Lithium

[Only Natural]

I number of guys lately are experimenting with lithium, some along with DMSO, and then a few are even "needling" their scalps prior to applying this concoction.  There are also a few adding the lithium and DMSO to their shampoo. (I am not endorsing this btw..nor am I doing this myself)

What are your thoughts on the use of lithium in particular, and if it's safe and seems worth a try- would you be able to have it available via The Formulator? There is some discussion that DMSO is needed or desired for a synergistic effect. The "needling"(a dermaroller would also work) is to cause "wounds"- to promote a "wound healing response". Some say this "wound healing" can create new follicles.

Obviously that's a very condensed version of what goes on with all the above. It's amazing how complicated just the growth of hair is.

Also, are you aware of any other "natural" ways/ingredients that can stimulate noggin?  Supposedly lithium does this(among other things).

Thanks

[DrYechiel]

Hello, Only Natural. Thank you for your questions.

Follicles are not a mere accumulation of cells in the shape of a little bulb. Each follicle is actually an organ, made of different cells with connections to blood flow, nerve endings, and muscles. Each cell type in the follicle may have a different and even contradictory (between different cells) mechanisms of activation and deactivation, and of activity and resting phases. People often speak about the follicles as if they have a button switch which activate or shuts the follicle but in effect, there are many different mechanisms for different cells and for different phases. The other issue which people ignore is the physical shape of the follicle. The specific location of each cell type in the little bulb and their different exposure (even within the same cell types) to other cells is also important. Many damaged follicles show clear changes in shape from healthy follicles and the location and distribution of some cell types is also very different from healthy follicles.

Now, if someone believes that new cells may grow as a “wound healing response” after inflicting a wound to the scalp, he is correct. He will most likely grow scar tissue on his head. Follicles are more difficult to regrow than regular skin cells such as fibroblasts. Damage to a follicle will many times be irreversible. I think that the people who speak about damaging their skin, or using mood-changing drugs such as lithium, are resorting in their mind to dangerous short-cuts which are typical to people in panic.

No wounding for the sake of healing under any conditions! and use of lithium only after consulting a physician. No penetration of skin by mechanical means under any conditions!

Generating new follicles via primary stem cells may have a good prospect of success. Stem cells in skin or scalp are not primary and will grow skin cells when they are induced to do so. The noggin gene is thought to produce a molecule (a water-soluble protein) which can act as an inducer of skin stem cells (which I believe you are referring to) to shift from their normal function (maybe by shifting stem cells to a more preliminary developmental role before they become skin stem cells) and maybe create new follicles. Use of skin or scalp stem cells is believed to be the best thing after primary stem cells implantation (which is currently subject to political conflict). However, none of those alone appear so far to be sufficient to generating new follicles. Not even primary cells, nor skin or scalp stem cells. The reason is that follicles are an organ and the conditions for generating an organ are very complex. It is not enough to install a stem cell (even a primary stem cell) into the scalp and expect the generation of a follicle. It may happen but there are many conditions yet unknown which have to be met before a follicle will grow. However, it is a hopeful avenue. If the noggin protein shifts a skin or scalp stem cell into a primary state (even if it turned it to a primary stem cell) it is not enough to grow a follicle. The use of stimulants for the internal synthesis of more and more noggin molecules (by stimulating the noggin gene, for example) is not risk free since much has yet to be studied about its activity. So far I cannot safely point at a safe natural material for the stimulation of noggin synthesis.

BTW: The foreskin in infants is loaded with early stem cells and primary differentiated cells. That tissue could be frozen and used later in life for generation of replacement tissues and spare parts without immunological suppression (coming from the same individual). Imagine that, nowadays they just throw it away.

[Only Natural]

What about just using Lithium w/out the "wounding"?  And actually they're talking about lithium orotate or chloride- probably should have mentioned that in the beginning. I don't know if that changes things or not..

These same supplements are being touted as a way to prevent  Alzheimer's etc..and have the added benefit of clearing up greasy heads(reduce sebum).

Thanks for the previous response btw.

[Only Natural]

There's too much talk about shedding from the use of it...I doubt there's going to be as much interest in it as some thought.  At least not topically.

[BobTheBuilder]

DrYechiel,

You total disregard the studies.

Lithium Chloride has shown to play a part in WNT signaling, there are many studies to date.

http://www.google.com.au/search?hl=en&q=lithium+wnt+signaling&btnG=Google+Search&meta=

Please have a read and comment.

Your words are spoken like a western doctor.

Regards,
Bob

[DrYechiel]

To "Only Natural":

Well, since you responded to your own posting you save me the time for doing that. The contibutions (or alleged contributions, if you read the studies critically) of lithium are not beyond any other good ingredient which is currently used and it does not have a special activity which cannot be achieved by another ingredient. It is neither unique in having special activities nor in the magnitude of its activities (provided it is indeed active as claimed). Therefore, there is at least one other consideration and that is, can something go wrong with this ingredient? The answer is simple, consult your physician because lithium application for non-mental conditions may be a case-by-case issue (good for some and very bad for others).

To "BobTheBuilder":

Hello Bob, if you could hear me say my words you would know that I aint talking like no western doctor, No Siree Bob!

See my comment to Only Natural, it is directed to you as well. Your link does not point to a specific website, just a list of 57,000+ hits in which the words  “lithium wnt signaling”  appear in some way, so I don’t know what part of all that (much of it about bipolar disorder) is of interest to you. Do a search for “water wnt signaling” and 184,000 hits are returned, proving that water is a vastly more potent treatment.

Now, joking aside, to your point. Lithium is powerful and affects many biochemical parameters. We now have only a narrow glimpse into its vast reaches. Because it is powerful it can do much good and much bad at the same time. It can even do some good and much bad for hairloss at the same time. Ingredients can have contradictory activities on biochemical chains and cycles. What we do know about lithium, especially as a mood-changing ingredient, calls for extreme caution. It is very simple: I am not going to suggest to anyone to do something risky, and this is risky. I would not recommend to others something I would not recommend to myself if I was in their situation. If you want to do something risky, you are a grownup and can do what you want and you don’t need moral support for your own decisions when they apply to your own health, but you should definitely discuss the matter with a physician before experimenting on yourself with a drug. And by the way, I am a Ph.D. and not an MD, and I can assure you that messing up delicate biochemical steady-state relationships is not something to take lightly.

[BobTheBuilder]

To DrYechiel,

Lol yes 57000 hits is my point well to an extent.

I total understand you cannot recommend anyone doing this because its risky etc.. as most scientists would.

My point can you comment on what methods good and bad lithium would work on hair loss?

If you were to tell me lithium would grow hair this is still not you recommending lithium, you are simply just expressing your opinion.

So lets see you talk like a non western man LOL

[BobTheBuilder]

DrYechiel,

Here some links with use of lithium chloride and hair loss.

http://www.pharmcast.com/Patents100/Yr2005/Aug2005/080205/6924141_Hair080205.htm

http://www.patentstorm.us/patents/6924141-description.html (this is great read)

http://www.genesdev.org/cgi/reprint/14/10/1181.pdf (great read about wnt3a)

""it was found that agents, such as inhibitors of GSK3ß kinase, e.g., lithium chloride or similar small ions, which can mimic an effect of Wnt promoted signal transduction, e.g., inhibition of ß-catenin phosphorylation, e.g., by inhibition of GSK3ß kinase, or accumulation of ß-catenin, can regulate the ability of DP cells to promoter hair growth.""

""Lithium chloride (LiCl) inhibits the activity of glycogen synthase kinase-3 (GSK-3 ), allowing the accumulation of free -catenin and leads to activation of the -catenin- dependent pathway [14]. We applied topical LiCl (20 mM) to murine wounds until wound closure (14 days) and harvested the wounds on day 28 for histology. The mice in these experiments were age and sex-matched with the control group to control for the natural hair cycle. Five out of the 6 mice showed histologic evidence of epi- thelial appendage formation in their wounds on day 28. As seen in figure 3b, the simple stratified epithelium that typically forms over the wound displayed numerous inclusion cyst-like structures superficially within the epi- dermis and occasionally, formation of primitive hair fol- licle structures and sebaceous glands (Fig. 3c). These structures were noted well within the wound, not near or in the adjacent normal skin (Fig. 3a). No changes in the healed dermis with respect to the inflammatory cells, col- lagen deposition or mesenchymal cells were noted in any of the mice. These findings demonstrate that the adult interfollicular keratinocytes are capable of converting to a follicular phenotype during wound healing, provided the appropriate cell signals are present.""

"" These studies demonstrate that lithium activates the Wnt signaling pathway, which normally involves inhibition of GSK3, an action that may account for numerous observations of developmental effects of lithium (Hedgepeth et al., 1997).""

[DrYechiel]

Hello BobTheBuider,

Of the three links, two describe patents. Patents are not reliable as scientific sources. Patents are not designed to replace research articles, but to claim commercial rights to a new technique, even if it is not yet proven or even if it is still just a hunch or an idea, and even it is not clear at all that the hunch or idea will ever materialize or prove to be for real.

The third link, a 2000 article from Genes and Development, is OK as a source and it conforms with the current general understanding of GSK-3ß, Wnt, and ß-catenin regulation, but it’s not enough on its own and so I collected some information from high quality sources and I will present that below. However, the patents mentioned “lithium or other small ions” and maybe they knew why “lithium” was not enough and why not to reveal what the other ions are. Lithium is not the only way to achieve inhibition of GSK-3ß; so is berilium (not recommended) and… good old zinc, which is a very safe ingredient to use and can be physiologically tolerated in relatively large quantities. You are probably aware of the fact that our JuveLine™ has nano-zinc-oxide for extra penetration. Let me give you a hint: every ingredient with sugar-lowering ability or with insulin-mimetic characteristics  (which of course includes zinc) is a suspect for being able to do some other good, including possibly direct or indirect effects on GSK-3ß. Please read my posting to “teacup” on the NanoScalp™ ingredients and you will realize how many of them have sugar-lowering or insulin-mimetic activity (we formulated NanoScalp™ several years ago).

The activity of lithium is assumed to be via displacing magnesium ions. Lithium’s competition with the similarly-sized magnesium cation inhibits the activity of enzymes which require magnesium for their activity at therapeutic concentrations. Inhibition is achieved via competition with a magnesium-binding site on the enzyme. Glycogen synthase kinase-3ß (GSK-3ß) is such an enzyme.

In 1996 it was discovered that lithium was a direct inhibitor of GSK-3ß (Klein and Melton, 1996; Stambolic et al, 1996). This effect was later identified to be through competition for magnesium. While other Group I metal ions (sodium and potassium) did not inhibit GSK-3ß, a Group II ion, beryllium, did inhibit its activity in both a magnesium-competitive and ATP-competitive manner (it also binds to the ATP binding site of the enzyme). Zinc has also been identified as a GSK-3ß inhibitor both directly (Ilouz et al, 2002) and indirectly through phosphorylation (An et al, 2005). Similar to lithium, zinc's direct actions appear to be via competition for magnesium binding. However, only recent extensive pre-clinical research accumulation gave solid scientific merit to the notion that it is via inhibition of GSK-3ß that the effect of lithium is achieved.

As I stated before, insulin-like effects of zinc should have hinted at the possibility that it may also act via inhibition of GSK-3ß, which is also linked to insulin resistance and type 2 diabetes. In an experiment, treating HEK-293 type cells with zinc resulted in increased activity of glycogen synthase and intracellular levels of ß-catenin, providing evidence for inhibition of GSK-3ß by zinc. In addition, zinc ions enhanced glucose uptake 3-fold in isolated mouse adipocytes, an increase similar to activation with saturated concentrations of insulin. The author then hypothesized that the in vivo insulin-mimetic actions of zinc are mediated via direct inhibition of endogenous GSK-3ß.

If these are to be true, then potency of Li+ inhibition should depend on Mg2+ concentration. This was found to be true: GSK-3ß inhibitory concentration of lithium responded inversely to introduction of a magnesium chelator. This was another confirmation of the theory.

Why not simply use lithium?
1. Lithium has many serious side effects.
2. Lithium has a narrow dose range for its activity. Its effective and poisoning concentrations are very close to each other, which is a major problem in a drug. Part of testing any drug is determining at what point it begins to have an effect, and at what point that effect becomes poisonous. In a safe drug, there is a substantial enough gap between those two points that it can be administered to people (who all vary in how their bodies absorb and respond to every substance) without constant worry of causing permanent damage. Lithium does not have this safe operating range, and its administration must be constantly monitored by medical professionals. In addition, it is not very effective in sub-therapeutic concentrations, so lithium must always be given in doses which are too close to poisoning concentrations. In a topical, the variations in skin absorption and vehicles make such an endeavor very risky to undertake.

Zinc is a safe ingredient with the potential for many good effects. We use zinc and nano-zinc in several Elsom Research products.

[BobTheBuilder]

Hello DrYechiel,

Thank you for your detail response.

I think patents are a great resource, half the products never reach the public due to a money driven world "FDA", but yes total understand the scientific data.

"However, the patents mentioned “lithium or other small ions” and maybe they knew why “lithium” was not enough and why not to reveal what the other ions are" I didn't really read it that way, I thought on the terms of just small ions in WNT department, not meaning there were other ions. Patents all ways try to cover every part.

I can prove i have grown some hair with lithium added in shampoo (e.g. microscope photos) but I can say you are very right in the risk's with lithium which people forget due to there wanting - does this change your response?

I used lithium in a organic shampoo with DMSO this cause major shed's, i would not recommend anyone adding DMSO with lithium.

also funny you mention Lithium with Magnesium seems a fellow board member has regrown some hair with this method using both Lithium and Magnesium topically.

So in the above theory this mean magnesium should not be used?

"Li+ salts have been successfully used in the treatment of bipolar disorder without knowledge of its exact mechanism of action.  One hypothesis states that Li+ and Mg2+ compete for Mg2+binding sites due to similarities in their chemical properties"

I know why lowering sugar in the scalp has a major part in hair loss and I have the key/cure on hair loss that many scientists have missed.

What is your theory in why lowering sugar in the scalp has a part in hair loss?

[BobTheBuilder]

Also do you believe with these extreme measures of using lithium could cause tumors (topical use)?

"Aberrant activation of the Wnt signaling pathway is implicated in the development of a broad spectrum of tumors (1-3). Up-regulation of the Wnt-associated genes has been slow to play a role in the development of cancers. For example, Wnt16 is overexpressed in the pre-B subtype of acute lymphoblastic leukemia, which is characterized by a t(1;19) chromosomal translocation that results in the E2A-PBX1 fusion protein. Wnt16, a target gene of E2A-PBX1, plays a key role in leukemogenesis in such cases (4,5). However, although many Wnt genes (Wnt1, Wnt3a, and Wnt16) are thought to have oncogenic potential, others (Wnt5a and Wnt7a) have the characteristics of tumor surpressor genes (2). For example, most lung cancer cell lines and tissues show loss of Wnt7a, and the restoration of Wnt7a expression up-regulates E-cadherin and inhibits proliferation on non-small cell lung cancer cells in a peroxisome proliferator-activated receptor y-dependent manner (6-8). Loss of expression of ß-Catenin and E-cadherin is considered a marker of poor prognosis for lung cancer patients (9-12). Taken together, the evidence suggests that Wnt pathway activation may have opposing functions that depend on the ligand/receptor combination. Because of the multiple functions of the Wnt family, inhibition of all Wnt signaling may not be a perfect strategy for tumor therapy. One solution would be to target only Wnt signaling molecules that contribute significantly to tumorigenesis."