actually a very well studied (fairly potent) AR & ER-β ligand (also known as 3α-diol) and metabolite of T that we do indeed see produced by various 5α-androstan-3-ones as well. We even have luciferase data for its potency to transactivate the nuclear receptors from Houtman's Supplementary Data (if you need this data I'll be happy to send it to you) [AR: logEC50 -7.88, RTA(%): 80, REP(1=DHT): 0.0121; PR: undetectable; ER-α: logEC50: -6.70, RTA(%): 108, REP(1=E2): 0.00; ER-β: logEC50: -6.30, RTA(%): 90, REP(1=E2): 0.00; GR: undetectable].
- A curious aside: we know that ER-β is involved in muscle tissue remodeling (some of these metabolites have comparable ER-β potency as ecdysterone) do you think that a fair amount of the 5α-androstan-3-ones & androgen 5α-reductase products could effect muscle anabolism via ER-β as a result?

All that I have done with modeling of 17α-methyl-5α-androstane-3α,17β-diol - (I think the most interesting of the intermediate & excreted metabolites of oxymetholone) - is plug it into SwissADME (for PK) & SwissTargetPrediction (for molecular target prediction). It's probably worth also plugging into PASS online (Way2Drug) to look at agreement between the models as there can sometimes be divergence in results. SwissDock may be useful for looking at oxymetholone with respect to glycosylation & conjugation as it looks at interactions with cytochromes and metabolism generally. Some additional PK data can be gleaned from tools like FAFDrugs4.

I must admit my data on mARs feels thin. The last that I looked, there are some putative and identified mARs & sensors:
- GPRC6A: mAR; class C G protein-coupled receptor activated by L-α-amino acids & modulated by Ca.
- ZIP9: mAR; member of the Zinc transporter ZIP (SLC39A) family; mediates androgen-dependent intracellular signaling and apoptosis
- TRPM8: proposed sensor; transient receptor potential melastatin 8; Ca channel that acts as a pain receptor and mediates androgen- and menthol- induced increases in Ca levels and survival of prostate cancer cells. T is a ligand.
- OXER1: sensor; oxoeicosanoid receptor 1; member of G protein-coupled receptors; T competitively binds vs. its major ligand (5-oxo-ETE) and antagonizes 5-oxo-ETE's inhibition of cAMP production. However, T treatment alone does not alter cAMP signaling, therefore OXER1 fails to meet mAR criteria.

We know megalin and endocytosis of SHBG-androgen complexes confer some likely bioactivity in a broad array of cells but this is not well understood. I think it'll be a very interesting to watch further understanding unfold in that line of investigation.

Thank you for this data on mER (I'll take a look through everything you've referenced!)

If you do decide to write an article on this subject, people like myself will eagerly read it. If you want the data that I do have from SwissADME, SwissTargetPrediction for oxymetholone's 17α-methyl-5α-androstane-3α,17β-diol feel free to PM me and I'll share with you my e-mail address and send them along to you. I'd also look favorably on sharing notes with you on androgens, rhGH, etc generally. I doubt our raw notes are for public consumption, but could very well be interesting to exchange and bolster further understanding.

 

[specter]

Hey IIx,

Thanks for your input! You, too, provide a massive amount of info. to the board here (and perhaps fall prey now n' again to the fact the some folks don't know WTF you're talking about... LOL! ) I've got limited parameters in terms of time and background knowledge of the listeners to work within. (My co-host does a good job of rapidly steering me to another topic either directly or in that I can see from subtle facial expressions it's time to abandon ship, though... )

I'd have to go back to listen to what I said, but I addressed MPMD's best guess b/c it was part of the question asked. (Only a very small % of oxymetholone makes its way to the urine as a glycosylated metabolite, it seems however. https://eje.bioscientifica.com/view/journals/eje/67/4/acta_67_4_009.xml As I type this, I can imagine eyes glazing over... LOL)

Yes, there are so many possibilities here. We know that 5α-androstane-3α-17β-diol binds ERbeta and that this 17 alpha methyl counterpart is a metabolite (https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.1407), but I certainly didn't run it through ligand binding modeling software. (Do you have a platform you recommend?... )

As far as membrane receptors, there's also the possibility of binding to membrane ER's, too that could be contributing (on a background of other factors) toward a propensity for gyno. https://academic.oup.com/endo/article/146/2/624/2878140

You're right, I only have so much time (in this case, it was one of the Q's that came across an hour or two before the podcast, I think). Even with a month to dig in and give my best, most detailed answer, I've come to recognize it wouldn't make sense for most podcast questions, as there are so many times when I've dug in on rabbit holes only to find / know that it's not appropriate for that audience. (This is why I might write an article, for instance.) I wonder sometimes if my co-host intentionally doesn't give me time to do that, so I'll have to be limited by "off the top of my head" thoughts... (Who's the smart one here?...)

-S

Thx for poppin in Scott

 

[homonunculus]

It's great to hear from you! You should know that I tremendously value your wealth of knowledge on androgens generally as well as expertise and personal successes in bodybuilding. The podcast that you did with Joe Jeffrey was an excellent brain dump on inter-individual variation in androgen response that aligned with the bulk of my notes on the topic and taught me some new facts as well (e.g., I hadn't fully appreciated the role of megalin, was unaware of bioavailability consequences of PDE7B isozymes). And now that you mention it, yes, the host has a massive influence on your ability to hone in on particular aspects of a subject and he truly only gave you the ability to skim the topic: quite understandable from both of your perspectives. In many ways it hearkens to the power of editorial review that guys like Chuck Poliquin and Christian Thibadeau have had to contend with - though more perniciously perhaps - writing for T-Nation.

Ah, yes, I think that podcast was a couple years ago. I put together a "101 level" (with some nifty bits like the PDE7B info.) talk on Bodybuilding PED's that I like to give, just b/c I think my feedback tells me the understanding of the basics is lacking for many. I think this is changing somewhat lately, given how much more open things are vs. say 5-10yr ago.

Yes, I know a couple other guys who experienced that as well with T-Nation.

With respect to the data on oxymetholone and phase II metabolism, I'll take a look, this isn't something I've investigated at all. It's interesting, worth a closer look.

The rabbit holes abound, and so often with these things lead to simple speculation, as you know. (It's good to know you're so avidly digging into this space.)

On 5α-androstane-3α-17β-diol: this is actually a very well studied (fairly potent) AR & ER-β ligand (also known as 3α-diol) and metabolite of T that we do indeed see produced by various 5α-androstan-3-ones as well. We even have luciferase data for its potency to transactivate the nuclear receptors from Houtman's Supplementary Data (if you need this data I'll be happy to send it to you) [AR: logEC50 -7.88, RTA(%): 80, REP(1=DHT): 0.0121; PR: undetectable; ER-α: logEC50: -6.70, RTA(%): 108, REP(1=E2): 0.00; ER-β: logEC50: -6.30, RTA(%): 90, REP(1=E2): 0.00; GR: undetectable].
- A curious aside: we know that ER-β is involved in muscle tissue remodeling (some of these metabolites have comparable ER-β potency as ecdysterone) do you think that a fair amount of the 5α-androstan-3-ones & androgen 5α-reductase products could effect muscle anabolism via ER-β as a result?

Yes, exactly - 5α-androstane-3α-17β-diol is def. well studied! For those following along, here's a metabolism schema I just quickly pulled from this article: https://academic.oup.com/mend/article/20/2/444/2741464



As far as ER-beta, yes that would be my guess.

Folks might find these interesting:

1. Parr MK, Zhao P, Haupt O, Ngueu ST, Hengevoss J, Fritzemeier KH, Piechotta M, Schlörer N, Muhn P, Zheng WY, Xie MY, and Diel P. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone. Mol Nutr Food Res 58: 1861-1872, 2014.
SCOPE: The phytoectysteroid ecdysterone (Ecdy) was reported to stimulate protein synthesis and enhance physical performance. The aim of this study was to investigate underlying molecular mechanisms particularly the role of ER beta (ERβ). RESULTS: In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17β-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERα) or ERβ, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERβ in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERα (ALPHA) and ERβ (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERβ-selective antagonist (ANTIBETA). In summary, our results indicate that ERβ is involved in the mediation of the anabolic activity of the Ecdy. CONCLUSION: These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia, and cachectic disease, but also imply that such a substance could be abused for doping purposes.

2. Weigt C, Hertrampf T, Zoth N, Fritzemeier KH, and Diel P. Impact of estradiol, ER subtype specific agonists and genistein on energy homeostasis in a rat model of nutrition induced obesity. Molecular and Cellular Endocrinology 351: 227-238, 2012. https://www.sciencedirect.com/science/article/pii/S0303720711007404
Estrogens are known to be involved in the control of energy homeostasis. Here we investigated the role of ER alpha and ER beta in a model of nutrition induced obesity. Ovariectomized Wistar rats were fed a high fat diet and received either vehicle, E2, ER subtype selective agonists (Alpha and Beta) or genistein. After 10weeks, body weight, visceral fat, serum leptin, blood lipids, and in the soleus muscle anabolic markers were determined. Treatment with E2 and Alpha decreased body weight, total cholesterol and VLDL. Visceral fat mass, adipocyte size, and serum leptin were reduced by E2, Alpha and Beta. In the soleus muscle, treatment with E2 and Beta modulated Igf1 and Pax7 gene expression and resulted in larger muscle fibers. Our data indicate that blood lipids are affected via ER alpha, whereas activation of ER beta results in an increase of soleus muscle mass. Adipose tissue homeostasis seems to be affected via both ERs.



And taken from here:
1. Katzenellenbogen BS, and Katzenellenbogen JA. Estrogen receptor transcription and transactivation Estrogen receptor alpha and estrogen receptor beta: regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Research 2: 335, 2000. https://doi.org/10.1186/bcr78
"In vivo studies have indeed shown that, compared with estradiol, the soy phytoestrogen genestein is more effective in providing vascular protection, presumably mediated through ERb, than uterine stimulation, presumably mediated through ERa [10•]. SERMs such as hydroxytamoxifen and raloxifene that are partial agonists on ERa [11•] were found to be complete antagonists on ERb [12,13]."

All that I have done with modeling of 17α-methyl-5α-androstane-3α,17β-diol -<SNIP d/t message being too long!>

THANK YOU for those resources!

I must admit my data on mARs feels thin. The last that I looked, there are some putative and identified mARs & sensors:
<SNIP>

I think you may have gotten a hold of the same excellent review I did:
1. Thomas P. Membrane Androgen Receptors Unrelated to Nuclear Steroid Receptors. Endocrinology 160: 772-781, 2019.

(Each time I ponder the depth of these interaction beyond the classical genomic nuclear receptor, I'm left with that "we don't really know didley here do we?..." feeling.

We know megalin and endocytosis of SHBG-androgen complexes confer some likely bioactivity in a broad array of cells but this is not well understood. I think it'll be a very interesting to watch further understanding unfold in that line of investigation.

Absolutely, especially given that megalin binds other steroid hormones, too and there's interrelationships with Vitamin D, for instance.
1. Garcia J, Krieger KD, Loitz C, Perez L, Richards ZA, Helou Y, Kregel S, Mesaros CA, Gann PH, and Vander Griend D. Vitamin D deficiency increases prostatic megalin expression and globulin-bound testosterone import, increasing prostatic androgens in African American men. bioRxiv 2021.

Thank you for this data on mER (I'll take a look through everything you've referenced!)

No problemo!

If you do decide to write an article on this subject, people like myself will eagerly read it. If you want the data that I do have from SwissADME, SwissTargetPrediction for oxymetholone's 17α-methyl-5α-androstane-3α,17β-diol feel free to PM me and I'll share with you my e-mail address and send them along to you. I'd also look favorably on sharing notes with you on androgens, rhGH, etc generally. I doubt our raw notes are for public consumption, but could very well be interesting to exchange and bolster further understanding.

Thank you and I / when I do, I'll definitely call on you. (I'm resisting the temptation now, as I have a couple other projects I *need* to focus on first...)
Mostly I put my notes either in a book-related mega outline or gather references and organize in folders in endnote, adding my comments and keywords therein. This seems to help when digging up info when needed in the future.
And yes, those kinds of info. dumps can be a bit overwhelming / nonsensical to many (essentially encrypted for your brain and partially intelligible to other sciencey types... LOL).

-S