Patrick Arnold's Prohormones
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TLDR; A new and very effective test booster probably exists, it just needs to be synthesized
Background
For those who are not aware, Patrick Arnold is a synthetic organic chemist most well known for his involvement in the BALCO scandal that involved the distribution of "undetectable" steroids through Victor Conte's network to several high profile athletes.
The first undetectable steroid, was dubbed "The Clear" because when people who were taking it were internally tested, their bloodwork would come back "clear". It was also known as Norbolethone. Structurally, it is nandrolone with an ethyl and methyl group on carbon 17 and 18, respectively. It was an abandoned synthetic steroid from earlier in the 20th century.
Norbolethone
The second and most famous, was Tetrahydrogestrinone (THG). It was Arnold's original invention. He was the first man in history to have synthesized it. It was called "The Clear" as well, but was also known in Arnold's inner circle as "Tren stuff". Structurally, it differs from Trenbolone only by an ethyl and a methyl group, on carbon 17 and 18, respectively.
THG
Trenbolone
Prohormones
In addition to his fame from developing undetectable steroids, Arnold also developed several prohormones available as nutritional supplements from the now extinct company ErgoPharm.
The concept of a prohormone is a substance that the body converts to an active hormone. The prohormone has little biological activity of the kind that the active hormone has. In that sense, the body transforms the prohormone into a much more active compound. In Arnold's case, he wanted the active hormone to be an AAS.
The prohormones that Arnold developed followed a similar developmental progression as his Clear drugs.
The first prohormone he considered was orally administered Androstenedione.
Androstenedione is a so-called one step precursor to testosterone because the action of a single enzyme is sufficient to transform it into testosterone. As the -one suffix suggests, androstenedione has ketone groups on position 3 and 17, while testosterone has a ketone on 3 and hydroxyl on 17. Therefore, 17B-HSD converts androstenedione to testosterone. The conversion rate is approximately 6% in man (https://web.archive.org/web/20110318185140/http://www.patentstorm.us/patents/5880117/description.html)
Naturally, that is pretty disappointing. Therefore, Arnold investigated 4-androstenediol (4-AD),
which is naturally present in humans. This molecule is also identical to testosterone, except for a hydroxyl group on position 3, which must be oxidized by 3B-HSD. Unlike Androstenedione, 4-Androstenediol converts at 15.6% to testosterone when given orally.
In fact, after given at a dose of 100mg orally, subjects experienced a 48% increase in total and 43% increase in free testosterone 90 minutes post ingestion.(https://web.archive.org/web/20110318185140/http://www.patentstorm.us/patents/5880117/description.html)
Obviously, 4-androstenediol is about three times as effective as androstenedione. Arnold, however, took things even further with the even more potent 1-androstenediol.
1-androstenediol (1-AD) is also naturally occurring, but in tiny amounts. It has the same hydroxyl structure as 4-androstenediol, but a different ring structure. Instead of having an unsaturation from carbon 4 to 5, it has one from 1 to 2. This anomaly is also seen in powerful AAS like Boldenone,Dianabol and Turinabol. The 1,2 delta bond makes the androgen much more anabolic.
It is pretty clear that Arnold gained the knowledge that the 3B-HSD is much more efficient than 17B-HSD when acting on orally administered androgen analogues, hence his pursuit of 1-AD and not 1-androstenedione. Oxidation at position 3 creates 1-testosterone AKA Dihydroboldenone, which is a very powerful androgen.
1-AD was known across the industry when it was sold by E-pharm as very powerful, similar to oral steroids.
Unfortunately, the FDA banned all of his prohormones. They are no longer available at all. To my knowledge, not even underground peptide websites or steroid dealers have them simply because no one synthesizes them anymore.
Currently Available Products
Arnold is still around, and makes supplements for Prototype Nutrition.
Many of the supplements on his site have excellent research behind them, including D-Serine and DHEA. He posts research supporting the use of the supplements on the product pages.
Among the most interesting anabolic products he sells are an 11-Ketotestosterone (11KT) spray and an Adrenosterone(11-OXO) oral suspension. Notably, Adrenosterone (11-OXO) has the same relation to 11KT as androstenedione has to testosterone.
11-OXO
11-KT
That is to say, 11-OXO is converted to 11KT by 17B-HSD. If we assume 17B-HSD can convert the former to the latter with the same efficiency as it can convert androstenedione to testosterone, a 100mg oral dose of 11-OXO would equate to 100/20=5 mg of 11KT. 11KT is the dominant circulating androgen in fish, and is known to possess biological activity in human males comparable to testosterone.
5 mg of a testosterone equivalent circulating around the body is significant, and anecdotal reports suggest that indeed 11-OXO is both non-suppressive and powerful in aiding fat loss, which makes sense given that it can reduce 11B-HSD type I expression.
Somewhat remarkably, it also turns out that 11-KT is the dominant androgen during Adrenarche in humans, which is a period that extends from about 2 years prior to puberty to about 20 years of age in healthy populations. It is therefore highly likely that it is a powerful libido booster. (https://pubmed.ncbi.nlm.nih.gov/30137510/)
If users want to try experimenting with something, then 11-OXO or 11KT could be a good option. Perhaps people will have excellent responses, and we can pressure IdeaLabs into creating their own product.
Future Development
Given that the FDA permits the sale of 11-OXO, then we can take Arnold's previous research to once again develop what should be a legal and powerful prohormone.
What should the chemical structure be? Well for those who have been paying attention, it would replace the ketone groups of 11-OXO with hydroxyl groups, thus allowing for its conversion to 11-KT via the more efficient 3B-HSD pathway.
I think it would be called 11-keto 4-androstenediol.
In time there is life but no knowledge; outside time there is knowledge but no life
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@jamezb46 do you think there will be another Patrick Arnold ? Seems like since the millennia, there has been no interest in discovering new steroid hormones…. perhaps this is justified. We have all the tools necessary, introducing a patented steroid hormone will probably due more harm than good. Allopregnenolone and Fluasterone are the only recent steroids under investigation that come to mind.
Any further research into steroid hormones clinical application is put into non steroidal drugs that selectively activate or block receptors in different tissues or inhibit enzymes such as 11b HSD.
Is there perhaps a current chemist researching and releasing new SARMs? That would be cool.
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@jamezb46
Not about his prohormones, but the other things he sells:
The way he describes ursolic acid (the Ur spray product) makes it appear powerful and wholesome and a much better choice than all that SR9009, RAD140, cardarine etc. stuff.
But if it really contains c. 249mg per recommended daily transdermal dose that is way more than the <4mg daily which Mauritio and cs3000 had figured out, although its effectiveness could perhaps follow an inverted bell curve, and the topical (trans)dermal route may cause less systemic effects:
https://bioenergetic.forum/topic/1797/ursolic-acid-anti-serotonin-anti-estrogen-pro-dopamine-and-more
The raw ingredient is comparatively cheap as I can find 1kg of 98% ursolic acid for about $25. That's 11years of 250mg daily. Or >900years of 3mg daily.
A little surprising to see that he sells BHB(-K?) spray for fat loss. I don't doubt that it could be effective, as I've noticed healing effects by topical butyrate (if mixed into a suitable cream or solution; there are also unsuitable body lotions). Anyhow, that would imply effects predominantly on the skin and subcutanous fat deposits. -
@CrumblingCookie the BHB is a dietary supplement not a spray
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The problem with the reasoning that 4mg of oral ursolic acid is effective is that ursolic acid is not bioavailable. It doesn’t solubilize in stomach acid and it isn’t readily absorbed.
If the 4mg per day was calculated from an in-vitro study, that represents a fatal flaw. The issue with ursolic acid is absorption. That is why petri dish studies may not translate to equivalent oral doses.
The Ursolic acid in the Ur-spray product is Arginine Ursolic Acetate. That is a synthetic derivative that Arnold invented as far as I know.
No other company I am aware of sells it. It is soluble and thus will absorb through the skin.
Keep in mind I am no Patrick Arnold shill, but with that product specifically, there is some nuance and it is known that standard ursolic acid does not absorb transdermally or orally.
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@alfredoolivas Ah, yes. I'll just wait for the raw powder then to spoon-feed on.
@jamezb46 Thanks for your clarification. I hadn't known about his Arginine Ursolic Acetate specialty. So regular ursolic acid would mainly exert only indirect systemic effects via its intraluminal workings in the GIS. Which may be powerful, but a different ball game.
Have you already tried any of these products like the Ur, 11KT or 11OXO? -
It's my understanding that regular Ursolic acid would not exert any effects. Perhaps it can disrupt bacteria in the gut but I don't think it's getting absorbed.
I have not tried any of his products yet. If I had to go with one I would actually go with the D-Serine for the mental effects.
Like I indicated in the OP, I think that 11-Keto-4-Androstenediol would be a highly effective oral prohormone.
The only problem is that it doesn't exist. It is found in tiny amounts in animals but AFAIK no one has synthesized it into a supplement.
But for the reasons I presented, it should be a quite efficient precursor to 11-KT orally in humans.
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The point of this post is not to propose some new fancy end-point androgen.
We already have highly effective AAS, and we don't need new ones.
The point of this post is to point out that, despite appearances to the contrary, the door to prohormones sold as legal, dietary supplements IS NOT closed.
The 11-keto-4-androstenediol should be legal and highly effective as an oral precursor to 11-KT.
THe key is in the marketing. If it is marketed as "anti-cortisol" "adrenal support" it should not be declared illegal by FDA.
The additional anabolic control act laws passed in the early 2000's have to do with analogues to androgens that are marketed for muscle building.
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@alfredoolivas do no harm and due no harm are both correct ... somehow..
