Hair Loss Cure 2020

I originally wrote this post on the arrector pili muscle (APM) in 2017, with an update in 2020.

Recently, I discovered a 2021 video in which the semi-retired dermatologist Dr. Andrew Messenger of the UK makes some important claims. He thinks that current hair loss treatments mainly impact the hair cycle. They do not reverse miniaturization, and he presents proof of this phenomenon.

Moreover, he theorizes that the structural changes in miniaturized hair follicles are perhaps more profound that previously foreseen. In particular, the irreversible destruction of the arrector pili muscle and subsequent fat infiltration. He presents an image from Dr. Rodney Sinclair’s 2014 paper on this subject, which I discussed in one of my past updates further below.

However, I am skeptical about the irreversibility of hair regrowth once the APM is beyond repair. It seems like Dr. Ralf Paus in the second half of the above video is also optimistic about the potential reversal of miniaturized hairs via a number of treatments.

I am especially curious as to how hair transplants on people with extensive Norwood 5-6 level balding work so well (since arrector pili muscles throughout their scalp are destroyed). Even body hair to scalp transplants often work well (especially beard hair). Can body hair follicles that are moved to the scalp help reinvigorate dead arrector pili muscles? Or can you actually move arrector pili muscles from the body to the scalp?

Also of interest, there are quite a few spectacular male-to-female transition hair growth results that are solely credited to medications such as Dutasteride, Spironolactone and Estrogen.

Please see the section titled “My Points of Contention” at the bottom of this post, where I elaborate further on these arguments. I have e-mailed both doctors to see if they have any further feedback.

Update: August 7, 2020

Goosebumps, the Sympathetic Nervous System and Hair Growth

Yesterday, Taiwanese and US researchers published an important paper titled: “Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells.” The work was led by Dr. Lin Sung-jan of National Taiwan University, in collaboration with researchers from Harvard University (US).

Arrector Pili Muscle and Goosebumps — Goosebumps, Arrector Pili Muscle and Hair Growth.

The scientists made some important discoveries in relation to the arrector pili muscle (APM), and the sympathetic nervous system. The APM maintains sympathetic innervation to hair follicle stem cells. (HFSCs) The sympathetic nerve activates HFSCs via synapse-like contacts and norepinephrine. An important quote:

“APMs are often lost in the scalp skin of people with androgenetic alopecia. It is possible that in such skin, loss of APMs leads to the loss of sympathetic nerves, making HFSCs more difficult to activate. Our results also suggest the potential of using selective β2 agonists to promote HFSC activation.”

Lin’s team found that the biological mechanism behind baldness in men is closely connected to the sympathetic nervous system. Hair follicle stem cells activate after receiving signals via what are known as ADRB2 receptors. Based on these findings, the researchers hope to develop small molecule drugs that can activate ADRB2 receptors as a means of regenerating hair.

Goose bumps are a sympathetic nerve response involving the contraction of tiny muscles all over our bodies. These arrector pili muscles causes hair to stand up straight on the skin when we are fearful and under threat. The scientists aim to ultimately control the muscle-nerve system that drives hair regeneration. A video of these findings is embedded below. It is quite something to see Dr. Lin Sung-jan being mobbed by the media.

Jan 10, 2017

Androgenetic Alopecia: New insights into the role of the Arrector Pili Muscle

Several weeks ago, the arrector pili muscle got significant coverage in a few newspapers around the world. Famed Australian dermatologist Dr. Rodney Sinclair co-authored an important paper titled “The arrector pili muscle, the bridge between the follicular stem cell niche and the interfollicular epidermis” that was just published this month.

Dr. Sinclair has been involved in this area of hair loss research for a few years. See his 2014 paper titled: Beyond goosebumps: Does the arrector pili muscle have a role in hair loss? Also see the very interesting new insights on the APM section of his website. Australian newspapers were especially interested in this latest study and its findings as evidenced by articles such as this one and this one.

The Arrector Pili Muscle

Arrector pili muscles are small muscles attached to individual human hair follicles on both the scalp as well as body (so we have millions of these muscles throughout our bodies). Contraction of these muscles causes hairs to stand up, a phenomenon that is known as goosebumps. Therefore, the musculus arrector pili is often referred to as the goosebump muscle.

Every hair root is connected to the arrector pili. This smooth muscle contracts in response to signals from the “fight or flight” sympathetic nervous system.

Arrector Pili Muscle Degeneration and Hair Loss

In recent years, a few studies have come out that suggest a possible connection between the arrector pili muscle degenerating (where it gets replaced by fat) and hair loss due to the subsequent disconnection between various hair follicle stem cell populations. It is possible that an intact arrector pili muscle plays a crucial role in the maintenance of follicular integrity and stability.

However, there are many uncertainties about this theory that I discuss in the next section. It seems that while in alopecia areata (AA) patients the arrector pili muscle remains intact, this is not true in androgenetic alopecia (AGA) patients. Unfortunately, over 95 percent of balding men suffer from AGA. So this could be why it is much easier to grow back hair for people with AA compared to people with AGA.

However, the rate at which the arrector pili muscle degenerates and gets replaced by fat varies substantially between patients and between individual hairs on the same scalp. Some miniaturized vellus hairs in balding regions might even never lose most of their arrector pili muscle connection.

My Points of Contention

According to Dr. Sinclair’s own quote from a past paper, “It remains unclear whether arrector pili muscle regression is a cause or effect of permanent follicle miniaturization“. I think this is the crux of the issue surrounding this theory/hypothesis.
I am curious why hair that is transplanted from the back of a person’s scalp to the front grows so well if the arrector pili muscles in front have been destroyed? Surely the transplanted hair cannot just automatically regenerate the arrector pili muscle?
Related to the above, an important Japanese study from 2012 concludes that correctly transplanted hair can re-enable “connectivity and cooperation” with the arrector pili muscle and nerve system. In effect, it might be very possible to reactivate or regenerate the APM.
In Dr. Tsuji and his team’s groundbreaking technology “the transplanted primordium also forms connections with surrounding tissues (arrector pili muscle and nerves) and repeats normal hair cycles”.
There are 100s of online anecdotal reports with before and after photos of people regrowing long-lost hair in bald scalps. Miracle results are especially common in people undergoing male-to-female transition regimens. You can also find many reports of surprising hair regrowth in many old men who recently started taking dutasteride for enlarged prostate issues. Maybe they regenerated their arrector pili muscles; or maybe those muscles always remained intact in spite of severe AGA; or maybe one can regenerate hair without the need for having any intact arrector pili muscles?
It is unclear when exactly we have a point of no return where the arrector pili muscle is largely or entirely replaced by fat and hair stops growing (either as a cause or effect). It seems like there is significant variation depending on person and hair follicle. In many cases, the arrector pili might not be entirely degenerated and replaced by adipose tissue even in areas of the scalp where one has been bald for several decades. In such cases, subsequent hair and muscle regeneration could then be possible via something like Dutasteride or Finasteride.

In this post, I cover two potential hair thickening ingredients in Stemoxydine and Resveratrol. A number of readers have mentioned both of these over the years. We now also have a product that includes both ingredients (see bottom of post), although no miracle results are expected.

When writing my 2017 post on the Kenogen phase of the hair growth cycle, one ingredient that I read about was Stemoxydine. According to a study from 2014, Stemoxydine acts as a kenogen phase shortener, leading to an increase in scalp hair density. Note that men with androgenetic alopecia have longer kenogen stages.

Stemoxydine

Stemoxydine is a topical hair loss product (not FDA approved) that was patented in 2012 by the cosmetics behemoth L’Oreal. It is classified as a prolyl-4-hydroxylase (P4H) inhibitor and its chemical structure consists of Diethyl pyridine-2,4-dicarboxylate. According to L’Oreal researchers, P4H inhibition leads to the creation of hypoxic (low oxygen) conditions.

This hypoxia environment is favorable for thicker denser hair growth due to a shorter kenogen phase. Stem cells product hair more effectively under the low oxygen conditions. Besides the earlier mentioned 2014 study from L’Oreal, there is no new evidence on the efficacy of Stemoxydine towards hair growth. L’Oreal uses Stemoxydine 5% in a few of its hair products.

Stemoxydine likely has fewer side effects than Minoxidil based on anecdotal reports and customer reviews.

Resveratrol and Hair Growth

Before NAD and NMN supplements along with TA-65 became popular for their potential anti-aging effects, there was Reservatrol (RSV). The latter “red wine molecule” was originally discovered in Japan in the 1930s, but became famous in 2004 courtesy of Dr. David Sinclair. Over the years, a number of people wondered whether Resveratrol would benefit hair, even just by making it thicker.

In 2021, a study from China concluded that Resveratrol prolongs the anagen growth phase of the hair follicle cycle. It delays progression to the catagen transitional phase when hair stops growing. Moreover, the researchers found hair growth promoting effects of RSV in mice, human hair follicles and dermal papilla cells. They concluded that RSV is expected to become a potential drug for the prevention and treatment of hair loss.

Serioxyl Denser Hair Treatment

Serioxyl with Resveratrol and Stemoxydine 5%. — Serioxyl denser hair solution with Resveratrol and Stemoxydine 5%.

When I originally wrote my best hair loss shampoos post, one product that got mentioned in various reviews was L’Oréal’s Serioxyl denser hair scalp solution. I did not think too much of it at the time.

However, more recently, L’Oreal came out with a new formula version of Serioxyl that contains both Stemoxydine 5% and Resveratrol. It currently has an average rating of 4.3 out of 5 stars on Amazon.

The company also published a study on this product in April 2020. They claim that the synergistic effect of using both Resveratrol and Stemoxydine (pyridine-2, 4-dicarboxylic acid diethyl ester) leads to denser hair.

In an interesting 2020 video, hair loss celebrity “MattDominance” discussed making a combination hair loss product. It contains topical finasteride plus topical Stemoxydine (via Serioxyl). Also check out Australia based “The Hair Loss Show” channel’s 2021 coverage of Stemoxydine.

The Arrector Pili Muscle (aka Goosebump Muscle)