Updated Research and Knowledge - Cutting Edge

[JDW]

Total respect to all those on this topic who are pushing the boundaries and testing out these new potential solutions. You're doing a top job

[InBeforeTheCure]

Ironically many people have also tried olive oil with little success = oleuropein doesnt work?

People at the other hairloss forum have tried: http://www.*****************/interac...r-growth-study

Some guy claims to have seen results:

http://www.regrowth.com/hair-loss-forums/topic/my-results-with-egcg-and-ode-to-my-methodology/

Someone has been using it on their face to reduce facial hair too:



This patent by Gillette on syrian hamsters that have AR dependent hair, showed that EGCG significantly reduced hair size and growth at concentrations up to 30%.

I think alot of people that try different stuff probably try them in a vaccuum, and if it works then only very small minority will post their findings on the internet whereas the vast majority will say that it didnt work. The theory is there, and on paper/animals there is convincing evidence of its efficacy. But we dont know for sure if using it in a proper vehicle or along side other treatments will yield results. Like Josh has said, this is still an experiment, I'll never know until I try.

It does say in the abstract of the mouse hair EGCG study:

Topical EGCG down-regulated the T-induced expression of androgen receptor but did not down-regulate 17β-hydroxysteroid dehydrogenase (HSD) and three β-HSD expression.

Perhaps the continued expression of β-HSD could limit results despite AR inhibition? So using EGCG alongside ketoconazole or miconazole (or maybe setipiprant?) to downregulate the ER-β pathway could have a nice synergistic effect.

By the way, the following protocol is the one I'm (tentatively) considering.

- Oleuropein
- EGCG
- Setipiprant
- PGE2
- Valproic acid

Is there anything critical missing? Something like ketoconazole or miconazole for example, or does seti take care of all the downstream effects of ER-β?

[dunester01]

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.

[Chemical]

That should be perfect. The Seti might augment this protocol, but skip if for a few weeks since you've already got a heavy stack. If you dont see any change, then you might want to throw it in. I wish you all the best!

[joshuk]

chemical about to make my first mix of EGCG/OLE do you think a mixture of 50ml ethanol 10ml of PG is ok?? its about 80/20 split.

also i was thinking of applying this all over my scalp as i shaved my head for this experiment lmao looks wierd but im gonna give it a good go.im gonna use 1/2 cap of OLE and 1 cap of EGCG. so its about 1.35mg/ml OLE in the mix.

i have 50grams of seti that i have not started do you think it will help benifit the WNT/BetaCatenin pathways?? i just dont have any capsules to put it into and dont want to use it topically as im already using a fair amount

[Chemical]

I'm sorry I forgot to answer this question. Setipiprant is a PGD2 blocker, I'm under impression PGD2 isnt the main culprit but it's metabolite 15-dPGJ2 that kills hair follicles - as stated by Cotsarelis. By reducing the expression of COX-2, PGD2 should be rate limited and subsequently result in less 15-dPGJ2 being synthesized. Its a factor, but not the only or most important one, I will investigate this matter in detail later on.

PGDTS can be induced by Estrogen (aromatased from Testosterone), but exactly which receptor mediates this effect I do not know. My guess is the ER Beta, which ketoconazole and miconazole address via 3BetaDiol suppression. Keto/Mico are like the poor mans version of Seti.

Chemical, when you say wait as somebody can have a batch mixed this would be totally without minox yes? (hoping so).
Happy to order and test as soon as someone can mix a batch!

Without minox yes, we will have to wait for Keeper and the outcome of our experiments to devise an optimal formulation with the help of Keeper's contact.


I've been doing some more research and I came across some new information on DKK-1. We know that oxidative stress (ROS) induces the expression of DKK1, but until now I didnt know how that happened. This excerpt sheds some light on this matter:

To investigate the upstream stimuli responsible for JNK pathway activation and DKK1 up-regulation by lenalidomide, we analyzed changes in gene expression that correlated with DKK1 up-regulation following lenalidomide treatment in vivo. Microarray analysis showed a clear indication of the activation of genes involved in the cellular response to oxidative stress, which is in line with previous reports indicating that thalidomide could induce oxidative injury in the rabbit model system by forming free radical-initiated reactive oxygen species. Interestingly, in the 40 most highly correlated genes, we identified genes encoding caspase 4 (CASP4, 8.7-fold increase; most up-regulated gene) and calpain 2 (CAPN2, 5.3-fold increase), which are involved in endoplasmic reticulum stress-induced apoptosis, and glutaredoxin (GLRX, 7.45-fold increase), glutathione peroxidase (GPX1, 5.7-fold increase), and glutathione S-transferase (GSTO1, 5-fold increase), which play important roles in cellular detoxification, suppressing activities of JNK and its upstream kinases through direct in,eractions.

Therefore, to determine whether oxidative stress plays a role in mediating lenalidomide-induced DKK1 up-regulation, we administered the drug along with the antioxidant agent PBN. As shown in Figure 3A, pretreating cells with PBN significantly reduced lenalidomide-induced DKK1 up-regulation (expression reduced 1.5- to 3.3-fold; mean: 2 ± 0.1; P < .01). Interestingly, preincubating cells with PBN alone could reduce the basal level DKK1 expression (data not shown). Furthermore, in line with previous reports, PBN counteracted c-Jun–binding activation (P < .01; Figure 3B) and JNK phosphorylation (data not shown). Taken together, these data demonstrate that oxidative stress is an upstream stimulus responsible for JNK pathway activation and DKK1 up-regulation induced by lenalidomide.

The antioxidant PBN could prevent the oxidative stress induced DKK-1. Just like Ascorbic Acid. Oleuropein is also a free radical scavenger. But the interesting point here is that, antioxidants could reduce DKK-1 below basal levels without a stress response stimulus. This explains why oleuropein reduced DKK-1 in the mice study. In the presence of testosterone, anti-oxidants will probably only keep DKK-1 at basal levels, but if AR is suppressed significantly, DKK-1 can be further reduced thus allowing WNT to freely bind whenever and however it wants! It seems DKK-1 is a solved case, its now time to find agents that can activate the canonical WNT pathway.

Baicalin activates the WNT pathway
Baicalin inhibits AR and grows hair

The only problem is its not very water soluble. Heat can increase the solubility of baicalin in ethanol. As can a surfactant like tween 80/polysorbate 80.

This excellent study goes over some of the effects of the different flavanoids on WNT/BetaCatenin. Flavanoids have differential effects depending on cell type, exerting pro-apoptotic factors in tumors and promoting survival in others. Does anyone else have any knowledge on herbs/extracts that can increase BetaCatenin and has good solubility properties?

[TubZy]

just mix the OLE powder into adenogen. That is what I do..I used to use neogenic but it doesnt contain PG and adenogen does so I switched to adenogen as my vehicle

[Sogeking]

@Sogeking

So long as you're getting 65% actual oleuropein and the not the leaf extract at 65% of the solution, then the dosing math should be accurate. The only concern is making sure you get less than 2mg/ml HealthMonthly deliver to europe (if you're in EU?), and they stock the oleuropein that I use, maybe thats another option? http://www.healthmonthly.co.uk/swans...FasBwwodO5oO6g

Ah yes. Thank you for that mate. It is the leaf extract at 65 % of the solution. I will most likely order from your link. In which case I just use 1 pill diluted in 50 ml of ethanol/pg mix.

[potato1987]

Trial

Chemical, when you say wait as somebody can have a batch mixed this would be totally without minox yes? (hoping so).

Happy to order and test as soon as someone can mix a batch!

[iroquoispliskin]

Found this on amazon for US people:

http://www.amazon.com/Foods-Olive-Glycerite-Oleuropein-ounce/dp/B0019LWTWQ

Its in liquid form standardized to 18% oleuropein. Would there be any problem in using this directly as a topical? The liquid is glycerol and water. From what I've read, glycerol is a penetration enhancer when used on skin (its in a lot of soaps and cosmetic products) Only thing is based on the numbers its 22mg/ml of oleuropein, which is way more than what Chemical said. Is there a reason that exceeding 2mg/ml is detrimental? Could always dilute it further if necessary.

[Chemical]

@Sogeking

So long as you're getting 65% actual oleuropein and the not the leaf extract at 65% of the solution, then the dosing math should be accurate. The only concern is making sure you get less than 2mg/ml HealthMonthly deliver to europe (if you're in EU?), and they stock the oleuropein that I use, maybe thats another option? http://www.healthmonthly.co.uk/swans...FasBwwodO5oO6g

[Chemical]

A good vehicle is REALLY important to have real result ! Using eth/pg is not a good idea. You can improve it, here is a good formula :

-> Ethanol / DMI / Polysorbate 80

The DMI is a good option, it helps carry molecules quite well across the skin layer. The poly 80 not so sure, I've seen no literature on it although its commonly used in alot of creams. But we want to keep the vehicle lean, cheap, and easily made. I can do some reading but is there really a compelling advantage in using DMI + emollient?

Is it possible for someone to list the items required (amazon, ebay) and instruction on what to do, perhaps a youtube video to ensure we are consistent?

I think if you can wait, you should wait. Keeper has a manufacturer that is willing make a consistent formula which can be distributed to users free of charge for trialling, otherwise you will potentially be wasting money on an experimental protocol.

If you're in the US:

Amazon US - Oleuropein - $7.99
Amazon US - Propylene Glycol - Pick whichever is cheapest
Everclear 95%/190 proof - $16.99 - You should try and find the best deal available instead of just using this link since I cant vouch for this site.

For those that want to use minox:

Amazon US - Kirkland Minoxidil 5% - 6 month supply - $29

Simply drop the capsule contents into the solution, and shake vigorously, this isnt chemistry whatsoever.

Amazon US - Teavigo EGCG - Healthy Origins - $14
Amazon US - Teavigo EGCG - Swanson - $14

Haven't people tried topical EGCG before with no substantial results?

Ironically many people have also tried olive oil with little success = oleuropein doesnt work?

People at the other hairloss forum have tried: http://www.*****************/interac...r-growth-study

Some guy claims to have seen results:

http://www.regrowth.com/hair-loss-forums/topic/my-results-with-egcg-and-ode-to-my-methodology/

Someone has been using it on their face to reduce facial hair too:

Personal note. As many of you know, Ive been trying topical homemade green tea extract on one side of my face to see if it will reduce hair. I haven't even been doing it a month yet, but the beard on my right cheek is weaker, smaller in circumference, and lighter colored than on my left when I look close. I can also feel the difference when I run my hand down each side. I think I have found the topical anti-androgen Ive been looking for to add to my internal finasteride. Im going to call it a day on further research on a topical anti-androgen. I really think this one is sufficient

http://www.*************/hair-loss/b...casc-DESC.html

This patent by Gillette on syrian hamsters that have AR dependent hair, showed that EGCG significantly reduced hair size and growth at concentrations up to 30%.

I think alot of people that try different stuff probably try them in a vaccuum, and if it works then only very small minority will post their findings on the internet whereas the vast majority will say that it didnt work. The theory is there, and on paper/animals there is convincing evidence of its efficacy. But we dont know for sure if using it in a proper vehicle or along side other treatments will yield results. Like Josh has said, this is still an experiment, I'll never know until I try.

I asked this previously but, what is your opinion on Setiprant? On page 1 you suggested that the body will compensate by creating more DHT. Would you apply the same reasoning to Seti?

I'm sorry I forgot to answer this question. Setipiprant is a PGD2 blocker, I'm under impression PGD2 isnt the main culprit but it's metabolite 15-dPGJ2 that kills hair follicles - as stated by Cotsarelis. By reducing the expression of COX-2, PGD2 should be rate limited and subsequently result in less 15-dPGJ2 being synthesized. Its a factor, but not the only or most important one, I will investigate this matter in detail later on. If you want to use Seti and can afford it - I dont see any harm, unlike fin. It's probably not going to be anything groundbreaking in my opinion.

15-dPGJ2 induces apoptosis (fig. S2A), as evidenced by plasma membrane blebbing and cell retraction/shrinkage. 15-dPGJ2 also decreased cell density, cell division, and live-cell numbers (fig. S2, B to D). Perhaps because the origin of these keratinocytes was not the hair follicle, PGD2 had no such effect on the cells. However, 15-dPGJ2 did increase sub-G1 DNA quantities and activated caspase 3 in human keratinocytes, which are features of apoptotic cell death (fig. S2, E to G). We therefore hypothesized that at least 15-dPGJ2, if not also PGD2, could directly inhibit hair growth in vivo.

Let me just check if I got everything right. I found liquid form of 65% oleuropein with 270mg per mL. I though about using one ml of this oleuropein diluted in a 180-200 ml mix of ethanol and PG.

Josh is correct. Whats the oleuropein brand you're using (link)?

[Sogeking]

i guess you could do that yes, that should give you about 1.35mg/ml for 200ml of eth/pg and 1.5mg/ml in 180ml which would seem about right what chemical says, the only thing is 270mg/ml IS ALOT of oleuropein are you sure thats the correct dosage as i was using a very strong oleuropein tincture of amazon and that was only 31/mg per ml. yours is 8 x the strength???

Yes I know. A really strong concentration. Of course this is listed on the website of the shop in my country that sells it. It may be wrongly written down. Because on iHerbs most oleuropein liquids come at concentrations ranging from 6% to 20%. Have to check in person. But if does come at concentration of 65% at least it should last me a long time.
I'm gonna order PG from that site you linked, already ordered ECGC. Gonna buy oleuropein on Thursday. I plan to put pics here and I plan to test this out for 3-4 months. If it starts showing some results I'll add minox to the mix at some small concentrations.

[joshuk]

Let me just check if I got everything right. I found liquid form of 65% oleuropein with 270mg per mL. I though about using one ml of this oleuropein diluted in a 180-200 ml mix of ethanol and PG. m i getting this right? And afterwards dropping one teavigo capsule in that as well.
I'll probably add minox to the regime later.

i guess you could do that yes, that should give you about 1.35mg/ml for 200ml of eth/pg and 1.5mg/ml in 180ml which would seem about right what chemical says, the only thing is 270mg/ml IS ALOT of oleuropein are you sure thats the correct dosage as i was using a very strong oleuropein tincture of amazon and that was only 31/mg per ml. yours is 8 x the strength???

[Sogeking]

dont think the premade stuff is going to work to be honest, cant you get kirkland liquid minoxdil from costco or walmart, im in the uk so i dont know for sure but i have heard of people getting it from these places.

failing that get everclear and propelyne glycol and make your own mix like im doing would be alot better. the reason for the premade stuff not working is the ethanol content is not high enough or stays long enough on the scalp to absorb properly.

i bought the ethanol tincture earlier in this thread and it did not absorb properly and left a brown stain on my scalp,not only that the oleuropein content is way to high chemical said you need it to be around 1.5mg/ml the one that you are using is the one i had and the oleuropein is 31mg/ml. have you applied it yet you will see what i mean by the staining of the scalp

hope this helps... but i would honestly make your own solution if you can if not use minoxil liquid as a vehicle and add the caps into that

Let me just check if I got everything right. I found liquid form of 65% oleuropein with 270mg per mL. I though about using one ml of this oleuropein diluted in a 180-200 ml mix of ethanol and PG. m i getting this right? And afterwards dropping one teavigo capsule in that as well.
I'll probably add minox to the regime later.