I have done some more reading and research on the subject of which version (R, S, or racemic) of equol would be most ideal for treatment of hair loss, and come up with some fascinating results.
The primary reason Brotzu is using S-equol is almost certainly the same reason they are using DGLA instead of PGE1. S-equol is a completely natural dietary product. So is DGLA. By using these "natural dietary products", they completely escape any significant regulation, and get to release their product as a "natural health product". This saves an enormous amount of money on testing for safety or efficacy.
But if we want to look at the question of what is truly best on a deeper level than that, we need to review the evidence again.
First of all, we should review again that in the rat prostate study comparing all three,
only R-equol led to a significant decrease in prostate size. S-equol did not cause any significant change in prostate size.
We also have a very good skin study (
ref) comparing all three which showed again that for skin purposes, R-equol was much more potent in almost every way. This included the following effects, of which one in particular was an absolute shock to me when I saw it, and likely completely explains the difference in prostate activity of both equol forms:
- Overall, 16 genes were more powerfully regulated by R-equol, while only 3 genes were more powerfully regulated by S-equol.
- Genes for collagen production, elastin production, and production of a skin breakdown inhibitor were all much more strongly activated by R-equol than S-equol.
- Genes for three proteinases which break down skin during age were significantly more inhibited by R-equol compared with S-equol.
- The gene for making the 5-alpha reductase (type 1) enzyme was significantly inhibited by R-equol, but not S-equol.
This finding of R-equol decreasing 5-AR (type 1) expression is mindblowing to me, because we have no other agent that I am aware of that does this, and it completely explains how equol is so good at controlling prostate problems. Given that both R-equol and S-equol bind equally to DHT, if the DHT binding effect was the primary mechanism of action, we would expect both forms to be effective at reducing prostate size. However, only R-equol has been shown to have a significant effect on prostate size.
The fact that R-equol has this unique ability, and that R-equol, not S-equol, is the type of equol proven to reduce prostate volume suggests that:
this is likely a big portion of the mechanism of action by which equol works (though not everything), and just like with prostates, we should expect S-equol to be much less effective for hair.
We can get some clues as to how important this 5-AR effect is from the human prostate study, where men were treated with a mix of R/S-equol. In the men with the largest prostates, a significant decrease in DHT levels was observed. But notably,
no decrease in DHT was seen in most men overall, despite their prostate symptoms improving. This suggests that the mechanism of action for equol overall in this study was probably a combination of the DHT binding effect (which does not change hormone levels) and the decrease in 5-AR expression (which does change hormone levels).
This represents a completely new mechanism of action, which I will add to my original post.
For reference, here is a table of some skin genes affected by S-equol, R-equol, and racemic equol and their differing effects:
View attachment 84178
This makes R-equol actually very similar to finasteride/dutasteride in effect, but it is slightly unique compared to both. There are three types of 5-alpha reductase enzymes which convert testosterone into DHT - type 1, 2 and 3. Finasteride works by blocking 5-alpha reductase (type 2&3) from converting testosterone to DHT. Dutasteride works by blocking all three types of 5-AR.
R-equol accomplishes essentially the same thing by decreasing the amount of 5-alpha reductase (type 1) enzyme that is made in the tissues exposed to it. With less enzyme, less DHT will be made in the same fashion. We don't know if R-equol also reduces expression of 5-AR type 2 or 3 as well, as they weren't studied. Either way, this provides a very plausible mechanism for high effectiveness in stopping hair loss if racemic equol is used topically.
Unfortunately, this also suggests that people who have been sensitive to DHT-related (finasteride/dutasteride) side effects might be sensitive to the same side effects from R-equol if it goes systemic to any significant extent. Some people have claimed decreased finasteride side effects from topical administration. So perhaps the effect of equol could be similarly localized.
Equol has so many mechanisms of action that are completely unique. This is yet another and probably the most important (along with the DHT binding capacity). But it also goes to show, there is nothing for free in this world. Dealing with the androgen problem of male pattern baldness will always be a compromise regardless of how you choose to attack it. I think it's a matter of finding the approach that best suits each individual, and that unfortunately can usually only be determined through trial and error.
Overall I think this very clearly shows that racemic equol will be far more powerful for hair loss than S-equol (what is being used in Brotzu). If Brotzu is proven to work, it might represent a "cleaner" mechanism of action, as S-equol will work only by binding DHT and stimulating ER-beta to reduce androgen receptors.
However, whatever benefit S-equol (Brotzu) might provide, racemic equol will undoubtedly provide a dramatically more potent effect in the treatment of male pattern baldness, due to its ability to reduce expression of the 5-alpha reductase enzyme.