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I glanced over the Garza et al paper and I found out something interesting. AGA scalp has all the stem cells needed, but it is lacking only two progenitor cells: CD34 (aka CD34+) and CD200 (aka CD200hiTGA6hi). In an update to the thread I stated how wounding effects the hair follicle. When the scalp is wounded, Lhx2 is activated in the hair follicle. Lhx2 inhibits Lgr5 which regulates bulge and secondary germ stem cells. Inhibiting Lgr5 will keep hair in anagen by inhibiting stem cell activation.
Here is the problem. Lgr5 is a marker for activated bulge and secondary hair germ cells. In the Garza et al study, they state that Lgr5 is reduced in bald scalp. Lgr5 is directly correlated with CD200hiITGA6hi cells (the cd200 cells that balding hairs lack). This means that we need to express Lgr5 in order to potentially regain the CD200 cells ( specifically CD200hiTGA6hi) that are lacking in androgenetic alopecia. What is interesting is that Lgr5 is considered as a tumor suppressor gene (Wikipedia).
This should mean that while wounding may help keep your existing hair in anagen for a short duration (5-7 days) it is inhibiting Lgr5 which has been shown to be responsible for CD200 (CD200hiTGAGhi).
If you have been wounding your scalp on a weekly basis, you are only keeping your terminal hair and thinning hairs that are not vellus in the anagen phase. This may be your cure if you have not receded or lost much hair; but be aware that suppressing Lgr5 for a long time and stopping wounding may have terrible consequences for your hair. Not to mention that long term wounding may lead to cancer. Lgr5 and CD200 is needed to form thick, terminal hair. I may have found one way to induce Lgr5/CD200. It would be nice if some of you can do some research and find potential other ways to do so. There needs to be some more medical research done on this as well.
There are studies showing that low dose Reactive Oxygen Species (ROS/Oxidants) can cause JNK and Lgr5 activation. JNK and tcf4 (activated by wounding via Lhx2) work together in tumorgenesis. Remember I stated before that our hair follicles are being treated like a tumor/cancer and in order to get regrowth we need to promote tumor like pathways. This is starting to get interesting.
Now for an update on CD34. The reason why Garza et al paper states that CD34+ is lacking is because of the decrease of the wnt/canonical pathway in AGA. In the thread where I made my second post, I said that I had discovered that TCF7 is directly involved with CD34. This is now a fact. Also, another fact is that when TCF7 is downregulated, CD34+ turn into CD34- cells. In order for us to increase CD34+ cells in the hair follicle, we need to activated the wnt canonical pathway and/or inhibit GSK3 Beta. A link below proves that LITHIUM can upregulate the proper type of TCF7 that will allow CD34+ cells to proliferate.
People have used the following topically, often separately, with relative success: oxidants, lithium chloride, androgen receptor inhibitors, and wounding. Many have had some success with them, but no cure. The reason is because each one is lacking or inhibiting something critical for the regrowth of terminal hair. Here is where I believe we have a potential cure:
Androgen Receptor Inhibition--stop the AGA pathway/cascade (inflammation, senescence, etc)
Lithium Chloride--Induce the Wnt B-Catenin pathway and CD34+ progenitor cells
Wounding--Induce anagen. Angiogenesis. Break fibrotic plaque. SOX9, Lhrx2, tcf4 hair follicle progenitor stem cell production
Low dose ROS (oxidant like hydrogen peroxide)-- induce Lgr5/CD200/CD200hiTGA6hi
This is what all 4 of the above should do--Regrowth of thick terminal hair
Now the question is if we need to cycle these or can we use them together. I have tried my best to understand AGA, the hair cycle, and all the factors involved with hair loss. I try to understand most of the material I read, but I am no expert. This is where we need the medical research community to get involved.
Inhibiting androgen receptors will cause the cessation of the androgenetic alopecia pathway of miniaturization, inflammation, and apoptosis . This is not a cure in itself because there has been senescent damage done to the androgen sensitive hair follicles. There are two types of damage. One is thinning of the hair follicle, but still retains the ability to grow. The other is miniaturization into vellus hairs. We have learned that we contain all the stem cells needed to regrow hair, but lack 2 progenitor cells (CD34 and CD200). Both of these cells are involved with the hair follicle cycle. Cd34 is more involved with anagen and CD200 with the diameter of the hair. We now have the potential to induce the proliferation of CD34 via lithium and CD200 via low dose ROS (hydrogen peroxide). Lithium and wounding will promote anagen. Wounding the scalp will allow (please read the 3 page pdf I posted a link to below) the other progenitor/stem cells proliferation involved with the hair follicle. Wounding will allow us to break fibrotic plaques and during healing will allow angiogenesis (blood vessels, etc) to take place; so that we can have the optimal environment for thick terminal hair. The low dose ROS oxidant should counteract the inhibition of Lgr5/CD200 during wounding.
Not all my links are about the hair follicle. If you want more proof, do your own search. Better yet, start talking to potential medical researchers about this and see if they can verify it. I would like to see a future study regarding this idea. I believe if I can do a simple online search, reading articles, and finding information as what I wrote above, there can be a way to cure Androgenetic Alopecia. The sad truth is that there is no money involved in a cure; especially if it is as simple as what I posted above. The money is in hair transplants, synthetic medicines, topicals, and injections. If we were to fund our own research or if the medical community obliges to sincerely help, we can find a cure.
Links:
http://www.sciencedirect.com/science...92867411007562 (download the 3 page pdf)
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anteup, your research is great.
I think you'd get more help if you ended your posts with 1-2 sentences, bolded, that you consider next steps. Also, the tl;dr conclusion would be good.
eg.
TAKEAWAY: You have awesome posts, but need to finish strong in your conclusion/wrap up
NEXT STEPS: You should edit takeaways/next steps into your past posts, and plan to use them in the future postsComment
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The biggest barrier though is how do you apply that knowledge to safely and effectively achieve what you want? Twenty years later there are still few if any safe ways to actually inhibit the androgen receptors for instance even though we knew that for 20+ years. You say RU or CB but that fact is right now there are no proven ways to even do that safely. A lot of them get into grey areas of how effective is something at actually achieving that? I think turning the theory into practice is by far and away the most expensive and hardest part
Androgen Receptor Inhibition--stop the AGA pathway/cascade (inflammation, senescence, etc)Comment
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Your research is great. I really have the hope that you/we can find something if we continue. Maybe there is already the cure based on these treatment ways but ofcourse the Pharma Companys are more interested in treatments which let them earn money over a long period of time such as fin or minoxidil. Keep on bro.Comment
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This is an awesone topic.
I had some extra money and I'm getting desperate. I realize in terms of practical applications there's nothing, but the science makes sense so I bought a couple of lotions and pills. I truly feel it's all about your body attacking your scalp and it's just finding the right balance of drugs to tell it to stop. That's why I don't have a lot of faith in the Big 3, because it's just a shot in the dark. These writings have much greater understanding of what's going on than Merck or Rogaine or other big pharmas.
Here's what I got, all available from Amazon:
SesDerma Sebovalis: Lithium Gluconate 4%, Piroctone Olamine, Salicylic Acid. Will use 2-4 times a week. I guess I will skip my minox-fin applications on those days.
DMSO 70% / Aloe Vera 30%: Will put on for an hour to scalp before showering.
Organic Fenugreek Seedpowder: It says this is supposed to help breastfeeding? I'm already suspectible to gyno from Fin, I hope this doesn't get me lactating. Good God. Will take a pill every day or every other day.
Litsea Glutinosa Shampoo: It's supposed to have Brevilin A. Will use every other day.
Neogenic: I have some lying around. Any help on how to fit that into this regimen? How long does it need to stay on my scalp. How many times a day/week?
On top of that I have a minox, fin, azelaic acid, and tretinoin mix that I use. Ante's now saying azelaic acid is not good, but I just ordered 2 new bottles so that's not really an option.
So please give me some comments on this regimen, guys. Anyone, hellouser, anteup, etc.Comment
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I was misinformed about Azelaic Acid. I did a more in depth research about it and found out information that has made me to forever stop using it for hair loss. The only way I would use this if I had some type of over proliferative problem like in psoriasis, rosacea, etc. I high recommend anyone who is using Azelaic Acid topically for hair loss to stop using it.
First it decreases mitochondrial ATP synthesis. This is terrible for those of us that are trying to regrow hair. However, this is the reason why it works for over proliferation like in psoriasis and conditions like rosacea.
Second, take note if you are wounding, that it decreases p53 and p21. These two are anti senescence, however in order to prevent fibrosis we need to eventually inhibit myofibroblasts via p53 and p16. So, using azelaic acid daily after wounding may actually CAUSE fibrosis.
More reason why Azelaic Acid is bad: it inhibits oxidoreductases
Information taken from http://press.endocrine.org/doi/full/...0/er.2006-0020 :
It helps to recall a few basic facts in estrogen biology to understand the mechanisms by which estrogens may affect hair follicle growth and cycling. E2 de novo synthesis starts from cholesterol precursors. The final step essentially requires androgens as substrates. For the conversion of testosterone to E2, testosterone is converted to 19-hydroxytestosterone by a monooxygenase (EC 1.14.13.), then to 19-oxotestosterone, which is then converted to E2 by an oxidoreductase (EC 1.14.99.).
An alternative route is via 4-androstene-3,17-dione, which is converted to estrone by a monooxygenase (EC 1.14.13.), and then by an oxidoreductase to E2 (EC 1.14.99.). Estrone can be metabolized to E2 by 3β (or 17β)-hydroxysteroid dehydrogenase (Ref. 119) (EC 1.1.1.51) or estradiol 17β-dehydrogenase (Ref. 120) (EC 1.1.1.62). The only known pathway connecting testosterone to E2 is the cytochrome P-450 enzyme aromatase (EC 1.14.14.1, CYP19A1; ARO) pathway (Fig. 2). The CYP19 gene is localized on chromosome 15. It spans nine coding exons and a few untranslated exons, upstream of exon II, namely exon I1–I5.
Basically, Azelaic Acid is not allowing testosterone to convert to E2 (estradiol) in the hair follicle. This is via the mitochondria.
Estrogens are able to modify androgen metabolism within distinct subunits of the hair follicle (e.g., in the dermal papilla), diminishing the amount of 5α-dihydrotestosterone formed after incubation with testosterone (38). It is not yet known whether this effect is mediated directly by an inhibition of 5α-reductase within the hair follicle or indirectly through estrogen-induced increased conversion of testosterone to weaker androgens (38). Because aromatase, the enzyme that converts testosterone to E2 is also found at many of the sites of ER and androgen receptor expression (39), the local balance between E2 and androgen levels may serve to fine-tune E2 and androgen action in their target cells (40). This is further supported by the growing evidence that steroid receptors can cross talk with one another, showing an interdependence of estrogen-, progesterone-, and androgen-receptor signaling pathways (33, 41).
The transformation of terminal to vellus hair follicles in androgenetic alopecia is also associated with a discrete infiltration of perifollicular macrophages and with mast cell activation, which has been proposed to be inherent to the terminal-to-vellus switch itself (77, 78). Also, mast cells and macrophages likely play at least an important modulatory (although nonessential) role in the control of hair follicle cycle (73, 76 ; for review, see Ref. 34). Therefore, although this remains entirely speculative, the well-recognized immunomodulatory properties of estrogen (79, 80, 81) may indeed be relevant to hair cycle control.Comment
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I might give Ru a second try, I was on it for a very short time, but I freaked out when I saw that my erections were being affected and quit immideately.
As for Tofacitinib, there's no way I can get a hold of that. How did you obtain some? I barely got Fin because there's an online website that gives you prescriptions.
As for chlorine dioxide, I don't know how to prepare it. Ordering something off the shelf is so much easier. And Indon't want to lose hair, which I think is expected at first on CD.
AnteUp, thanks. I'm gonna see if I can drop AA from my topical. Unfortunately, I just put a new order in right before yesterday.
I used to dermaroll but because of the pain, I could only do it once a month, which matches your recommendation. However, I stopped that, but am now plannig to get back on it. I guess 1.5 mm isn't deep enough? But that's basically about as big as dermarollers get and I don't want to go experimenting with other woundig methods at home unless you have a reasonable method for it.
Ante, what do you think of lithium gluconate? Do you think that will cover the lithium topical aspect of your suggestions or does it have to be a specific form of lithium? And what about neogenic, do you still rate jt?
Thanks, guys.Comment
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So let me know if I got this right.
According to your research we should be wounding our scalp every 30-40 days, and we should be applying lithium as well as hydrogen peroxide?
If so, should we apply the lithium right after wounding the scalp or should we wait a day or two? Also should we apply the hydrogen peroxide with the lithium or should they be on separate days?Comment
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AnteUp,
What can we do now to kick start all this in my regimen?
I bought the Jinda JAK inhibitor shampoo and will apply it 5 times a week (Nizoral 2 times a week).
Minoxidil foam 5% twice every day.
Vitamin B-complex (biotin etc.. included) + Resveratrol + Green Tea extracts every morning.
What else can I apply? Pygeum powder for Atraric Acid? Lithium Chloride how, is it available in herbal form or shampoo or something topical? Alzaic Acid? How can we try all this?
Your study is very intriguing and I want to give it a try given the fact that it can be tried herbally by using supplements but i just don't know where these substances are found for me to use them.
Could you make a list ?Comment
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Any updates, Ante?Comment
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