GansterBoy and his hypothesis on hairloss

What do you guys think of this? he might be on to something... I would like cs opinion this.


"V2 hypothesis all started by study of 22 march. Vinman and I started working together, and this is some info of it. this page will be updated from time to time.

Knowing these facts about the pgd2 study is very useful, like you can see, in the study(http://www.ncbi.nlm.nih.gov/pm...in/nihms366359f2.jpg)
, the hair follicle is stained by PGD2 and its stronger metabolite J2.. (I recommend to read the study at least 2-5 times). what we know from studies before is that p53 is over expressed in bald scalp, DKK1 is over expressed in bald scalp, Now what the fu*ck has this to do with pgd2? is it coincidental? No! also one of cots studies showed us 10x lower Progenitor cells, (what a coincidence) with the currently known data...

Now yes it begins by the androgen receptor sensitivity which I will cover later Its not very important for now) there are studies that show markers of active androgen receptor in bald scalps...(which ultimately seem to elevate LPGDS)

Quote by Ganster Boy

PGD2 in hair follicles is not caused by HPGDS - hematopoietic prostaglandin D synthase BUT, by LPGDS lipocalin pgds.

Source? read the 22 march study of DR. cots. LPGds levels are highly elevated....

http://www.ncbi.nlm.nih.gov/pm...bin/nihms366359f2.jpg


Increased PGD2 pathway activity in balding scalp of men with AGA. (A) Expression of lipocalin-type PTGDS mRNA in bald versus haired scalp, as tested by qPCR. Data are means ± SEM (n = 4). (B and C) The amount of PTGDS protein in paired bald (B) and haired (H) scalps (n = 4), as shown by Western blotting with Ponceau stain used for verification of equal loading (B) and its quantitation as normalized to haired scalp (C). Data are means ± SEM. (D) PGD2 production in bald scalp, as tested by ELISA. Data are means ± SEM (n = 3). (E and F) Fold change in PGD2 (n = 17), 15-dPGJ2) (n = 7), and PGE2 (n = 17) expression in bald scalp compared to haired scalp (E). Total prostaglandin content is quantified in (F). Data are means ± SEM. *P < 0.05; **P < 0.01. In (F), P value compares haired versus bald samples for each prostaglandin.






knowing this, explain why cetrizine and other mastcell stabilizers, will NOT help against the elevated PGD2 in hairflocles.. so your basically missing the boat with hpgds stabilizers.






lets pass this for some other time. now lets start with elevated LPGDS.(lipocalin Pgds enzyme).(cots study).

PGD2 is formed by the following sequence of enzyme reactions after cell activation 1) cytosolic phospholipase A2 is translocated to the endoplasmic reticulum and perinuclear membranes in a Ca2+-dependent manner, where it cleaves arachidonic acid from the membrane phospholipids; 2) arachidonic acid is converted to PGH2, a common precursor of various prostanoids, by the membrane-bound cyclooxygenases (COXs); and 3) PGH2 is further isomerized to PGD2 by PGD synthase (PGDS) (source vinman)


okay well now we have over expressed PGD2 and its active metabolite J2xx.


PGD2 upregulates p53 which causes Endothelial Cell Apoptosis (anti angiogenesis), p53 induces dkk1, dkk1 --> Result == Anti angiogenesis + apoptosis (with otuer words catagen + apoptosis == HAIRLOSS! <--pgd2 induces Caspase 3 which leads to pkc-> apoptosis -> Lpgds, bdnf.... its w whole loop back chain reaction.


15-Deoxy- (12,14)-prostaglandin J2 (15-dPGJ2)Induces Vascular
Endothelial Cell Apoptosis through the Sequential Activation
of MAPKS and p53
http://www.jbc.org/content/283/44/30273.full.pdf


now p53 in aga.

The frontal bald area of patients showed significantly higher levels of X-ray Cross Complementing-1 (XRCC1; P<0.001) and p53 (P<0.001) expression when compared with occipital hairy area of patients and frontal area of controls
http://www.ncbi.nlm.nih.gov/pubmed/18702626



so wtf p53 role with dkk1?
Dickkopf-1, an inhibitor of the Wnt signaling pathway, is induced by p53
http://www.nature.com/onc/jour...14/full/1203503a.html


You know the role of igf in aga, we know that some people taking finasteride and respond well have increased levels of igf.
Here for example http://www.alopezie.de/diskuss...upregulated_igf-1.pdf
also http://www.ncbi.nlm.nih.gov/pubmed/22363152

So there is a relationship with dht and igf...
See what's behind this

The prostaglandins (in order of potency) PGJ2 > PGA1 > PGA2 all significantly repressed IGF-I gene expression
http://www.ncbi.nlm.nih.gov/pubmed/9545524
The 15d-PGJ2 is Cyclopentenone prostaglandin...



Are you starting to see the puzzle in AGA?.....

You know the role of igf in aga, we know that some people taking finasteride and respond well have increased levels of igf.
Here for example http://www.alopezie.de/diskuss...upregulated_igf-1.pdf
also http://www.ncbi.nlm.nih.gov/pubmed/22363152

So there is a relationship with dht and igf...
See what's behind this

The prostaglandins (in order of potency) PGJ2 > PGA1 > PGA2 all significantly repressed IGF-I gene expression
http://www.ncbi.nlm.nih.gov/pubmed/9545524
The 15d-PGJ2 is Cyclopentenone prostaglandin...

Hey i can see the aga image in the puzzle!!! I believe for the full 100% in this approach and I know this is It with full confidence!.
Yes off course the wnt pathway can be activated/inhibited by so many genes and most info on the net supports it TNF-a for example->dkk1...., this is most likely the It, with hard evidence. also we DO know,aswell, that its known pgd2 exhibits pge2s (lost the source its somewhere here on forum).

All by all, if we can create the original growth environment, (normal PGD2 signaling), will lead to at least stabilization (which is currently the case on most users), but in long term, the damage of all years Anti angiogenesis and apoptosis effect of PGD2, could be reversed. But off course it will take time. We can help speeding up this process, by adding exogenous PGe2, using things like tb4, minox, vpa, Hif1 inducers. This is how I see it and Im 100% confident about it. take some DAYS to read everything over and over, before replaying.

Yes we all want know why this happens to us at early age, its hard to tell, and there are more than 10000 reasons. It could be the environment, food, water, mutating genes, due to alcohol/smoking.. proteins like Smad7 which associated with inflammation/bdnf etc, are usually higher on older people who are likely to go bald, but we people seem to going bald much and much sooner.. one or more of these genes are likely mutating, which causes higher androgen receptor sensitivity/lpgds over expression. Who knows. Also now days we're eating much and much more omega 6 and less omega3, these omegas are the basis of all prostaglandins/ and affect the way how we feel/ how our body works .... Its complicated. What can we do about it, eat as healthy as possible, do plenty of exercise etc. Locally we can block the pgd2 action, and induce progenitor cells, by the above mentioned methods...

Big Thanks to Vinman from Greek without him this was not possible!, we have been digging into this case for month, countless hours to find all the links and put them together. and here it is for free. You can ignore it or use it, its up to you guys. . I don't mind.

Soon a more detailed post, this is just a quick snapshot of our info."

here's the link to the source
http://www.hairlosshelp.com/forums/messageview.cfm?catid=7&threadid=103373&enterthread=y

A lot of this data is really relevant and has been discussed in its separate parts for years on the site, thanks for the summary though! I would only add that it's merely looking at a forest from the sky, downwards, missing the view of the roots and the creatures that dwell below.

Ill post more when I have the time as I have much to add to the thread, keep up the good posts!

Awesome post. The piece of the puzzle related to IGF-1 might also shed some light on why estrogen therapy has been shown to regrow hair in some studies. Certain types of estrogen promote IGF-1 signaling, probably through some action on the pituitary > growth hormone.

http://www.biomedcentral.com/1471-2458/9/82

Throw this study into the mix and work it in so that it makes sense and I think you'll really have one of the best understandings of this issue I've seen.

>> http://www.biomedcentral.com/1471-2458/9/82

Very interesting. What could be the cause for those problems? Iodine is related to sulfur metabolism isn't it?

It's multifactoral, to a great extent, in a very very oversimplified view I'd say it stems from the gut, bacterial translation, endotoxemia, impaired bile acid conjugation impairing stomach acid use, etc etc, interacting to produce low level inflammation and metabolic stress.

Mind you I'm citing no studies and that's very oversimplified, it'll all go into a thread once I have time to cut and paste it together. As the user who started this thread will know, it takes hours to put something like this together.

Fin raises test +e2 so it make sense that the extra estrogen will also increase IGF much like soy isoflavons.

props on the post man, this is a great attempt at trying to tackle the tip of the tree of problems. i feel like it will be a matter of time before some new discovery will be able to pinpoint the exact step in the error pathway and not drugs like propecia which inhibit the pathway way too early to be biologically safe.

anthonyspencer54 wrote:Awesome post. The piece of the puzzle related to IGF-1 might also shed some light on why estrogen therapy has been shown to regrow hair in some studies. Certain types of estrogen promote IGF-1 signaling, probably through some action on the pituitary > growth hormone.

what types? 17b-estradiol? estriol? 17b-estradiol is much stronger than estriol.

i read 17b-estradiol can promote scalp hair growth in men, but not women?
follacure.com/t/estrogenB

i also read it can induce tgf-b in the buttock skin of women, i dont know if this is good or bad, because there is body hair in that region which would be negatively affected by estrogens.
ncbi.nlm.nih.gov/pubmed/15955089


i want to make my own topical 17b-estradiol using oestrgel as a base, but mixing it with water and something that will help prevent it from metabolizing quickly so it has time to stay in the skin and do it's job. any suggestions? i read that glyceryl ocelot might help.

This is one of GansterBoy theory of fixing hairloss, check it out


"Thanks bro, I'm glad at least someone understands my posts..
About my exams they went much better than expected. My score was 86%, which is very high
since, I'm currently neglecting my study because I'm putting almost all my time and energy in reading all these PHD studies out there..
It's now days very hard for me to sum studies up. its not that i read 1 or 2 studies per day..
some days I'm sitting for more then 8 hours per day, analyzing these studies, and laying the links with other stuff I read
before and the material that I knew before , trying to figure out every single detail of this hairloss puzzle.
And more and more, I get an Aha Woow this is amazing moment !, but on the other side I think by myself about some hairloss studies, (how can a PHD team make such a conclusion.. if they do this, it weill affect the other factors in a bad way(they think in sort range, without take into account with other factors)

Anyways. Why Am I doing all this, spending this much energy and time in hairloss?

It's for me very simple. The doctor can't help me, If I go to the doctor and tell him I want to stop my hairloss he gives me propicia,
which I cannot take due to sides, I have tried all the anti androgens and stimulators out there, without much success and had to quit due to the sides. and no one les can help me regrow my hair.
At this point I had 2 options. 1 Accept the fact that my body is ultra sensitive and give up + complaining around + feel bad,
or do everything that is in my power to still fix this. I choose the last option. I don't accept this issue and 100% believe its reversible and the answer is in our hands, we just need to grab it. they key is research. (and I really hoped to get some more help on this forum).
So I do this because I feel I have no other choice. Its for me reverse hairloss or reverse Hairloss, and I do everything within my power to get my goal. Nothing will stop me from doing it my way. Its just the way who I am.

Some particular guys here , seem to be a bit negative and skeptical around here. I'm not going to argue those, I simply don't have the time and energy for that. And its totally okay with me. I totally respect that. I think everyone should do and say what they like. Its just if these persons took the time to read and try to understand at least 50% of what I write here + the studies, they would at least as confident as I am
.
Anyways after all the info about pgd2, hypoxia, hif1, cytokines, WNT pathway.dkk1,smad7, progenitor cells etc..
I have looked to the difference between BALDING people and Non balding people. the composition of their genes,
androgen receptors (active/non active) and the above typed genes/proteins. And mad a list for myself, to create the same environment as non balding people and hopefully even better. With 1 thing in my mind, Work as effective as possible with minimal side effects (thats why you will not see me using anti androgens). Also I got very much inspiration from Vinman! and the patent from HISTOGEN.

I Have composed a treatment plan which I'm super confident about. It hits the problem on cell stamcel level.
instead of the old school steroid level treatments.

see this post for more explanation about why we cannot use just 1 treatment:

In this post I explain why we cannot just use anti androgens only (they have effect on vegf, hif1 in negative way)
http://www.hairlosshelp.com/fo...1985&filtmsgid=884731

In this post I I give further explanation why we cannot use just 1 treatment to see regrowth or to just stop the hairloss:
http://www.hairlosshelp.com/fo...9747&filtmsgid=858084

So what Am I going to use to get the best growth environment possible for now?

1- OC000459 (it stops apoptosis "CELL DEATH") according to PGD2 study of 22March
2- Valproic Acid (wnt b pathway and progenitor cells)
3 Ciclopirox Olamine (HIF1 inducer"Hypoxia")

So what is hypoxia and why is this good for my hair??

I will try to explain in short what this is. For people who are interested in details, I will post some study links.

Hypoxia basically means LOW Oxygen environment.
what is HIF-1? its Hypoxia Inducible factor.

When a bodypart/tissue becomes in sort of in a low oxygen. the body starts to express HIF1.
HIF1 is responsible for allot of actions in the human body. It increases allot of Genes and growth factors. More than 40!.
VEGF, progenitor cells, derma papilla cells !!, so basically, it will release a Cocktail of growth factors, which will help restore body parts, and for example VEGF, it will take care of angiogenesis. (maturation of blood vessels for better blood supply and oxygen for the tissue + the cocktail of growth factors, progenitor cells etc.
We have collected allot of useful studies and every study confirms the other. all the blocks are actually falling together.


-Loreal has released neogenic., the active compound is stemoxydine. I have not much information about this product so I cannot say how effective/ safe it is.

I'm going to use Ciclopirox Olamine. its an hif1 stabilizer. Its FDA approved and very cheap. It should be available in some countries without prescription. Its also for cheap available in china in raw powder.

some studies regarding hypoxia and hypoxia + hair.(credits also goes to Vinman)

http://univisgroup.com/wp-cont...a_and_hair_growth.pdf
http://www.nature.com/ncb/jour...g_tab/ncb2102_F1.html
http://www.sciencedirect.com/s...pii/S0006291X07010091
http://jtcs.ctsnetjournals.org...nt/abstract/135/4/799
http://www.fasebj.org/content/21/12/3346.full#F1
http://clincancerres.aacrjourn...content/9/7/2416.long

http://profiles.wizfolio.com/T...cations/19044/136174/
Hypoxia Promoted The Proliferation And Maintained The Functions Of Human Hair Follicle Outer Root Sheath Cells

http://www.ncbi.nlm.nih.gov/pubmed/17536272
Effect of hypoxia inducible factor-1alpha on cells of hair follicle


This in short about hypoxia, read the studies and you will get as excited as me about the studies .
so basically in simple words:

OC000459 will stop PGD2 from causing apoptosis (cell death).
Sodium Valproate(VPA) = growth factor.
Ciclopirox Olamine (HIF1 Inducer) = Cocktail mix of growth factors.
This together should be super promising.

I'm going to use the simple 70/30(70% ethanol/30% PPG or glycerin) vehicle for now, my skin absorbs everything, and this vehicle worked always perfect on my skin type. But I will be using Ziom's solution soon. so for vehicle questions, contact ziom.
the dosage I'm going to use:

OC 0.1%
VPA 1%
Ciclopirox Olamine 1%

All in liquid 70/30 vehicle for now.

I'm very happy because , I can finally start my dream treatment this week. If everything goes well, I will receive my my other meds: OC + Ciclopirox Olamine this week.

Does this mean, I'm now finally satisfied and I'm going to quit research? No Absolutely not, I will keep looking for better ways.
If you read my post couple times, you might understand why I have replaced Ciclopirox Olamine for PGE2. So I dropped PGE2 because Ciclopirox Olamine should be better in almost every way and its a hif1 inducer.

I think people should decide for themselves what to do and what treatment they will be using. I share my info, and its up to you guys to use this info or not. If you want to add this treatment to your current regime RU58841 for example and you can afford that, and you are okay with the RU sides, that's Okay. this will be a synergy. So please don't ask me What do you recommend me? All the info is in my posts. explained as best as I can. "

link to the source
http://www.hairlosshelp.com/forums/messageview.cfm?catid=7&threadid=99747&enterthread=y

Fyi, I just copied and paste what GansterBoy wrote on hairlosshelp, so all the credit to him.

While this has been covered before, it bears repeating.

A few points to consider:

Using a drug approach isn't necessary.

Omega-6 fatty acids are not evil...just the processed variety are.
In fact, Omega-6 fatty acids are even more anti-inflammatory than Omega-3.
A prime example is GLA.

Taking fish or krill oil is a natural way to reduce PGD2, as is Quercetin.

Unless I'm eating grass-fed beef, I'm not going to go a day without some EFA's.

PGD2 is not everything in hair loss. The inflammatory pathways can go much deeper.
Phospholipase A2 is another way to tackle this problem, PPARgamma, and there are many others.

^ Yeah, but as we've seen, natural isn't always enough. Just because EPA is good for PGD2 doesn't mean it's good enough. Sometimes drugs are neccessary. What's so wrong with drugs anyways? I get the need for natural supplements for overall good health, and to aid in a largerly natural approach, but even with this, and spironolactone, my hair loss progresses. Drugs save lives, and sometimes hair too, so if one of these CRTH2 or PGD2 antagonist drugs work out, I wouldn't shove them away.

PDG2 and its precursors are stimulated for an important reason. One of the reasons is to protect against ischemia/reprofusion injury (lack of oxygen in the heart tissue).

All drugs do is poison enzymes and block physiologic pathways.

Rather that go all out and destroy PDG2 and its precursors, consider looking at the underlying reason for its stimulation.

"The synthesis of PGD2 from its precursor PGH2 is catalyzed by two PGD synthases (PGDSs) [4]. Prostaglandin D2 (PGD2) is involved in a wide variety of neurophysiological functions, such as regulation of body temperature, hormone release, modulation of odor and pain responses, and regulation of the sleep-wake cycle in mammals. PGD2 is further dehydrated to produce PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12,14-PGJ2. PGD2 acts through two receptors (DP1 and DP2 CRTH2), whereas 15d-PGJ2 can activate peroxisome proliferator-activated receptors or inhibit a range of proinflammatory signaling pathways, including NF-κB [1, 2, 5].

The importance of the role of PGD2 in the pathogenesis and resolution of inflammation and innate immune response is increasingly recognized [6, 7]. However, the effect of PGD2 on inflammation is complex because PGD2 either promotes or suppresses inflammation depending on the inflammatory milieu. This is further complicated by the fact that PGD2 undergoes nonenzymatic processes to generate 15d-PGJ2, an anti-inflammatory lipid."

http://www.hindawi.com/journals/mi/2012/503128/

PGD2 is so very complex and has so many roles in the body, that if any pro-hair drug tries to marginalize its anti-hair effects by lowering it systemically, there are going to be consequences. It plays a huge role in our stress response, especially physiological stress in the gut (hint hint) where it protects from mucosal damage (endotoxins and alcohols). Our patterns of waking and sleeping are highly tuned in to our stress response, and so PDG2 is also involved in this.

The study points out that the pro or anti-inflammatory behavior of PGD2 is highly regulated by the other inflammatory markers present.

I'm extremely interested in the connection between stress/the gut/sleep/allergy and PGD2. But I only say this to strengthen what CS is saying about drugs, they are often a take-it-or-leave it solution, meaning if you take them you'll probably just knock PDG2 out if that drug acts on the cycloxygenase enzymes. Oh, and this would also really lower the immune response. This might be good for some, but not all.

Nice post anthonyspencer54

That gut connection among others you cited is has multiple links to hair loss.
Probably the reason why conventional medicine is just an abject failure is because
the focus is using a blunt hammer to whichever pathway without addressing the cause.

Gut health plays a major role in many of these connections, including stress response and brain activity (neuronal response).

Funny thing about balding is it is loaded in contradictions, but really these paradoxes are false.

Low testosterone more MPB
Only unbound testosterone is a problem.
Suppressing DHT by chemical gene suppression causes anxiety and depressive tendencies
Various "psychoses" appear to accentuate the balding process.
How the HTPA works is not properly coordinated with such psychoses.

I think we will begin to see more and more research focused on the connections between hair and brain responses,
which include the gut.

What are the best supplements to improve your gut health?

CS, I completely agree. The frustrating aspects is that the brain/neuronal response is one of the most difficult to control. But at least trying to eliminate the problems we're getting from physiological sources like the gut is a step.

Natural alternatives for gangster boy

1. I think most of the stuff we take should help vs his drug. Healing the gut, detoxifying etc.

2. Valerian root. Not sure if orally or topically is best.

3. Manual methods. Which one is best is debatable but some have gotten results.

There's a lot of things worth experimenting with. At least we are becoming more informed about the cause which helps in deciding the right treatment.

PGD2 is so very complex and has so many roles in the body, that if any pro-hair drug tries to marginalize its anti-hair effects by lowering it systemically, there are going to be consequences. It plays a huge role in our stress response, especially physiological stress in the gut (hint hint) where it protects from mucosal damage (endotoxins and alcohols). Our patterns of waking and sleeping are highly tuned in to our stress response, and so PDG2 is also involved in this.

fin/dut are the begining and end of internal hair loss drugs (discounting the desperate few who drink minoxidil and eat bicalutimide)

the goal would be to address it locally not systemically. this has been stated by cotsarelis et al in their paper, and this is clearly the trend in upcoming hairloss treatment (histogen, replicel, allegan trialing bimatoprost, etc)

I was thinking about bimatoprost when I was typing that, Law.