Hi! I’ve created another account so I can test how the sign up process.

The complexity with understanding the hair loss with Accutane is that it doesn’t follow the traditional process of hair loss from the perspective of Androgenic Alopecia, that being hair follicle miniaturisation by androgens such as DHT. This is because Accutane actually lowers cutaneous formation of DHT, by downregulating the enzyme 5-alpha-reductase. The most pronounced effect is observed in cutaneous tissue, where there’s an 80% reduction in DHT formation. [1]

The incidences of hair loss as a result of Accutane treatment might therefore appear paradoxical, as Finasteride treats androgenic alopecia by inhibiting 5-alpha-reductase. To understand why Isotretinoin isn’t instead beneficial for hair growth, we must examine why it is that DHT is damaging to hair follicles. One of the general effects of Isotretinoin throughout the body is in triggering stem cell differentiation, whilst inhibiting stem cell proliferation. [2] Many tissues that undergo continuous renewal throughout adulthood rely on these pools of progenitor cells. One such tissue is epithelial/skin tissue – which includes the scalp tissue.

Many of the mitogenic (cell division) pathways that ensure the maintenance of these progenitor/stem cells are repressed by Accutane. The mechanisms involved in this are broad and varied, including enhancing p53, disrupting IGF-1 signalling (the functional metabolite of Growth Hormone), blocking PI3K etc. [3] A primary effector of many of these mitogenic pathways is beta-catenin e.g. IGF-1 supports the growth of Liver cells by increasing beta-catenin activation. [4] I’ve written fairly extensively on the role of beta-catenin in stem cell proliferation in tissues throughout the body.

Androgen signalling is one of the pathways that interact with beta-catenin. The nature of this interaction depends on the tissues and androgens involved. In some tissues beta-catenin can potentiate androgen signalling, making the effect of mild androgens stronger. However in other tissues, such as the scalp, it appears that beta-catenin and DHT compete for the same transcription factors to regulate gene expression.

By essentially competing with beta-catenin signalling, DHT inhibits the processes that would for stem cell growth and maintenance in dermal papilla cells (the progenitor cells for hair follicles). This is the mechanism that drives androgenic alopecia.[5][6] So in effect, Accutane mimics the effect of high levels of androgens in the scalp by repressing beta-catenin signalling, despite the fact it also inhibits androgen signalling.  

So the question is, what enhances beta-catenin signalling in the scalp? What performs the inverse process of Accutane?

One of the candidates I’ve previously highlighted is Castor Oil. As it turns out Castor Oil extracts enhance beta-catenin signalling, which underlies its efficacy in treating hair loss. [7] People are sometimes underwhelmed by the effect of Castor Oil in practice, because the cutaneous absorption is relatively low – however oral formulations are available over the counter as a constipation medicine.

The most direct approach would be to boost IGF-1 signalling, such as through Ibutamoren. However this comes with some significant risks. Chronically elevated IGF-1 leads to insulin insensitivity, and could accelerate the growth of cancers. 

There are a number of molecules being investigated for treating hair loss through modulation of the Wnt/Beta-catenin pathway. One that’s showing some promise is Curcumin. Topical preparations of Curcumin have been found to block the adverse effects of DHT on hair growth via Wnt/Beta-catenin. [8] In this study, a mixed preparation including Curcumin was found to be almost as effective as minoxidil. [9] There’s several other candidates I’ve been looking into, and I’ll update this thread over the coming weeks. 

In conclusion, Accutane mimics the harmful effect of DHT on scalp progenitor cells, despite also having an anti-androgenic effect – this is on account of directly repressing beta-catenin signalling. 

[1] https://academic.oup.com/jcem/article-abstract/78/5/1064/2650318

[2] https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.22417

[3] https://www.mdpi.com/2073-4409/12/22/2600

[4] https://www.jstage.jst.go.jp/article/csf/28/4/28_4_255/_article/-char/ja/

[5] https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01528/full

[6] https://link.springer.com/article/10.1007/s00403-018-1826-8

[7] https://koreascience.kr/article/JAKO201724655836736.page

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334826/

[9] https://onlinelibrary.wiley.com/doi/abs/10.1111/jocd.14931

Thanks for the response. I have seen curcumin serums available for sale. Should I be looking for a certain concentration?

Is there a risk of the curcumin going systemic as an anti androgen like with topical finasteride?

I have also read that this could stain my scalp? Is that true?

Would it be another nightly topical? Would microneedling help?

Should I combine it with minoxidil and/or castor oil?

Would this be more effective on someone with Accutane hair loss than with someone suffering from general baldness?

My hair loss is in a diffuse pattern, the hairline has moved up leaving miniatures where the old hair was. And an island is being formed around my old frontal region. The top is also curly when before it was straight. My sides and back are fine, but all the hair is generally more dry than it used to be. I have seen this pattern also on other users on reddit reporting accutane hair loss but I’m not sure it’s a reliable pattern.

@philipjfry 

My point isn’t necessarily that Curcumin is the only/best way to resolve the Accutane induced hair loss – rather that it illustrates that enhancing beta-catenin signalling is an effective approach in general.

There aren’t too many studies exploring the use of Curcumin for hairloss, however this six-month double blind, placebo controlled study did find that a nutraceutical blend containing Curcumin gave a “statistically significant increase in the number of terminal and vellus hairs based on phototrichograms obtained through macrophotography analysis”. [1]

Other supplements or medicines that are also conducive to Wnt/beta-catenin signalling also show promise in supporting hair growth. In another article I look at the possible role of Melatonin, which is tightly interconnected to Retinoic Acid signalling in the body. 

Through its action on beta-catenin, melatonin increases the viability of Dermal Papilla cells (the cells that generate hair follicles). [2] 

I’ll continue to update this thread with supplements (or other interventions) that similarly show promise in modulating Wnt/beta-catenin signalling. 

[1] https://pubmed.ncbi.nlm.nih.gov/29742189/

[2] https://peerj.com/articles/13461/#

Isn’t the best beta catenin stimulator simply minoxidil? 

https://pubmed.ncbi.nlm.nih.gov/21524889/#:~:text=Minoxidil%20activates%20%CE%B2%2Dcatenin%20pathway,for%20its%20anagen%20prolongation%20effect

@philipjfry 

Minoxidil does indeed enhance nuclear accumulation of beta-catenin in dermal papilla cells. This prolongs the anagen growth phase of the hair cycle. [1] Boosting the Wnt/beta-catenin signalling pathway is common to all hair growth medications and supplements. Even finasteride works by inhibiting the androgen receptor from competing with beta-catenin for TCF/LEF transcription factors. 

However minoxidil requires continual application to support hair growth, as so doesn’t appear to as effectively support Mesenchymal/Dermal papilla stem cells proliferation. As it currently stands only epigenetic agents (such as Butyrate, Valproate etc.) can support the expression of pluripotent cell transcription factors. [2]

One of the era defining studies on epigenetics by Yamanaka founds that pluripotent stem cell induction is possible via several transcription factors. This forms this basis of his epigenetic theory of aging. In previous posts I present the evidence that Lithium (as well as Butyrate) is able to enhance these pluripotent stem cell factors. [3] It’s unsurprising therefore that Lithium can also prolong the anagen phase when applied directly to dermal papilla cells. Additionally these cells experienced a 70% reduction in telogen resting phase of the hair cycle. [4]

However Lithium isn’t typically considered to be beneficial for hair growth, as the almost toxic doses used to treat Mania will typically also cause thyroid disruption and subsequently hair shedding. As far as I’m aware there aren’t studies on the effect at low supplemental doses.

Given that Accutane works by essentially depleting progenitor/stem cell pools in the tissues throughout the body, I remain hopeful that future studies on the effects on HDACi’s like Butyrate or Lithium will open the door to reversing this process of forced ‘epigenetic aging’.

[1] https://www.sciencedirect.com/science/article/abs/pii/S0923181111000521

[2] https://www.mdpi.com/1420-3049/28/14/5517

[3] https://www.nature.com/articles/cr2011108

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116182/#:~:text=Partial%20proteasomal%20inhibitors%20(PaPIs)%20appear,anagen%20and%20dramatically%20shortened%20telogen%C2%A0.