Understanding and modelling the hairloss process

[Baldie101]

Hmmm...Ginger...no onion/garlic family? :wow:
DHEA?
The negative effect of Omega3 when overdose? (...think it was cancer or something.)

I read somewhere that sulfur was good for the head or something, which brings me to stuff like biotin (Vitamin B) and MSM which is about faster hair growth than regrowth.

Anyway I agree with the chart except the ??? boxes :hairy:

 

[Sitesearchers]

Wow thank you!! Where do crth2/gpr44 and igf-1 fall under this?Also caspase-9 and tgf-b?

Hve you read this? http://www.hairlosstalk.com/interact/showthread.php/42928-It-s-all-to-do-with-inflammation

this really helped me see the process clearly, and puts everything together that you all have been whispering about these past few years

 

[Sitesearchers]

Thank you for this post! It really helps me see clearly all the things you guys have been whispering about for years.


Where do crth2 / gpr44 and igf-1 fall on this chart? Also what about caspase-9 / caspase-3 and the tgf family, esp tgf-b?



Have you read this? http://www.hairlosstalk.com/interact/showthread.php/42928-It-s-all-to-do-with-inflammation

 

[Sitesearchers]

My post wi a link is being approved, so until then....


Thank you for this post! It really helps me see clearly all the things you guys have been whispering about for years.


Where do crth2 / gpr44 and igf-1 fall on this chart? Also what about caspase-9 / caspase-3 and the tgf family, esp tgf-b? Pkc and tnf-a?

 

[benjt]

Guys, again thanks for the input. I will deal with it in detail:

@Baldie101
The garlic/onion family has not been included because their anti inflammatory features are quite weak compared to all the others there. Also, there is evidence that suggests that while onion/garlic reduce inflammation, they upregulate immune system mechanisms leading to quicker aptosis. This is usually a desirable effect, but in our case of Androgenetic Alopecia/male pattern baldness it certainly is not.
Indeed there are quite a lot of posts about using garlic as an Androgenetic Alopecia treatment, but none of them actually provides any source. Anyone got such a source?

I did not include the whole vitamin thing on purpose. While they are critical to hair growth in general, they do not play a role in the medical condition we have here (which Androgenetic Alopecia as an erroneous immune response basically is).

@sitesearcher:
Your input has been very valuable and indeed crucial to the model. Without the whole TNF and TGF complex, it was just incomplete till now (well, it is anyway, since we still do not know the most important ???-box that triggers the whole cascade down from the autoimmune reaction). It was missing half of what the immune system does in trying to defend the body and sort out damaged cells.
TNF and TGF both regulate the life cycle of any type of cells. In immune responses, they are upregulated by the body on purpose to force potentially damaged cells into death. Thus, they are definitely not the root cause, but they are one half of the crucial part of the hair loss process. As far as I can tell, the autoimmune response triggers two counteraction sequences of actions:
1) killing off of cells that the immune system thinks might have been damaged by whatever the immune system thinks attacked them (using TGF and TNF)
2) inflammation and fibrosis of scarred tissue (using PGD-2 mostly, probably to harden the local tissue against further damaging, or due to the fact that healing just does not work as nicely as in embryonic state anymore)
So one step kills off the old, potentially damaged or virally infected cells, and the other creates newer, tighter and stronger tissue (which we do not want on our heads, as this blocks hair follicles!).

I also included caspase in the model now. In general, I found some very reliable sources that indeed hint at a whole aptosis cascade of steps. First, the immune system becomes active, then it upregulates TGF and TNF, they in turn upregulate caspase, and ultimately these lead to celldeath. I found very good evidence for at least 3 different types of caspase doing exactly that.

Could you please detail why you would want IGF-I somewhere else in the model?


Here is the full new model. Click on it for full resolution:

 

[odalbak]

Again thanks benjt for this great and huge work. Who knows, maybe you're the only person in the world that's ever done that cool job. The only minor downside I see is that someone who wouldn't know anything about male pattern baldness wouldn't be able to distinguish the factors that are supposedly minor in the process (like ejaculation or diet), from the main ones.

The question that immediately comes to my mind when I look at this model is, once you're unlucky and have the bad genetic profile, what is the very first element that is faulty in the whole process of hair production, the initial culprit that initiates the male pattern baldness process?

 

[benjt]

The whole profile of Androgenetic Alopecia/male pattern baldness looks a lot like that of pollen allergy. Both in Androgenetic Alopecia/male pattern baldness and in pollen allergies, the immune system thinks it needs to combat some substances and thus releases huge amounts of PGD-2 (and in Androgenetic Alopecia, some other things which would not make sense with pollen allergies, such as TGF and TNF - though I dont know if they are maybe not even increased in pollen allergic reactions too). And we also still don't know what triggers pollen allergy. Thus, it would be really useful to know the allergy situation of people with Norwood 3 and above. Gonna start a poll on that soon. There really might be a correlation.

The "initial culprit" probably is either the ??? box leading up to the immune reaction, or the immune reaction itself. The crucial part is to find out what triggers that reaction, and why. The what and why would actually be the ??? box to the left of the immune reaction. That ??? is the holy grail.

By the way: pollen allergies can actually be treated with non-pasteurized, fresh cow milk (as in: fresh and directly from the udder). This might sound freaky, but maybe such fresh, unheated cow milk might also help against Androgenetic Alopecia when drunk? Such cow milk has HUGE amounts of anti inflammatory substances and enzymes that help the body get rid off superfluous immune substances and cells.


I compiled the whole model for a couple of reasons:
a) help us assess if any newly promised treatments actually address the root cause of Androgenetic Alopecia/male pattern baldness. With any PGD-2 treatment, it should be pretty obvious by looking at the model that itis not the cure.
b) help us get an overview of all knowledge on Androgenetic Alopecia thus far and maybe find connections that were previously unknown
c) compile a list of treatments and their side effects for a quick overview of all options of battling Androgenetic Alopecia/male pattern baldness
d) just be a general knowledge base
e) I'm a scientist by profession and just cannot sit idle with this I need to get some model of things to feel comfortable working with them

 

[Sparky4444]

Isn't non-pasteurized fresh cows milk supposed to be one of the best things to boost Glutathione???

 

[benjt]

I don't know about this, and also I don't know what Glutathione would have to do with Androgenetic Alopecia/male pattern baldness. If you got any info on that, post it, but always with reference please.

 

[Sparky4444]

I don't know about this, and also I don't know what Glutathione would have to do with Androgenetic Alopecia/male pattern baldness. If you got any info on that, post it, but always with reference please.

Just search Glutathione on here...it's a big one, but not necessarily linked directly to male pattern baldness...Squeegee was all over this

 

[odalbak]

The "initial culprit" probably is either the ??? box leading up to the immune reaction, or the immune reaction itself.

I'm surprised you're not referring to dht excess, not as the initial culprit but as that situation happening right before the immune reaction in the male pattern baldness chain of events. Tell me if I'm wrong but balding areas have been shown to have higher levels of dht than average despite normal levels of testoterone (serum and local).

 

[benjt]

Note: The following is only my interpretation and not taken directly from papers.

I think that local excess DHT is the trigger, but not the cause. Systemically, many of us Androgenetic Alopecia sufferers actually dont have that much more DHT in our serum as compared to non-balding people, if at all. I read through a lot of blood values by now and many high Norwood have indeed very low serum DHT values. DHT by itself is probably not harmful, but just perceived harmful by either the immune system or the hair follicles noticing they are being surrounded by a lot of DHT (much like in allergies: pollen are not harmful, just the immune system has a problem with a lot of them around). The question is, what leads to clogging with DHT? Probably microvascular problems and/or collagen buildup, as a consequence of fibrosis in the first place. So in the beginning of the cascade of events, there is an immune reaction, probably already to very low local DHT accumulation.*
Our bodies' reaction to DHT is probably wrong. Our body, or rather the scalp area and/or follicles, is hypersensitive to it, for whatever reason. That triggers and immune reaction. Or its just the immune system itself overreacting there, like in allergies.

Either way, I am pretty sure that serum DHT and male pattern baldness/Androgenetic Alopecia are not linked. DHT could only be the culprit if they were, otherwise its local or immune hypersensitivity.


* This might also explain the pattern of Androgenetic Alopecia/male pattern baldness: A local, very weak fibrosis happens and leads to microvascular insufficiencies and buildup of collagen. As a result, DHT in that particular place builds up even more; the body's reaction to that DHT buildup becomes even more severe, till the tissue gets tighter and tighter... if you got that locally, DHT can not flow back from there anymore. What might actually happen is that there is a "dam" or "blockade" being constructed, be it due to microvascular insufficiency and/or due to hard collagen formation (both are probably even related). And thus the dam/blockade gets bigger, and bigger, and progresses slowly over your whole scalp.

 

[odalbak]

Benjt,

I've got a two questions.

- allergies tend to come for unknown reasons and often disappear by themselves, and they can also be tamed with small exposure; as far as I know excessive immune responses don't seem be related to genetics, so what about the G letter in Androgenetic Alopecia?

- You speak about fibrosis, tightness of scalp, microvascular deficiency, dht clogging… What's your opinion about the role, or no role, of the galea? As you know it is a membrane that's stuck to the scalp and is tightened on the sides by muscles, like a drum skin. No blood vessel goes through it. Couldn't it play also a role in the process?

 

[Armando Jose]

Aaaah, the "P" in male pattern baldness. this is the key
I think that the "G" in Androgenetic Alopecia is an error, all hairs over the scalp are equals genetically.
And there is another thing, the asynchronicity of scalp hairs and the production of androgens in the pilosebaceosu unit, even years before puberty.

Not all is writen yet

IMHO problems in sebum flow could be tied at the term in the box ?????

 

[Helios]

I agree with that theory benjit. Like i said before in another topic, some people like myself have encountered Androgenetic Alopecia/male pattern baldness after their testosterone peak thus DHT peak aswell. Since we never lost hair during that period it only sounds obvious that DHT is not the main issue with male pattern baldness, but only one of the ingredients.

Was thinking today that maybe male pattern baldness is due to a Y-chromosome defect, because i've seen that when a X-chromosome is defect it can repair itself by coping from other X-chromosomes, but a Y-chromosome can't do that, cause there is only one of them. Hence why it's only male related. But that was just thinking to far i guess.

 

[Sparky4444]

...I for one do not think DHT is the be-all-and-end-all either...

 

[benjt]

Someone else just opened another topic on how Androgenetic Alopecia basically shows the same pattern as initial hair growth in babies, just in reverse. So even at that age, when there is no DHT at play at all, the hair growth process shows that pattern. This, I think, supports that DHT is not the cause, but only the trigger/reason for other processes to happen which should not be happening usually, even with DHT around.

@odalbak:
1) In fact, allergies do not just appear and disappear like that. It's pretty obvious: Some suffer from them, some don't. Why is that? It is not really a matter of genetic predisposition, but of gene expression and activation. That is also the only way to explain why they disappear at one point in time again (no matter if spontaneously or through therapy), or why they appear at completely different times for different people. Remember that DNA is activated and deactivated in our bodies all the time. Maybe the same goes on with Androgenetic Alopecia: it's a matter of expression, and something triggers it.

2) I've read about the whole galea theory a couple of times on these forums by now. While I do not claim 100% certainty for most of my theories, I'm almost absolutely sure that the whole galea theory is complete nonsense. The galea is, for the most part, a tendon, and in front it is a muscle. Its microvascular supply is independent of the one for the skin around it, and also the follicles are not located inside the galea, but above. Furthermore, I do have quite a "flexible" one, and still Androgenetic Alopecia. Finally, there has not been real scientific backing for that theory, i.e. no peer-reviewed papers. I'm 99.9% sure the galea has nothing to do with Androgenetic Alopecia at all.

 

[Armando Jose]

good points benjt, initial hair growth in babies,.....DHT is not the cause,....., and the independent microvascular supply from galea support a nonsense theory,..... all very interesting issues

 

[ganonford]

Someone else just opened another topic on how Androgenetic Alopecia basically shows the same pattern as initial hair growth in babies, just in reverse. So even at that age, when there is no DHT at play at all, the hair growth process shows that pattern. This, I think, supports that DHT is not the cause, but only the trigger/reason for other processes to happen which should not be happening usually, even with DHT around.

How do you know there is no DHT?, during the first 4 to 6 months the testosterone in male babies is very high, just like in puberty (although it is not yet understood completely why), and then it drops for the next decade until the real puberty hits you.

- - - Updated - - -

Wait a minute... but now that I think about it... even female babies show the same pattern...

 

[Quantum Cat]

can the genes that cause male pattern baldness be deactivated or removed?