Orin said:
*Harold*
I think you're right, and I would like to add that (though as bold as it may be) that it's really, at this point, about us (or me in any case) starting to implement things. I grew about 30 hairs give or take a few, on ONE run of dermabrasion with only some hard-to-solve lithium (orotate) in, quite frankly, gin of all alcohols.
Hardly ideal, but there you go
I do would like to ask you something, and that is if you think lithium (in any composition I guess) signals "the right kind" of WnT. Again, don't know much about chemistry and all that, but I do seem to remember someone posting that a certain WnT-signal (or is it a protein? Anyway, you know what I mean), I think called WnT-10 is the one WnT-signal in the skin that actually governs, or atleast strongly influences hair-generation (and surely regrowth also).
What are your thoughts on how lithium targets this specific signal? Lithium is talked about in broad strokes, and it's used because we really don't have anything more precise readily available. Perhaps it ups all WnT-signaling, but I recognize the danger of over-simplifying something as complex as the human body.
OK. Lithium mimics wnt7a. This is one of the wnt ligands that stimulates the "canonical wnt pathway". This means that it acts to increase the stability and hence the production of beta-catenin. So its effects are mediated via beta-catenin. (lithium is actually a GSK3-beta inhibitor and since GSK3-beta degrades beta-catenin thats why you get the build up of beta-catenin with lithium) The "non-canonical pathway" acts independently of beta-catenin and off the top of my head I dont know much more than that.
I have seen a coupe of studies that claim that wnt10b is the most important ligand for at least some part of the hair maintenace/induction process. However I also know that of the ligands tested that were ineffective/less effective wnt7a was not one of them. At any rate I dont think there is too much to be gleaned from it beyond that though I will post the relative abstracts below so people can make up their own mind.
Biochem Biophys Res Commun. 2008 Mar 7;367(2):299-304. Epub 2007 Dec 26.Click here to read Links
Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft growth.
Ouji Y, Yoshikawa M, Moriya K, Nishiofuku M, Matsuda R, Ishizaka S.
Program in Tissue Engineering and Department of Parasitology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Although Wnts are expressed in hair follicles throughout life from embryo to adult, and considered to be critical for their development and maturation, their roles remain largely unknown. In the present study,
we investigated the effects of Wnts (Wnt-3a, Wnt-5a, Wnt-10b, and Wnt-11) on epithelial cell differentiation using adult mouse-derived primary skin epithelial cell (MPSEC) cultures and hair growth using hair follicle organ cultures.
Only Wnt-10b showed evident promotion of epithelial cell differentiation and hair shaft growth, in contrast to Wnt-3a, 5a, and 11. Our results suggest that Wnt-10b is unique and plays an important role in differentiation of epithelial cells in the hair follicle.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):516-22. Epub 2007 May 29.Click here to read Links
Effects of Wnt-10b on hair shaft growth in hair follicle cultures.
Ouji Y, Yoshikawa M, Moriya K, Ishizaka S.
Program in Tissue Engineering and Department of Parasitology, Nara Medical University, Kashihara, Nara 634-8521, Japan.
oujix@naramed-u.ac.jp
Wnts are deeply involved in the proliferation and differentiation of skin epithelial cells.
We previously reported the differentiation of cultured primary skin epithelial cells toward hair shaft and inner root sheath (IRS) of the hair follicle via beta-catenin stabilization caused by Wnt-10b, however, the effects of Wnt-10b on cultured hair follicles have not been reported. In the present study, we examined the effects of Wnt-10b on shaft growth using organ cultures of whisker hair follicles in serum-free conditions. No hair shaft growth was observed in the absence of Wnt-10b, whereas its addition to the culture promoted elongation of the hair shaft, intensive incorporation of BrdU in matrix cells flanking the dermal papilla (DP), and beta-catenin stabilization in DP and IRS cells.
These results suggest a promoting effect of Wnt-10b on hair shaft growth that is involved with stimulation of the DP via Wnt-10b/beta-catenin signalling, proliferation of matrix cells next to the DP, and differentiation of IRS cells by Wnt-10b.
From
Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding
"We discovered that hair follicle neogenesis following wounding paralleled embryonic follicle development at the molecular level.
The regenerated hair follicles expressed KRT17, Lef1, alkaline phosphatase, Wnt10b and Shh (Fig. 1i–o), which is analogous to embryonic follicles10."
"We then asked whether overexpression of the secreted ligand,
Wnt7a, in KRT14-Wnt7a (which targets the epidermis) transgenic mouse epidermis (Supplementary Fig. 6), would enhance hair follicle neogenesis following wounding.
Wnt7a has been shown to maintain the hair-follicle-inducing capacity of cultured dermal papilla cells25. The overexpression of activated beta-catenin, an intracellular Wnt effector, in epidermis induces new hair follicles26, 27, and exogenous Wnt promotes formation of cysts with hair follicle differentiation28; however, to date, there has been no evidence that extracellular Wnt ligands can promote actual hair follicle neogenesis in adult skin. Wound closure (time to re-epithelialization) was normal in KRT14-Wnt7a mice. However, the transgenic mice developed over twice the number of hair follicles within the wounded area compared with controls (Supplementary Table 1, Fig. 4i, j, l, m). The increased hair follicle number was due to a larger area within the wound that developed follicles (18 plusminus 4% in controls versus 40 plusminus 15% in KRT14-Wnt7a mice, P = 0.05) at the same density as controls (Supplementary Table 2). Thus, excess Wnt in combination with wound healing potentiates regeneration of hair follicles, perhaps by altering cell fate and increasing the number of cells competent to produce hair."
Regarding my own experiments... I will probably do both temples, and a line all along my hairline where I do not have hair left, or have very wispy hair. This is just in case something with the TCA goes wrong - which I also of course will try out in different strenghts on other parts of my body, and perhaps in my sideburn or something, to see what an area with thick scalp hair looks like after treatment, and if it leaves the hair unharmed.
I won't pluck the hair beforehand; not because I don't think it helps, I know it does (it's scientific fact now, I suppose). But I'm trying to do this as painfree as possible, and given how I would look if I had to pluck the hair from the treated areas beforehand, and at the same time continue to exist inconspicuously in society, I'm willing to sacrifice whatever effect it has as of now. I remember reading something of a ten-fold net-gain, but that's in rats, so who knows.
For all we know, some deep needling all over the scalp might produce a similar effect, so that's probably what I will do - just in case. In the end, I'm willing to go through an additional 3-4 treatments to get the same results as someone who went ahead and plucked their whole scalp. As long as there's a steady gain, I don't mind.
When I get the chance I am going to try and look and see if there is a method of anagen induction that is less traumatic than plucking. I suspect I may have read something on this and forgotten it. But the whole 11 fold difference does sound nice.
I'm thinking about doing one temple with high-grade EGCG + lithium in an alcohol mix, and the other temple with EGCG mixed in water (or alcohol, I haven't decided. There is a question of absorbation into the skin). I think this is as "scientific" as it can get, since I am my own experimentation-ground and I don't have the luxury of dealing with "virgin-scalp", as both my temples have by now have gone through one pass of dermabrasion.
So it's possible, that if I get good results, that it can also be because I am on (at that time) my second dermabrasion, and the phenol-study showed that dermabrasion on average takes 3 passes (without any additives) before you get substantial - or "excellent" - results.
So yeah, it's all a mess really..lol. It's truly a home-grown thing, but given the circumstances, I think this is the best we can do. At this point, it's really about getting results to begin with, and THEN, if that goes well, we can get into the headache of trying to make an optimized walkthrough or guide or something, for those that are just about to jump into this. Anyway, that's months away, and I'm over-thinking, as per usual.
If I would allow myself to make any predictions, based on semi-substantiated data, and backed up (albeit not entirely) by the two Follica patents, I'd think this is the way things will pan out:
* Dermabrasion alone gets the (comparatively) worst results
* Dermabrasion + lithium gives better results.
* Dermabrasion + lithium + caffeine gives better results.
* Dermabrasion + lithium + caffeine + some manner of EGFR-inhibitor such as EGCG gives better results.
* Dermabrasion + lithium + EGCG + caffeine + minoxidil (if they don't cancel eachother out) gives better results.
* Dermabrasion + lithium + EGCG + caffeine + minoxidil + DMSO (if the "no disinfectant thing" doesn't hold water) gives better results.
I think caffeine is going to be largely ineffective. (I hate to say that as I know you bought a whole bunch). EGCG should theoretically be helpful. I think minoxidil will be quite helpful when combined with wounding. What ever factors that it upregulates that prolong anagen seem to predispose to the creation of more hair follicles. I dont think DMSO will have any effect though it might make everything else, particularly lithium and EGCG penetrate better and more effectively.
If I had to guess, I think that is the order of effect, but I'm fully aware of how wobbly that 1+1 logic is, and there are probably a myriad of ways each chemical interacts with eachother. But as a very, very rough game-plan, I think that will suffice for now, and right now I'm at stage two, with meager, but clearly visible, non vellous hair as a result. The results, if any, on my right temple which I treated with lithium + caffeine (stage 3), should come in at about 3 weeks from now.
I shudder to think of the color that final potion will be though - pure witch-doctor.
I am interested if anyone canthink of a better way to wound/dermabrade areas that still have hair than using a brush with very fine bristles and possibly a metal brush that i have acquired (for cleaning BBQs
). Sandpaper and nail files are gonna take off hair also while these will at least let hair (I have buzzed it recently - very glad I did btw) move around the bits as they scrape at my poor suffering scalp. Might try a peel type thing later.
