S-equol again

[NeedHairASAP]

I'm trying to try it topically with Vesapro but I can't figure out how to get it

[PinotQ]

I'm trying to try it topically with Vesapro but I can't figure out how to get it

You might also think about trying it in a solution of ethyl alcohol and polypropylene glycol......i.e. the minoxidil formula. I checked equol and it is soluble in alcohol at about about 48mg per ml. 10 mg per ml makes a 1% solution so I believe you could get close to a 5% solution of equol. By my calculation, you would need about 24 pills per oz of alcohol. I also checked and all of the ingredients in Natrue's Sunshine are not soluble in alcohol so that if you put 144 pills in 6 ounces of alcohol and let them sit for a few days, you should have close to a 5% solution......but you would need to cut it with propylene glycol or it would likely be too harsh on your hair and scalp. You can google super zix where there is a guy who has been outlining instructions for mixing various topicals for years.

[Shinobi]

do we know the RBA (relative binding affinity) of equol on receptor ERa ? this can also induce catagen...

[PinotQ]

do we know the RBA (relative binding affinity) of equol on receptor ERa ? this can also induce catagen...

Shinobi, That is a great question. I have tried to do as much research as possible on the effects of estrogen on hair. Surprisingly, there is much conflicting information on this. Here is some research on the binding affinity of s & r equol;

Competitive binding studies were used to assess the estrogenic properties of R- and S-equol. On the basis of the ability of R- and S-equol to compete with [3H]E2 in ER binding, their affinities for ERs translated in vitro were shown to be very different. S-equol showed the greatest affinity for ERβ (Ki = 0.73 ± 0.2 nmol/L), whereas its affinity for ERα (Ki = 6.41 ± 1 nmol/L) was relatively poor. In contrast, R-equol possessed only 4.8% and 25.0% as much relative binding affinity, respectively, for ERβ (Ki = 15.4 ± 1.3 nmol/L) and for ERα (Ki = 27.38 ± 3.8 nmol/L) as did S-equol. For comparison, 17β-estradiol binds ERα with a Kd of 0.13 nmol and ERβ with a Kd of 0.15 nmol. S-equol thus shows ER selectivity with a high affinity for ERβ, whereas R-equol can, at best, be classified as a weak estrogen.

WHere did you get your information on ERa's induction of catagen?

[Shinobi]

Shinobi, That is a great question. I have tried to do as much research as possible on the effects of estrogen on hair. Surprisingly, there is much conflicting information on this. Here is some research on the binding affinity of s & r equol;

Competitive binding studies were used to assess the estrogenic properties of R- and S-equol. On the basis of the ability of R- and S-equol to compete with [3H]E2 in ER binding, their affinities for ERs translated in vitro were shown to be very different. S-equol showed the greatest affinity for ERβ (Ki = 0.73 ± 0.2 nmol/L), whereas its affinity for ERα (Ki = 6.41 ± 1 nmol/L) was relatively poor. In contrast, R-equol possessed only 4.8% and 25.0% as much relative binding affinity, respectively, for ERβ (Ki = 15.4 ± 1.3 nmol/L) and for ERα (Ki = 27.38 ± 3.8 nmol/L) as did S-equol. For comparison, 17β-estradiol binds ERα with a Kd of 0.13 nmol and ERβ with a Kd of 0.15 nmol. S-equol thus shows ER selectivity with a high affinity for ERβ, whereas R-equol can, at best, be classified as a weak estrogen.

WHere did you get your information on ERa's induction of catagen?

thanks for that study!

here we go:

ndocrinology. 2005 Mar;146(3):1214-25. Epub 2004 Dec 9.
Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling.
Ohnemus U, Uenalan M, Conrad F, Handjiski B, Mecklenburg L, Nakamura M, Inzunza J, Gustafsson JA, Paus R.

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Between the two recognized estrogen receptors (ERs), ER alpha and ER beta, only ER alpha had been detected in murine skin. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.

[PinotQ]

thanks for that study!

here we go:

ndocrinology. 2005 Mar;146(3):1214-25. Epub 2004 Dec 9.
Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling.
Ohnemus U, Uenalan M, Conrad F, Handjiski B, Mecklenburg L, Nakamura M, Inzunza J, Gustafsson JA, Paus R.

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Between the two recognized estrogen receptors (ERs), ER alpha and ER beta, only ER alpha had been detected in murine skin. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.

Thanks I have seen that research. Have you seen this letter to the editor of another significant study: http://www.nature.com/jid/journal/v1.../5602254a.html. I can't find the full text to the actual research article but much of the pertinent information is quoted in the letter. I'm not sure what to make of it all. There appears to be varying effects of estrogen based on sex and scalp location. They suggest that, at least in women, "E2 inhibits hair shaft formation, thus lowering the rate of hair growth, i.e., how much new hair shaft is generated by the anagen hair bulb per time unit, yet prolongs anagen duration". And they refer to a study on male frontotemporal scalp skin where they found that "Surprisingly, compared to the vehicle control, the hair shaft elongation of male frontotemporal scalp hair follicles was significantly stimulated by 1–100 nM E2 already as early as 1 d after the start of organ culture, and this stimulation became even more pronounced at the end of organ culture" and that "a slight, though not statistically significant, anagen-prolonging effect of E2 was seen in E2-treated test hair follicles as compared to vehicle controls". They go on to say that "This is well in line with the ill-documented, but widely shared clinical experience of topically applied E2 on the male scalp in vivo (i.e., hair growth stimulation; Schumacher-Stock, 1981) and supports the anagen-prolonging effect of E2." And what does this mean: "Our observation in a single, yet carefully analyzed male patient* raises five basic questions that must be addressed much more systematically by subsequent work on the effects of E2 on human hair growth in order to better explain the seemingly contradictory results obtained with occipital (Kondo et al, 1990;Nelson et al, 2003) versus frontotemporal scalp hair follicles" Does this mean that E2 had inhibitory effects on occipital hair?

And see this study where genistein inhibited hair growth by approximately 60%. http://www.nature.com/jid/journal/v1...ication_detail
Equol is a metabolite of diadzein and I don't believe genistein but given the research above I don't know what to make of it. Counter balancing this is the fact that 60% of Asians produce equol naturally and there are studies ( http://www.ncbi.nlm.nih.gov/pubmed/12269873) showing that Asians have a lower incidence of MPB.

I am very interested in your take on this.

[PinotQ]

thanks for that study!

here we go:

ndocrinology. 2005 Mar;146(3):1214-25. Epub 2004 Dec 9.
Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling.
Ohnemus U, Uenalan M, Conrad F, Handjiski B, Mecklenburg L, Nakamura M, Inzunza J, Gustafsson JA, Paus R.

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Between the two recognized estrogen receptors (ERs), ER alpha and ER beta, only ER alpha had been detected in murine skin. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.

Shinobi, Here is a bit more on s-equol's binding affinity to ERa & ERb taken from Nature Made's website http://www.naturalequol.com/about.html :

S-equol Biological Activity

The molecular and physical structure of S-equol is similar to that of 17-estradiol, the naturally occurring main sex hormone found in women, also referred to as estrogen. When comparing their relative affinities to bind to the human estrogen receptor alpha (ERα) S-equol has only about 1 percent of the affinity possessed by 17-estradiol. S-equol has a stronger affinity for the human estrogen receptor beta (ERβ), yet this affinity is just 20 percent of estradiol's affinity for ERβ. The preferential binding of S-equol to ERβ, compared to ERα and to estradiol's, indicates that S-equol shares some, but not all, of the characteristics of a selective ER modulator (SERM).12

One question you might ask here is that if estrogen is a positive influence on hair, does s-equol put the brakes on that due to it's affinity for ERb and the silencing effect noted in your study.

[NeedHairASAP]

so equol is potentially bad for hair?

thanks for rundown on how to make a topical. I'd much rather use a creme than alcohol based vehicle... but we'll see.


I also noted that asian have low mpb rates and above average in ability to make equol naturally... nobody seemed to find this of any interest for some reason. I think I even made a separate post about it that elicited zero discussion.

[PinotQ]

so equol is potentially bad for hair?

thanks for rundown on how to make a topical. I'd much rather use a creme than alcohol based vehicle... but we'll see.


I also noted that asian have low mpb rates and above average in ability to make equol naturally... nobody seemed to find this of any interest for some reason. I think I even made a separate post about it that elicited zero discussion.

I'm not sure what to read into all of the estrogen research. Even the authors say it raises more questions than answers once again pointing to how very complicated hair growth is. Despite the research highlighting various discoveries of the different pieces of the estrogen puzzle, they all seem to say the anecdotal evidence points to estrogen being a positive. My guess is that on a clinical trial basis, they just don't know how it all works together. I agree with you on the asian equol/mpb point. I think it is telling in terms of safety and if equol were bad for hair, I doubt asians would have a much lower incidence of MPB. Also note here: http://techtransfer.byu.edu/products...weight-control where the lead researchers on this state that "Equol also has an affinity for estrogen receptor subtypes that have positive influences on skin and hair."

[Shinobi]

Thanks I have seen that research. Have you seen this letter to the editor of another significant study: http://www.nature.com/jid/journal/v1.../5602254a.html. I can't find the full text to the actual research article but much of the pertinent information is quoted in the letter. I'm not sure what to make of it all. There appears to be varying effects of estrogen based on sex and scalp location. They suggest that, at least in women, "E2 inhibits hair shaft formation, thus lowering the rate of hair growth, i.e., how much new hair shaft is generated by the anagen hair bulb per time unit, yet prolongs anagen duration". And they refer to a study on male frontotemporal scalp skin where they found that "Surprisingly, compared to the vehicle control, the hair shaft elongation of male frontotemporal scalp hair follicles was significantly stimulated by 1–100 nM E2 already as early as 1 d after the start of organ culture, and this stimulation became even more pronounced at the end of organ culture" and that "a slight, though not statistically significant, anagen-prolonging effect of E2 was seen in E2-treated test hair follicles as compared to vehicle controls". They go on to say that "This is well in line with the ill-documented, but widely shared clinical experience of topically applied E2 on the male scalp in vivo (i.e., hair growth stimulation; Schumacher-Stock, 1981) and supports the anagen-prolonging effect of E2." And what does this mean: "Our observation in a single, yet carefully analyzed male patient* raises five basic questions that must be addressed much more systematically by subsequent work on the effects of E2 on human hair growth in order to better explain the seemingly contradictory results obtained with occipital (Kondo et al, 1990;Nelson et al, 2003) versus frontotemporal scalp hair follicles" Does this mean that E2 had inhibitory effects on occipital hair?

And see this study where genistein inhibited hair growth by approximately 60%. http://www.nature.com/jid/journal/v1...ication_detail
Equol is a metabolite of diadzein and I don't believe genistein but given the research above I don't know what to make of it. Counter balancing this is the fact that 60% of Asians produce equol naturally and there are studies ( http://www.ncbi.nlm.nih.gov/pubmed/12269873) showing that Asians have a lower incidence of MPB.

I am very interested in your take on this.

Thanks PinotQ to had a look into this !

Yes equol is converted from daidzin after being converted in daidzein. But this doesnt change anythin their activity are very similar with genistein.

Actually to date I still cant totally explain but it makes me understand why asian are less touched by MPB but are more willing to get diffuse and less hair per cm² (this is what i noticed during travels in asia, and confirmed in a global study saying less hair count for asian than occidental people). I was shocked by the number of people having diffuse, especially women.
I think these phyto hormones dilute and compete both androgen and receptor which bring to less hair but also less androgen damage.

In contradiction to the knows benefits of genistein there is the fact its a pro oxidant (stimulating nitrate synthesis) :

http://www.ncbi.nlm.nih.gov/pubmed/12720581 (but dont forget minoxidil does same (so my theory : give regrowth but kill these regrowth within some time)

more about this topic on endothelial cells and the release of Ca2+ from the endoplasmic reticulum :



Here you can see the difference between both ERa dominant and ERb dominant.

Also, genistein blocks formation of new blood vessels (antiangiogenic effect) in some kind of cells (inhibit growth factors > inhibit cell disivion and survival):

http://www.ncbi.nlm.nih.gov/pubmed/15302513

If you want to look further for the difference pathway between genistein and daidzein :



Regarding purely on the ERa : genistein is much more potent agonist than E2… even if less potent on the ERb : http://press.endocrine.org/doi/full/...ndo.138.3.4979 (do we need to make a perfect ratio ?)

Again is the ERa a good or a bad thing ? at the end all is a question of balance. The difference between vertex and frontal region still very strange to me.

Anyway, im almost sure activate ERb still good, and we confirm that (less or more indeed) here :

Rβ-selective compounds suppressed the expression of cytokines and MMPs in activated keratinocytes and fibroblasts-based in vitro models of photoaging. Further, in activated dermal fibroblasts, ERβ-selective compounds also inhibited COX 2

The full study : http://molpharm.aspetjournals.org/co...62877.full.pdf

Furthermore a study showing a reverse of baldness and even more (regrowth) using estrogen therapy (mainly estradiol, estrone, coumadin, minoxidil) :

http://www.ncbi.nlm.nih.gov/pubmed?t...ogen%20therapy

Come back to the ERa and b theory :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1815392/

this study explain that : « Based on the ER distribution, ERβ binding is generally considered beneficial based on the relative tissue distributions of the two receptors (40,41). The red clover extract preferentially bound to the ERβ receptor nine-times greater than to ERα. The hop extract had nearly a two-fold preference for ERα compared with ERβ. Since all of these studies were carried out using cell-based assays with ERα positive cell lines, it is important to note that the hop and red clover extracts had equivalent ERα activity »

also interesting because hops and especially his active 8PN are know to be good for hair and anti libido like :because its a potent anti androgen (so its molecular 3D structure) :

http://www.ncbi.nlm.nih.gov/pubmed/14598215

8PN prevents the binding of DHT to its receptor and therefore inhibits its activity



While in opposition genistein was shown to have no anti androgen activity, i even read in a RU study that high dose of genistein has a slight but significant androgen activity !

Some others studies about estrogen therapy :

Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-Beta signaling in aged human skin in vivo.

http://www.ncbi.nlm.nih.gov/pubmed/15955089

Influence of estrogens on the androgen metabolism in different subunits of human hair follicles.

http://www.ncbi.nlm.nih.gov/pubmed/11358723

17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.

http://www.ncbi.nlm.nih.gov/pubmed/12190948