The Cause Of Baldness

[CLASH]

@ivy
I apologize, I assumed based on the statement (You know what they say about assuming hahah). Thank you for the additions, I'll look into them some more.

You could still chew on the diet, its not elemental in the literal sense. Its elemental in that the only foods that would be reaching the colon would be dairy products. The animal products on the diet require chewing unless you want to make a liver milk shake hahah. Its also not low carb, if you see from what I posted I am following the diet myself and eating around 500g of sugar a day. I think raw milk has unique benefits, as does raw grain cultured kefir.

 

[kayumochi]

Unmodified potato starch has done wonders for my gut. Making kefir has been on my to-do list for quite some time ...

 

[Mossy]

In an effort to reduce costs, and avoid another time-consuming DIY (by not making the kefir myself), I purchased and tried this kefir: Organic Kefir Archives - Nancy's Yogurt.

This did a number on me; irritated my stomach and gave me overall flu like symptoms for a few days. I have one caveat: I did have a new brand of oysters the same day -- so, I can't count that out. But, prior to this, oysters have not done that to me.

If it was the kefir, should I assume that A2 kefir would be easier on me? I need a few more days of normalcy before I venture down this road again and test to make sure it was the kefir.

P.S. I should add that I had started the kefir 2 days prior to having the oysters, and unless my imagination is kicking in, it did feel like something was brewing that came to a head a couple days later.

 

[helpmyhair]

@CLASH

I was the one posting about decreasing gut bacteria. I am open to your suggestions, however raw milk is illegal where I live.. so there is no access to it here. What is my alternative? Store-bought pre-made kefir?

 

[CLASH]

Do you live in the US if you don't mind me asking? You'll have to try out different things and see what works. I think raw milk is ideal to be honest. Many of my friends/ family who try store bought have issues and who they switch to raw they have no problems. I would really try to source raw. If you tell me where you are (country and state if thats not too much info) I can give some suggestions (depending on where you live) to source the milk. If theres a will theres a way, most of the time :)

Btw I don't disagree with decreasing. I just think balance is way more important. Amount does probably play a part though.

 

[CLASH]

@Mossy
you can experience a "here" reaction when first starting kefir, I had brain fog, and fatigue for a week. Then all of a sudden I felt great, no more bloating from food, no brain fog, no weird pains. I really think it needs to be a grain culture. The industrial probiotics are akin to taking low quality b vitamins instead of eating liver (not a perfect example but the first thatches to mind).

@kayumochi
depending on your flora resistant starch= butyrate producers. what does "wonders" entail specifically?

 

[Mossy]

@Mossy
you can experience a "here" reaction when first starting kefir, I had brain fog, and fatigue for a week. Then all of a sudden I felt great, no more bloating from food, no brain fog, no weird pains. I really think it needs to be a grain culture. The industrial probiotics are akin to taking low quality b vitamins instead of eating liver (not a perfect example but the first thatches to mind).

Thanks, CLASH.

I'll look into the grain culture and try that when I'm feeling better. Now dealing with a bad allergic reaction to something else: weak, dizzy, light-headed, itchy, cold feet, heart palpitations, low temp, and low pulse. I'm hardly taking anything, just niacinamide and hydrolyzed collagen. It could be either one -- I've had trouble with these in the past. Normally, if I take niacinamide with other Bs, I'll be ok. And, at one point, I had written off this particular brand of collagen as causing trouble. I thought I had built my system back up, but obviously not. Maybe the kefir left my system in a vulnerable state; but, just yesterday I felt great. Maybe that was it: I felt so great I had a hard workout -- too hard.

I don't mean to segue the thread with my description, but it is kind of a side road of it -- if the kefir was the catalyst to my state. But, I can't definitely say that.

P.S. Just realized my poor logic -- a hard work out wouldn't give me allergic reactions. But, it could leave my system weak and vulnerable. Too many variables!

 

[CLASH]

@Mossy
I would say its endotoxin. I cannot eat powdered gelatin or hydrolyed gelatin at all.

"However, very few of the collagen or gelatin preparations used as tissue engineering material have been prepared with low levels of endotoxin, which may trigger fever, shock and a fall in blood pressure even in very minute quantities. Therefore we decided to decrease the content of endotoxin in gelatin so that this biomaterial is not harmful to the body "

Development of low endotoxin gelatin for regenerative medicine. - PubMed - NCBI


I think this is the mechanism, I've done alot of research on it to figure it out. The collagen is made by soking hides in a lye solution for I think it was 3 months. These are then either hydrolyzed and spray dried or spray dried. Imagine the bacteria in a NaOH water solution for three months with raw animal tissue. Heating kills bacteria but it doesnt get rid of endotoxin. So the final product winds up with enotoxin. So much so that a filter is required to use the product in medical applications like grafts where it is not being used in massive quantities. I think bone broth also causes issues because it contains aminoglycans that other carbohydrates that are not absorbed and thus fermented. The long lived people of abkhasia (who have a dairy based diet) do not eat broth, they believe it causes sickness or something along those lines. I cant quote it for you because I have a hard copy of the anthropological study of them from the 80s (I read it on my free time on a saturday night....)

Besides I think amino acid ratios are the last thing to worry about. You couldn't possibly restrict methionine to the point you would see any real longevity anyway. Not worth restricting leucine for mTor if you want to enjoy your life and tryptophan is dependent on your metabolic state and requirements. Too much minutiae with the amino acids and we dont know all the interactions. Atleast this is why I gave up collagen .
Plus, @Amazoniac posted some studies showing wierd interactions with collagen and nitrogen balance in rats. Just get your glycine to balance out the methionine and support your fascial network and you should be good, atleast thats how I think about it. You can get a decent amount from meat, dairy isnt too great a source.

 

[Mossy]

@Mossy
I would say its endotoxin. I cannot eat powdered gelatin or hydrolyed gelatin at all.

"However, very few of the collagen or gelatin preparations used as tissue engineering material have been prepared with low levels of endotoxin, which may trigger fever, shock and a fall in blood pressure even in very minute quantities. Therefore we decided to decrease the content of endotoxin in gelatin so that this biomaterial is not harmful to the body "

Development of low endotoxin gelatin for regenerative medicine. - PubMed - NCBI


I think this is the mechanism, I've done alot of research on it to figure it out. The collagen is made by soking hides in a lye solution for I think it was 3 months. These are then either hydrolyzed and spray dried or spray dried. Imagine the bacteria in a NaOH water solution for three months with raw animal tissue. Heating kills bacteria but it doesnt get rid of endotoxin. So the final product winds up with enotoxin. So much so that a filter is required to use the product in medical applications like grafts where it is not being used in massive quantities. I think bone broth also causes issues because it contains aminoglycans that other carbohydrates that are not absorbed and thus fermented. The long lived people of abkhasia (who have a dairy based diet) do not eat broth, they believe it causes sickness or something along those lines. I cant quote it for you because I have a hard copy of the anthropological study of them from the 80s (I read it on my free time on a saturday night....)

Besides I think amino acid ratios are the last thing to worry about. You couldn't possibly restrict methionine to the point you would see any real longevity anyway. Not worth restricting leucine for mTor if you want to enjoy your life and tryptophan is dependent on your metabolic state and requirements. Too much minutiae with the amino acids and we dont know all the interactions. Atleast this is why I gave up collagen .
Plus, @Amazoniac posted some studies showing wierd interactions with collagen and nitrogen balance in rats. Just get your glycine to balance out the methionine and support your fascial network and you should be good, atleast thats how I think about it. You can get a decent amount from meat, dairy isnt too great a source.

That is interesting, about the endotoxin, and makes a lot of sense to me, considering my experiences. So, do you know, does making Jello and processing the dry gelatin do nothing to eliminate/neutralize the endotoxin?

I would've thought bone broth would've been a good alternative, but right now, I'm open to what you're saying -- I can see a possible link to my issues. At the very least, it's worth further evaluating.

So, you get most of your glycine from meat? What do you think about supplementing it?

P.S. Prior to your post and mentioning endotoxin, I had an inclination to have a Peat carrot salad -- pretty telling if my body was craving that.

P.P.S. What do you think of pork rinds?

 

[Travis]

I went down this rabbit hole a bit more last week, and I found-out some interesting stuff.

There is an enzyme in the skin which turns cortisone into cortisol, but it has a counterintuitive name. It's called 11β-hydroxysteroid dehydrogenase type I; and if you look it up, you will probably find that it converts cortisol into cortisone like the name implies—the reverse reaction. This is true, but the enzyme is reversible; it goes both ways, and this depends on the NADH/NAD⁺ ratio. In the skin, this enzyme runs in the nonintuitive direction at a rate about 10:1 that of the reverse. It goes both ways everywhere, but which direction and how much depends on the tissue. This is why this enzyme is so confusing at first.

Cortisol inhibits growth everywhere; this appears to be one of it's main function. No hormone can slow the growth of hair follicles more than cortisol.

There is a strong natural inhibitor of this enzyme called glycyrrhizic acid, and it's found in licorice root. This has been demonstrated to increase the hair's rate of growth in mice. As far as I know there has only been one study on this, but the mechanism is clear: glycyrrhizic acid inhibits the enzyme 11β-hydroxysteroid dehydrogenase preventing the conversion of cortisone into cortisol in the skin. Other drugs which inhibit this enzyme show increased cell growth, proving that cortisol is normally-produced on the skin by this enzyme.

But this is not to be taken internally, as it inhibits a related enzyme called 11β-hydroxysteroid dehydrogenase type II. This exists in the kidney in high amounts and drives the reverse reaction: it turns cortisone into cortisol. Both type II and type I have the same name, but they are different enzymes. Type II is not reversible and goes one way, while type I is found to work in either direction. In some articles, biochemists refer to the 11β-hydroxysteroid dehydrogenase type I as 11β-hydroxysteroid oxidoreductase, or simply 11β-hydroxysteroid reductase. This name is less confusing because now it does what we are actually calling it, reducing cortisol to cortisone. It could also be called 11β-hydroxysteroid hydrogenase.

So instead of writing 11β-hydroxysteroid dehydrogenase type I (oxidoreductase function) every time, I propose writing it as such: 11β-hydroxysteroid de-dehydrogenase. The double negative. I want to start using the term 11β-hydroxysteroid reductase, but it's only been used in seven articles. If someone searchers for it, they probably wont be able to find it. It's unfortunate that it has such a confusing name.

So with the enzyme, the hair follicle cortisol levels could be higher than that plasma levels. And since it converts cortisone into cortisol, this adds another steroidal risk factor for hair loss. The baldness-inducing mineralcorticoid receptor of this skin can be activated by aldosterone and cortisol, with cortisone becoming cortisol through 11β-hydroxysteroid dehydrogenase. Cortisone is proto-cortisol in this framework. This enzyme can easily be blocked by topical glycyrrhizic acid.

And spironilactone is a good inhibitor of the mineralcorticoid receptor itself, if you can source it. Cyclosporine A is another good one, but its a very large molecule and it has a hard time getting into the cell. But when it does, it works like nothing else.

I don't think that any these things should be taken internally.

 

[ivy]

I went down this rabbit hole a bit more last week, and I found-out some interesting stuff.

There is an enzyme in the skin which turns cortisone into cortisol, but it has a counterintuitive name. It's called 11β-hydroxysteroid dehydrogenase type I; and if you look it up, you will probably find that it converts cortisol into cortisone like the name implies—the reverse reaction. This is true, but the enzyme is reversible; it goes both ways, and this depends on the NADH/NAD⁺ ratio. In the skin, this enzyme runs in the nonintuitive direction at a rate about 10:1 that of the reverse. It goes both ways everywhere, but which direction and how much depends on the tissue. This is why this enzyme is so confusing at first.

Cortisol inhibits growth everywhere; this appears to be one of it's main function. No hormone can slow the growth of hair follicles more than cortisol.

There is a strong natural inhibitor of this enzyme called glycyrrhizic acid, and it's found in licorice root. This has been demonstrated to increase the hair's rate of growth in mice. As far as I know there has only been one study on this, but the mechanism is clear: glycyrrhizic acid inhibits the enzyme 11β-hydroxysteroid dehydrogenase preventing the conversion of cortisone into cortisol in the skin. Other drugs which inhibit this enzyme show increased cell growth, proving that cortisol is normally-produced on the skin by this enzyme.

But this is not to be taken internally, as it inhibits a related enzyme called 11β-hydroxysteroid dehydrogenase type II. This exists in the kidney in high amounts and drives the reverse reaction: it turns cortisone into cortisol. Both type II and type I have the same name, but they are different enzymes. Type II is not reversible and goes one way, while type I is found to work in either direction. In some articles, biochemists refer to the 11β-hydroxysteroid dehydrogenase type I as 11β-hydroxysteroid oxidoreductase, or simply 11β-hydroxysteroid reductase. This name is less confusing because now it does what we are actually calling it, reducing cortisol to cortisone. It could also be called 11β-hydroxysteroid hydrogenase.

So instead of writing 11β-hydroxysteroid dehydrogenase type I (oxidoreductase function) every time, I propose writing it as such: 11β-hydroxysteroid de-dehydrogenase. The double negative. I want to start using the term 11β-hydroxysteroid reductase, but it's only been used in seven articles. If someone searchers for it, they probably wont be able to find it. It's unfortunate that it has such a confusing name.

So with the enzyme, the hair follicle cortisol levels could be higher than that plasma levels. And since it converts cortisone into cortisol, this adds another steroidal risk factor for hair loss. The baldness-inducing mineralcorticoid receptor of this skin can be activated by aldosterone and cortisol, with cortisone becoming cortisol through 11β-hydroxysteroid dehydrogenase. Cortisone is proto-cortisol in this framework. This enzyme can easily be blocked by topical glycyrrhizic acid.

And spironilactone is a good inhibitor of the mineralcorticoid receptor itself, if you can source it. Cyclosporine A is another good one, but its a very large molecule and it has a hard time getting into the cell. But when it does, it works like nothing else.

I don't think that any these things should be taken internally.

What a great contribution, @Travis !

How could one make glycyrrhizic acid absorb? Do you think it would it work better combined with Spiro and Cyclo or with just one of those?

 

[Thoushant]

@Travis Sweet thanks for the explanation
Emodin, a natural product, selectively inhibits 11β-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice
Emodin IC50 of 186 and 86 nM, but I recall emodin affecting hair color, giving grey hair.
Coffee inhibits the reactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1: A glucocorticoid connection in the anti-diabetic action of coffee? - ScienceDirect
Coffee extract! 0.7% IC50, 7-10 times more potent at HSD1 than HSD2(EDIT: I have decaf insant.. you know the rest)
Curcumin as a Potent and Selective Inhibitor of 11β-Hydroxysteroid Dehydrogenase 1: Improving Lipid Profiles in High-Fat-Diet-Treated Rats
Curcumin IC50 2.29 and 5.79 µM, respectively, with selectivity against 11β-HSD2 (IC50, 14.56 and 11.92 µM)

 

[Travis]

Glycyrrhizic acid is the glucose ester found in the plant. When this is ingested, this bond is hydrolyzed and you get active glycyrrhetin. This is the active drug. Of course you don't want to take this internally; I just had to point-out that some molecules are naturally attached to glucose and this can confer a different name to the entire molecule.

Glycyrrhetin has a synonym: enoxolone.

Enoxolone | Dehydrogenase inhibitor | Read Reviews & Product Use Citations

It is actually a flavoring agent so it is easy to find.

Glycyrrhetin (enoxolone) looks like it would have excellent coconut oil solubility. This, along with spironolactone, would sound most effective according to the Cortisol/Aldosterone Theory of Hair Loss.

 

[Mossy]

Glycyrrhizic acid is the glucose ester found in the plant. When this is ingested, this bond is hydrolyzed and you get active glycyrrhetin. This is the active drug. Of course you don't want to take this internally; I just had to point-out that some molecules are naturally attached to glucose and this can confer a different name to the entire molecule.

Glycyrrhetin has a synonym: enoxolone.

Enoxolone | Dehydrogenase inhibitor | Read Reviews & Product Use Citations

It is actually a flavoring agent so it is easy to find.

Glycyrrhetin (enoxolone) looks like it would have excellent coconut oil solubility. This, along with spironolactone, would sound most effective according to the Cortisol/Aldosterone Theory of Hair Loss.

Thanks for the interesting find.

Would it be as simple as mixing licorice root extract with coconut oil and topically applying it?

P.S. I just noticed your distinction of Glycyrrhetin from Glycyrrhizic acid; is Glycyrrhetin preferred, or just an alternative to Glycyrrhizic acid?

 

[inmyhead]

Check out these pics from histogen (upcoming hair loss treatment ). It seems to me that blood pressure was decreased ( skin less red after a year ) which resulted in more hairs. Any ideas?

 

[CLASH]

@Travis
Thanks for your posts, I find your understanding of discrete mechanism greatly aids my global perspective. So it seems the goal here isnt to use topical drugs but to lower systemic cortisol upregulation which is caused by adrenal upregulation. This explains why androgenetic alopecia in a lot of men looks alot like cushings syndrome. The drugs are cool to look at for the mechanism but I dont think I would ever take any of them even topically. They seem more quick fixes to a systemic issue. But the mechanism sheds light on the systemic process in the same way ketoconazole, finasteride, stemoxydine and minoxidil do. Your info goes to support the idea that hairloss is adrenal upregulation, thyroid downregulation similar to W.D Dencklas experiments. I also think it is fibrosis of the galea driving hypoxia which drives DHT upregulation based on an oxygen gradient with the aromatas and 5AR enzymes* and DHT increase tendonocyte proliferation** (the galea is basically a tendon) hence the pattern of hairloss and I think fibrosis stems from the gut via TLR4 from gram neg bacteria. It seems that gut bacteria upregulate the HPA axis as well depending on species present. So fibrosis + adrenal upregulation (increased cortisol, aldosterone, DHEA which converts to DHT at the skin especially in hypoxia which is causes by fibrosis) causes hairloss (and hirsutism and stretch marks and weight gain hahah i.e. Subclinical cushings syndrome). Its all driven by bacteria in the gut in my opinion.

*Hair Loss Help Forums - The real reason why balding scalps have more DHT
**Effect of dihydrotestosterone on cultured human tenocytes from intact supraspinatus tendon. - PubMed - NCBI

@inmyhead
Looks like less inflammation not less blood pressure. Inflammation causes fibrosis.

 

[CLASH]

"Studies conduced on GF animals have also demonstrated that microbiota influences stress reactivity and anxiety-like behavior, and regulates the set point for HPA activity. These animals generally show a decreased anxiety [23,24,31-33] and an increased stress response with augmented levels of ACTH and cortisol [31,34]. Microbial colonization of the gut leads to a normalization of the axis in an age-dependent manner, with reversibility of the exaggerated stress response being observed after GF colonization "

The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

 

[Travis]

Interesting. I'll have to look into how bacteria raise mineralcoticoids.

Your info goes to support the idea that hairloss is adrenal upregulation, thyroid downregulation similar to W.D Dencklas experiments.

Yeah, but it could also be partly the prevalence and 11β-hydroxysteroid dehydrogenase and which direction the reaction is going. With the NADH cofactor, it can only make cortisol from cortisone—it needs NAD⁺ to run the reverse reaction. Since this enzyme is freely reversible, the redox balance is actually what's causing this. This ties-in with those obscure gas theories, as sulfur containing blood gasses can theoretically affect redox balance.

Simply considering the adrenals themselves does nothing to explain why hypercorticolism doesn't cause hair loss on the entire head. Cortisol and aldosterone are a huge part of the puzzle, but I think the selectivity towards the scalp can only be explained through a combination with one of the following:

• Decreased blood flow: The crown of the head gets less blood; this seems to be the place where the arteries terminate and become veins. Hats can decrease blood flow even further. The fact that minoxidil works lends support to this idea, but the fact that it doesn't work that well implies other factors.
• Gasses: Blood-born sulfur gases could effect the NADH/NAD⁺ ratio by stealing electrons. Blood-born gasses concentrate in the finer terminal capillaries, a fact which has been used to explain the role of alkyl nitrites in Kaposi's Sarcoma.
• Lack of Sunlight: The skin has a vitamin D receptor. Besides mineralcorticoid receptor-upregulated mice being totally bald, mice genetically-engineered to lack the vitamin D receptor are likewise (though not as extreme). These are the two receptors which influence hair growth in the mice the most.

It would be nice if we could find that one thing to pin it on, but I think it has to be a combination of at least two of these things—with high cortisol, cortisol, and aldosterone being the main factor. But perhaps just aldosterone or cortisol coupled with the inherently-reduced blood flow of the scalp is enough to explain all of it?

Perhaps I will look at a few more DHT studies. This could be a symptom of the same NADH/NAD⁺ ratio—as DHT is simply testosterone with two extra hydrogens. You would think that the enzyme 5α-reductase is NADH-dependent as well. If the DHT/T ratio correlates with the F/E ratio, then redox balance could be a factor.

 

[CLASH]

@Travis
Thanks for your response. I don't think my first reply was too clear (I really dislike having to write my thought processes down haha). I agree with you, I think its a combination of decreased blood flow, adrenal up regulation and thyroid down regulation. Is the NAD+ to NADH ratio not dependent on thyroid status and oxidative respiration indicating that the enzyme is unregulated in a situation of decreased thyroid function/ oxidative metabolism in the body?

In hypoxia, which at the galea is caused by fibrosis as the galea is a tendon essentially, testosterone (via DHEA from adrenal up regulation) is converted to DHT due to the gradient caused by hypoxia from my understanding. DHT causes increased de-differentiation and proliferation of collagen producing cells in tendons. With an inflammatory stimulus like endotoxin with TLR4 which directly causes fibrosis and an up regulation in collagen producing cells via the mechanism I think there is a recipe for excessive fibrosis. This fibrosis enhances hypoxia further up regulating DHT which increases collagen producing cells. Its a viscous cycle that fibroses the whole galea. In conjunction with the disturbed hair cycles from thyroid down regulation, cortisol and adrenal up regulations there is a recipe for baldness. Once started the cycle is a bit self perpetuating at the scalp with hypoxia and DHT up regulation and DHT's effect on tendons. I think all of this is coming from the gut environment via HPA axis regulation and gram negative bacterial activation of TLR4. I think the explosion of bald men in this time period is because of formula feeding, c-sections usage and excessive antibiotic usage with high grain and starch diets. Vit D may be deficient not because of lack of sunlight (I was severely vit D deficient but i lived in miami and tanned in the sun at around 2 everyday atleast 30 min) but because of ups regulation of immune system function due to the gut, decreased calcium intake and increased TLR4 activation which if I recall correctly is a antagonized by Vit D. So I think the usage of Vit D gets skyrocketed creating an inadequate intake. Also, if endotoxin is high then cholesterol may move towards protection against endotoxin as opposed to be utilized for Vit D production. These Vit D statements are my hypothesis, not directly based on studies so do what you will with it haha.


"Hypoxia and the androgen receptor (AR) play important roles in the development and progression of prostate cancer. In this study, the combined effects of dihydrotestosterone (DHT) and hypoxia on AR-mediated transactivation were investigated. Hypoxia alone did not induce a detectable ARE-mediated response in the absence of DHT. DHT-induced AR transcriptional activity was dramatically increased by hypoxia or ectopic expression of HIF-1?, as determined by introducing ARE-responsive reporter plasmids into LNCaP prostate cancer cells. The secretion of VEGF was enhanced by the combination of hypoxia and DHT as compared to each treatment alone. These effects were not due to increased expression of the AR or HIF-1? as a result of hypoxia and DHT treatment. These results provide evidence that hypoxia may stimulate as yet unknown factors, which further stimulate AR signal transduction pathways."
Hypoxia enhances ligand-occupied androgen receptor activity. - PubMed - NCBI




"Estradiol synthesis, however, should be stoichiometrically decreased in a hypoxic environment. Three moles of oxygen are required to convert one mole of testosterone to one mole of estradiol. In a hypoxic region, the ratio of DHT to estradiol (DHT/estradiol) should be increased. Sawaya has shown that men with MPB have nearly a two fold increase in 5-?-reductase activity of hair follicles in balding frontal scalp, than in hair bearing occipital scalp. However, hair follicles in the frontal region had nearly three times less aromatase activity than hair follicles in the occipital region in men with MPB. Sawaya, M. E. Ann. N.Y. Acad. Sci. 1991:642:376-383. Finding that the DHT/estradiol ratio is elevated in bald scalp as compared to hair bearing scalp in MPB subjects, is consistent with what would be expected in a hypoxic tissue environment. [00065]


If one were to develop a gradual local tissue hypoxia of the frontal scalp, the DHT/estradiol ratio might increase locally to a critical level at which point receptor hormone interactions might result in down regulation or inhibition of hair follicle cell function. In turn, this might result in the ultimate conversion of terminal hair to villus hair, and the development of MPB. This inhibition may take the form of altering the number of hair follicle cells in anagen phase as compared to telogen phase."
US 6299893 B1 - Method To Reduce Hair Loss And Stimulate Hair Regrowth The Lens



"DHT-treated tenocytes showed an increased proliferation rate at DHT concentration higher than 10(-8) M. Differences in cell numbers between control and DHT-treated cells were statistically significant (P < 0.05) after 48 and 72 h of treatment with DHT concentrations of 10(-8) and 10(-7) M. The tenocytes treated with DHT (10(-8) and 10(-7) M) became more flattened and polygonal compared to control cells that maintained their fibroblast-like appearance during the experiment at each observation time. In conclusion, in vitro, progressive increasing concentration of DHT at doses greater than 10(-8) M had direct effects on male human tenocytes, increasing cell number after 48 and 72 h of treatment, and leading to a dedifferentiated phenotype after 48 h of treatment"
Effect of dihydrotestosterone on cultured human tenocytes from intact supraspinatus tendon. - PubMed - NCBI


btw theres a new drug stemoxydine that works in a similar fashion in regards to the concept of blood flow as minoxidil. Its a P4H inhibitor that signals hypoxia and blocks collagen production. The signaling of HIFa (I think this is what it is) leads to increased erythropoiesis and angiogenesis, essentially increasing oxygenation. I have a post about it in this thread. L'Oreal created it I think and is marketing it.

so we have:
minoxidil: blood flow
stemoxydine: blood flow
glychyrrizic acid: anti-glucocorticoid of sorts at scalp
ketoconazole: anti-glucocorticoid
spironolactone: anti-glucocorticoid/ anti-androgenic effects
finasteride: anti- 5ar androgen
dutasteride: anti- 5ar androgen
cyclosporine: immunosuppressant

with these drugs all being used for androgenic alopecia I think a nice theory is created (the one we discussed) in conjunction with knowing that scalp oxygenation is decreased and the galea is fibrosed.

 

[Thoushant]

@CLASH
Picture is from Bazzano 1986, Doesn't mention amount in this picture, but humans used topical 0.025% retinoic acid with 5% minoxidil. Old people in the study had regrowth solely from RA, but took like 18 months