1. Introduction
2. Accutane: A differentiating agent
3. β-catenin signalling
4. Restoring Stem Cell Renewal
5. Castor oil: Snake oil or Science?
6. Conclusion
7. Castor oil
8. Article Summary
9. Related Articles
10. References

Introduction

Acne can take an enormous toll on self-esteem, particularly during the vulnerable years of teenagerhood. However, many who reached out to Accutane as a solution found themselves substituting one form in insecurity for another. It’s true that Accutane can permanently remediate acne, but its many other side effects can be lasting too – including hair loss.

Around 10% of patients treated with the acne drug reported experiencing hair loss, however there’s an element of subjectivity involved in identifying hair loss so estimates vary. What is better established is that higher doses exacerbate this symptom. Analyses over 22 studies found that being treated with daily doses greater than 0.5mg per kilogram almost doubled the prevalence of hair loss versus those treated below this threshold (from 3.2% to 5.7%). [2]

Hair growth is divided into three main stages (although there are others): anagen, catagen and telogen. During the anagen phase the hair is under active growth. The hair follicle produces hair fibre and can last for years. Following after the anagen phase is the catagen phase, where the hair begins to thin and even shed in a process lasting week.

This stage is proceeded by the telogen or resting phase, where the hair follicle remains dormant. Depending on the location of the hair and other factors (hormonal status, vitamins etc.) this final dormant stage can last from anywhere from weeks to years. [3] The cause of diffuse thinning that troubles so many treated with Accutane, is an acceleration of the transition from the growth (anagen) phase to the thinning (catagen) phase. [4]

Accutane: A differentiating agent

This has all to do with Isotretinoin being a “differentiating agent”. If you want a better understanding of what’s meant by this term, read my article on the cause of Post Accutane Syndrome here. To summarise this concept briefly, certain tissues through the body rely on continual growth and repair (brain, skin hair etc.)

The cells in these tissues can undergo active renewal by drawing upon “supplies” of stem cells. These cells don’t have the full features of the tissue they will eventually specialise into, and act as a reserve for future growth.

The variety of cells that a stem cell can differentiate into. Haileyfournier, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

Stem cell populations can increase through a process called proliferation. This proliferation is opposed by the process of specialising into specific tissues in a process called differentiation. In the skin, epidermal stem cells allow for wound healing, whilst hair follicle stem cells are needed for hair growth. As a person ages, the number of stem cells depletes as does their capacity to regenerate. 

Retinoids in general repress proliferation by speeding up the cell turnover by forcing rapid differentiation. [5] This can hamper the proper development of the tissues that undergo active renewal and repair such as the hair.

The application of Retinoic acid (the active metabolite of Accutane) impedes hair shaft elongation. Secondly, retinoic acid prevents the adequate proliferation of the primary cell found skin called Keratinocytes, which triggers the early onset of the catagen phase. [4] The combination of these effects results in shorter, thinner hairs that are more prone to shedding. The vitro evidence bears a striking resemblance to the many anecdotal reports from Accutane patients.

β-catenin signalling

The key mechanism by which the balance between stem cell proliferation and differentiation is managed is through a particular pathway called Wnt/β-catenin signalling. β-catenin is a growth-signalling protein central to the Wnt pathway, which is essential for tissue growth and development. β-catenin is essential for maintaining the stem cell populations to maintain healthy hair growth. Accutane inhibits β-catenin signalling by enhancing a complex that continually breaks it down, called the ‘destruction complex’ (read more).

This action of Accutane on β-catenin is analagous to the process of Androgenetic Alopecia (commonly referred to as ‘male pattern balding’). The effect of androgens (male hormones like Testosterone and DHT) on scalp tissue has some similarity to Accutane, since they also interfere with β-catenin signalling, and thereby disrupt the renewal of stem cells (read more). Nearly all treatments for hair loss aim to stimulate the proliferation of stem cells in hair follicles, known as dermal papilla cells.

Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436., CC BY 3.0, via Wikimedia Commons

Dermal papilla cells are located at the base of the hair follicle just below the hair matrix, as depicted in the above figure. Minoxidil is perhaps the best known medication for hair loss, which promotes the nuclear accumulation of β-catenin, thereby fostering dermal papilla proliferation. In contrast, the opposing effects of Minoxidil and Accutane on β-catenin lead to directly opposite outcomes for hair growth: Minoxidil treatment extends the anagen (growth) phase of the hair cycle. [17]

Restoring Stem Cell Renewal

Various medications and supplements show promise in promoting dermal papilla cell proliferation, thereby supporting hair growth. While Accutane acts as a “differentiating agent,” these contrasting treatments can be seen as “proliferating agents.” One such agent I’ve highlighted in previous articles is lithium. Although most people associate lithium with psychiatric medication, this trace mineral is also present in low doses in various foods and even in the water supply. Lithium has the mirror opposite the effects of Accutane, by slowing down cell turnover and enhancing stem cell proliferation (read more). [6]

So what’s the evidence for Lithium on hair growth? Well, it’s completely depends on dosing. Lithium is used to treat mania and bipolar in doses up to a thousand times greater than might naturally be acquired through ground water. This can have some detrimental effects on hair growth by disrupting thyroid hormones. [7]

What about topical or lower supplemental doses? The evidence lines up exactly with what could be expected from a “proliferating agent”. Topical lithium encourages new growth and was even found to reduce the dormant “telogen” phase by a massive 70%! [8] Lithium encourages the growing “anagen” phase whilst Accutane suppresses it.

While the evidence for using lithium to support hair growth is still in its early stages, its potential is further supported by findings related to a closely related mood stabilizer, valproate. Like lithium, low-dose or topical valproate promotes hair growth by inducing the anagen phase and encouraging cell proliferation. [9] Topical applications of both valproate and lithium help delay the catagen transition and shorten the telogen phase, leading to longer hair shafts and increased hair density.

However, lithium is generally not regarded as beneficial for hair growth in clinical settings, as the high doses used to treat mania can disrupt thyroid function, often resulting in hair shedding. Whilst the in vitro evidence for topical Lithium is encouraging, there is a lack of studies on the effects of low supplemental doses.

Another compound that shows promise in stimulating stem cell proliferation through enhanced β-catenin signalling is melatonin. Notably, melatonin is also recognised for its positive effects on hair growth by well-known biohacker Bryan Johnson, who includes topical melatonin in his hair serum. I’ve written extensively about the opposing effects of melatonin and Accutane in this article.

Castor oil: Snake oil or Science?

Unfortunately, the application of these agents isn’t yet an established therapy for hair loss so we must turn to other possible treatments. Given the almost foundational importance of hair in the cosmetics industry, there’s an abundance of pharmaceuticals and folk treatments that purport to restore your follicles (for the right price of course).

Separating science from the snake oil can be a challenge, but one particular folk treatment shows surprising promise. Castor oil, whilst more commonly used in manufacturing, also appears in many hair serums. And the science would suggest for good reason too. The main fatty acid in castor oil is Ricinoleic acid, which studies have now found also suppresses GSK3β. [10] This is the mechanism that underlies Lithium, Valproate and minoxidil in enhancing β-catenin.

This isn’t the only benefit of castor oil in the context of hair growth, as it also activates Prostaglandin E2 to dilate blood vessels. [12] Another unexpected yet welcome effect of Castor oil is in encouraging film lipid layer on the surface of the eye, making it a potentially effective treatment for Meibomian Gland Dysfunction, which blights so many treated with Accutane. [13]

Conclusion

Now the prescient question is whether castor oil is safe. Anybody completely unfamiliar with castor oil might be surprised to learn that castor oil is sometimes delivered orally to women to induce labour, where the baby is overdue.[14] Additionally, castor oil also finds some value as a laxative at a dosage of around 15ml. [15]

The use of castor oil in the context of a laxative has recommended dose of 15ml to 60ml and is only recommended for 1 to 2 weeks. [16] It’s difficult to say how these guidelines should be adjusted for the context of hair loss, and individual tolerance might play a significant factor. Nonetheless, “proliferating agents” such as Lithium, Valproate and potentially even Castor oil, show incredible promise in resolving the full range of adverse effects that follow treatment with Accutane.

Article Summary

• Accutane and Hair Loss: Accutane is effective in treating acne but can cause lasting side effects, including hair loss, reported by about 10% of users, with higher doses worsening the problem.
• Mechanism of Hair Loss: Accutane accelerates the transition from the growth (anagen) phase to the thinning (catagen) phase of hair, resulting in shorter, thinner, and more easily shed hair.
• Impact of Retinoic Acid: The active ingredient in Accutane, retinoic acid, impedes hair growth by reducing the proliferation of essential cells (keratinocytes) and inducing early onset of the thinning phase.
• Lithium and Hair Growth: Lithium, a trace metal and mood stabilizer, has effects opposite to Accutane. Topical Lithium promotes cell proliferation and enhances hair growth by extending the anagen phase and shortening the dormant telogen phase. Similar to Lithium, Valproate encourages hair growth by inducing the anagen phase and supporting stem cell proliferation, making hair longer and denser.
• Castor Oil as a Folk Treatment: Castor oil, rich in ricinoleic acid, suppresses the same enzyme (GSK3β) as Lithium and Valproate, promoting hair growth and offering additional benefits like improving eye health.
• Safety and Application of Castor Oil: Castor oil is used in various medical contexts, such as inducing labor or as a laxative. However, its use for hair loss lacks specific guidelines, and individual tolerance may vary. While Lithium, Valproate, and Castor oil show promise as “proliferating agents” to counter Accutane-induced hair loss, their use is not yet an established therapy.

Related Articles

The Real Cause Of Androgenetic Alopecia

What Does Accutane Actually Do?

References