Update: June 30, 2021 — We demonstrated that sulforaphane has the potential to become a highly effective functional hair cosmetic to relieve hair loss with AGA.
Update: I did not realize that the Technion University team from Israel (which I covered briefly last year under 3D printed comb) has a few pages on their website covering this very subject of the 3-alpha-hydroxysteroid dehydrogenase (3α-HSD) enzyme. See their overview page, cofactor page, comb/design page, expression page, modeling page, secretion page and results page for more. Looks like they started this work in 2015.
FYI: “Roman” is now answering questions in the comments to this blog post. At some point I might delete most of the pasted chat messages at the bottom of this post.
On very rare occasions such as this one, I write a blog post that is almost entirely based upon some random person (typically a passionate intelligent hair loss forum member or e-mailer)’s unique thoughts that I find very interesting and logical, even if I barely understand half of such thoughts unless I am able to devote significant time deciphering various acronyms and scientific terms. Generally, I trust and defer to my intuition in these cases and promote such people and their theories without devoting more than several hours of research unless I really have a lot of free time on my hands. FYI: An example of such a past recent post: Intelligent balding men post their theories.
Roman’s First E-mail
On April 16th, a person by the name of “Roman” sent me the following interesting e-mail:
“Hi, below, I am pasting my messages on your chat for what I believe is the most under researched avenue for the hair loss cure and the polar opposite of the approach that finasteride takes. I think with the power you have you can get this out there as this is something that has been very poorly researched and possibly even hidden. Anyways, enjoy researching but I believe it really does tie the whole pgd2, dht and maybe even wnt pathway approaches under one enzyme: 3-alpha-hsd.”
He ended his e-mail with pasting his prior hair loss chat messages from this site, but I will paste those and other future chat messages that “Roman” made all together at the end of this post since the organization is very haphazard.
Roman’s Second E-mail
I replied to Roman, mostly in the form of an excuse that I could not devote time on research this past week even though I found his thoughts highly interesting. Below is his second e-mail to me from April 18th:
“Thanks for your reply and I totally understand your work load. As for a compressed version of my research, as we both know alpha 5ar converts T to DHT. Well there turns out to be an “antimatter” sort of enzyme present in every human’s musculoskeletal structure called 3 alpha hydroxysteroid dehydrogenase (3a HSD) which converts all T and DHT to 3 adiol g (another testosterone by-product which is not harmless to hair and way less androgenous). Now if propecia can work so well off blocking off alpha 5ar then in theory the exact same should be the case for promoting 3a hsd in synthesis in the body. And finally, the side effects of 3a hsd upregulation should be fractional compared to alpha 5ar downregulation as the reason for the most of the propecia side effects is the lack of DHT being created. Conversely, DHT will be allowed to generate under this treatment, however, the 3a hsd will instantly de-activate it. The big hope from my side is that there is a topical way to introduce 3a hsd to the scalp as that will exterminate DHT from the scalp (as it does in the muscles). Even if there isn’t there’s easily another (potentially a lot safer) variant of propecia waiting to be developed.
A link to start off your research is:
Note the paragraph on DHT deactivation in the muscles. Its basically local DHT deactivation which is what everyone has been longing for for decades. It happens everyday in our own body without any negative effects!
Anyways, I hope you find this topic as captivating as I do and I wish you the best of luck on everything to do with your blog and your research on this matter.
PS. if you were on the chat “ihavethecure” “klijom” and “klijomss” were all my names because people kept stealing my name lol!”
Roman sent me two additional e-mails with several useful individual links in there that I discuss below.
My Initial Thoughts and Various Links of Interest
I get many e-mails every week, and typically I only learn something truly interesting from 20-30 percent of them. Right away I knew that Roman’s e-mail was one of those. It does seem like increasing the expression of the 3α-hydroxysteroid dehydrogenase enzyme will reduce DHT and lead to a reduction in hair loss and perhaps even lead to regrowth of hair that has been lost in recent years. Perhaps this approach will lead to far fewer side effects than the current approach of using Finasteride or Dutasteride to reduce DHT?
Roman pasted the following 2006 study link in his e-mail that also mentions a PGD2 connection (a difficult read for non-scientists):
— Increased expression of type 2 3-alpha-hydroxysteroid dehydrogenase/type 5 17-beta-hydroxysteroid dehydrogenase
(AKR1C3) and its relationship with androgen receptor in prostate carcinoma.
In one of Roman’s later chat messages, he posted the following recent 2016 study link that is much more relevant to our hair loss cause and easier to understand in its abstract format:
Key quote from above:
“Dihydrotestosterone (DHT) causes the regression of human hair follicles in the parietal scalp, leading to androgenic alopecia (AGA). Sulforaphane (SFN) increases the expression of DHT degrading enzymes, such as 3α-hydroxysteroid dehydrogenases (3α-HSDs), and, therefore, SFN treatment may improve AGA.”
— Another interesting link on Sulforaphane and DHT reduction that someone on the chat posted (could be Roman). Seems like broccoli has yet one more benefit.
— Finally, on April 18, someone who read Roman’s chat messages on this blog started this useful thread on the hairlosstalk forums that is well worth following.
It seems like antidepressants (SSRIs in particular) can also impact 3-alpha-hydroxysteroid levels…I will write more on that later if there is any interesting potential going that route.
Roman’s Hair Loss Chat Messages
Note that “Roman” has used a few different names in the chat as he mentioned in his e-mail. One person might have used his chat name with minor modification for some reason (I do not require registration on the hair loss chat on this site). In any case, I have tried to post only Roman’s chat messages below and those from others that were related to the subject. In reverse chronological order from the past week with some dates deleted by mistake (4/22/16 –> 4/16/16):
asfasas 4/22/2016 3:10
“conclusion kijom ??”
I am not yet at the conclusion I am still actively researching the matter. What I have discovered though is that 3a hsd is an enzyme which is located in various parts of the body where it deactivates DHT. Now I am researching there is sufficient presence of 3a hsd in the scalp and if not, whether there are viable ways to introduce it to the scalp.
2020 4/21/2016 9:42
Can someone please simplify this for me
2020 4/21/2016 9:42
This is so confusing what you guys are talking about.
yazed 4/21/2016 7:41
conclusion kijom ??
klijom 4/21/2016 4:33
okay idk why its putting an emoji in it but I promise it works lol
klijom 4/21/2016 4:33
klijom 4/21/2016 4:33
extremely interesting article for the (medically aware) people to read : http://press.endocrine.org/doi/full/10.1210/en.2002-0032?view=long&crazymid=12810547&
lmlmlm 4/21/2016 4:10
type 3 3a hsd **
lmlmlm 4/21/2016 4:09
basically whoever is researching this needs to find a way of upregulating akr1c2, or more specifically type 3a hsd in the scalp.
lmlmlm 4/21/2016 4:04
Thinking behind Ursodeoxycholic acid is that it is an akr1c2 upregulator but I am trying to see if it has any scalp benefits.
lmlmlm 4/21/2016 4:01
as a starting point in 3a hsd boosting medications is sulforaphane. I have just ordered some. Also if anyone has the medical capacity to research Ursodeoxycholic acid, that would be great as I keep running into walls.
jkjnk 4/21/2016 10:17
Localised deactivation of DHT happens all over your body; in your muscles, brain, liver etc etc. Now we just have to find a way to introduced localised deactivation in the scalp. Peace xoxo
jkjnk 4/21/2016 10:15
Looking deeper into the highest expressions of 3a hsd, you discover that in your muscles, DHT levels have no androgenic effects whatsoever, and this is all due to the constant life long deactivation of DHT by 3a hsd. Now that is the goal I am aiming for in the scalp; a life long deactivation of any DHT that comes into the scalp by 3a hsd without feminising the body the way that propecia does.
jkjnk 4/21/2016 10:12
The main problem why SSRI’s arent cropping people with full heads of hair is because the conversion of DHT to 17 b adiol is a reversable on. Therefore any dht converted to to 17b adiol will later be converted back to dht by alpha 5ar present in the scalp if there is no 3a hsd present.
jkjnk 4/21/2016 10:09
Also a pattern I noticed, no research behind this, is that morbidly obese men more often than not have full heads of hair. Curiously looking deeper in to this, I discovered that obese men express more 3a hsd in their systems http://joe.endocrinology-journals.org/content/191/3/637.full.pdf
jkjnk 4/21/2016 10:07
There is so little research on 3a hsd. 3b hsd deficiency is topic that is researched way more. Basically type 3 3a hsd is the enzyme we are after and that comes under the akr1c2 gene. Now I am currently in the process of identifying how well 3a hsd is expressed in the scalp (if at all). The goal is to bring increased akr1c2 (increased type 3 3a hsd) expression to the scalp.
Klijomm 4/20/2016 11:08
i read of a 5 fold increase in 3ahsd activity following levothyroxine treatment in trial. any idea how this might relate to activity at the scalp? would any ssri amplify considering net impact? http://www.jle.com/en/revues/ejd/e-docs/steroidogenic_enzymes_in_skin_100522/article.phtml
kilojom 4/20/2016 3:08
Hi test. I have seen the post and will make an account to comment
ok 4/20/2016 4:37
klijommm, it’s me, “test” (I had to change my username in the chat). I made a HLT thread about 3a hsd the other day and people think it is really interesting. It would be great if you made an account and joined the discussion over there, since you have a lot of knowledge about this.
Also this is bearing in mind that there is little 3a hsd present in the scalp and people are still noticing an improvement in their hair. Now if we could introduce higher amounts of 3a hsd to the scalp then i think that is game over rip gg for the hair loss industry. (PS stop stealing “klijom” lmao)
Sulforaphane is currently the best avenue for 3a hsd promotion in the body. Check the review (on a totally non hair loss related website) from the lady who is talking about its effects on her hair.
if anyone wishes to get in touch with me regarding any 3a hsd matters pls email me at firstname.lastname@example.org (please dont spam lol I’ll just delete the account)
@m also equol is a non steroid estrogen whereas 3a hsd directly converts DHT to a less androgenous derivate of testosterone (not an estrogen) hence your point holds no substance
@m here is a link to offer you some insight into the work that 3a hsd does and where it is present
@m yes SSRI’s do increase 3a hsd activity but the problem is that there is not enough 3a hsd present in the scalp. Also SSRI’s are not designed to increase 3a hsd activity, it is merely a side effect. If a drug/method could be developed to introduce 3a hsd to the scalp then we are on to a real winner
@test I would be more than happy for you to take over the topic and get it onto the HLT forum as I am not a member on any forum website. I really do appreciate your interest in the topic however and can assure you it (although it is difficult due to the lack of research done on the matter) it is totally worth researching!
klijom, 3a hsd sounds very interesting, I really hope that you are onto something here
Or else I’ll do it to get your word out there, I believe what you’re saying is very important! I’ll credit you of course
killjom, could you please make a thread on the HLT forum (new research, studies and technology) about this 3a hsd enzyme? That would help a lot
this 3a hsd topic sounds really interesting, especially the anti matter comparisons with alpha 5ar.
the best chance of a cure coming out is if someone takes 3a hsd seriously and finds a way to introduce it to the scalp. If I had any sort of background in biomedical science I would be working on it right now as it does not seem too difficult to introduce enzymes to the scalp (no chance of rejection if enzymes developed are taken from your own body) and virtually no chance of mutations (cancer).
There seems to be a recently formed small team in Israel called Technion who have also identified 3a hsd as the main culprit. It is interesting to see their valiant but a little amateurish experiment results.
… to block alpha 5ar. WE SURE AS HELL can create something to magnify 3a hsd activity. And it is my understanding that formulating a topical treatment is a million times easier when you are trying to boost a function than inhibit (hence the difficulties in formulating a topical propecia).
Also check this out, isoretinoin, better known as accutane is a drug infamous for causing hair loss. the reason? Isotretinoin causes upregulation of D2 receptors. Upregulating D2 receptors is bound to lead to hair loss (see Dr Cotsarelis). Another side effect of isoretinoin?? IT INHIBITS 3A HSD ACTIVITY…..! It’s clear that the antimatter to alpha 5ar is indeed 3a hsd and if we can make propecia
SOMEONE NEEDS TO GET THIS OUT THERE ITS THERES AN ANTI PROPECIA OUT THERE SOMEWHERE AND THE BEST PART IS IT WONT GIVE US LIMP d**k LOL
I really hope the admin sees this and decides to address it in some form in the next article.
…be at least a permanent topical (worst case scenario oral) treatment. The link of 3a hsd and prostate cancer again seems to solidify this claim as this is the exact route that propecia and alpha 5ar inhibition came from.
Also it seems that many of the “hair loss fads” that we hear about e.g. coconut oil, olive oil etc may actually be increasing 3a hsd activity (in however small effect). Now if this effect can be harnessed and magnified which may be a lot easier than most of the other methods being developed at the moment (follica histogen etc) then we will have something that although not a cure but would
…be a lot easier than trying to remove an enzyme from a scalp (alpha 5ar). I honestly am starting to believe this a massive avenue which has been completely ignored and I don’t see why (ethics aside) 3a hsd supplements for the scalp could not be created to “neutralize” dht as soon as they interact (as they do in the muscles).
Also that thread, is more than ten years old and I tried googling 3a hsd to find only 2 or 3 semi-serious discussions of it regarding hairloss. 3a hsd is a natural enzyme present within the muscular structure of the body which prevents the conversion of testosterone to dht wherever it is present. Now to me it would seem that introducing an enzyme to the scalp (3a hsd) should in theory…
klijom4 4/16/2016 6:52
@bigt1 I think he does have a point though. Why try and fight alpha 5ar when you have a natural mechanism in your body designed to do just that? It shocks me how poorly this issue has been (or not been) covered.
@Ihavethecure this where your getting your info from?
@Ihavethecure 4/16/2016 2:54
hair loss is being researched by monumental retards who are taking all your money.
article linking 3a-hsd with the long heralded pgd2 cure branded about by cotsarelis.
It’s way easier (and safer) to augment 3a-hsd levels rather than inhibiting 5alpha reductase levels.
SSRIs fluoxetine, fluvoxamine, sertraline, and paroxetine, the SNRI venlafaxine, and mirtazapine. All current treatments used as anti depressants to increase 3a-hsd levels
Anyways, that’s your cure, go spread the word, took my a*s long enough to find it. I don’t know how to produce a treatment to administer the appropriate therapy but if testosterone therapy can overcome 5-alpha reductase deficiency then the exact mechanisms with a different drug make up would provide adequate doses of 3a-hsd to the scalp.
All the pharmaceuticals know about 3a-HSD and the natural DHT eliminating property that it has. But then again, replicating an enzyme is something only the very top pharmaceuticals can do and they wouldn’t want to lose such a steady stream of revenue lol.