The future of oral testosterone
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For over 70 years, pharmaceutical attempts have been made to create a chemical with the following properties:
- Converts to an anabolic substance after oral ingestion
- Is devoid of toxicity (hepatic or otherwise)
- Is not estrogenic or otherwise anti-androgenic at doses that create an anabolic effect
State-of-the-Art
Among the first attempts after testosterone itself was discovered to be poorly orally bioavailable (3-5% oral bioavailability in those with healthy livers, much higher for those with alcoholic hepatitis) were derivatives of testosterone with a methyl group attached to the 17 alpha position.Those derivatives, such as fluoxymesterone, metandienone (dianabol), chlorodehydromethyltestosterone (CDMT) (turinabol), oxandrolone, oxymetholone, stanazolol, are all orally bioavailable due to methylation, but are all to some extent toxic and some of them estrogenic.
Therefore, those who want to benefit from the clear performance-enhancing benefits of androgens, find themselves in the unfortunate circumstance of being stuck between the rock of some degree of toxicity and the hard place of having to use injectables.
For the current orally available options that exist, it is overwhelmingly true to say that "insofar as they are effective, they are toxic".
That is at least true for the vast majority of options, with the possible exception of mesterolone (proviron) (1-alpha methyl-DHT). Proviron is, however, expensive, and there are doubts as to how anabolic it is to skeletal muscle, because if the current thinking about deactivation of DHT in skeletal muscle by 3b-HSD is correct, then proviron would not be significantly anabolic because it is subject to 3b-HSD, unlike other DHT-derived oral AAS, such as oxandrolone (anavar) whose 2-oxa substitution is supposed to provide steric hinderance to that enzyme.
With the current environment, it is easy to think that the present options represent, more or less, a law in biology. Namely, that if an oral is to work, it must be somewhat toxic.
That, however, is almost certainly false. That is because there is already research showing not only that orally available precursors to testosterone exist, but one in particular should be easy and cheap to synthesize.
The Future
The one I have in mind (for now) is the famous discontinued prohormone 4-androstenediol. It has been shown to have an approximately 16% oral bioavailability. Because it is not methylated, it is not liver toxic. In a clinical study, 100mg increased total and free testosterone 90 minutes post administration by about 50%. Doses of 300-500mg/day split over 3-5 doses would absolutely achieve an ergogenic effect. Furthermore, 4-A-Diol is not significantly estrogenic.
https://en.wikipedia.org/wiki/4-Androstenediol
What is special about 4-A-Diol is that it is easy to synthesize from testosterone. It is only one step away from it, and testosterone is cheap and available. The only potential issue is making the reaction selective for the 3-beta isomer of 4-androstenediol, but any chemist should be able to do that.
There are, of course, even more effective non-toxic prohormones, like 1-androstenediol, but they are harder to synthesize. But they are also much more effective. For now, 4-A-Diol is probably better to try to get synthesized.
In conclusion, it seems ridiculous to me that people are still stuck trying to take liver toxic orals to get the benefits of fast-acting androgens when we know that non-toxic, effective, and easy to synthesize alternatives exist.
We just need to pressure manufacturers to make them and they will appear on the black market, just like DHT-E apparently did.
LETS GET THE HYPE TRAIN MOVING ON 4-A-DIOL.
In time there is life but no knowledge; outside time there is knowledge but no life
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@jamezb46 Why not just take testosterone undecanoate dissolved in oil, orally?
It's been shown to have around 70% bioavailability and increases testosterone concentrations for several hours when taken orally.
I know its not legal, but you can get testosterone undecanoate oil from many vendors in the US and EU, and you can simply inject the testosterone undecanoate into gelatin capsules.
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I am not aware of any studies that show that testosterone undecanoate (TU) has 70% oral bioavailability.
Instead, consider the recent (2021) article by the manufacturers of JATENZO
, a TU oral product.https://pubmed.ncbi.nlm.nih.gov/34354245/
"Specifically for TU, this modification allows testosterone to be absorbed via the lymphatic system and therefore bypass liver degradation. An early oral TU formulation (ANDRIOL
) was approved for use in many countries but never in the United States. This formulation is heavily reliant on dietary fat intake as a means of increasing absorption and therefore leads to significant intra- and inter-patient variability in testosterone response""Self-emulsifying drug delivery system (SEDDS)
TU has been formulated in a unique self-emulsifying drug delivery system (SEDDS) that was initially evaluated in multi-institutional placebo-controlled studies in Europe [27]. SEDDS formulations combine hydrophilic and lipophilic components that enable the solubilization of lipophilic molecules such as TU in the gut (Fig. 2)."So, simply taking testosterone undecanoate in a carrier oil, and swallowing it will at best give you a decent result if using hundreds of miligrams of TU AND the required 30 grams of fat (which is insanely expensive and hard to source, assuming bought on the black market)
https://24hreup.biz/product/nebido-2/
The improvement that contemporary products like JATENZO have over their predecessors ANDRIOL exist because the JATENZO are SNEEDS products. In other words, they are highly, insanely expensive pharmaceutical drugs that require special processing in order to work.
Even at their insane price, people are far from "blown away" by their oral TU, whether JATENZO or otherwise.
In contrast, 4-A-DIOL and especially 1-A-DIOL have already proven to be ergogenic, and should be much cheaper to produce.
For some incomprehensible reason, superdrol stuck around after the prohormone era, and it still exists on the black market. It is quite liver toxic. My argument is essentially that 4-A-DIOL, and 1-A-DIOL should have been taken up my the UG market because they work and they're not liver toxic.
In time there is life but no knowledge; outside time there is knowledge but no life
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edited to remove aggressions
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So, simply taking testosterone undecanoate in a carrier oil, and swallowing it will at best give you a decent result if using hundreds of miligrams of TU AND the required 30 grams of fat (which is insanely expensive and hard to source, assuming bought on the black market)
You don't need 30 grams of fat. This study used 100mgs of testosterone undecanoate, in 5ml of arachis oil
https://link.springer.com/article/10.1007/BF00605634#citeas
Sure bioavailability is more than doubled when given with a fatty meal: but oral testosterone undecanoate in arachis oil has a 40% bioavailability.
Tesosterone undecanoate is not hard to source at all - it's a mildy popular and an extremely useful ester as it has a half life of almost a month, allowing for very infrequent injections, which is useful if you are going on holiday etc.
Not in the US, but a simple 5 minute search on a big domestic site revealed dozens of test undecanoate products:
https://www.napsgear.org/advanced_search_result.php?keywords=testosterone+undecanoate -
Please post any evidence, either in the form of bloodwork or a scientific study, showing that testosterone dissolved in tocopherols indeed has good oral bioavailability.
It is known that dissolving progesterone in tocopherols does lead to a substantial increase in its bioavailability, but that is likely due to progesterone have a higher logP value than testosterone, thus increasing its affinity for chylomicron uptake, and with differences with how the liver handles the two hormones.
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@jamezb46 It is currently being sold:
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@eduardo-crispino Sushi chill brother
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I think the study you linked is the one that @haidut used on the old forum to poo poo over TU.
As you can see, the TU in arachis oil only spiked Testosterone in the blood highly when it was given with a fatty breakfast. Otherwise (in the fasting participants) it did not perform better than base testosterone.
I actually think that using testosterone as "free crystals" should also work well if you want to do an oral protocol that is devoid of liver tox. As you can see, only 100 mg of free testosterone elevated even fasting levels by about 350 ng/dL. So, using 300 mg twice a day (maybe once in morning once per workout) should also be performance enhancing.
To be clear, using 600 mg free test base per day is dirty cheap. It is about 50 cents per day!
How much would TU be per day?
In time there is life but no knowledge; outside time there is knowledge but no life
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@alfredoolivas That is NOT 4-androstenediol. That is 4-DHEA, which is a prohormone to 4-androstenediol. No one dares sell 4-androstenediol on the open market in the U.S after what happened in the early 00's. But my point is that UGLs don't give a damn about the law anyway, so if enough people ask for it, they should be able to sell the real thing (not the B.S 2 step precursor)
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@jamezb46 said in The future of oral testosterone:
As you can see, the TU in arachis oil only spiked Testosterone in the blood highly when it was given with a fatty breakfast. Otherwise (in the fasting participants) it did not perform better than base testosterone.
Testosterone Undecanoate in Arachis Oil has a 40% bioavailability, and it increased tesostereone by 10 n/mol.
It does spike testosterone. However, when you compare it to the levels when eaten with a fatty meal? Sure it spikes it less.
But it does spike testosterone effectively... as shown with the 40% bioavailability.
Furthermore, a large proportion of people eat a fatty breakfast. So if you eat a fatty breakfast? You can expect 100% bioavailability. So testosterone undecanoate seems like an excellent option, especially for those that eat a high fat diet, which many Americans do.
@jamezb46 said in The future of oral testosterone:
To be clear, using 600 mg free test base per day is dirty cheap. It is about 50 cents per day!
If you buy 100g of TU from Purple Panda Labs, each gram costs 1.14 dollars.
600mg each day would cost 68 cents a day.
TU has a much longer half life than Test base, so thats why I reccomend it
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@alfredoolivas Fair point on the TU. I concede that it should work too.
But, the long half life is a double edged sword. What if I specifically want a big peak in the morning and pre workout so that overnight I can recover from any suppression?
For me, though, I would want to just go with the base hormone (testosterone) due to weird interactions that may happen with the esterified hormone not being recognized by the body and because if I want to dose it multiple times per day, I may not do it with a fatty meal (like pre-workout)
What I really want, however, is for 1-A-DIOL (1-AD) to come back to the market.
In time there is life but no knowledge; outside time there is knowledge but no life
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@jamezb46 Does 1-AD turn into 1-testosterone and does it turn into to 1-dihydrotestosterone (dihydroboldenoe)? Any reason why the double bond on carbon 1 is better than carbon 4?
Glucocorticoids thhat have the added unsaturation between carbon 1 and 2, bind to higher affinities to the GR, but androstane steroids have a very low affinity for the GR, regardless of their unsaturation; they exert their anti-catabolic effects via genomic changes from activating the AR. So I assume thats not why you want the unsaturation of carbon 1.
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@jamezb46 btw, I finished by bottle of tren. I don't see anything very special about it, after running 100mg a week subcutaneously for a month. I don't think I will be buying it again. Apart from turinabol, are there any other (available) AAS I should look into or perhaps you are interested in?
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It turns into 1-testosterone, which is DHB. The androgen with the normal 4,5 delta bond AND the 1,2 delta bond is boldenone.
Steroids with the 1-2 double bond are thought to be more anabolic than steroids without the 1-2 double bond. I don't know if that is because they bind better to the AR or if they are more anti-catabolic by stopping glucocorticoid induced catabolism or if they work through some other means.
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@jamezb46 very interesting - it can turn into dihydroboldenone without being 5 alpha reduced ?
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1-AD is saturated at the 4-5 position so it is already "5 alpha reduced". All that it needs to turn into DHB is for the alcohol on position 3 beta to be oxidized to a ketone.
1-AD
DHB
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@jamezb46 Very interesting, thank you! I am learning a lot; 5 alpha reduction is the simple removal of the carbon 4 double bond; the addition of the extra hydrogen that is bonded to the carbon, simply occurs because the carbon isn't sharing 2 electrons to the other carbon atom anymore, so a hydrogen shares its electrons to give the carbon a full valence shell.
So a dihydro-steroid is simply a steroid that is missing it's double bond on carbon 4 and therefore has an extra hydrogen. I guess the conversion of 1-AD to 1-testosterone is exactly the same as the conversion 3alpha androstanediol into dihydrotestosterone.
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Almost the same. Technically 3 alpha androstanediol (if it ever is converted back to DHT) would have to do so through 3 alpha HSD. But 3 alpha HSD is not very active as an oxidant, it usually only reduces DHT to 3 alpha androstanediol.
Since 1-androstenediol has the hydroxyl on 3 at the beta position, 3 beta-HSD coverts it to DHB, and that happens much more readily.
BTW: Since you asked about compounds to try, I think 11-keto testosterone should be interesting. It cannot aromatize, is equipotent to testosterone as an androgen, and has anti-cortisol effects due to the ketone on 11. Sounds like winstrol w/o the liver tox
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In this video, Haidut claims (in technical details) that mixing androgens with saturated fats like ghee or egg yolks helps a lot with effective absorption https://youtu.be/lfdNtcc0P4I
