Understanding and modelling the hairloss process

benjt

Experienced Member
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Hi everyone,

suffering from major minoxidil side effects and not wanting to jump on the finasteride/dutasteride train fearing it might also have bad sides, I did a lot of research in the last few weeks. I read approx. 100 scientific papers and studies to get a thorough understanding of the male pattern baldness/Androgenetic Alopecia hairloss process.

The result of my research is this model:

(click for full image)

Every edge in this graph is backed by at least one scientific publication. No edge automatically means "x causes y", but rather denotes correlation, i.e., "when x is present, y has also been found". Sometimes this means causality, sometimes it does not. Also, each edge only means "x contributes to y", and not "x is the reason for y".
Red edges denote negative effects, green edges denote positive effects. Often, a green edge can be read as "x counteracts y".

To find a solution or cure male pattern baldness, one needs to find additional aspects counteracting the steps in the middle row in this model. I denoted such potential solutions with "???", as there likely is something else to exist.
The problem is also that there might be correlations of aspects "down the line" with aspects that I modeled up the line. For example, from my layman's understanding, hypoxia can also cause inflammation...
Also, please note that things upstream in the process are not necessarily (and not likely) to be the root cause of Androgenetic Alopecia/male pattern baldness. I only modelled correlation here, not causality. Also, the relative level of contribution has not been taken into account at all.

This model can help forum members in getting an overview of potential treatments and regimen additions, be it drugs, diet, etc., but also help our understanding for maybe finding some hints as to what might cause Androgenetic Alopecia/male pattern baldness in the first place. My aim is to create a model as complete as possible.

A rather recent find I have not yet added is pomegranate.

Of course, as I only started doing my research 6 weeks ago, my understanding is far more limited than that of other forum members.
Any additions, feedback, and discussion would be much appreciated.


Edit:
Updated Version 1.3. Again click for full resolution:



Edit2:
Updated to Version 1.4. Again click for full resolution:
 

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Thank you very much for what you have done.
We need more and more forum members like you who are willing to do a lot of reseaches and read a lot of scientific papers, maybe one day we will have a bright future.
 

Armando Jose

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good work, but waht coul be ??? in the center of the image causing inflammation in/around follicles? maybe alteration in sebum?
 

benjt

Experienced Member
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Some researchers say that the ??? might just be PGD-2 (most notable, the research group led by Cotsarelis). However, I am not quite sure about this, as PG levels (PGD, PGE and PGF) are usually adjusted in immune responses. Thus, PGD-2 might only be elevated as a consequence of an immune reaction. The root cause would then be something else, i.e., whatever triggers the autoimmune reaction. I think that this is the holy grail of AGAP/male pattern baldness: Finding out what triggers the autoimmune reaction. Inflammation and PGD-2 elevation only occur as results of immune reactions.
For some other forms of alopecia it has alsoready been proved without doubt that an autoimmune reaction is the root cause. The circumstances of these other forms of alopecia are surprisingly similar to those of Androgenetic Alopecia/male pattern baldness. They have an autoimmune response, they have inflammation, and they have microtissue scarring/fibrosis. I think the autoimmune reaction might as well lead to inflammation, and not the other way around. Anybody who knows something in that regard?

Nonetheless, PGD-2 being blocked or inhibited might still yield a successful approach in completely halting the balding process. Still, it does not erase the root of all evil, i.e. the autoimmune reaction. By inhibiting COX-2 and PGD2 we only weaken the local immune response, i.e. the microscarring/fibrosis and follicle miniaturization.

By the way, I updated the model a bit to include P450 (P-450), L-cartenine, and the role of certain types of omega 3 acis on COX-2 (and thus PGD-2). If anyone could shed some light on the role of P450 and L-cartenine, that would be great. The studies I found are partially contraditory, and partially useless.

We also need a greater understanding of possible side effects of lowered PGE-2 (as a result of COX-2 inhibtion). I don't want to experiment with COX-2 inhibitors if I don't know what lower PGE-2 may cause.

- - - Updated - - -

There is one aspect here that I would really like to discuss, which might yield a different approach at treatment:
Many forms of alopecia are 100% confirmed to be (auto)immune reactions, which are immune system hypersensibilities. They are pretty similar in effect compared to Androgenetic Alopecia/male pattern baldness (autoimmune reaction leading to inflammation leading to fibrosis leading to follicle miniaturization and dormancy). Allergies are just the same: immune system hypersensibilities. All my friends, including me, who suffer from Androgenetic Alopecia/male pattern baldness also suffer from pollen allergies. Furthermore, Cetirizine is an anti-allergen and is quite effective at halting male pattern baldness/Androgenetic Alopecia by reducing immune system reaction and thus down-regulation PGD-2.
What about the others? Do you also suffer from allergies?

I just also found out that PGD-2 levels are elevated in people with strong pollen allergies!
 

benjt

Experienced Member
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Graph updated to Version 1.1, now including topical antiandrogens (currently) without FDA approval. To be included in 1.2: tricomin. I also added the allergy theory, because allergies definitely increase PGD-2 all over your body, thus also in your scalp.
Any other suggestions/additions?
 

Armando Jose

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benjt, what do you think about the special pattern of common baldnes? Why this pattern?
 

benjt

Experienced Member
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What do you mean by "special pattern of common baldness"?

As far as I can tell, many forms of male baldness (and also some female baldness) are very similar:

  1. Trigger for immune reaction - the big question mark in Androgenetic Alopecia/male pattern baldness
  2. Immune reaction
  3. PGD-2 elevated
  4. Inflammation
  5. Fibrosis
  6. Hard collagen accumulation
  7. Follicle miniaturization and squeezing by surrounding, now hard, collagen (collagen also partly clogging shaft)
  8. Hair production stop
Interestingly, in Androgenetic Alopecia/male pattern baldness, it has also been shown that PGD-2 is not only elevated, but accumulated inside hair follicles. Perhaps, if there is some reason for PGD-2 not being transported away, this would lead to chronicle inflammation.

At any rate, this course of events is definitely the same for alopecia areata, alopecia totalis, androgenetic alopecia, and some other forms (e.g., induced by radiation treatment). The difference lies in step 1. In Androgenetic Alopecia/male pattern baldness, this is the result of DHT and something else. The "something else" is the big problem and as of yet unknown. While Cotsarelis' research group says that PGD-2 is the culprit, I really doubt that. PGD-2 is usually elevanted as a response of the immune system to some (perceived or real) threat, causing inflammation in order to battle the threat and its negative consequences on cells. PGD-2 being elevated is thus not the root cause here, but only one step down the line towards Androgenetic Alopecia/male pattern baldness - though a very crucial one, because w/o PGD-2 there is no inflammation, thus no fibrosis, and thus no follicle miniaturization.

Anyway, what do you mean by "special pattern of common baldness"? This common pattern of different types of baldness that I just detailed? Or do you mean the way that Androgenetic Alopecia/male pattern baldness advances over the male scalp?
 

Helios

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Nice graph.
According to new research Omega 3 supplementation can raise prostate cancer, maybe something to add in your graph.
 

benjt

Experienced Member
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Just updated to Version 1.2. Version 1.2 now contains everything I could find on the topics of...
1. hair loss process
2. treatments
3. side effects
which is backed by scientific studies and publications.

As now 100% of my current knowledge is in there, any additions or remarks by other people would be greatly appreciated.
If you have something to add, please always provide a source so I can ensure that everything in the graph is backed by science.
 

Sparky4444

Senior Member
Reaction score
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Just updated to Version 1.2. Version 1.2 now contains everything I could find on the topics of...
1. hair loss process
2. treatments
3. side effects
which is backed by scientific studies and publications.

As now 100% of my current knowledge is in there, any additions or remarks by other people would be greatly appreciated.
If you have something to add, please always provide a source so I can ensure that everything in the graph is backed by science.

Between you and Squeegee, this hairloss thing should be licked pretty soon now!! :punk: Good work!
 

Helios

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I see you have nothing with pomegranate: in a small addition i know it raises testosterone and that it prevents NO from being destroyed, but don't know in what way DHT is effected by this.

Testosterone: http://www.askmen.com/dating/dating-news/pomegranate-juice.html
http://www.democraticunderground.com/11423008

NO: http://www.livestrong.com/article/308144-risks-and-benefits-of-pomegranate-juice/

Omega 3 supplements and risk of prostate cancer:
http://www.telegraph.co.uk/health/h...lements-could-raise-prostate-cancer-risk.html
 

benjt

Experienced Member
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Between you and Squeegee, this hairloss thing should be licked pretty soon now!! :punk: Good work!
Ha, I wish it was ;)
Problem is, I can only piece together things others found out, but not find out anything new. The big question mark, namely the ??? leading up to the immune reaction in the model, is still completely unknown. The scientists in this area need to solve this riddle; I cannot do that, unfortunately.
I already asked squeegee via PM if he has anything to add to the model, but nothing from him since then.
The only way for me to find out something new would be to give me access to blood data of a lot of Androgenetic Alopecia/male pattern baldness patients. I am a scientist myself, though not in the areas of biology or medicine, and I have fairly good data mining skills. If anyone knows of a data set that I could use or of somebody that could provide me with one, that would be great.
I will also look into theories behind the cause of alopecia areata. As AA has, past step 1 described in my last post, the same course of steps as Androgenetic Alopecia/male pattern baldness, maybe the underlying cause is at least similar.

@Helios:
Thanks for contributing :)
Problem is, the first two sources basically make completely wrong statements. They say that high Testosterone leads to better sexuality. However, this is completely wrong if, for instance, Testosterone is high because 5aR is low, or because something else hinders the conversion process from T to DHT, as certain phytoestrogens can. However, if in fact T is high and DHT low at the same time due to ingestion of pomegranate, this means that pomegranate is capable of limiting the conversion. On this we can only speculate though, without ny proper sources. The fact that the third source you provided on pomegranate - the only trustworthy - states that pomegranate is beneficial for NO activity AND lowers your chances of prostate cancer supports this idea. However, I will not add speculations made from my own conclusions - the model shall be 100% correct, so that we can rely on it for further theories.

The problem with the "Omega 3 and prostate cancer matter" is threefold:
a) it contradicts other studies in the same field
b) it only refers to supplements, which could have different chemical composition than natural compounds
c) it provides no explanation why Omega 3 could improve risks of getting prostate cancer.

So, for the same reason as above, i.e. to keep the model 100% confirmed, I will also not add Omega 3 side effects.

Nonetheless, thanks for the effort. If you find anything else, please post it, and I will look into it.
 

Armando Jose

Senior Member
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980
What do you mean by "special pattern of common baldness"?

As far as I can tell, many forms of male baldness (and also some female baldness) are very similar:

  1. Trigger for immune reaction - the big question mark in Androgenetic Alopecia/male pattern baldness
  2. Immune reaction
  3. PGD-2 elevated
  4. Inflammation
  5. Fibrosis
  6. Hard collagen accumulation
  7. Follicle miniaturization and squeezing by surrounding, now hard, collagen (collagen also partly clogging shaft)
  8. Hair production stop
Interestingly, in Androgenetic Alopecia/male pattern baldness, it has also been shown that PGD-2 is not only elevated, but accumulated inside hair follicles. Perhaps, if there is some reason for PGD-2 not being transported away, this would lead to chronicle inflammation.

At any rate, this course of events is definitely the same for alopecia areata, alopecia totalis, androgenetic alopecia, and some other forms (e.g., induced by radiation treatment). The difference lies in step 1. In Androgenetic Alopecia/male pattern baldness, this is the result of DHT and something else. The "something else" is the big problem and as of yet unknown. While Cotsarelis' research group says that PGD-2 is the culprit, I really doubt that. PGD-2 is usually elevanted as a response of the immune system to some (perceived or real) threat, causing inflammation in order to battle the threat and its negative consequences on cells. PGD-2 being elevated is thus not the root cause here, but only one step down the line towards Androgenetic Alopecia/male pattern baldness - though a very crucial one, because w/o PGD-2 there is no inflammation, thus no fibrosis, and thus no follicle miniaturization.

Anyway, what do you mean by "special pattern of common baldness"? This common pattern of different types of baldness that I just detailed? Or do you mean the way that Androgenetic Alopecia/male pattern baldness advances over the male scalp?

Common baldness aka androgenetic alopecia where hairs on sides are no affected, Why? inflammation, inmune reaction, fibrosis, PGD-2 elevated only in frontal, crown or top hairs, but not side saclp hairs?
IMHO any theory must explain the special pattern and the differet incidence between sexes, among other things.

But, I like your work.....
 

Sparky4444

Senior Member
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Common baldness aka androgenetic alopecia where hairs on sides are no affected, Why? inflammation, inmune reaction, fibrosis, PGD-2 elevated only in frontal, crown or top hairs, but not side saclp hairs?
IMHO any theory must explain the special pattern and the differet incidence between sexes, among other things.

But, I like your work.....

AMEN TO THAT!! I think a lot of this kinda of conjecture is just a waste of time...but maybe through this all someone will stumble onto the critical understanding of hairloss -- which involves everything AJ pointed out here
 

ninjaxnew

New Member
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how about the role of sebum?

- - - Updated - - -

how about the role of sebum?

- - - Updated - - -

how about the role of sebum?
 

Armando Jose

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sebum is an unstable material which modifies physical chemistry and biologically over time.
Moreover, it is necessary to produce and remove continuously.
If the sebum flow stops, problems arise.
What locations on the scalp are areas where there is no flow arrest? The sides of the head because they are several hours every day (better at night when we sleep) in contact with an absorbent surface.
 

IDW2BB

Established Member
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What do you mean by "special pattern of common baldness"?

As far as I can tell, many forms of male baldness (and also some female baldness) are very similar:

  1. Trigger for immune reaction - the big question mark in Androgenetic Alopecia/male pattern baldness
  2. Immune reaction
  3. PGD-2 elevated
  4. Inflammation
  5. Fibrosis
  6. Hard collagen accumulation
  7. Follicle miniaturization and squeezing by surrounding, now hard, collagen (collagen also partly clogging shaft)
  8. Hair production stop
Interestingly, in Androgenetic Alopecia/male pattern baldness, it has also been shown that PGD-2 is not only elevated, but accumulated inside hair follicles. Perhaps, if there is some reason for PGD-2 not being transported away, this would lead to chronicle inflammation.

At any rate, this course of events is definitely the same for alopecia areata, alopecia totalis, androgenetic alopecia, and some other forms (e.g., induced by radiation treatment). The difference lies in step 1. In Androgenetic Alopecia/male pattern baldness, this is the result of DHT and something else. The "something else" is the big problem and as of yet unknown. While Cotsarelis' research group says that PGD-2 is the culprit, I really doubt that. PGD-2 is usually elevanted as a response of the immune system to some (perceived or real) threat, causing inflammation in order to battle the threat and its negative consequences on cells. PGD-2 being elevated is thus not the root cause here, but only one step down the line towards Androgenetic Alopecia/male pattern baldness - though a very crucial one, because w/o PGD-2 there is no inflammation, thus no fibrosis, and thus no follicle miniaturization.

Anyway, what do you mean by "special pattern of common baldness"? This common pattern of different types of baldness that I just detailed? Or do you mean the way that Androgenetic Alopecia/male pattern baldness advances over the male scalp?
http://www.ncbi.nlm.nih.gov/pubmed/23883581
Oxidized phospholipids (oxPLs) generated non-enzymatically display pleiotropic biological actions in inflammation. Their generation by cellular cyclooxygenases (COX) is currently unknown. To determine whether platelets generate prostaglandin (PG)-containing oxPLs, then characterize their structures and mechanisms of formation, we applied precursor scanning- tandem mass spectrometry to lipid extracts of agonist-activated human platelets. Thrombin, collagen or ionophore activation stimulated generation of families of PGs, comprising PGE2 and D2 attached to four phosphatidylethanolamine (PE) phospholipids (16:0p/, 18:1p/, 18:0p/ and 18:0a/). They formed within 2-5 min of activation in a calcium, phospholipase C, p38 MAP kinases, MEK1, cPLA2, and src tyrosine kinase-dependent manner (28.1 +/- 2.3 pg/2E8 platelets). Unlike free PGs, they remained cell associated, suggesting an autocrine mode of action. Their generation was inhibited by in vivo aspirin supplementation (75 mg/day), or in vitro cyclooxygenase-1 (COX-1) blockade. Inhibitors of fatty acyl re-esterification blocked generation significantly, while purified COX-1 was unable to directly oxidize PE in vitro. This indicates that they form in platelets via rapid esterification of COX-1 derived PGE2/D2 into PE. In summary, COX-1 in human platelets acutely mediates membrane phospholipid oxidation via formation of PG-esterified PLs, in response to pathophysiological agonists.
This complete study is free access in PDF.
 

Armando Jose

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Thanks IDW288 for this recent study
It show a link between oxidized phospholipids and inflammation
 
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