Minoxidil side effects (wrinkles, dark circles) and alternative

[benjt]

Sup everyone,

my situation in short: Recent college grad, male pattern baldness startet manifesting at 18. Now 23, startet treatment exactly 1 year ago.
status: NW3 (yeah, it's going quick)
regimen: 5% minoxidil twice daily, dropped three weeks ago

Symptoms: Massive face wrinkles, massive dark circles around my eyes.

When the minoxidil sides first kicked in, I was really not sure what was going on. My diet and lifestyle are very healthy (non-smoker, usually lots of sleep, moderate alcohol consumption, workout twice a week). Initally, I only started getting these dark eye rings approx 5 months into minoxidil treatment. Did not suspect minoxidil being the reason, as such circles can be caused by a lot of things. Approx two months later (i.e., 7 months into minoxidil), I first noticed huge wrinkles forming around my eyes. Note: I am not only talking about color here. The wrinkles I got below and around my eyes are extreme by now. Forehead wrinkles also showed up, and the skin right below my eyes got porous and quite saggy.
Then I startet to wonder. Did my research online, and many people complain about these sides. My derm basically made fun of me for being "paranoid" and "imagining things", telling me I should get a good night's sleep. When explaining to her that I sleep 9 hours every night, she told me straight in the face that I'm lying. Foto lab guys documented my status, and even they told me they had never seen such bad dark circles around eyes before.
Dropped minoxidil altogether three weeks go. Guess what? Dark circles around my eyes slowly going away, as are the wrinkles. Very slowly, but it's visible.
I am 23. Three weeks ago, I was looking like a 30 year old drug addict. Right now it's still pretty bad, but at least people are no longer openly commenting on it. One month ago, I was told by my supervisor at work to call in sick and go get some sleep. I had slept 10 hours the night before. That should give you an idea about my facial looks right now.

Why am I posting this?
The primary reason is that most people on these forums and on Hair Loss Help (where I'll also post this) are not taken serious. These issues are played down and people with those sides are called paranoid or, to my surprise, even attacked. Often, "sceptical" (or downright aggressive, for whatever reason) posters say "you're imagining things, it's just natural aging, deal with it, don't spread lies".
With this post I want to confirm that this is not natural aging. While many posters are in their late 20s, I am in my early 20s and started treatment even earlier. My whole family is wrinkle-free till a very high age. Wrinkle count around my eyes is 5 or 6 very deep ones around each eye, and the color of the circles is still pretty bad. As mentioned before, dropping minoxidil immeditaley but slowly improved the situation.

So, minoxidil users out there: No, you're not just imagining things. One year of minoxidil 5% twice daily gave me massive black circles around my eyes that hadn't been there before, gave me wrinkles which hadn't been there before, made my skin look saggy, and made the single pores show real bad. Given my age and the improvement after dropping minoxidil, these side effects are not natural aging related.

Anything else noteworthy?
Obviously (or not?), not everybody is affected by these side effects. The most relevant part to be mentioned here is that even though I did not overdose, I had other side effects that are officially listed, i.e., brain fog/dizziness. This hints at larger amounts of minoxidil being absorbed systemically. On the other hand, the side effects only showed around my face, hinting at the minoxidil not being distributed system-wide. Either way, if the minoxidil did hit the blood stream (as indicated by the dizziness and inability to concentrate right after application), who knows what other ways it might travel?

What can I do now? I don't want to take minoxidil nor finasteride.
I started using Adenogen a couple of days ago. Right now I cannot say if it works. However, there are some indications:
- Recent research turned up pretty good evidence that the way minoxidil works is likely through up-regulating adenosine in the scalp. Please recall that it is not understood why or how minoxidil works. However, adenosine supply to scalp seems to be the best bet. (cp. https://www.ncbi.nlm.nih.gov/pubmed/11886528 )
- Overdosing on Adenogen gave me minoxidil-like side effects (i.e., in this case only dizziness/brain fog), though to a much lower extent. Adenogen works as a vasodilator, as does minoxidil. The side effects on skin did not show.
- Placebo-controlled (!) studies have shown improvements in hair thickness, which is also pretty much the only thing minoxidil does
The great thing about adenosine, adenogen's active ingredient, is its half life. In the human blood, it is metabolised (or collapses) within 10 seconds. This greatly reduces side effects, as minoxidil stays in your blood for more than 12 hours and does its negative workings. While there has been some criticism regarding adenosine's half life: This applies only to blood. In the scalp, its half time is much higher. Placebo-controlled studies have shown that it works, though there are no comparisons to minoxidil regarding effectiveness.

If you really want to experiment, you can use prostaglandin D2 inhibitors, through you will probably need a chemistry or med student for that. Also, it might become dangerous. However, PGD2 seems to be the substance effectively harming the folicles, NOT DHT. (cp http://stm.sciencemag.org/content/4/126/126ra34 ) I will not do this, but it might be an option for others.


That's it, folks. Long story short:
minoxidil does ruin your skin. I am 23 and it did that to me; it is not natural aging. My lifestyle is very healthy and I do not take any other meds.
Safest bet if you don't want minoxidil or finasteride is Adenogen. Recent research has shown that minoxidil in fact works through increasing adenosine levels in cells. I will report back with adenogen results. Meanwhile, I suggest people with minoxidil sides also use adenogen so we have a better understanding of how effective it is.

 

[benjt]

Sup guys,

just wanted to give you a little heads up on my recent developments and research. I both did my own "experiments" (i.e., trying adenosine and minoxidil in vayring dosage) and some major research. I get access to almost all medical research worldwide (full papers, not only abstracts) via my employer. While I did not study chemistry, biology, medicine or the like, due to my work (research assistant for biological process simulation) I have enough experience to read and understand biological and medical studies and research papers.
Highlights of this post:

1. An actually effective way to regrow long lost hair. On the downside, it might be quite risky.
   
2. A theory how minoxidil works in detail by upregulating adenosine. In other words, WHY it works.
   
3. How well adenosine/Adenogen works compared to minoxidil
   
4. How long it takes for minoxidil side effects to vanish.

Anyway, here goes:

Adenosine/Adenogen results

Adenosine does work, though not as well as 5% Minoxidil.
Dosage is seriously limited by "funny" side effects. Applying more than 10 drops in total to the scalp makes you so tired that you almost fall asleep on the spot. And no, there is no way around it. Adenosine is a transmitter triggering tiredness in the brain (or rather, blocking "waking transmitters"). Too much absorption - et voila, your body falls asleep. Increasing to 12 drops, by the way, makes you wanna puke. This is not only my own experience, but a well known side effect. So, unfortunately you HAVE to keep dosage low. Up until 8 drops of Adenogen I experienced no side effects; after that it slowly builds up towards the sides you got from 10 - 12 drops.
How can I tell it works? Ever since I dropped minoxidil, the tiny baby fluff hair that I had gotten in my temples from minoxidil disappeared. It started appearing again after starting to apply adenosine/Adenogen. Also, in my last post I mentioned a study that also showed its effectiveness. Given tha minoxidil just works BY allowing adenosine inside cells, this makes quite a lot of sense.
So yes, it does work, but not as well as minoxidil. My theory why it does not work as well as minoxidil is as follows: minoxidil, as has been shown, does work by allowing adenosine to enter cells. Adenosine is the actual vasodilatory, i.e., the actual active ingredient that prevents hairloss. Minoxidil is only what allows adenosine to do its workings by opening the adenosine channel of cells (or its equivalent, if no single channel exists). However, the human body already has sufficient amounts of adenosine without using Adenogen which are, by means of minoxidil, allowed to enter cells, which without minoxidil would not have been the case. Thus, the ALREADY AVAILABLE adenosine is admitted into the follicle cells by minoxidil.
Only externally applying adenosine to the scalp increases adenosine levels, but not directly INSIDE follicle cells. However, only a fraction of this new surplus is allowed to enter follicle cells, as there is no upregulation of this channel (which would be performed by minoxidil). Thus, on its own, without upregulating adenosine supply to cells, adenosine by itself will not have such a drastic effect; only parts of it will enter cells. minoxidil, on the other hand, makes the adenosine present in the human body available to cells.
In theory, this would also mean that combining minoxidil and adenosine/Adenogen should initiate MASSIVE HAIR REGROWTH. HOWEVER, with a very high probability this is not healthy or might be even downright dangerous. minoxidil can travel far inside the body, as can adenosine, and so the combined effects would spread systemwide.
If anyone is willing to try this, go ahead. As I said: MASSIVE HAIR REGROWTH. minoxidil will open cells for adenosine, and then you flood them with high amounts of adenosine, the actual cause of hair regrowth. This might even REVIVE LONG MINIATURIZED FOLLICLES. But it also might yield very high risks of something going wrong. If you want to try this, by no means apply more than 8 DROPS of Adenogen to your scalp (or into a minoxidil mixture, in case you want to mix minoxidil and Adenogen). Better start of with 6 drops.
Advantages of adenosine/adenogen: as long as you do not overdose, it is 100% side effect free, as a certain level is persistent in the body at all times anyway.
Disadvantage: Not as effective as minoxidil. If I had to give some numbers, I'd say it is 40% less effective than minoxidil.


Why minoxidil causes wrinkling and dark eyes

As some people on these forums already found out, minoxidil inhibits collagen synthesis by the body, as also proven by scientific studies. Lower layers of the skin are to a large extent comprised of collagen, providing the bulk part of the "elastic underground". This explains both wrinkles, as the underlying elastic structure is damaged, as well as dark circles around the eyes, since multiple layers in the skin (as far as I can tell, two or three) are basically completely gone. Thus, the skin itself gets thinner.
Furthermore, not only does it inhibit the activity of collagen synthesis proteins, it is also a free radical, thus damaging pretty much every type of cell. This might or might not play an additional role. In contrast, adenosine/Adenogen is not a free radical but actually a substance produced by your body. It is also not known to inhibit collagen synthesis, though this has never been researched. This might explain why adenosine/Adenogen probably has NO side effects like minoxidil does. But, on the downside, it is not as effective, and you cannot apply more than ~8 drops without getting so tired that you immediately fall asleep.
The vasodilatory function of minoxidil (or rather, of adenosine) leads to the circles below your eyes becoming darker as well.


How long it takes for minoxidil side effects to disappear

Collagen genesis/synthesis is dependent on a) age and b) the type of collagen. There are at least 28 types of collagen. In the skin, there are more than ten different types of collagen. As far as I can tell, type 1, 2 and VII are most important for skin elasticity and wrinkling effects. To completely synthesize full layers, the body takes between 6 months and 1 year, depending on your age.
The dark circles around your eyes are to at least 50% a cause of vasodilatory effects. minoxidil will be outside your system after three days. (yes, 3 days, not 12 hours - 12 hours is only its half life). Thus, on the fourth day after dropping minoxidil, the circles should improve significantly. However, as the other half of the effect is caused by collagen depletion, for these circles to go back to normal you have to wait between 6 months and 1 year.
So, now you know how long you need to stay off minoxidil until side effects vanish. Hope that's useful for some.


Own theory how minoxidil/adenosine works

Adenosine (active ingredient of Adenogen) is a natural vasodilator. Minoxidil upregulates cell supply with adenosine, causing them to dilate and flush their contents. As a side effect, they also retain water, leading to a puffy face. Anyway: By flushing substances that are not solid part of the cell itself, DHT is flushed out and then accumulation is prevented. Without harmful DHT permanently present in follicles, they are no longer constantly damaged. Hence, the mechanism of adenosine (and thus, minoxidil) might be that it triggers a DHT flush. Note, however, that DHT is still floating freely around and will again accumulate once cells go out of flush mode, i.e., when minoxidil/adenosine is no longer present.


Copper peptides

Some users claim that copper peptides stimulate hair regrowth. There is still a lack of hard evidence for this, and there are only empirical studies (of rather low quality) supporting this assumption. However, as those following the science behing RepliCel might know, their approach is to create growth stimulants that are usually present in wound healing which, surprisingly, also initiate hair regrowth (and actually even FOLLICLE GENERATION). Copper peptide is a wound healing stimulant. I guess you get where this is going. Copper peptides might in fact trigger the same mechanisms as the RepliCel product. There is also research supporting this theory: Uno H., Kurata S.: "Chemical agents and peptides affect hair growth", in Journal of Investigative Dermatology, 1993.


Side-effect free minoxidil dosage: Future tests

As I have found out that Adenogen/adenosine is not as effective as Minoxidil, I started trying to find a dosage of Minoxidil that does not have these terrible side effects on your skin. I have now been on a regimen of applying 0.75 ml of 5% minoxidil once a day. This is still too much, i.e., side effects ae on the rise again. Surprisingly though the fluffy hair and thickening of existing hair did not cease or even decrease. This hints at 0.75 ml of 5% minoxidil once per day are still a sifficient dosage FOR ME. As other people do not experience side effects at all at much higher dosage, this hints at people experiencing those side effects just absorbing much more minoxidil. This in turn means that all those only NEED A MUCH LOWER DOSAGE to still achieve maximum effects. In other words: For people experiencing side effects on the skin, 0.5 ml of 5% minoxidil once a day probably is just as effective as 1 ml of 5% minoxidil twice a day, due to much higher absorption.
My next step is to reduce my regimen to 0.5 ml of 5% minoxidil and observe for a couple of weeks. If this still triggers those bad side effects, I will switch either to 2% minoxidil or to Adenogen again and compare. As significant amounts of minoxidil are still in your system 48 hours after application (to be precise, 6.25%) another idea would be to apply minoxidil only every second day - minoxidil levels during the first 36 hours after application are still quite high.


That's it. I know this is a lot of text. I'm trying to figure out the whole hair loss process and treatment by myself and think I am fairly successful with that, as my theories are backed by research and make sense. Hope some people will profit from this. Maybe someone will even try mixing or combining minoxidil and Adenogen (at your own risk!) to regrow long lost follicles. Also, some reports by other Adenogen users would be nice to have a more reliable understanding.
I will keep you updated on dosage and how effective it is, and whether side effects keep showing.

Furthermore, any feedback or additions to my ideas would be much appreciated.

 

[benjt]

And another update...

[Adenosine] is also not known to inhibit collagen synthesis, though this has never been researched. This might explain why adenosine/Adenogen probably has NO side effects like minoxidil does.

I was wrong about that. Adenosine is not only the one substance that lets you keep your hair, but also the one that inhibits collagen synthesis. It is not the minoxidil itself, but again the effect is only caused by minoxidil upregulating adenosine.

Adenosine inhibiting collagen synthesis has been shown for non-dermal cells, but it is highly probable that it will show the same behavior with the dermis.
Sources:
PubMed: Adenosine inhibits collagen and total protein synthesis in vascular smooth muscle cells.
PubMed: Adenosine inhibits collagen and protein synthesis in cardiac fibroblasts

So yeah. Both minoxidil/Rogaine and Adenogen/adenosine will make your skin age faster.


Furthermore, I think I found the reason for small dosages like 0.75 ml once a day of 5% minoxidil being still effective with me and also increasing my puffy and dark circles around the eyes again. The reason is the collagen depletion that already happened. Due to the lack of collagen, the skin itself is much thinner. As a consequence, absorption of exogenous substances is much higher as compared to skin with collagen in tact.
Source: European Union: Dermal absorption guidance document

This in turn means that I need to let my collagen recover before I can reinitiate any minoxidil or Adenogen/adenosine regimen, i.e., if this is correct I have to wait one whole year before I can continue application. Sure sucks.


For documentation purposes, I also uploaded a photo. Note that on that photo, I am slightly smiling, and that I am only 23 years of age. Also pay attention to the "cave" which formed around the eye and the color right beneath. Keep also in mind that right now I am looking much better than 4 and a half weeks ago. There are also some wrinkles right on my nose. Nothing of that was there one year ago. Though not to be seen on the photo, the wrinkles on my forehead increased as well. And yeah, some of the wrinkles on that photo are, as of now, permanent, i.e., even persistent when I do not smile.

https://imageshack.us/a/img855/4417/stk6.jpg

Believe me, it sucks when on every photo with friends where everyones smiling you look like a wrinkly geezer.

 

[medilook]

I have the wrinkles to when I cringe close my eyes but I had that before using minoxidil. Do u have a full face shot of u smiling naturally instead really hard? Everyone has those lines when they laugh hard

 

[benjt]

I am not even laughing hard in that pic, just slightly. I will not upload a full face shot, though. I have my own photos for comparison of myself from one year ago, and even when bursting out in laughter, none of those lines were to be seen.

You can also check the last two posts before mine here: http://www.hairlosstalk.com/interac...gen-synthesis-reduction?p=1131796#post1131796

I am certainly not the only guy to witness those side effects. I'll do a compilation of reports on that later.



And the next update. I did some more research throughout the whole weekend, and finally got a complete understanding of how Minoxidil works. Furthermore, I might have found out what causes the follicle miniaturization. What makes it highly likely to be true, though, is that both theories support each other. It furthermore even explains why blood flow in balded areas is significantly decreased.

How Androgenetic Alopecia/male pattern baldness is caused
Androgenetic Alopecia/male pattern baldness seems to be 100% an immune reaction. As everybody knows, follicle miniaturization is preceded by inflammation signs in the same area. Now here comes the interesting part: Permanent inflammation in dermal cells leads to fibrosis. In fact, it has been shown that the skin in bald areas of men with Androgenetic Alopecia/male pattern baldness is thicker than in the not yet bald areas (source: http://www.omicsonline.org/215.../2155-9554-3-138.pdf). Do the math: fibrosis occurs in the dermis due to inflammation, bald areas have thicker dermis. Obviously, it is fibrosis occuring there. How does fibrosis work? By accumulation of massive amounts of collagen. The collagen tissue all around the follicles becomes so thick that it basically squeezes the follicles until they are so small they can no longer work. There is even some speculation that, following fibrosis around the follicle, the lowest part of the follicle is basically completely clogged: The follicle still produces hair, but because of the fibrotic tissue around it, it cannot break through and is stuck in the follicle. Finally, the hair that is stuck in the follicle (but is still growing) and the fibrotic collagen tissue around the follicle squeeze the follicle to a degree where it can no longer fullfill its purpose. Additionally, even if it could, the hair would no longer be able to break through the fibrotic tissue composed of collagen anyway.

Source: "Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: implications for collagen cross-linking and treatment of fibrosis."


The whole theory of fibrosis causing baldness has, by the way, been backed by studies that showed the same happening to women WHO HAD FIBROSIS IN THEIR SCALP. These women, though, did not have any DHT susceptibility. Their fibrosis was a result of chemotherapy.
Source: CICATRICIAL ALOPECIA AFTER CHEMOTHERAPY/RADIOTHERAPY, by Misciali C, Tosti A, Vincenzi C, Iorizzo M, Fanti PA Department of Dermatology, University of Bologna, Italy.

As you can see, fibrosis is a known cause of baldness. With people suffering from Androgenetic Alopecia/male pattern baldness, inflammation reactions occur and later on, the scalp skin is much thicker. This hints at fibrosis taking place as a result of inflammation, as is the usual case with inflammatory reactions in the dermis.

I don't know if this has been a well established fact around here or if anybody's surprised by that, but at least to me it's new and it does make sense. Also, given that Minoxidil is known to inhibit synthesis of healthy collagen, as collagen is the material fibriotic tissue is made of.

Further reading on this theory: http://www.hairloss-reversible...html?1173668946



How Minoxidil works
Collagen depletion is not a side effect, but actually the effect of Minoxidil (or rather, of adenosine upregulation caused by Minoxidil). Minoxidil (or rather, adenosine) keeps the inflammated areas from generating collagen. As a consequence, no new thickened tissue is formed that can press and miniaturize the follicles.
My theory why adenosine does that: It dilates cells, thus prevents them from accumulating any hard substances (such as collagen parts).

To be more precise: When minoxidil, and throug it adenosine, is present, collagen is still produced, but it is much weaker. (Source: "Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: implications for collagen cross-linking and treatment of fibrosis.", Zuurmond AM; van der Slot-Verhoeven AJ; van Dura EA; De Groot J; Bank RA; Matrix Biol. 2005; 24(4):261-70 (ISSN: 0945-053X))).

The side effects many people experience are actually how Minoxidil protects our follicles from miniaturizing. The only problem with people experiencing side effects is that the minoxidil does not only work locally.
If you want to continue using minoxidil, find out what makes it spread from your scalp to your face, or potentially even system wide.

---

The thing about these two findings I made is: They are sound. The theory on how Androgenetic Alopecia causes baldness by thickening fibriotic collagen tissue makes sense. It also explains why Minoxidil, upregulating adenosine, which is known to inhibit collagen and thus fibrosis works. The theory of follicles being squeezed and miniaturized by sourrounding fibriotic tissue (made of collagen) is also backed by the fact that skin in bald areas is thicker than in not yet bald areas.

To me, all of this makes perfectly sense.

Furthermore, all of this also explains why zinc works (and actually has to work!) for treating Androgenetic Alopecia/male pattern baldness: It is anti-inflammatory. I hope all of you can see the soundness in those theories.

---

The next questions that need to be answered are:
a) What causes the auto-immune reactions in the scalp?
b) How can they be treated?
c) How can they be stopped?
d) How can we counteract fibrosis?


My own theories on these matters:

a) No idea. It might actually be that it is not the DHT causing the immune reaction, as many studies have shown that DHT values of people with Androgenetic Alopecia/MBP and of people without Androgenetic Alopecia/MBP do not differ very much. What has been shown, however, with 100% certainty is that SHBG is much lower in men with Androgenetic Alopecia/MBP. Lowered SHBG just causes DHT to be higher - which is why often DHT is higher with Androgenetic Alopecia affected men. This does not mean, however, that DHT is the cuplrit causing the local inflammation in the scalp that leads to fibrosis that leads to collagen tissue being generated that squeezes follicles which in turn are miniaturized by all the fibrotic tissue around them.
What has to be found out, through, is
a.1) What potential causes there are for SHBG to be very low. This might lead us to the root of the problem of Androgenetic Alopecia/male pattern baldness.
a.2) What other effects low SHBG has. This might lead us to the substance which causes the inflammation of the scalp. It might be DHT, but it might also be something completely different.

Expanding on why DHT might wrongfully be thought to be the culprit: finasteride/dutasteride work by inhibiting 5a reductase. Its primary function is metabolising T to DHT. However, lower DHT has a number of side effects, including higher SHBG (as less SHBG is bound by DHT). So, ultimately, one of the side effects of lower DHT (such as higher SHBG) might actually be what makes Androgenetic Alopecia/MBP stop, not the lower DHT itself. This hints at some other hormone that can bind to SHBG being the culprit (but does not deny the possibility that it can in fact be DHT - this is supported by the fact that Androgenetic Alopecia is much less frequent in women). Anybody care to compile a list of hormones that can bind to SHBG?

b) Any local treatment that reduces immune reactions and/or inflammation. Any strong wound healing creme with high zinc concentration will help fight Androgenetic Alopecia/MBP, completely side effect free. Anything else that fights inflammatory reactions will also help. Anybody got some ideas what else could help? Furthermore, local immune suppressiva will also help reduce the speed of Androgenetic Alopecia/MBP progress. Any hints on local immune suppressiva?
I will start using zinc shampoo (Head & Shoulders has some) and also using highly concentrated zinc wound healing creme and report back.

c) The trickiest question and the holy grail. Finding this out means finding the cure for Androgenetic Alopecia/male pattern baldness. Essentially, we are dealing with some immune reaction that should not occur. Typically, this is known as allergies. Funnily enough, all friends of mine who suffer from Androgenetic Alopecia/MBP also suffer from pollen and/or fruit and/or nut allergies. People with a lot of allergies are often also more allergies they do not know of. Furthermore, allergies are a sign of an overreactive immune system. This is basically exactly what we are facing here.

Alternatively, instead of trying to control the immune system, we can also try to find out what exact substance/hormone/condition causes the immune reaction and try to reduce/elliminate that. This is not trivial, obviously.
Substances whose blood concentration is linked to Androgenetic Alopecia/MBP:

• T3
  T4
  TSH
  Cortisol
  Progesterone
  Prostaglandin D2
  SHBG
  Insuline
  Insuline-like growth factors
  Ethanol and methanol (!! - the theory is that ethanol and methanol have a negative effect on a) the liver where many of the above mentioned substances are produced, and b) on the immune system - in fact, it has been shown that very frequent consumption of high amounts of alcohol slows down MBP/Androgenetic Alopecia)

The problem with those substances is that they are linked. T3, T4 and TSH regulate SHBG. Insuline also regulates SHBG. The next problem is, that the chain of actions is not always clear (at least not to me). E.g., it could be that T3/T4/TSH regulate insuline and insuline-like growth factors which in turn regulates SBHG. Then we would need to find out how to correct T3/T4/TSH.
It could also be the other way around, with Insuline -> T3/T4/TSH -> SBHG.

d) Kerastase might be helpful here, as it was developed to untighten collagen sheaths. Product names are Aminexil, Capiplus and Densitive. All of them should help in one form or the other; Capiplus contains saw palmetto, densitive helps break up fibriotic collagen. Anybody knows something about these products?


As you can see, the whole matter is very complex. However, by understanding how Androgenetic Alopecia/male pattern baldness works, I think we got a whole step further.

Again, any input would be much appreciated. Also, any anti inflammatory and anti fibrosis products you know of, please list them here.



Edit: All of this of course also means that Androgenetic Alopecia/MBP is pretty much irreversible. You can plant new follicles into your scalp all you want - if the scalp skin is too thick for new hair to penetrate, you will not profit from newly grown follicles at all. Unless somebody knows a way to remove fibriotic tissue and replace it with new, soft tissue, newly grown follicles will not help at all.
Also, it would completely suffice then to "unclog" the old follicles and transform the fibriotic scalp skin to "new skin" - if that was so easy... but actually, this also means that the "scarring" approach that destroys old tissue might be promising, or triggers growth of completely new, unfibriotic tissue from the lower dermal layers. I have no idea if this is possible, though.

- - - Updated - - -

Update: The scalp fibrosis might be reversed using a hormone called relaxin. A biotech company has also found a different approach, where they take fibroblasts (the collagen producing cells) from non-bald areas and insert them multiplied into bald areas, so they can produce new non-fibriotic tissue. Source: http://www.news-medical.net/news/2005/05/03/9736.aspx A funny side effect: These areas also started producing hair again!
Might as well be that Androgenetic Alopecia/MBP is reversible after all.

Furthermore, Androgenetic Alopecia/MBP might be caused by a lack of relaxin in the scalp in the first place. An idea worth looking into. Funnily, relaxin is reduced by ejaculation.


Edit: In case anybody can use that info, TGF-b is the hormone triggering the fibrosis of the tissue around the follicles. Anyone know how to inhibit that? But please not systemwide, as it is needed for wound healing.

Edit2: For the record, T3 and T4 up-regulate SHBG. (Source: http://jme.endocrinology-journ...g/content/43/1/19.full ). Now, the question is: How do we get T3/T4 to increase? One way seems to be intense work-out (source: http://www.nel.edu/26-2005_6_pdf/NEL260605A14_Ciloglu.pdf ).

Edit3: Bad news: T3, and as a consequence SHBG, decrease as a consequence of inflammation, not the other way around (source: http://chriskresser.com/inflammation-strikes-again ). In case there is no circular dependency here, this means that increasing T3 or SHBG will not help stop or slow down Androgenetic Alopecia/MBP, as they are only low as a consequence of the inflammation causing Androgenetic Alopecia/MBP. They are not the reason for or a contributor to Androgenetic Alopecia/MBP (unless there is circular dependency, which I have no knowledge about as of now.)

Edit4: There are some hints that there is a circular dependency: http://immortalhair.forumandco...and-hair-growth
Means:

• Androgenetic Alopecia/male pattern baldness triggers lower T3/T4
• Lower T3/T4 accelerates Androgenetic Alopecia/male pattern baldness

Edit5: Iodine seems to play a key role in a) T3/T4 regulation and b) body inflammation handling. In fact, it is crucial for transporting growth and healing agents to areas of inflammation. Given that huge portions of the population lack sufficient iodine supply and its role in inflammation handling, it likely play a role in Androgenetic Alopecia/male pattern baldness. In some parts of the world it has been used in traditional medicine to treat hair loss successfully.
So: Inflammation does not cause T3 and T4 to be low, but lack of iodine causes a lack of T3 and T4 and inflammation. Thus, there is a correlation, but no causality of T3/T4 and inflammation. A discussion on this matter with a lot of sources for further reading can be found here: http://immortalhair.forumandco...male-pattern-hair-loss

Edit6: Next candidate found, Prostaglandin D2. It has been shown that in Androgenetic Alopecia/male pattern baldness affected persons, Prostaglandin D2 concentration was three times higher in bald areas than in non-bald areas. And guess what?
"They are mediators and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue. [...] Smooth muscle-containing tissue needs to be stretched often, so elasticity is an important attribute of smooth muscle. Smooth muscle cells may secrete a complex extracellular matrix containing collagen (predominantly types I and III), elastin, glycoproteins, and proteoglycans." Source: Wikipedia.
Question is, now: is Prostaglandin D2 increased because of inflammation, or due to another reason? Also, how can we decrease Prostaglandin D2?

 

[Petchsky]

what brand of minoxidil did you take Benjt? I've been using it for ten years, only noticing puffy eyes rarely, no dark circles, or from what i can tell bad wrinkles. It's only from the last few years that i've ever seen posts about minoxidil having these effects on people, which is odd, but i'm not denying your experience, or others, as it's very possible some people absorb more minoxidil from topical application than others, or are simply more prone to side effects from it.

Spectoral DNC has both min and adenosine, but as this also has emu oil, which increases absorbtion, so probably not a good idea for you.

How's the low dose min working for you?

 

[benjt]

I took the original minoxidil, i.e., Rogaine. By now I also met an old friend that I had last met before starting my minoxidil regimen, and he told my that I look like a geezer with a drug problem. Yay :-/ But this shows pretty well that it's not just "in my head".

The lowered dose did not help at all; instead, my whole face and especially the areas beneath my eyes became puffy and the skin there increasingly haggard again. I have a theory for that, though, which is more or less based on science.
1. minoxidil inhibits collagen synthesis (fact)
2. The skin barrier mostly consists of collagen (fact)
3. minoxidil also affects the skin barrier's collagen. Because of the diminished skin barrier, more minoxidil even at lower doses is absorbed into the blood stream (my theory)

I dropped minoxidil now completely. Hair is already coming down, but I'm really hoping that my face will start looking normal again. Collagen synthesis can take up to one year, depending on your age and sun exposure (which is rather high right now). Should my face recover by then, I will assume that my skin barrier has also recovered and start with minoxidil again, though at a lower dose. I will then closely monitor my facial skin for any changes. As I now know what to look out for - unfortunately - this should be a rather safe way.

Wish me luck. I'd rather be a NW3 or worse at 23, than have a head full of hair but have the facial skin of a 40 year old (or worse) at my age. The reaction of people to my facial looks right now is just awful.
Other people with the same side effects as me say that they largely recovered after about 5 months, others state they never recovered...

 

[SDK]

This is a legitimate problem. I was on foam for three months and started noticing faint grey circles around my eyes and almost down to my cheekbones.

 

[vladut50]

Very interesting information. Can these side effects be completely gone and your face fully recovered?

 

[vladut50]

I guess you're right, but we must be alert however.

 

[saintsfan92344]

I have been on minoxidil 2 weeks and am laying down with cucumber on my eyes right now to get rid of the circles. Listed sides or not it happens. I also notice i get them a bit with nizoral use which is kind of weird i guess i just cant tolerate anything

 

[vladut50]

Circles after 2 weeks of minoxidil only?

Could derma rolling the entire face once every 2 weeks solve this problem?

 

[saintsfan92344]

Yep after 2:weeks and not every day either but i will say i think its worse when i use nizoral also. I guess i am just very sensitive to this stuff. I get a kick out of the people that say it doesnt happen or its not a listed side effect

 

[dcjenkins]

benjt,

I just wanted to thank you for sharing all of your research and personal findings. Should you have any additional information and personal experiences to share since your last post, please do.

Your research has confirmed for me, why I've had dark circles, wrinkles, etc, with DNC-N, and possibly Revita shampoo. DNC has Adenosine, and a modified version of minoxidil, callled Nanoxidil.

Another point of interest, is that I believe the effects were being magnified with my use of Serrapeptase, which from my very limited understanding produces fibrosis (If I'm even phrasing that correctly), which may help the scalp, but probably hinder good collagen production on the face. I'm a major newbie on this, so you're welcome to set me straight.

Thanks.

 

[cthulhu2.0]

I have to agree with Fred, this whole face wrinkles phenomenon you are experiencing is either due to diet/other causes or is all in your head. I say that because 1) as fred mentioned, this was not observed in the trials and 2) very minute quantities are absorbed into the blood stream and in patients of these trials, the blood levels of the drug were undetectable.

 

[benjt]

You know people can't just come here and claim things like that without any evidence, that would be bad for the reputation of this forum.

Oh wow. First Fred claims that he only wants to protect new users from trying out things and thus holds back information. Now his concern is "the reputation of this forum". Gotta love those altruistic people!

You do have pictures of yourself taken every now and then like everybody right?

Perfect! I thank you in advance to provide us with some evidence that minoxidil gave your wrinkles.

As you like to ignore, I for one did put up a photo in one of my posts. The problem with facial photos is - duh - that you're identifiable.

I have to agree with Fred, this whole face wrinkles phenomenon you are experiencing is either due to diet/other causes or is all in your head. I say that because 1) as fred mentioned, this was not observed in the trials and 2) very minute quantities are absorbed into the blood stream and in patients of these trials, the blood levels of the drug were undetectable.

Having recovered almost completely by now, I can say that it was definitely not in my head. Or how often have you heard of people magically losing wrinkles?

What's more, I'm currently running an on/off regimen. Currently I apply minoxidil (1ml once a day instead of 1ml twice a day) for two to three weeks in a row. After approx. three weeks, the dark circles around my eyes become quite noticable again. I then stay off minoxidil for a couple of days and the circles disappear again. Repeat.
As I can (and do, until I hop off again) recreate the dark circles consistently in a relatively short amount of time which always correlates with my minoxidil usage, it's pretty safe to say that it is caused by minoxidil. If it was anything else than minoxidil, it would need to be something that also directly follows my on/off regimen.

cthulhu2.0, I can also only ask you to read through the research that I posted earlier in this thread. Overdose on minoxidil has reportedly lead to huge-*** facial sagging in one patient; the study is linked in my first or second post, I think. If an overdose can confirmedly lead to the whole face becoming saggy, it is not very surprising that lower doses can lead to less extreme effects of the same kind, i.e. single wrinkles.
Also take into account that collagen destruction is how minoxidil works. While this is a good thing on our scalps, as fibrotic collagen is an "intermediate culprit" in the hair loss process, this is not a good thing in our faces, as collagen keeps our skin elastic and firm.
Given how minoxidil is known to inhibit collagen generation, it lies at hindsight that minoxidil' effects on facial skin tissue would create wrinkles. Collagen loss is the reason for wrinkles as part of the aging process. Collagen inhibition, as done by minoxidil, would lead to the same.

So take into account how minoxidil inhibits collagen production and that one study, which Fred likes to completely ignore, has shown that a guy OVERDOSING on minoxidil had his whole face sagged to the ground. If an overdose can cause massive sagging and wrinkles, lower amounts can cause "minor" wrinkles. These wrinkles are not so minor when you're just 23/24, though, when your face should have no huge-*** wrinkles at all, which were also noticed by my friends.

Also consider that the "puffy face" that some users report is among the officially listed side effects of minoxidil. This shows that minoxidil does not stay 100% local to where it was applied, but that it does spread to the face.


@dcjenkins:
Fibrosis is what you want to prevent. Fibrosis = generation of fibrotic collagen. Fibrotic collagen is one of the intermediary effects somewhere in the complicated process of male pattern baldness/Androgenetic Alopecia. The more advanced your baldness is, the more fibrosis is going on in your scalp, i.e. the more fibrotic tissue you have. That is caused by PGD2 overexpression.

I can give you an update on my current state, as I haven't updated this thread in quite a while:

As you know, I went off minoxidil completely. I lost a lot of ground within 2 months of going off minoxidil, and I decided not to take that. As you know from my previous posts, the effectiveness of minoxidil is determined by the amount of minoxidil sulfotransferase present, which given me being a very good responder is probably very high in me. (My theory is that all people suffering from these side effects have very high amounts of minoxidil sulfotransferase, which also explains why these sides were not find in the clinical trials). I started applying minoxidil again at 0.5 to 0.7 ml once a day (as opposed to 1ml twice a day), which already restored quite some hair. This dose seems to be safe for me so far, except I get dark circles again after a bit more than two weeks of continued use (my uneducated guess: probably due to buildup), so whenever the dark circles around my eyes become too proclaimed again, I drop minoxidil for a couple of days. The dark eye circles go away again within a couple of days, and I start the whole thing over.
I recently increased my dosage to 1 ml once a day again, trying to see if this is safe for me. Given how this leads to my face getting puffy (Fred, before you start spitting your bullsh*t again, a puffy face is even listed among the known side effects), this dose is likely not safe for me in the long run.

Long story short: I want to be neither bald nor wrinkly and looking like a geezer, so I'm attempting to get the maximum amount of hair saved with the highest dosage of minoxidil that I can use without getting wrinkles again. Obviously, a reduced minoxidil dosage is the way to go.

Regarding recovery: I can joyfully say that 100% of the forehead wrinkles are gone again. The wrinkles around my eyes are also for the most part gone. And, as I said, when the dark circles start to show again I just hop off minoxidil and they subside within a few days. However, the skin in the area around my eyes which got dark and where I got the wrinkles never went back to 100% "elastic" again and its surface is also quite unfirm. other people suffering from the circles and wrinkles also reported similar things, referring to the skin's "texture" being ruined. I guess that is what I'm experiencing here. This hasnt improved at all and I guess it will never go away. Either way, pretty much everything else is back to normal (only some minor wrinkles showing around my eyes, but nothing too visible anymore) and I'm extremely happy about that. I also found my "safe dose" which I can keep on using, only having to go off minoxidil once every two to three weeks so I can have my eyes back to normal.

For another explanation of the side effects, without knowing it I might've in fact overdosed to begin with (and keep in mind that these effects are scientifically confirmed for minoxidil overdoses). My hairloss as of now is only at my hairline, so I applied the full 1 ml twice a day at my hairline - but this dose might've indeed been too much. If the tissue at the site of application is 100% saturated with minoxidil, the remaining minoxidil will obviously spread, and that might've lead the minoxidil to spread to my face.

Long story short, I found my safe dose and can safely say that the dark circles are definitely caused by minoxidil, as I recreate them on a bi- to tri-weekly basis anyway. Same goes for the wrinkles, which have almost completely disappeared by now.

 

[benjt]

So you're scared about showing your face on the internet? Well, I'm not.

Good for you.

I've used minoxidil for almost 5 years, consistently, sometimes I would put a lot of it, way more than 1 ml. Tell me, where are my wrinkles?

I've never claimed that it happens for everybody, but instead stated myself that I also consider it to be extremely rare. As I've explained a few times, this will only affect people with high levels of minoxidil sulfotransferase.

Oh and of course too long didn't read, as new hair loss sufferers will do too I hope. For anybody who is worried about minoxidil wrinkles, just look at my picture.

Your lengthy posts about such trivial matters indicate by themselves obsessive compulsive behaviour. It takes away any of your credibility.

Your level of arrogance is purely marvelous. "Oh, I didnt read it because it is lengthy, but it is obviously wrong because it is so long." Great how you base your evaluations on the length of a post you didnt read instead of its content.

Whoever is interested in the details can read my posts, whoever isn't doesn't need to. Pretty simple.

 

[Luka]

Hi All, I have been reading these threads lately after taking Minoxidil 2 percent for a month. My face got puffy and the stories here caused me to to go off the minoxidil immediately. After three days of taking Arnica 30c twice a day, I can see a remarkable improvement in the puffiness. Arnica is also considered to be a hair loss treatment so I am hopeful.

 

[maher]

Welcome to the forum. Yes I just downvoted your post, for it is useless without pictures.

You know people can't just come here and claim things like that without any evidence, that would be bad for the reputation of this forum.

.

hilarious!

 

[Masakage]

I've used minoxidil for almost 5 years, consistently, sometimes I would put a lot of it, way more than 1 ml. Tell me, where are my wrinkles?

You've been using minoxidil for 5 years, where is your hair? That is the question you should be asking. 80% of the people who I know/seen use minoxidil, started gaining hair after 2-3 months. You obviously didn't as you got a transplant in turn.

Oh and of course too long didn't read, as new hair loss sufferers will do too I hope. For anybody who is worried about minoxidil wrinkles, just look at my picture.

I looked at your picture, how the f*ck does it help me with minoxidil sides? yeah, it doesn't. Do you see how your logic faceplants right on the curb? Again, something that you may not understand since you're too self-centered, just because you didn't get them, doesn't mean no one else did.

Your lengthy posts about such trivial matters indicate by themselves obsessive compulsive behaviour. It takes away any of your credibility.

Actually I thought it was an interesting read. I'm fairly a new minoxidil user, although did conduct massive research on it, I've definitely gained knowledge. Compulsive Obsessive behavior? Lol, this is just another example of you spewing bullshyt, just like when you claimed that I was a hypochondriac. Trivial matters? Yeah, of course when you're not dealing with it. Do you know who's obsessive? YOU ARE. You spend 5-6 hours a day here, you post every fukking minute, you bytch about how girls give no attention to bald men, and you obsessively defend minoxidil as if it was the holy grail.

Ohh, and you're still stupid, you thought that Benjt was derailing minoxidil, when he actually created a solution and tested it out himself. I was going to quit too, but because he experimented it in an efficient manner with no sides, I'm going to continue with it.

You see, you're just a di*k, that's what it is.