Updated Research and Knowledge - Cutting Edge

[JustParker]

Bought myself Oleuropein capsules from amazon (extra strength), and mixed it with minoxidil. I had one bottle left so I dissolved like 5 capsules into the liquid and gave it a good shake. I also added a few saw palmetto capsules which I regret because it did not dissolve at all. I let it sit for 24 hour then shook it again.

Just wanted to point out that the Oleuropein capsules are 750mg total, but only 20% Oleuropein, so each capsule is only 150mg of Oleuropein. Not sure if you accounted for that (as I don't know about uM so sorry if you already caught that). That being said, I look forward to trying this.

Also, thanks for the great initial write up, I know Lithium and Zyrtec (no joke) have both had studies showing hair growth, so I might go back and reevaluate those to see how they fit into the cycle you covered.

[joshuk]

looks promising do you have small vellus hair throught the zone as in across the nw1 hairline and in the affected zone, but having two terminal hairs grow is awesome from nw0 hairline. if those 2 terminal hairs were from only just a month on your new regime thats positive news!! as it take awhile for hairs to grow from vellus to terminal..so intersting to see what happends in the coming months and if you get any more.

when i noticed my vellus hairs getting longer i licked my finger (i know i know) and then brushed at them and i noticed over the course of 2 weeks i had more and they were getting longer. if all these vellus hairs were to go terminal i would go from an NW4 to an NW2 thats why im excited to see if this works as that would be crazy regrowth, but im realistic as its unheard of unless your a super minox responder to get that.

it looks like your temple is not slick bald anyway as you still have pigmented hairs though out but if you were grow hairs down to the hairline then things would get really intresting. my temples are worse so i can see any changes happening, im hoping with the CB blocking my AR the EGCG/OLE can get to work as growth stimulant and turn some of these vellus terminal, if only it was that easy though lol.

still chemical were stepping into the unkown here but i would rather think outside the box then be stuck in a mindset of only using the big 3. your doing an excellent job keep it up!!! im learning all the time

[joshuk]

Just wanted to point out that the Oleuropein capsules are 750mg total, but only 20% Oleuropein, so each capsule is only 150mg of Oleuropein. Not sure if you accounted for that (as I don't know about uM so sorry if you already caught that). That being said, I look forward to trying this.

Also, thanks for the great initial write up, I know Lithium and Zyrtec (no joke) have both had studies showing hair growth, so I might go back and reevaluate those to see how they fit into the cycle you covered.

thats fine parker tip one capsule into 60ml minox or make your own solution its up to you im going to use 1/2 of one of those caps and 1 cap of EGCG into an 80/20 ethanol/pg mix cant use minox unfortuantly

[iaskdumbquestions]

Hi Chemical - First, add me to the growing number of posters (and lurkers) in these forums grateful for your willingness to wade through the scientific lit related to AGA and share your insights. While the prospect of a standardized formula that incorporates oleuropein or ECGC (or both) is exciting (I'm referring to Keeper's efforts), I want to experiment on my own. I've had decent results using 5% Minoxidil so I want to continue to use it. If I understand your recent posts correctly, to replicate the formula that you'd currently recommend, I'd simply add 1/2 capsule of the Swanson's Superior Herbs Olive Leaf Extract Super Strength and 1 capsule of either the Swanson's Superior Herbs Teavigo EGCG or the Healthy Origins Teavego EGCG to a single 60 mL bottle of 5% Minox. Please correct me if I've misunderstood, and thanks again for your consideration.

http://www.amazon.com/Olive-Leaf-Extract-Super-Strength/dp/B00GZRIW5C/ref=sr_1_1?ie=UTF8&qid=1451590553&sr=8-1&keywords=Swanson%27s+Superior+Herbs+Olive+Leaf+Extract+Super+Strength

http://www.amazon.com/Healthy-Origins-Multi-Vitamins-Count/dp/B000JLA7Y4/ref=sr_1_fkmr0_1?ie=UTF8&qid=1451590617&sr=8-1-fkmr0&keywords=Herbs+Teavigo+EGCG

http://www.amazon.com/Rogaine-Men-Extra-Strength-Minoxidil/dp/B0000ZREGI/ref=sr_1_1?ie=UTF8&qid=1451590720&sr=8-1&keywords=minoxidil+60ml

With those three items we can begin the regiment? By 'add' do you simply mean dropping the pills/capsules into the liquid minoxidil? Will it dissolve easily?

[Chemical]

t looks like your temple is not slick bald anyway as you still have pigmented hairs though out but if you were grow hairs down to the hairline then things would get really intresting. my temples are worse so i can see any changes happening, im hoping with the CB blocking my AR the EGCG/OLE can get to work as growth stimulant and turn some of these vellus terminal, if only it was that easy though lol.

still chemical were stepping into the unkown here but i would rather think outside the box then be stuck in a mindset of only using the big 3. your doing an excellent job keep it up!!! im learning all the time

http://imgur.com/a/g6TdQ

I was slick bald in that region before the emox protocol. You can see the vellus hairs in the first picture, but thats technically bald because you cant see them under normal lighting. I'm not seeing miraculous growth in the vertex, but the surrounding hairs are getting thicker and thicker. You can see in the first picture the hair I was talking about sticking out in the middle, it was there for a while. Vellus hair seems to become terminal where the surrounding follicles are terminal - paracrine growth factors I presume. Going from vellus to terminal is difficult, its the timing and duration of treatment that increases probability of hair follicles getting a blood supply attached to DPC and then you have to sustain growth factors until the anagen cycle kicks in. Once anagen kicks in you've got a greater chance of keeping it in anagen. Its like beard growth, you start off with vellus and slowly you start to see terminal hairs. You would think that the testosterone peak at 20-22 would suddenly give people thick beards lol. My theory is; the more beard hairs you have, the quicker each individual hair will grow because every single follicle is releasing IGF-1 to nearby follicles. You can see how the IGF-1 levels start stacking up. Unfortuneately the AGA hairs sabotage nearby follicles by releasing TGF-Beta and DKK1, that's the best explanation for the gradual recession rather than patchy or complete synchronised frontal shedding.

I agree, once I get my nw0 back we can say this protocol is worth something, until then its nothing extraodinary. And not to forget, I have to be able to keep the hairs. And the real challenge lies with people that have been bald for years. With your stack, when you start to see alot of vellus hairs, it'll only be a matter of 1-2 months before they go terminal - I'm fairly confident. Since the new anagen hairs will start off as miniaturised follicles (giving the impression of vellus hairs) but will gradually get thicker at the base once the blood vessels have a chance to latch on. Otherwise they'll constantly be in limbo, trying to grow but not fully getting there.

We are indeed stepping into the unknown. Its amazing what people can achieve with enough motivation or should I say desperation, and a bit of hope.

http://www.amazon.com/Olive-Leaf-Ext...Super+Strength

http://www.amazon.com/Healthy-Origins-Multi-Vitamins-Count/dp/B000JLA7Y4/ref=sr_1_fkmr0_1?ie=UTF8&qid=1451590617&sr=8-1-fkmr0&keywords=Herbs+Teavigo+EGCG

With those three items we can begin the regiment? By 'add' do you simply mean dropping the pills/capsules into the liquid minoxidil? Will it dissolve easily?

The Oleuropein and EGCG in your post and this minoxidil:

http://www.amazon.com/Kirkland-Minoxidil-Strength-Regrowth-Supply/dp/B002VLZHLI/ref=sr_1_1?ie=UTF8&qid=1451596397&sr=8-1&keywords=kirkland+minoxidil

Dont drop the capsule themselves, open them, and drop in the contents - the powder into the minoxidil liquid. Only half an oleuropein capsule. Then shake until you cant see any powder at the bottom. It will dissolve fine.

[drgs]

http://www.amazon.com/Olive-Leaf-Ext...Super+Strength

http://www.amazon.com/Healthy-Origins-Multi-Vitamins-Count/dp/B000JLA7Y4/ref=sr_1_fkmr0_1?ie=UTF8&qid=1451590617&sr=8-1-fkmr0&keywords=Herbs+Teavigo+EGCG

http://www.amazon.com/Rogaine-Men-Extra-Strength-Minoxidil/dp/B0000ZREGI/ref=sr_1_1?ie=UTF8&qid=1451590720&sr=8-1&keywords=minoxidil+60ml

With those three items we can begin the regiment? By 'add' do you simply mean dropping the pills/capsules into the liquid minoxidil? Will it dissolve easily?

http://www.skinactives.com/Oleuropein.html

http://www.skinactives.com/Green-Tea-Extract-with-EGCG.html

http://www.skinactives.com/Keratinocyte-Growth-Factor-BT-KGF.html

http://www.skinactives.com/Saw-Palmetto.html

http://www.activeformulas.com/products/oleuropein

http://www.activeformulas.com/products/green-tea-extract-with-egcg

[iaskdumbquestions]

http://imgur.com/a/g6TdQ




The Oleuropein and EGCG in your post and this minoxidil:

http://www.amazon.com/Kirkland-Minoxidil-Strength-Regrowth-Supply/dp/B002VLZHLI/ref=sr_1_1?ie=UTF8&qid=1451596397&sr=8-1&keywords=kirkland+minoxidil

Dont drop the capsule themselves, open them, and drop in the contents - the powder into the minoxidil liquid. Only half an oleuropein capsule. Then shake until you cant see any powder at the bottom. It will dissolve fine.

Perfect. Just purchased and everything should be delivered by latest January 10th. Will 100% post progress pictures.

[Seuxin]

Hello Chemical,

Your idea to coumpound a special formula with a labs is very good !

Somes substances to look :

-Vitamine B6
-Zinc or Zinc sulphate
-Azelaic Acid
-Saw Palmetto
-Beta Sitosterol

You should read this blog, it explain how to coumpound an enhanced formula with these : http://www.qdbd.com/hair_formulas_12.htm

--> Warning, if i'm not wrong it's bad to mix zinc with minoxidil.

In addition, you should learn about Apple Polyphenol, it appear to be very important, read this please : http://www.applepoly.com/procyanidin-b-2/

It appear to enhance a lot topical solution for hair.

Then, learn about TransReserveratrol too

[SriHanuman]

Just started using:

http://www.amazon.co.uk/Ethanolic-Tincture-Concentrate-Oleuropein-Glycerine/dp/B00B2U9MW4

A drop per area, there is absolutely no staining, absorbs quickly. Will report in a month or two with results, if any.

[InBeforeTheCure]

Minoxidil increases 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase activity of cultured human dermal papilla cells from balding scalp.

40% increase in 17βHSD from minoxidil. This might be the reason why Keto is included in the big three. HIF-1 stabilization probably maintains sustained VEGF expression, and a decrease cuts off the blood supply, I'm unsure if it makes a big difference given that β-Catenin can induce VEGF independently, albeit for unknown amount of time. Seti would eliminate all probability of PGD2 and its metabolite killing hair cells, thats the only guarantee you get.

Keto and mico quite potently reduce 3BetaDiol, although no numbers. This study shows bifonazole, keto and mico to be very potent at reducing only 17 alpha-hydroxylase in the testes. Bifonazole managed to bring the Ki down from 1090 to 86 +/- 3.3, and keto managed: 160 +/- 4.92. Mico wasn't as strong: 599 +/- 7.22. My assumption is that Keto and mico are additive hence my recommendation for both, but if you must choose one, get keto. They noticed a dose dependent inhibition, and thats why I use it twice a day (dont exceed 3x/week with shampoo).

And since ketoconazole's half-life is only a few hours, the 2x per day stuff would presumably be better for sustained HIF-1 stabilization.

Your choice of valproic is surprising, its quite harsh on skin according to anecdotal reports. Even at ~8% this study shows there was some irritation. If you must satisfy your curiosity, use no more than 2% and with an anti-inflammatory like emu oil. I will look into dosing a little more because GSK3b inhibitors are showing more and more promise. I am tempted to suggest LiCl but not until I've done testing first.

I'm planning to use 5-7% (others have used it at 7% with no problems). If it causes irritation, I'll lower the concentration.

Now for some more research findings!

It turns out activating β-Catenin pathway triggers a feedback loop increasing Axin2 (minoxidil study) (another). Axin2 can substitute axin1 and I'm not sure if the prostaglandin receptors or even EGCG can reduce Axin2 expression. Without Axin2, you'd have sustained β-Catenin level which could become cancerous in sensitive cell types. For hair this would translate to ridiculous hair regrowth rates. (More reading)

Axin1 is the rate limiting factor for β-Catenin degradation, so if its substituted with Axin2, you're back at square one - β-Catenin will be destroyed. But if you reduce GSK3b, regardless of Axin1/2, β-Catenin will stay elevated.

Indirubin from Angelica sinensis extract - Dong Quai can inhibit GSK3b. Another study.

Androgens increase GSK3b:



I suspect this is due to AR's negative feedback loop found in the prostate cells, wherein GSK3b represses AR activity (controversial atm).

By reducing AR this additional increase in GSK3b will be negated. Its becoming very complex again so I will make another diagram soon.

I also realise PGE2 is a beast:



PGE2 -> EP2/4 -> PKA ¬ GSK3b
PGE2 -> EP2/4 ¬ Axin1

Castor oil anyone?

PKA inactivates GSK3b expression. Since PGE2 is so hard to effectively upregulate, other agents that increase cAMP mediated PKA can also inhibit GSK3b:

Effects of the cAMP-elevating agents cilostamide, cilostazol and forskolin on the phosphorylation of Akt and GSK-3beta in platelets.

PTH/cAMP/PKA signaling facilitates canonical Wnt signaling via inactivation of glycogen synthase kinase-3beta in osteoblastic Saos-2 cells.



So why hasnt anyone tried forskolin yet?



Interpret that however you wish. Apparently PGE2 should inhibit facial hair growth too.

This study shows procyanidins (found in apple skin) paired with forskolin increases hair growth rate.



Furthermore: Pi3K/AKT ¬ GSK3b.

I know puerarin activates Pi3K quite strongly, so I googled, and whaddayaknow!

http://www.healthmonthly.co.uk/swanson_kudzu_root?af=gaw&gclid=CKDe7fbDhsoCFYMIwwodQfgN3Q

Puerarin;s solubility in water can be increased with higher temperatures. Adding in a starch and using steel balls to mix the solution ridiculously enhances bioavailability lol: this.

Puerariae Flos (the flowers of Pueraria thomsonii) was found to inihibit 5ar and grow hair in mice: http://www.ncbi.nlm.nih.gov/pubmed/21822606

Not sure where to get this specfic extract since kudzu is broad and we need that flower specifically to inhibit AR, but the standard swanson kudzu I linked should inhibit GSK3b - in theory.

Theres conflicting literature on PKC regulating GSK3b, I'm looking into it. I will be experimenting with various GSK3b inhibitors over the course of next few weeks, including lithium chloride and forskolin to see if they hold any value for us.

Interestingly enough, PGD2 activation of CRTH2 supposedly activates GSK3, but also results in phosphorylation of AKT.





Link: New Drugs and Targets for Asthma and COPD

@InBeforetheCure
Your stack is ideal, but I'm curious about the PGE2 - where are you getting it from?

Thanks for the opinion. I'm getting PGE2 through a group buy.

It's new years eve, fvck it. You be the judge.

http://imgur.com/a/usmLd

Today I saw two terminal hairs growing right in the centre of that region, where my nw0 hairline was. You cant see it but it was more than 2 inches long. I pulled one of them and it wasnt coming out, so I pulled it until it broke halfway - thats a terminal follicle. The hair felt weird though, really really tough. I've got soft fine hair so somethings definitely going on.

Encouraging so far. Hopefully it keeps progressing.

[SriHanuman]

Chemical, what is your opinion on this publication:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092984

[BRIANBOY]

Chemical, I think you are on the right path here. Initially I was a norwood 3+. Then had 2 transplants. The results were very moderate after a year. Hair growth was very sparse and thin. The doctor did a biopsy on my scalp and the results came back as a variant of alopecia areata. So, I have both mpb and a form of alopecia areata (jackpot!!). When I started using a 4%-5% solution of (green tea w/50% egcg) in a water / alcohol vehicle, the hair growth really took off. Within a year, I had grown a lot of hair. I kept upping the percentage of green tea, thinking it would further increase the hair growth. (I was up to a 13% solution.) The hair started to get quite thick. Almost too thick in front to even style properly. It was as if the transplants grew in and the hair that was there before started growing back strong as well. I thought, there's no such thing as too much hair. People told me I was lucky to have all my natural hair at my age. At that time, I was a norwood 0 - 1. (And, I was 58 at the time. I also workout / bicycle a lot. So, most thought I was in my mid - late 30s) Then, I developed an allergic reaction (probably because the concentration of green tea was too high). I had to stop all treatments. I didn't use anything for about 6+ months. All the hair that had grown started falling out. After 2 years, I was back where I was before, with very thin hair even though I was using minoxidil. Whenever I challenged using green tea solution again, the allergic response would kick in immediately. I backed off again for another 2 years.

I am now back using a 4% solution of green tea w/50% egcg (in a 74 mil - 75/25 - water / alcohol solution) with rosemary officinalis extract - 1 mil, and 10 drops tea tree oil, 1 mil jojoba oil. Currently using 2x daily. My hair is starting to grow back again. I am also using minoxidil foam and ketoconazole cream daily. I find I cannot go higher than about 4-5% green tea/egcg 2x daily, otherwise it causes folliculitis / allergic reaction as it did before. Folliculitis is something to be careful of, as it can spread rapidly. My theory is that the keratinocytes that have been stimulated to multiply are not moving up the follicle canal properly and thus trigger an infection which then leads to an immune / allergic response. But, green tea/egcg seems to be a potent stimulator of hair growth at higher concentrations. Most users have used very low concentrations. There is some solid science behind green tea / egcg (as you have pointed out) and rosemary extract (strong androgen inhibition and immune modulating factors). Both are also water / alcohol soluble, and penetrate the skin easily. I am also adding oleuropein as per your research. I would caution users to be careful about adding too many ingredients. Too many substances can trigger an immune / allergic response on the scalp. Once you trigger an immune allergic response, you will have to stop using everything for a rather long period of time (months or longer) to let the immune system back off / reset. I wouldn't underestimate this possibility.

I realize my testimony has to be taken with a grain of salt, considering multiple factors ... i.e. my age, alopecia areata + mpb, transplant, no pics, etc. So, I'm just throwing it out there. I will keep an update on my progress from time to time. I am encouraged by the regrowth that is restarting again, and by the potential of oleuropein being added to the mix. Here is a link to the rosemary extract research.

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

[Chemical]

And since ketoconazole's half-life is only a few hours, the 2x per day stuff would presumably be better for sustained HIF-1 stabilization.

I'm planning to use 5-7% (others have used it at 7% with no problems). If it causes irritation, I'll lower the concentration.

Interestingly enough, PGD2 activation of CRTH2 supposedly activates GSK3, but also results in phosphorylation of AKT.
Link: New Drugs and Targets for Asthma and COPD
Thanks for the opinion. I'm getting PGE2 through a group buy.
Encouraging so far. Hopefully it keeps progressing.

If you look at figure 2E, you can see PGD2 being elevated 2.5 fold compared to normal haired scalp.

PGD2 levels were then measured using ultra–high-performance liquid chromatography–mass spectrometry (UHPLC-MS) because of its reported superior accuracy in measuring prostaglandins compared to immunoassay (17). In a larger series of paired bald and haired samples from 17 men with AGA, we noted an increase in PGD2 in bald scalp compared to haired scalp (Fig. 2E).

PGD2 activating GSK3b is a very plausibly mechanism for its DPC growth inhibitory effects, so far there hasnt been any evidence of how PGD2 might inhibit hair - just that it does so via GPR44. Cotsarelis also says that PGD2 rises with anagen cycle progression, and peaks during catagen, perhaps there is a feedback loop? There is also the issue of reduced PGE2 increasing the amount of substrate abailable for PTGDS - and androgens apparently reduce PGE2 synthesis (not conclusive).

Regarding HIF-1 destabilisation, I'm still trying to find some more info on whether destabilizing HIF-1 can reduce VEGF expression induced via other mechanisms like BetaCatenin. But blocking ERBeta activation with keto 2x/day should cover all bases and reduce any chance of the HSD family causing any damage. The HSD family can increase locally synthesized androgens possibly adding to the already detrimental testes produced T/DHT.

I came across this study on topical Valproic Acid and LiCl vs minox on mice hair growth: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323655/

Looks like LiCl isnt too suitable due to its aberrant epidermis thickening effects which wasnt seen in VA. It turns out, anything that activates AKT/(PKB) will inactivate (phosphorylate) GSK3b, which includes minox and IGF-1. OL significantly increased IGF-1 more than minox, so stacked with minox theres serious potential of synergy. For people that cant use minox then Valproic Acid seems like a better alternative with equal efficacy.

Chemical, what is your opinion on this publication:

http://journals.plos.org/plosone/art...l.pone.0092984

The study was focusing on FAS-l mediated signalling cascades which is not really indicative of general hair growth promoting effects, but it increase KGF moderately. It can also activate the Pi3K pathway and promote angiogenesis so its definitely caught my attention. I will look into this a bit more when I'm free.

@BRIANBOY

You are a very interesting case study. Its unfortuneate that you've got both MPB and AA, so I can only sympathise, but holy frickin sh*t, you grew back all your hair with EGCG. When did you find out you had AA? And when did you start receding?

My theory is that the transplanted hairs started secreting growth factors to nearby follicles since they're probably less AGA prone, so as soon as the EGCG reduced AR the AGA follicles had a chance to grow. I am curious about the allergic reaction, I dont understand why EGCG might elicit that kind of reaction - then again you noticed it happen out of the blue. Its something to keep in mind for my own experiments. Rosemary oil could also provide additional 5AR inhibition just to add to EGCG's effect, excellent find Brian. Thank you for sharing your experience with us, and I am more than delighted that you understand you might be an outlier/special case given your circumstances, but your anecdote is helpful none the less.

Update

I received by ketoconazole 2% cream last wednesday which I've been using 2x a day. And I also got my EGCG today, which I've mixed with my mxol solution.

~1.5mg OL + 5mg EGCG / 1ml Minox. Now things will start to get interesting.

[joshuk]

chemical i put 1 cap of EGCG into 60ml of my eth/pg mix which equals 2.5mg/ml i see your using 5mg/ml is it worth putting an extra cap in or just carry on for 1 for a month then add to it.

[Seuxin]

WARNING : Using too more Keto is not bad for the body (especially your liver) ?