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I'm currently on no regimen...I'm up for it!
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I wouldnt mix them unless you know what you're doing. Theres only one study on ginkgo's effects on hair: http://www.ncbi.nlm.nih.gov/pubmed/8254481
Its not too reassuring imo.
My current protocol is:
1/5 of a oleuropein cap dissolved in 30ml minox. (1mg/ml) ~0.5mg absorption per the molecular mass.
I use this minox solution in the morning, 0.5ml. Then once its dried, I use emu oil (just emu oil). Helps rehydrate the skin after the ethanol dries up. If I feel like it I'll use miconazole 2%.
At night, same thing, but I use the emu oil with the oleuropein and minox mixed in.
The stubble hairs that I noticed a week ago are actually getting longer, i tried to take some pictures but my stupid camera over exposures the pictures so you cant see jack. I'll have to invest in a camera or wait for the area to fill in properly so I can see the difference in the before and after pics. Right now I'm 80% sure the oleuropein is augmenting the minox. I never saw this many vellus to anagen transition this quickly. The region where I concentrate the treatments is actually turning grey, the same colour as when you shave facial hair to the skin. Frontal shedding has completely stopped. I cannot explain how excited I am about, but I'm trying to stay skeptical and critical because this is not just about me. Theres alot of people out there sufferring from this stupid condition, its wrecks havoc on a persons self esteem - I know first hand.
The task now is to find something that will keep hair. I've ordered some EGCG:
The highest potency I could find. I'll be mixing a cap with minox, I'll get it when I go back to work on Jan 4. Theoretically EGCG should increase the rate of hair regrowth and shaft elongation by inhibiting AR protein, downregulating it, and preventing the paracrine action of TGF-beta (which causes nearby follicles to stop proliferating).
Its a marker of oxidative stress, so a reduction doesnt really tell us much, especially since its measured via urine. Prostaglandins can promote hair growth when overpresssed/stimulated, but theyre not the main factors that actually control hair growth in people who arent affected by AGA. Its the WNTs.
I'm doing some research on WNT3a which is known to stimulate hair growth, so if we can find an agonist, it'll be deadly in combination with oleuropein.
I think this is an excellent idea! Great stuff Keeper! The only issue I have is, when involving commercial companies I fear they will let their greed take over. IF it works on a preliminary group of people, this'll become a market. I don't like the idea of people paying companies for something they can make themselves, or companies trying to make money off something that should be non-profit. On the other hand this will allow people to actually test this to see if it works on the general population, before investing in overseas shipping and whatnot. We need to verify their ingredients and where they're sourcing the extracts. I like this idea, We'll have to talk more about this.
I've made some changes to my own formulation, so emu oil isnt actually necessary. Its only good for keeping irritation/inflammation at bay when using propylene glycol and ethanol. A pure formulation of ethanol + propylene glycol (some people are sensitive to this) + oleuropein, 3mg/ml max would be the ideal formulation. If people want to see a trial then I will have to insist that people wait a few more weeks while I test the EGCG or discover anything else that might help or warrant modifications. It would be nice to run a full blown study with controls but oleuropein is not a cure and it requires additional treatments like (minox, keto/mico, AR suppressors) to fully maximise its benefits. I've been concentrating the treatment only on side, and I can definitely see the difference. The right side hasnt improved as much as the left. Perhaps this would be better than having controls on placebo, the local untreated skin can act as the control which should give a better indication on its efficacy since everyones got different feedback loops and environments working against hair follicles.
The studies that I've read showed that it takes sustained dosing for 2 weeks straights to see any change in WNT10b expression, my own observation isnt valid because I was inconsistent but I guess 30 days is sufficient to see any change. The dose is also another concern because I'm pretty sure its got a biphasic effect i.e too much and it wont work as good, plus its got around 70% absorption rate through skin due to it 540 molecular weight. Having a fixed dose for everyone may or may not be optimal, theres just too many variables at play.Comment
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Hey Chemical, glad you like the idea. Just some thoughts of me. I talked to a nice woman, she didn't seem to be greedy. She said its a funny idea we have and she likes it. She was also talking about mixing oleuropein and emu oil and so on. They are not a big pharma company (she was talking about that oleuropein is shown to be effective for so reducing so many issues in health and they have evidence about it but its sad, that the "school medicine says: take this and this medicament". And even if they take advantage of our survey. Why not ? IT can not be mich more expensive than now. They already have a lot of different combinations of ingredients. It won't change too much I guess. And even if it works, they will be really quick really much competition and since you can not really have a patent about oleuropein and emu oil they is not much greedy possibilities in it. I think they just like that people understand that oleuropein can have many positive effects and that we dedicated to our ideas. It also didn't sound like it must be a super strict survey. They would send us free samples of what we need. They can also produce cremes out of the extract and so on. Wit emu oil or propylene glycol or ethanol or what ever.
We should just make sure to optimize the formula in the way you (are we all together) think it makes sense to have a good effect, reading as much studies as possible. Maybe even some variations of the forumlas. Of course they want some photos or so to know whats going on. I think its a fair trade and they are really helping. (They also know a lot about stuff like emu oil, that it is important where it comes from and so on. I think they tested a lot of it with there chemists...and so on). I m not too much in all the studies. Its not the easiest to translate or the studies but as soon as my exams are over I also want to read about it more. I m already happy, that somebody is endeavored to do sth like you Chemical. What I can do at the moment is too support this idea. I think you should think about the formula and probably discuss it with really experiences members here. And brainstorming all together we have at least a minimal chance to achieve sth
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Seriously guys....stop talking emu oil ! Emu oil is totally shitty for hair ! If you want good vehicles, there is true vehicles, Like a mix of Polysorbate 80 / DMI / eth for liquide, and if you want a cream based, you have to look for a liposomal cream vehicle !
Stop dreaming about emu oil ! Is totaly shit, and greasy...Comment
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I bought the liquid olive extract off amazon.co.uk and mixed 9ml (300mg oleuropein) into 60ml minox. I shall report back if I see any benefit - although I'm not too hopeful as minox by itself has only grown vellus hairs. I'm also currently on .25mg fin and OC.Comment
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We have our first participant!
@Keeper
You've convinced me. They seem to be genuine, and they're offering their help free of charge, this'll benefit alot of users. And we'll have a consistent formula. Lets make this thing happen.
Can they create formulations with ingredients besides oleuropein? Like EGCG.
Agreed. But it helps with the irritation I get from minox. I think we should think about other potential vehicles that might make applying the formula easier. Emu oil isnt ideal as a vehicle.
Which brand did you buy? Seeing as you've already taken the plunge to go with minox, do you think you could try topical EGCG too? It should achieve near 90% suppression of AR when stacked with minox. The oleuropein would have a better chance of working too. Keep us posted.Comment
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wrong threadComment
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Chemical, do you think it is ok if I mix EGCG with oleuropein; same ethanol mixture?
And it would be really great to hear your opinion on this:
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Hi Chemical I am willing to try this out.
I found a tincture in my local shop that has 65% olea europea (with water and alcohol but not sure of the exact ratio yet) and I also found 500 mg capsules of green tea which contain 15% ECGC. I intend to mix them by adding a bit more alcohol and water i n a seperate bottle.
What ratio would you use?
I'll take some pics and we'll see what happens. Have to be honest I don't expect much but I have nothing to lose so...Comment
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topicals, permeation, active metabolites
A couple of days ago I was reading up on minoxidil and it's mechanism of work. I read that minoxidil sulfate is the active metabolite that actually promotes hair growth. Minoxidil sulfate is made by the sulfotransferase enzyme. It is common knowledge that minoxidil doesn't work for everybody, possibly because we have different sulfotransferase enzyme activity. So I read up on it just out of curiosity and (if I understand it correctly) the sulfotransferase enzyme is really picky for pH changes (it is most active in 6,5pH) and temperature changes (it is most active in 30-35'C and rapidly loses its effectiveness in increasing temperature)
So I am wondering: Is it important to have a right pH balance for minoxidil and other treatments to work, or to work better? Is temperature important? I was always applying minoxidil after a hot shower to increase permeation but is it possible that at the same time I was inactivating the sulfotransferase enzyme? I don't know but from now on I will only wash my head with cold water
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To be honest I don't know what ingredients they can also mix in. I could ask them but I don't want too bother them too often, so I think the best is if we collect our ideas what could be in and how to mix it with what for producing sth, and then I will ask them in one rush. (I guess sth like a cream/topiclal solution would be the best.)
They emailed me that they can produce every Oleuropein concentration we want. Would be nice if more people would think about the ideas and try to help figuring out a plan.Comment
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I am not on any routine, the only thing I do at present is castor oil and derma rolling, I would be happy to document and take part, the only thing is on swisstemples he believes it may reduce PGE2, but I think castor oil increases it, so a mix Emu, Castor and Oleuropein? I would leave in over night and apply every night.
cheers,Comment
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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 shareComment
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Yes it should be fine, but before you go ahead, which brand of EGCG are you using? I'd recommend teavigo since you can get away with a lower concentration of the extract and get the raw EGCG that you actually need. I'm ot sure how the other polyphenols affect, so for now we'll stick to pure EGCG as used in the study. EGCG also has a dose dependent effect so start off with 1 capsule, then see if it leaves a residue after applying. If not, add another. Rub the skin softly to see if you get any residue, even if its just a little, dont add anymore to the solution. Also what concentration of ethanol are you using?
I would encourage you to try and source the extracts online because then you know what concentration to use. It's sometimes difficult to know exactly how much oleuropein a tincture has and if its got any additional unwanted ingredients. iherb is a great place to order extracts/supplements and they deliver worldwide. Theyre very cheap and alot of people including myself can vouch for them - that is if you cant find what youre looking for on amazon. 15% EGCG isnt a high enough concentration imo, so for those reasons I'd suggest acquiring the ingredients elsewhere. I'm not 100% sure on the EGCG mixing since I'm yet to try it, but use my answer to SriHanuman as a starting point.
Absolutely correct paleocapa89. Minoxidil sulfate is the active metabolite that stimulates hair follicles.I read that minoxidil sulfate is the active metabolite that actually promotes hair growth. Minoxidil sulfate is made by the sulfotransferase enzyme. It is common knowledge that minoxidil doesn't work for everybody, possibly because we have different sulfotransferase enzyme activity.
So I am wondering: Is it important to have a right pH balance for minoxidil and other treatments to work, or to work better? Is temperature important? I was always applying minoxidil after a hot shower to increase permeation but is it possible that at the same time I was inactivating the sulfotransferase enzyme? I don't know but from now on I will only wash my head with cold water
http://dmd.aspetjournals.org/content/37/5/1083.full
Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate.The variation in sulphotransferases enzymes impacts how people respond to minoxidil. You are also correct that PH and temperature affect the sulphotransferase enzymes. Enzymes in general have an optimal environmental state that allows them to catalyse reactions. I wouldnt worry to much about PH and temperature, your body's natural homeostasis should take care of that for you:Biochemical evidence for minoxidil sulphation by two phenol sulphotransferases has been found in human scalp skin[22] and Dooley[21] reported finding mRNA expression for four sulphotransferases in human epidermal keratinocytes. There are interindividual variations in scalp sulphotransferase activity and this correlates with the level in platelets.[22] In a clinical setting, scalp sulphotransferase activity was higher in men who responded to minoxidil compared with those who did not respond [23]
http://www.medscape.com/viewarticle/470297_3
Good idea, I agree that we should wait a little till I've got some more experimental outcomes to go on before bothering them with additional requests.Normal human body temperature of 37C provides a good internal environment for enzymes to work efficiently. Enzymes in the stomach, such as pepsin ( which digests protein ), work best in very acid conditions ( pH 1 - 2 ), but most enzymes in the body work best close to pH 7.
Thats an interesting site you linked, I'm going to go over the stuff wen I'm free to see if theres anything of interest. As for PGE2, my next post will be an in depth analysis on how PGE2 actually works to promote hair growth. In short, Ricinoleic acid (found in castor oil) activates the EP3 receptors in women. It should in theory do the same in men and exert it effects when applied topically. EP3/EP2 agonists increase Beta Catenin, and thats why they grow hair. Not sure about Castor oil inhibiting PGE2 synthesis - negative feedback? Anyways, I dont think castor oil is bad. My recent findings indicate oleuropein works faster if you use an ethanol vehicle, and using it in an oil based solution will yield sub par results. You want to aim for 1-2mg per ml and use the oils after the ethanol has dried up.
A caution for people making ethanol vehicles, you can only use ethyl alcohol/190 proof alcohol found in drinks, NOT denatured ethanol or Isopropyl/Isopropanol. This study on topical ethanol/PG formulations of minox shows that anything above 90% Ethanol/10 % PG results in absorption less than that of 50% ethanol/50% PG. With 50/50 to 90/10 having optimal absorption. PG seems to keep the minox from forming crystals/residue on the skin and improves absorption if my understanding is correct, whereas a 100% ethanol vehicle just doesnt work. This probably applies to oleuropein as well and possibly EGCG.Comment
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This is promising! Which brand are you using?
I've been doing some more research on PGE2 and thought I'd share my findings here. We'll start off with this study that shows PGE2's effects on β-catenin:
PGE2 inhibits axin mediated formation of the BetaCatenin destruction complex involving GSK3Beta. It does this via the EP2 receptor and also the EP3/4 receptors:Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis.
Abstract
We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein betagamma subunits and the direct association of the G protein alphas subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3beta from its complex with axin, thereby relieving the inhibitory phosphorylation of beta-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer.
Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor.
To understand what the Axin/APC destruction complex is, heres a graphical representation of what it looks like:
Wnt Signaling through Inhibition of β-Catenin Degradation in an Intact Axin1 Complex
The proteins surrounding β-catenin are involved in the destruction of β-catenin. First CKI prepares β-catenin for GSK3Beta. Once GSK3Beta has phosphorylated β-catenin, Axin and APC form a scaffold that that enables the β-catenin to be degraded. If any of these proteins are inactivated then β-catenin will not be destroyed and translocate to the nucleus and exert its effects with the help of TCF4. WNTs like WNT10b - which oleuropein upregulates - protect β-catenin from destruction:
Anything that blocks Axin or GSK3 or any of the proteins required to destroy β-catenin will lead to increased β-catenin. Thats why GSK3 inibitors like Valproic acid work topically. PGE2 -> ( EP2/3 ¬ Axin ) -> β-catenin. This is one possible explanation for castor oils hair growth promoting effects.The removal of β-catenin from the destruction complex is accomplished simply by direct degradation by the proteasome. This step recycles the destruction complex for another round of β-catenin degradation. We show that Wnt receptor-ligand interaction leaves the destruction complex compositionally unchanged and does not affect the activity of its kinases. The only change that we observe is the association of Axin1 with phosphorylated Lrp6 and the dissociation of β-TrCP. Indeed, phosphorylated β-catenin—still bound to the Axin1 complex—is no longer ubiquitinated and degraded. It saturates and thus effectively inactivates the Axin1 complex. We have previously reported that only β-catenin that is newly synthesized after initiation of the Wnt signal is signaling competent (Staal et al., 2002). This notion is in agreement with our current model, which predicts that newly synthesized, nonphosphorylated β-catenin will be stable in a free cytosolic form once the destruction complex is saturated. It can then translocate to the nucleus to associate with TCF and activate the Wnt transcriptional program.
PGE2 is quite difficult to increase and analogues are very expensive. Castor oil is a viable alternative however. If there was a different molecule that could inhibit Axin then we could use that to directly increase β-catenin bypassing WNT. Thats where EGCG comes in:
The anti-adipogenic effects of (-)epigallocatechin gallate are dependent on the WNT/β-catenin pathway.
Abstract
(-)Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea and reportedly has anti-obesity and anti-adipogenic effects. In this study, we determined that the up-regulation of the WNT/β-catenin pathway is the anti-adipogenic mechanisms of EGCG in 3T3-L1 cells. EGCG treatment down-regulates the expression of major genes involved in the adipogenesis pathway including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP)α, fatty acid binding protein (FABP)4 and fatty acid synthase (FASN), while up-regulating the nuclear level of β-catenin. Knockdown of β-catenin using small interfering (si) RNA attenuated the inhibitory effects of EGCG on intracellular lipid accumulation. β-catenin siRNA transfection also recovered terminal adipocyte markers such as FABP4, FASN, lipoprotein lipase and adiponectin, which were down-regulated by EGCG. The DNA binding activities as well as the expression levels of PPARγ and C/EBPα, which were down-regulated by EGCG, were significantly restored by β-catenin siRNA transfection. In addition, we found that EGCG efficiently up-regulates the WNT/β-catenin pathway. Among the members of the WNT/β-catenin pathway, the expressions of low density lipoprotein receptor-related protein LRP5, LRP6, disheveled DVL2 and DVL3 were significantly up-regulated, while AXIN expression was down-regulated by EGCG, and the phosphorylation of glycogen synthase kinase 3β was increased. These results suggest that EGCG activates the WNT/β-catenin pathway, resulting in the up-regulation of β-catenin, which down-regulates the major genes of the adipogenesis pathway. Taken together, our findings clearly show that the anti-adipogenic effects of EGCG are, at least partially, dependent on the WNT/β-catenin pathway.
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EGCG, in addition to inihibiting AR expression, downregulates Axin and reduces the amount of GSK3 available to destroy β-catenin.
So this is what the current treatment stack looks like:
(Oleuropein ¬ DDK1) -> natural WNTs can bind
Oleuropein -> WNT10b -> β-catenin
Minoxidil -> Adenosine Receptor -> β-catenin
(Minoxidil ¬ AR) -> β-catenin + TCF4 activity
(EGCG ¬ AR) -> β-catenin + TCF4 activity
(EGCG ¬ Axin) -> β-catenin
((Mico/Keto ¬ 3β-Diol) ¬ ERβ ) -> VEGF
And if you want to use castor oil:
(Ricinoleic Acid -> EP3 ¬ Axin) -> β-catenin
I think we should all try and find cost effective herbs/supplements that can downregulate AR or boost WNTs/β-catenin signalling. The more readily vailiable options we have, the greater the chance people can use what works best for them. We might even have a ridiculously powerful stack to reverse AGA or even cure it - and by cure I mean you only need to use the treatments infrequently to maintain density. I have hopes that next year we will have some interesting breakthroughs/discoveries, and we may no longer need to rely on or wait for big pharmaceutical companies for new treatments or only rely on expensive treatments to grow hair.Comment
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