Updated Research and Knowledge - Cutting Edge

[JustParker]

Does anyone know much about IGF-1's involvement with the PGE pathways? I've found a few studies related to increasing IGF-1 and hair growth, but wasn't sure if this thread would be the place for them

[pilipili]

Chemical what do you think about apple polyphenols /Procyanidin b2? It potentially looks like good additions.

http://www.applepoly.com/procyanidin-b-2

http://www.ncbi.nlm.nih.gov/pubmed/11841365

[bluesuedeshoes]

Chemical - I am currently using a 4% (2960 mg EGCG / 50% Green Tea blend, so about 1480 EGCG proper) in 74ml .......5% OL (it's a blend w/20% OL - so about 300mg of Oleuropein proper) ..... 1% Rosemary Ext ... 1% Jojoba Oil .... (.2%) Tea Tree Oil. This is in a distilled water solution. I add maybe 4 ml of 70% ethyl alcohol as well. Apply that, then wait for that to absorb and apply Minox foam, then finish with Ketoconazole 2% cream. I do this 3 times a day if possible. Scalp seems ok with this regimen so far (2 weeks). I would like to use even a higher dose of EGCG blend, but, the hair growth stimulation seems to occur just under the threshold of when the folliculitis starts. So, have to be careful. I don't want to be forced to stop treatments. Scalp feels in harmony and in a positive direction again.

Going to follow your instructions here. However, thinking about adding some DMSO. If I'm trying to increase absorption, should I add more eth and DMSO?

[BRIANBOY]

Going to follow your instructions here. However, thinking about adding some DMSO. If I'm trying to increase absorption, should I add more eth and DMSO?

I wouldn't add dmso. You are adding an additional factor that's not really needed, and might even have its own problems. EGCG is very soluble in water and crosses the skin barrier easily. The Jojoba oil will also act as a carrier. Just be aware that high dose topical EGCG can trigger / cause folliculitis. If that begins, you have reached your threshold and have to back the % down. I have also added 25 mcg of KGF, 1 ml of Polygonum Multiforum. As of now, my scalp seems comfortable with the percentage solution of 4% Green Tea/EGCG blend. I'm about 3+ weeks in now. I am applying it 3 - 6 times per day. So far, just an occasional single folliculitis which I can control with temporary ketocanozole / hydrocortisone. Not really a problem, so I will continue to use the high dose. Scalp feels very much like it did when a lot of hairgrowth increased 5 years ago. Losing very little hair daily. I am backing off on the Minox and Keto. Minox is giving me water retention and Keto is causing a slight bit of rash if I use it daily, so I am only going to use occasionally. 5 years ago, I only used the high dose Green Tea/EGCG blend in distilled water, so that is my mainstay and core. I remember it took about 2 months before I noticed dramatic changes.

[BRIANBOY]

deleted double post.

[joshuk]

chemical i have been using OLE/EGCG mix now for almost a month and im seeing improvement, but i think if i was to use minox with this i would get some serious regrowth. and i mean like 2+NW back

as i cant use 5% minox due to side effects puffy eyes dark circles etc, do you think 2% minox would have less sides or the same as it has a higher ethanol % than the 5% bottle.

anyone else can help here?? i really think i can get some serious regrowth if i add in minox but also dont want to have a loads more hair but a bloated and dark circles on face again...sucks

[Chemical]

hey Chemical do u have an email address i can contact u with?

I'd prefer not to give out my email, but if you truly must speak to me in private you can find it here.

So your of the opinion that RU is better than using fin? The big issue is there arent any good AR antagonists or no one would be using fin still. I mean we have known androgens cause MPB for like 20 or 30 years yet still have no real way to actually do anything about that. There is no practical way to stop androgens non systemically even still

RU is definitely preferable to Fin, alot of people have seen huge improvements using RU so its definitely effective at suppressing the Androgen Receptor and not just partially reducing DHT conversion.

This is where EGCG also comes in. Its a non systemic AR suppressor and increases BetaCatenin - I've covered the science in previous posts. Feel free to look back. I'm also experimenting with Evening Primrose oil which contains Gamma Linoleic acid - a 5ar inhibitor that also works topically. I realise it's quite difficult to go through all my posts to find what you're looking for and the moderators havent responded to my request so I might just make a new thread with all the research.

So your using 4 x EGCG caps and 1 half OL cap in 60MLS of minox .

roughly 4 caps of EGCG in 40ml. Its not dissolved completely so I'm going to use less for my next run. Also I found out EGCG degrades over time, especially in warm and humid conditions. (study) (study) So it might be better to make smaller batches - 30ml at a time?

What is your background Chemical? Doing any work/study related to biology? Or just pure interest.

I work for a Hedge Fund as a software engineer, and I've got a strong background in Big Data sciences, specifically application of machine learning to artificial intelligence. I developed an interest in biology when I was 15 while researching cognitive enhancement, and realised just how much you can manipulate the human body to get what you want. Its just a big system with rules and models, if you spend enough time understanding how it works you can find ways to fix it (or improve it). It's interesting for me because its just another puzzle that needs solving.

I'm planning to coumpound a custom cream for my temples.

-Adenosine (high amount like 5%)
-Baicailin
-Vitamin B6
-Zinc Sulphate
-Oleuropein high dosed (0.6gr in a 4oz cream jar)
-ECGC (-> Don't really know if usefull since oleuropein is antioxydant)
-Saw Palmetto
-Vitamin E Succinate ( cause an increase of PGE2)
-KGF (Keratinocyte Grow Factor) ( 50mcg)

I'm a little bit skeptical about zinc (It can potentiate binding of DHT to nuclear AR?). What makes you want to use zinc? B6 too.

I personally wouldnt use anymore than 1.5mg/ml of OL because its been shown to have biphasic properties, but it you're willing to try it at a high dose anyway then please report back if you notice any change.

The EGCG isnt for ROS scavenging, its an AR suppressor and inhibits Axin thus preventing the degradation of BetaCatenin. Other than that, your stack is fine.

Does anyone know much about IGF-1's involvement with the PGE pathways? I've found a few studies related to increasing IGF-1 and hair growth, but wasn't sure if this thread would be the place for them

Yes this is the perfect place to post studies!

Chemical what do you think about apple polyphenols /Procyanidin b2? It potentially looks like good additions.

http://www.applepoly.com/procyanidin-b-2

http://www.ncbi.nlm.nih.gov/pubmed/11841365

I made a post about PKC and apple polyphenols here. I'm yet to try it but it has promise.

Going to follow your instructions here. However, thinking about adding some DMSO. If I'm trying to increase absorption, should I add more eth and DMSO?

I wouldn't add dmso. You are adding an additional factor that's not really needed, and might even have its own problems. EGCG is very soluble in water and crosses the skin barrier easily. Just be aware that high dose topical EGCG can trigger / cause folliculitis. 5 years ago, I only used the high dose Green Tea/EGCG blend in distilled water, so that is my mainstay and core. I remember it took about 2 months before I noticed dramatic changes.

@Bluesuedeshoes,
I second what Brian has said about adding DMSO.

@Brian
the solubility of EGCG in water is <5mg/ml. Are you sure its such a good idea to use water instead of Ethanol (which has max 20mg/ml solubility) especially at such high concentrations? I'm a little concerned with your vehicle choice.

chemical i have been using OLE/EGCG mix now for almost a month and im seeing improvement, but i think if i was to use minox with this i would get some serious regrowth. and i mean like 2+NW back. As I cant use 5% minox due to side effects puffy eyes dark circles etc, do you think 2% minox would have less sides or the same as it has a higher ethanol % than the 5% bottle.

Improvement as in thickening or vellus hairs?
I doubt reducing the frequency or dose will help with those side effects seeing as you're prone to them. I'm going to be trying sodium valproate because I'm not seeing regrowth fast enough. If I see any improvement you might want to consider using it instead of minox?

I'm considering adding Rosemary extract and apple polyphenols to my stack.

Topical administration of Rosmarinus officinalis leaf extract (RO-ext, 2 mg/day/mouse) improved hair regrowth in C57BL/6NCrSlc mice that experienced hair regrowth interruption induced by testosterone treatment. In addition, RO-ext promoted hair growth in C3H/He mice that had their dorsal areas shaved. To investigate the antiandrogenic activity mechanism of RO-ext, we focused on inhibition of testosterone 5α-reductase, which is well recognized as one of the most effective strategies for the treatment of androgenic alopecia. RO-ext showed inhibitory activity of 82.4% and 94.6% at 200 and 500 µg/mL, respectively. As an active constituent of 5α-reductase inhibition, 12-methoxycarnosic acid was identified with activity-guided fractionation. In addition, the extract of R. officinalis and 12-methoxycarnosic acid inhibited androgen-dependent proliferation of LNCaP cells as 64.5% and 66.7% at 5 µg/mL and 5 μM, respectively. These results suggest that they inhibit the binding of dihydrotestosterone to androgen receptors. Consequently, RO-ext is a promising crude drug for hair growth.

http://www.ncbi.nlm.nih.gov/pubmed/22517595

I've stupidly mixed some evening Primrose oil with the remainder of my minox and then found out GLA enhances the skins barrier function. So I might not see any more regrowth for the next two weeks. My mid scalp is shedding and I've been skipping applications the last few days. Luckily the hairs that I regrew arent thinning and are getting longer so its not too bad. Ultimately I want to find a set of treatments that I can put in a cream and just use that for the rest of my life. This liquid vehicle formulation is very difficult to be consistent with and I have to keep my head tilted back until it dries, which sucks because I dont always have time/feel bothered to do.
I know about polysorbate 80 and DMI that can be used to create creams (courtesy of Seuxin), but I wonder if gels might be better suited for drugs that dissolve better in ethanol vehicles.

[Swooping]

What is your view overall on the pathology of AGA?

Do you find it likely that it is prostaglandin mediated?

Are you more in the camp of senescence/cell cycle arrest?

Perhaps something else?

Also, why do you think 17b-estradiol is so good at regrowing hair in men? Any particular targets you find interesting?

[Chemical]

I think the overall pathology is androgen dependent, which isnt anything new. But just because we've known about it for a long time doesnt mean its wrong and that there's something more special or a pathway that we havent yet discovered is implicated in the pathogenesis of AGA. Recent findings have revealed that the AGA pattern originates from females, and since all males start off as females in the womb, this explanation is very plausible. In females, the AGA pattern manifests itself as a positive modulator of hair growth, increasing the hair growth in response to Estrogens. Alot of womem have very rounded hairlines with thick temples(examples) - completely opposite to men who will typically have recessed temples. Evolution is responsible for a lot of polar opposite differences we see in genders and its quite common to see differential hormonal responses between the two sexes. I suspect this ability of estrogen to increase hair growth in frontal regions is still intact even in AGA males. I've talked about possible explanations of how Estrogen might increase hair growth here and briefly here.

My initial assumption that ERb was bad is incorrect. 3bDiol activates this receptor with different effects that cannot be reproduced by physiological doses of 17b Estradiol which indicate ERb is actually a positive modulator of hair. ERb is also the predominant receptor expressed in the hair follicle regions, except for the DPC where only ERalpha is expressed. Furthermore, Estrogen receptors are present in adipocyte precursor cells (they can induce hair canal formation via PDGF) so it could be that estrogens act on the stem cells directly. This area of research is still a work in progress but its clear that Estrogens can and do increase hair growth/regrowth in men.

I've talked alot about how Androgens suppress BetaCatenin expression at multiple levels, and given that the AR is significantly upregulated in frontal regions in comparison to occipital regions, its not at all surprising that hair growth is diminished.

I've had this discussion about PGD2 with InBeforeTheCure which I'd definitely recommend reading: here and here

In short, some people arent sensitive to PGD2. Also, the PGD2 levels seen in balding scalp isnt ridiculously high, but I dont know how one should interpret 2.5-4 fold differences. The consensus is that PGD Synthase activity is an Androgen dependent process. I've yet to find any other possible link explaining the rise in PTGDS.

The increased conversion of arachidonic acid to PGD2 reduces the production of PGE2 since they both use arachidonic acid as their substrate. This reduction in PGE2 paired with PGD2's PKC activating effects directly enhance the proteosomal degradation of BetaCatenin, so this works additively with other BetaCatenin inhibitors. Heres a post where I talk about PGE2 and how it works to grow hair.

Without BetaCatenin the hair follicles will stop prolifereating and end up in telogen permanently or senescent as you might say. The telogen - anagen cycle is blocked and the local paracrine feedback loop controlling the cycle is disrupted subsequently resulting in the hairs failing to recruit blood vessels necessary to keep growing. I believe that the DPC in AGA do not completely die - as in they dont disappear. Rather, like you say, the DPC become senescent (study).

This is good because the DPC can still be modulated to respond to PDGF-A originating from the Adipocyte lineage precursor cells, and reconstruct the hair follicle canal (post). One study showed that androgens can interfere with this signalling loop further antagonising hair growth (post).

In the case that DPC are actually dead and there is no physical intact DPC, then it's still not impossible to regrow hair. This study shows that transiently elevated BetaCatenin induces the formation of new hair follicle:

The formation of hair follicles during embryogenesis depends on a series of signals that are exchanged between the epidermis and the underlying dermis. In the embryo the initiating signal comes from the dermis and involves activation of Wnt signalling; the response in the overlying epithelium also involves activation of β-catenin. In K14ΔNβ-cateninER skin the dermal signal is not required and activation of β-catenin signalling in the epidermis leads to organisation of a dermal papilla (Fig. 3G-J). In each location where new follicles formed in K14ΔNβ-cateninER epidermis there was induction of Shh, Ptc and Lef1. Just as Shh drives anagen, Shh is downstream of Wnt signalling in hair follicle development: in mice lacking Shh hair follicle formation is initiated and the dermal condensate is formed but mature hair follicles fail to develop. Lef1 is a known transcriptional target of β-catenin, required for normal hair follicle formation. Although during normal hair placode formation expression of Lef1 is regulated by Noggin, produced by dermal cells, in our system Lef1 upregulation is independent of a pre-existing dermal signal.

http://dev.biologists.org/content/131/8/1787.long

This methodology of suppressing AR and increasing BetaCatenin may seem too simple to be effective at regrowing hair, but sometimes the simplest approaches are the best. And even though the goal is simple, inhibiting AR and increasing BetaCatenin are very challenging.

Other pathways that are heavily involved in hair follicle formation and growth (anagen induction) include Noggin (inhibits BMP's that negatively regulate growth) and Shh which regulates Noggin. Both are downstream targets of WNT which I havent covered yet.

[wwesley]

seriously need the article with all info contained in a single post :-)

For EU residents, which products do you recommend we buy? It'd be nice to have an easy table from which US/EU residents can easily buy the ingredients. Same for the new ones you seem to have added (apple polyphenols, rosemary extract, etc) - dosage, etc..

thanks for this thread!

[ledhead]

Is there a certain egcg I should look for on Amazon or will any do?

Thanks

[Sogeking]

I've stupidly mixed some evening Primrose oil with the remainder of my minox and then found out GLA enhances the skins barrier function. So I might not see any more regrowth for the next two weeks. My mid scalp is shedding and I've been skipping applications the last few days. Luckily the hairs that I regrew arent thinning and are getting longer so its not too bad. Ultimately I want to find a set of treatments that I can put in a cream and just use that for the rest of my life. This liquid vehicle formulation is very difficult to be consistent with and I have to keep my head tilted back until it dries, which sucks because I dont always have time/feel bothered to do.
I know about polysorbate 80 and DMI that can be used to create creams (courtesy of Seuxin), but I wonder if gels might be better suited for drugs that dissolve better in ethanol vehicles.

Chemical what Evening primrose oil? I finally got all the components and am also trying to add rosemary and apple polyphenols from the start. I also intended to add Evening primrose oil, should I add it independently from the ECGC/OL solution? Or do you think its not worth using it at all?

[BRIANBOY]

Chemical - I am using about 4-6 ml EtOH 70% in the distilled water solution of 74ml. Also, I am using the Green Tea / EGCG 40% blend, which I find better than just pure EGCG. I feel the compliment of green tea polyphenols as well as EGCG have a positive effect.

[Seuxin]

* Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study :

http://www.ncbi.nlm.nih.gov/pubmed/11841365

* Procyanidin B-3, isolated from barley and identified as a hair-growth stimulant, has the potential to counteract inhibitory regulation by TGF-beta1 :

http://www.ncbi.nlm.nih.gov/pubmed/12473061

* Procyanidin oligomers counteract TGF-beta1- and TGF-beta2-induced apoptosis in hair epithelial cells: an insight into their mechanisms :

http://www.ncbi.nlm.nih.gov/pubmed/16778458

* Investigation of the topical application of procyanidin oligomers from apples to identify their potential use as ahair-growing agent :

http://www.ncbi.nlm.nih.gov/pubmed/17168871

[Chemical]

seriously need the article with all info contained in a single post :-)

For EU residents, which products do you recommend we buy? It'd be nice to have an easy table from which US/EU residents can easily buy the ingredients. Same for the new ones you seem to have added (apple polyphenols, rosemary extract, etc) - dosage, etc..

I'm writing everything up as we speak. I'll put it all in a separate thread so its easier to find. I think we should have this thread for disussion and progress logs and the new thread just for research and treatment info.

Is there a certain egcg I should look for on Amazon or will any do?

I'm using swansons Teavigo which has EGCG standardized to 90% (150mg actual per capsule). You can use a different brand but if the EGCG is low you might end up saturating the solution with other ingredients reducing the amount of EGCG penetrating the skin.

Chemical what Evening primrose oil? I finally got all the components and am also trying to add rosemary and apple polyphenols from the start. I also intended to add Evening primrose oil, should I add it independently from the ECGC/OL solution? Or do you think its not worth using it at all?

I would recommend not mixing any oils with minox, I've learnt my lesson now. The EPO might absorb better after using an ethanol solution which will weaken the stratum corneum's barrier function. I think using the EPO by itself or mixed with Emu Oil would be ideal. Any subsequent treatment after EPO may not absorb properly until its completely gone or cut down by ethanol again. The EPO may not be convenient but if you want to use it, then using it at night after everything else has absorbed should be fine. I'm still testing it but I'm not sure if it'll work as good as EGCG or rosemary (I dont know how well it absorbs). I bought the capsules and dumped the contents of one cap into my minox. I noticed it leaves my scalp very smooth and soft.

Chemical - I am using about 4-6 ml EtOH 70% in the distilled water solution of 74ml. Also, I am using the Green Tea / EGCG 40% blend, which I find better than just pure EGCG. I feel the compliment of green tea polyphenols as well as EGCG have a positive effect.

Yes I do remember you saying that but wouldnt a 70/30 Ethanol/water solution be more optimal? And I did read that the other catechins present in green tea possess 5ar suppressing effects - I'm looking for the study.

Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study

Procyanidin B-3, isolated from barley and identified as a hair-growth stimulant, has the potential to counteract inhibitory regulation by TGF-beta1

Procyanidin oligomers counteract TGF-beta1- and TGF-beta2-induced apoptosis in hair epithelial cells: an insight into their mechanisms.

Investigation of the topical application of procyanidin oligomers from apples to identify their potential use as ahair-growing agent.

Excellent finds Seuxin! I will be adding these to the post on Apple polyphenols in the new thread (with credit to you).