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  1. #1
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    Default How Accutane can speed genetic baldness :

    here's how accutane can possibly accelerate genetic baldness, with 4/5 factors:
    (sorry for bad grammatical, sentences, and weird science vulguarisation, Im french and not that much bilinguist and scientist lol)


    First, as its written in studies, an exogenous apport of retinoic acid in the metabolism (like we had for treating acne) can make long term changes in the level of all trans retinoic acid (atRA) produced by each of our skin cells ( sebaceous glands cells, IF cells, dermal papilla cells, etc). Aldh1a3 is responsible of transforming the enzymes into atRA, his activity/expression determinate the level of atRA in dermal papilla cells. Aldh1a1 determinate the level of atRA in SB cells and aldh1a2 in the bulge region cells.(https://kb.osu.edu/dspace/bitstream/...ics_Thesis.pdf)
    Our treatment with high isotretinoin administration made a long term change on those genes expressions, so that they are now more active and so the level of atRA in each of our follicle cells are constantly higher than it should.

    Now if we look what high atRA level in our cells is doing, we can see how it can accelerate our baldness:


    1) atRA upregulate the rate of testosterone transformation into 5alpha-DHT

    "Administration of all-trans-retinoic acid to male rats increased the rate of 5alpha-dihydrotestosterone (5alpha-DHT) formation from testosterone in microsomal fractions in vitro."
    http://www.ncbi.nlm.nih.gov/pubmed/10423178


    2) The more atRA, the less WNT activity ! RA signaling and WNT pathway work together, they regulate each other for many things .

    "We identified a signaling cascade through which retinoic acid switches off Wnt"
    "these results further indicate that RA inhibits WNT signaling"
    "Our 3 preliminary studies indicate that RA does indeed interact with WNT signaling in the hair"
    ""Follicular localization sites (including hair follicle stem cells) of several WNT signaling molecules are similar to those of synthesis enzymes of retinoic acid (RA), a vitamin A metabolite."
    "All trans-Retinoic Acid Mediates Wnt/β-catenin Signaling through MED28 in Human Colon Cancer Cells"
    "All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation"


    Well I stop here (you can write the sentences in Google to find each study), they are hundreds of other studies explaining the interaction between RA activity and WNT and so in each of our follicle cells (more importantly DP cells), there's too high atRA level, so automatically less activation of WNT pathway.


    3) the more atRA, the less PPAR protection (alteration of vitaminA metabolism lead to hair loss)

    PPARy deletion is critical in cicatricial alopecias ( FFA, PCA, CCCA, LPP,..)
    http://dermatologytimes.modernmedici...-inv?page=full
    http://www.jidonline.org/article/S00...340-2/abstract


    And now they showed how altered retinoid metabolism (what we did with accutane) is involved in alopecias like CCCA,CA,..:

    -At the 2015 North American Hair Research Society Scientific Meeting, there this presentation : "Alterations of vitamin A metabolism and signaling in central, centrifugal, cicatricial alopecia patients"

    -or this study : "Retinoid metabolism is altered in human and mouse cicatricial alopecia"
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546159/

    -In this other recent study they explain how altered metabolism VItaminA regulation is connected to CCCAlopecia, and how excess of RA synthesis silenced the WNT signaling https://etd.ohiolink.edu/ap/10?0::NO...D_SUBID:103145

    -"Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss.
    "Our results show that normalization of RA levels is associated with reinitiation of hf development.
    "

    http://www.jbc.org/content/287/47/39304.full

    CCCA hair loss is diffuse long term hair loss beginning generally on vertex , BUT that work together in synergy with genetic baldness so the whole thing follow a classic baldness pattern (studies reporting the difficulty of diagnosting CCCA in patients because of that). So yes our genetic balness could also be accelerated by cicatricial alopecia factors (less wnt, less anti inflammation protection,etc ) because of our altered vitamin A metabolism that lead to too high atRA level in every of our follicle cells


    4) the more atRA , the less insulin-like growth factor-1 (IGF-1)

    "Short-term isotretinoin treatment decreases insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels"
    http://onlinelibrary.wiley.com/doi/1...618.x/abstract

    And atRA also interact with the NOTCH1 and TGFβ pathway !
    https://www.researchgate.net/publica...-beta2_in_the_

    http://www.jbc.org/content/early/201...bc.M115.638510

    __________________________________________________ __

    so it's easy understandable that if we have now higher atRA levels produced in each of our HF cells, we combine these 4 negative factors in each of them. And all met together to infine the destruction of the follicle: in each of our dermal papilla cells for ex there's a higher rate of DHT to 5ARdht transformation, a silenced WNT pathway, no more anti inflammation protection, and less HF growth factors, all because of higher atRA than normal, so the combination definitly aggravate (or even trigger ?)our hair loss.

    Don't forget that each individual metabolism don't react the same with exogenous RA administration. So for some people, the treatment will lead to dramatic changes in skin cells genes expression, and so high changes for life in cells atRA levels. For others the changes will be less strong, but still the atRA levels will be higher than it should. And for others the treatment won't be sufficient to impact the genes expression for long term;
    Everyone's metabolism react differently, but whatever the scale, if accutane made changes in your RA metabolism, that mean constant higher atRA levels in the cells for long term, and so it can induce those factors that are surely involved in the speed of our hair loss development

    __________________________________________________ ____

    THERE IS A SOLUTION
    we need to eradicate these 4 aggravating factors by lowering the atRA levels.

    What is determining the level of atRA in dermal papilla cells is the activity of Aldh1a3 (his role is to transform the enzymes into atRA, the more he is active, the higher level of atRA)

    So I search about this yesterday, and the first study that I found show that inhibition of aldh1a3 is possible via the inhibition of the STAT3 pathway ! What a good surprise

    "Inhibition of STAT3-NFkB activity allowed high levels of DDIT3 expression with increased formation of a DDIT3-CEBPβ complex. This reduced the occupancy of the ALDH1A3 promoter by CEBPβ, thus largely reducing the ALDH1A3 expression."
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494963/


    I'm sure you all aware of the jak/stat3 inhibitors recently tested for alopecias areata and universalis. So it was good surprise when i searched about aldh1a3 inhibition (to lower atRAs) and found the connexion with jak/stat3 pathway.

    all of this show that it could work well for us to at least suppress the aggravating factors by inhibiting aldh1a3 and so the atRA levels in our dermal papillas cells = less 5ARdht formation + more WNT + more PPAR protection + more IGF-1 and IGFBP3 + less negative interactions with TGF and notch pathway


    So I think we definitly have to correct with this what accutane changed in our follicles cells if we want to fight our balness progress.
    Everyone of us who have higher atRAs than the normal will benefit of it as we'll become free of the atRA induced consequences that kill the follicles. Some of us could even expect dramatic positive results i think

    So now I begin to search in France an open minded professional/clinic/dermato/etc, I will send them the whole facts theory with all the studies, and i think they will understand why testing a topical jak/stat could benefit my 'genetic baldness aggravated by acutane alteration of vitaminA metabolism'.
    If i don't find in France, i will already begin the natural way and search for a comprehensive doctor/clinic in other countries.
    So If you are in the same case as me and want to see how much your atRAs are involved in your hairloss, I encourage you to talk at some professionnals about it, ask them what they think about this, show the studies, and they will logically understand why you want to give it a try like in the other alopecias cases (AA and AU). they'll for sure understand why we feel the need to suppress the things that accelerate/aggravate/maybe even trigger our alopecia. It's sure we can find some professionals that could be interested to see what it does in cases like us. There's too much studies now that show how altered vitA metabolism lead to hair loss, so professionals should understand that we, ex accutane users, have the right to know if our genetic baldness is accelerated by this vitA metabolism alteration, and the best way to know would be the topical jak/stat3 6 months test.
    I begin the search in France but will also search in other countries, I need test to see what it does! With all those studies I can't wait for many more years, cause all suggest it'll for sure be benificial for my hair loss, but what I really want and can't wait to know is in which proportion! I fckn need that answer^^


    So tell me if you see some errors or contradictions above, but everything I wrote comes from the studies by well known scientists specialized in dermatology

    accutane can induce longterm high atRAs level expression in the cells =high atRAs induce 4/5 factors that induce hair loss = with this hell of a combination, we develop our predisposed balness faster (maybe even really faster) than what it should have been normally. And those factors could also explain why some of us also have thinning in the donor area at such a young age

    So post accutane (mega dose for acne) users, whats your thoughs?
    And escuse my english errors

  2. #2
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    My temples also started receding after finishing a years course of accutane in November 2015 I always felt as if accutane accelerated my mbp as my father started losing his hair by his mid 20s, I'm only 16!! Maybe it was meant to happen but since there is no baldness in my mothers side I'm still not sure
    Great research btw!!

  3. #3
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    Hello Lacazette,

    thank you initially for the publication of your research concerning the impact of the retinoids on the hair. I am myself, for other reasons that the use of Accutane, concerned with this problem and I also wish to continue further in this way. I undertook also researches on the Net (which arrived at the same conclusions) and am ready to contact doctors, dermatologists likely to help us. By the way, I'm from Belgium.
    I hope that you will be able to read this message and take the time to answer it.

  4. #4
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    Hello Lacazette, that's an interesting theory, i took accutane 3 years ago for about 3 months and my MPB developed almost immediately after. I was on a very low dose though and have a family history of hairloss so i don't want to jump to conclusions.
    Anyway, when you say long term effects, how much time are we talking about? Is it definitive? If not, will the hair texture and quality turn back to normal after the effect wears off? I really hope that you'll answer this message asap.

  5. #5
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    Hi, I have the same problems. I was 8 months on accutane and in the last month of it I got extreme hair loss that dind'nt stop. It only gets worse.
    The explanation here looks good.
    Does anybody asked a dr what he thinks about the thesis? Or does somebody have another thesis (sry for my english, I'm from germany)?

  6. #6
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    This whole thing seems like such a hassle. Is this theory confirmed? @lacazette what happened to u? What do I have to do to correct this? Or am I for ever doomed? I took accutane for 6 months (first 5 months 30mg and last month 60 mg) and have experienced acceleration of MPB since then. I asked several dermatologists and researchers and none of them said that their patients complained about onset/acceleration of MPB during/after accutane therapy and that accutane induced hair changes are generally reversible. I am 20 y/o (just about to turn 21) and have noticed thinner hair all around my head (sides and donor area as well) but also strong typical MPB signs (recessed hair line, visible crown, thin hair on top).. Dont want to take finasteride because of side effects so what the fuk am I supposed to do from here? How can I even be sure accutane actually accelerated my MPB? I mean I have a cousin (fathers side) who is my age and he is almost bald. My dad has a full head of hair and the dad of my mom had a full head of hair until his death. The brother of my mom and the brother of my dad are also bald so I tend to think that I have the genes for it... I mean so many guys take isotretinoin and if it really had any effect on MPB it would have been noted by now by medical research. But the only connection between accutane and acceleration of MPB can be found on online forums where people speculate.. No hard facts.

  7. #7
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    Hi, something new on this thread? I lost most of my hair within a year, I have strange hair loss a combination of MPB and Scarring alopecia from isotretinoin.

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