Updated Research and Knowledge - Cutting Edge

[FeelsBad]

It's not going to raise T levels when applied topically

[ryan82]

It's not going to raise T levels when applied topically

I understand. So if i buy olive extract pills and put it in minox for example, i can reduces DKK-1 ?

[lukey]

just thought i would post an update been using Oleuropein ethanol tincture of amazon for 2 weeks now, i stopped minox 2 months ago due to face/skin probs ( it was the minox my face is better not 100% but alot better now)

the small vellus hairs that minox made were about 1-2mm in length across the hairline since using the Oleuropein some of these have doubled in length to 3-4mm nothing groundbreaking but they are getting longer for sure so im hoping in the next few weeks they might keep growing.

this is not cosmetic regrowth as the hairs in question are not pigmented just thought i would share

Josh, have you got anything to update us with? I've decided to come off minox for a while - i'm sure it's what's causing the problems with my sinuses - and hoping the OL + EGCG mixture will at least help prevent further loss.

Chemical, what's your thoughts on OC?

[hammerhead]

I take a liquid Olive Oil leaf extract (contains Oleuropein) for general health and well being - works great especially if you are sick with a cold or flu. Do you think taking any of these items orally instead of or in addition to topically will help with hair loss? Amazing information on this thread - very educational - thanks.

[burtandernie]

If something dissolves completely does that mean its optimally absorbed into the correct layers of the scalp or dermal layer where it needs to be for the amount of time it needs to be to get used properly? Im not a chemist/biology person so I dont know if just mixing stuff together would ever even work topically. Everyone knows the skin is a very strong barrier to keep things out

[jamesst11]

If something dissolves completely does that mean its optimally absorbed into the correct layers of the scalp or dermal layer where it needs to be for the amount of time it needs to be to get used properly? Im not a chemist/biology person so I dont know if just mixing stuff together would ever even work topically. Everyone knows the skin is a very strong barrier to keep things out

If something dissolves completely in solution, it does not mean it will be delivered transdermally.

[InBeforeTheCure]

PGD2 is quite important for REM sleep and I dont like the idea of messing with neurotransmitters.

I think the PGD2 receptor involved in sleep is DP1, not the GPR44 receptor that affects hair growth and which seti blocks.

From those excerpts it seems they are saying having a combination of AR related alleles can predispose individuals to AGA, with EDAR/EDA2R being the most significant predictor.

EDA2R, but not EDAR, is associated. No other study has been able to replicate the result of EDA2R being the most significant predictor -- maybe it's the case in Sardinians, somewhat of a genetic isolate, but not other populations? Still, EDA2R is one of the most linked genes, along with AR itself, a region on Chr20 near PAX1 and FOXA2, EBF1, TARDBP, and HDAC9.

I dont particularly like lookng at nf-kb because its functions are so broad and it plays a hand in alot of signalling cascades which makes it difficult to see the bigger picture. But looking this picture from wikipedia I see PKC activating nf-kb.

I read previously that Andrpgens have the ability to upregulate or maintain AR transcriptional activity. There are feedback loops including GSK3b that try to inhibit AR, but we know PKC can phosphorylate GSK3b possibly preventing the feedback loop. AR also inhibits the PI3K/AKT pathway which prevents the additional degradation of GSK3b. However, inhibiting AR causes an increase in Pi3K/AKT signalling which is good. Without PI3K/AKT, PKA will not be as elevated (?) and PKA is known to upregulate AR. These feedback loops are ridiculously complex and we're only scratching the surface. I just wish it was simpler.

According to this, AR -> PTEN normally (?), which inhibits the Pi3K -> Akt step. But supposedly PTEN is widely expressed throughout the body as a tumor suppressor. I'm not sure how that would affect the efficacy of increasing Pi3K if AR's inhibitory effect on the Akt pathway is one step downstream of Pi3K. Any ideas?

About EBF1, I remember making a post about the relationship between adipocytes and hair. EBF1 is expressed during anagen and also from the study you posted, inhibits ERb. In mice ERb is known to be hair growth suppressive so thats probably a good thing? Or perhaps EBF1 is doing something else behind the scenes.

Theres a disparity between mice ERb receptor distribution and male ERb receptor distribution in the scalp. (females have different ER distribution too) (post).

I was going over the research on 3b-Diol again and found something I'd missed:





So Estrogen when applied topically in males doesnt inihibit hair unlike 3B Diol which has antiproliferative actions despite acting via ERb. Regardless of how AR is being increased, preventing the ability of AR to bind to the cell surface and also prevent the intracelluar nuclear trranslocation might be the answer we're looking for. I think given the variation in genetic components, theres a chance these treatments could be hit and miss.

Interesting. I'll have to read more about EBF1, ERbeta, adipogenesis, and so on.

[Chemical]

You really have to forget about emu oil ! There is really no REAL SCIENTIST STUDY about emu oil. Emu oil is just a scam for hairloss, it don't decrease 5AR or DHT.

What about Zinc/Zinc Sulphate, Vitamin B6, BetaSitosterol ?
You should find a way to increase grow factor...because if you want regrowth, you need grow factor (VEGF-> Increased with stemoxydine, but there is FGF ; KGF ; Follistatin).

I have to disagree with you on Emu oil. Its not really being marketed by big companies for anything spectacular. In fact, I am. I've used it when I first started receding at 17 by itself and I saw modest regrowth after 2 months. Its got BetaSitosterol which you've just listed lol. Its not a scam, its a weak treatment for hair, however it does posses potent anti inflammatory effects which are proven.

The growth factors you've listed all inevitably end up increasing β-catenin to mediate their hair growth promoting effects.

IGF-1 inhibits GSKb3 which increases β-catenin
PGE2 inibits Axin which increases β-catenin
VEGF is increased by β-catenin
β-catenin also upregulates PDGF-A which is required for hair canal formation and anagen induction.

Regardless of how you activate β-catenin, you will see hair growth.

Oleuropein: ¬DKK1, ->WNT10b, ->IGF-1, ->β-catenin
Emu oil: ¬5ar, ¬DKK1 (via antioxidant activity)
EGCG: ¬Axin, ¬AR, ->β-catenin
Rosmarinus Officinalis: ¬AR, ¬5ar (Only rosemary extract not oil or rosmarinic acid)
Gamma Linoleic: ¬5ar (Evening primrose extract)
Procyanidins: ¬PKC, ->β-catenin (Apple polyphenols/Grape seed extract)
Forskolin?: ->PKA
Valproic Acid: ¬GSK3b, ->β-catenin
Miconazole/Ketoconazole: ¬17bHSD ¬3bHSD

I have also added 50 mcg of KGF (from Skinactives.com) to 74ml of solution. Don't want to add anything else, as my scalp seems to be ok with the ingredients and percentages currently.

I'm intrigued by your usage of KGF. I will dig up some research on this soon.

I found this, similiar, can get the extract on amazon:

Effect of Dieckol, a Component of Ecklonia cava, on the Promotion of Hair Growth

Ecklonia Cava amazon uk

wnt agonist:

Hair growth-promoting effect of Aconiti Ciliare Tuber extract mediated by the activation of Wnt/β-catenin signaling

fo-ti, upregulating Shh and β-catenin expression:

Topical application of Polygonum multiflorum extract induces hair growth of resting hair follicles through upregulating Shh and β-catenin expression in C57BL/6 mice

Ecklonia cava is 40% fat soluble and water soluble (?) too which means it can be used in an oil based vehicle I take?

Unfortuneately:

When DPC were treated with E. cava enzymatic extract in the concentrations of 0.001, 0.01, 0.1, 1, 10 and 100 μg/mL, E. cava enzymatic extract significantly promoted the proliferation of DPC compared with the vehicle-treated control at all the concentrations, except the 100 μg/mL (Figure 3).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382810/

Figure 3 shows 100 μg/mL did worse. Not promising.

Couldnt find any solubility info on ACT, nor Fo-Ti which actually has alot of potential to work seeing as it uses the shh pathway.

Baicalin (study) however, directly activates WNT and is quite solvent in ethanol with increasing temperature.

At what concentrations should one use primrose oil, grape seed extract and rosemary extract?
Also it would be cool if we could find a source for Grateloupia elliptica.

Gamma Linoleic Acid is very soluble in ethanol and can be mixed with oil:

https://pubchem.ncbi.nlm.nih.gov/compound/linoleic_acid#section=Solubility

So perhaps straight ethanol + GLA or ethanol + oil + GLA. I've got my hands on GLA (primrose extract) and I'm thinking of how to go about this.

Rosemarinus Officinalis isnt soluble in water but is soluble in solvents (ethanol?):

http://www.jmloveridge.com/cosh/Rosemary%20Oil.pdf

Also the main constituents of Rosemary are carnosol and carnosic acid:

Soluble in DMSO (250 mg/ml), ethanol (8 mg/ml), methanol (5 mg/ml), DMF (35 mg/ml), and PBS(pH7.2) (<0.03 mg/ml).

http://www.scbt.com/datasheet-204672-carnosol.html

Water soluble too apparently @1,425 mg/L at 25 deg C (est).

its boost testosterone levels ? That is bad for hair?

http://www.ergo-log.com/oleuropein-boosts-testosterone-lowers-cortisol-stimulates-anabolism.html

It's not going to raise T levels when applied topically

So if i buy olive extract pills and put it in minox for example, i can reduces DKK-1 ?

FeelsBad is correct. Someone pointed this out earlier and I made a post here.

Yes the Oleuropein will reduce DKK1. In fact, anything that has anti-inflamatory properties has the potential to reduce DKK1.

Will reply to other posts tomorrow and with some updates.

[SriHanuman]

Fo-Ti seems to be solubale in distilled water:

http://www.scielo.br/pdf/bjmbr/v39n9/6134

[LongWayHome]

Chemical, thank you very much for this.
I'm sure that I'm speaking on behalf of everyone that is not registered to this forum and follows this.
I Hope it will lead to something this time.

[Chemical]

Chemical, what's your thoughts on OC?

I'm not too familiar with the efficacy OC versus seti. I cant really comment on its topical vs oral intake effectiveness either. I dont see it being a huge problem taking it orally given that it doesnt interact with PGD2 itself, but I'm not a fan of systemic usage.

Do you think taking any of these items orally instead of or in addition to topically will help with hair loss?

It could work but if does increase hair then you'd notice hair everywhere. OL and EGCG work differently when taken orally and I cant vouch for their oral effectiveness on hair growth. Theres not alot of research on oral supplements increasing scalp hair growth in AGA unfortuneately. You're much better off using them topically since they are quite soluble and have low-ish molecular weights.

If something dissolves completely does that mean its optimally absorbed into the correct layers of the scalp or dermal layer where it needs to be for the amount of time it needs to be to get used properly? Everyone knows the skin is a very strong barrier to keep things out

Good question. Simply dissolving in a solution does not mean it will permeate the skin. The molecular weight in addition to solubility properties are a much predictor of topical absorption. This is a probabilistic model where complete absorption and equal tissue distribution is not guaranteed. Ethanol has the ability to strip the skin of lipids and enhance the absorption of molecules. Heres a post I made on minox/OL molecular weight and absorption.

I think the PGD2 receptor involved in sleep is DP1, not the GPR44 receptor that affects hair growth and which seti blocks.

http://www.ncbi.nlm.nih.gov/pubmed/22024172

I apologise, you are correct. It is indeed the DP1, so CRTH2 anatagonists shouldnt be a problem. I think I need you to correct mistakes in my analysis lol.

EDA2R, but not EDAR, is associated. No other study has been able to replicate the result of EDA2R being the most significant predictor -- maybe it's the case in Sardinians, somewhat of a genetic isolate, but not other populations? Still, EDA2R is one of the most linked genes, along with AR itself, a region on Chr20 near PAX1 and FOXA2, EBF1, TARDBP, and HDAC9.

Two receptors for EDA were found that are specific for the two isoforms EDA-A1 and EDA-A2: EDAR and EDA2R, respectively. EDA-A1 and its receptor EDAR are capable of activating the NF-κB pathway and are implicated in hair growth. EDA2R is capable of activating the NF-κB pathway and also through TRAF3,6, JNK (c-Jun N-terminal kinase), which activates c-Jun. Mutations in EDA and EDAR give rise to ectodermal dysplasia, a clinical syndrome characterized by loss of hair, sweat glands, and teeth, whereas mutations in EDA2R do not. Recently, a preliminary report suggested that EDAR may influence hair thickness in Asians, A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.

EDA2R could influence the onset of AGA through the activation of the NF-κB pathway or by c-Jun, which has been shown to be critical for AR transactivation. Moreover, in adult mice, EDA2R is also expressed in the hair bulb and in differentiating hair matrix (Botchkarev and Fessing, 2005).

Our previous studies suggest that the proto-oncoprotein c-Jun is an AR coactivator that stimulates AR transactivation by mediating receptor dimerization and subsequent DNA binding. (study)

Indeed, its the EDA2R that is involved in AR transactivation. But the EDAR variant also activates nf-kb without negative effect on hair. It seems theres alot genes that can influence the AR and transactivation of AR via different mechanisms leading to increased nuclear translocation. A combination of these alleles that enhance AR be it subtly or directly, definitely have the ability to predispose individuals to AGA. The nf-kb pathway seems to have differential effects depending on its mechanism of activation? I think I'm missing something that doesnt explain why EDAR can increase hair thickness.

According to this, AR -> PTEN normally (?), which inhibits the Pi3K -> Akt step. But supposedly PTEN is widely expressed throughout the body as a tumor suppressor. I'm not sure how that would affect the efficacy of increasing Pi3K if AR's inhibitory effect on the Akt pathway is one step downstream of Pi3K. Any ideas?

So this means in the presence of AR, anything that wants to activate AKT via PI3K will be unsuccessful. This includes IGF-1, shh, EGF (wiki). Beautiful diagram here: https://en.wikipedia.org/wiki/File:M...thway-v1.7.svg

But does this mean beard DPC do not inhibit PI3K via PTEN in response to AR activation? Apparently PTEN deficiency results in accelerated hair follicle morphogenesis and enhanced AKT(PKB) activation (study). Very interesting.

Heres some more research on ERb and hair.

Recent in vitro studies have shown that 17β-estradiol inhibits female scalp hair shaft elongation (Nelson 2006), although stimulation occurs in hair follicles derived from frontotemporal male scalp (Conrad et al 2004). In addition, in female hair follicles the phytoestrogen, genistein inhibits hair shaft elongation to a similar extent as 17β-estradiol. Since genistein preferentially binds to ERβ, this opens the possibility that the inhibition of hair growth in response to 17β-estradiol may be mediated via ERβ rather than ERα (Nelson 2006). Therefore the development of selective estrogen receptor ligands may provide important clinical applications for the prevention and treatment of disorders of hair growth.

So in females, ERb increases frontotemporal hair growth but inhibits in other areas?

ERbeta was the major steroid receptor expressed in human skin. It was highly expressed in epidermis, blood vessels and dermal fibroblasts, in contrast to ERalpha and AR. In the hair follicle, ERbeta expression was localized to nuclei of outer root sheath, epithelial matrix and dermal papilla cells, in contrast to ERalpha, and the AR, which was only expressed in dermal papilla cells.

Studies say that estrogen prolongs anagen but inhibits hair shaft elongation (in females). Perhaps ERb in the ORS is inhibiting proliferation, but ERa in the DPC is maintaining BetaCatenin. But Estrogen acts differently in frontotemporal regions? Females have a differential scalp response phenotype. Males start off as females in the womb, so what if Androgens exploit this localised response in a detrimental manner? This sets off the chain reaction whereby follicles release DKK-1 and TGF-Beta into the ECM affecting nearby follicles that arent fully susceptible to AR's effects.

Anyways, I want to know what role ERa has in male DPC. ERb can increase proliferation of existing hair, but does it secrete growth factors in a paracrine manner? Or does ERa promote WNT activation by itself in DPC to prolong anagen?

Fo-Ti seems to be solubale in distilled water:

http://www.scielo.br/pdf/bjmbr/v39n9/6134

It can! This is excellent research SriHanuman. Unfortuneately I cant use this because I'm trying a different stack, so I wont be able to gauge its effectiveness. People who cant use minox might find fo-ti useful.

Chemical, thank you very much for this.
I'm sure that I'm speaking on behalf of everyone that is not registered to this forum and follows this. I Hope it will lead to something this time.

Thank you! We're uncovering so much research that I think it is already leading to something.

Update

Last week I increased the EGCG concentration totalling 12.5mg/ml. The hairs that I grew using minox + OL are 100% terminal. Really wasnt expecting results this fast. I'm seeing more tiny vellus hairs along nw1 hairline and the skin turning grey/green. My nw1/0 hairs grow sideways, as in they come out of the skin at very low degree angles. My nw0 is hairline is completely bald atm so it might be harder to regrow. I'm not sure if my aggressive micro-needling (3mm derma pen) last year has caused scarring. I hope not because I'd be devastated.

Bear in mind I'm using the MXOLCG once a day at night because of work and laziness, and Ketoconazole in the morning. During the weekends I use MXOLCG 3x day. If only I could use minox 3x a day everyday... I try to use Emu oil every two days, and I'll be adding the Gamma Linoleic Acid to the Emu oil (which has minox in it already). I'll be posting pics soon. I am tempted to use Rosemary but I'll wait.

I'm also going to ask the moderators to let me edit my first post so I can reorganise the research for people to find easily.

[UNBEAT]

HEY Chemical thank you for what are you doing.

Can you do a summarise of your invention, like what exactly to use( what products it contains) , the concentration ,and how often to use like instructions on drughs???

[scooterboy]

Chemical , Can you please tell me how much EGCG and OL pills you are now using in a 60 MG bottle of minox ? I was dumping in one EGCG pill and a half pill of OL . Can you update the mix ?

[pilipili]

There are a lot of new pages, sadly I did not find the courage to read everything ! ^^ So the idea to edit the first posts would be excellent.
Anyway I remember you said you don't take any anti DHT. According to you new hairs get thicker and potentially hold on thanks to EGCG but what about existing hair ? Do you apply the solution all over the scalp or only at temples ? Thanks for keeping us updated!

[bluesuedeshoes]

Thanks for the all the work Chemical and Brianboy. Ive purchased the supplies and keen to start soon.

Im already using seti in an etch/pg solution so keen to not add too much more ethanol to my scalp each day. That said, I want to ensure proper delivery to the follicles.

I have DMSO as well. Would a water/eth/pg/dmso be a good idea? What ratios are you both using?

I don't have any Keto to hand but I have some Dexamethasone, which apparently raises PGE2 and is an AA. Would adding that to the mix be too much? I see that you put your Keto on in the morning. Important to use it hours before the EGCG/OL mix?