Category Archives: Rodney Sinclair

Minoxidil as a Sublingual Tablet

Note that the increasingly popular low-dose oral Minoxidil for hair loss (taken via ingesting pills or tablets) acts a bit differently compared to sublingual Minoxidil (taken via dissolving under the tongue). Read the bottom half of this post for more details. Top half is all updates.

Sublingual Minoxidil for Hair Loss Updates

Update: February 2023 — A HRN forum member named “Viney” is posting excellent details with photos of his hair regrowth from sublingual Minoxidil and Dutasteride. He sees a dermatologist at Sinclair Dermatology (Melbourne, Australia).

Update: January 2023 — I posted something on Twitter about sublingual Minoxidil possibly being more effective than oral Minoxidil. Below are the interesting responses from Dr. Corralo and Dr. Bhoyrul:

Sublingual vs Oral Minoxidil

Sublingual Minoxidil Sulfate

Update: December 2022 — Also see this thread on Twitter in relation to the same subject.

Update: September 2021 — A clinical trial of 40 male and female patients receiving sublingual Minoxidil (SM) for androgenetic alopecia just ended. Per the summary, SM produced a dose-dependent increase in mean terminal hair count of the frontal and vertex scalp and an improvement in hair density. There was no affect on blood pressure. Quote from reviewer Dr. Mirmirani:

“The authors suggest that sublingual Minoxidil (SM) may have better bioavailability and fewer hemodynamic effects by avoiding first-pass liver metabolism. Although the data in this study are positive, it will take more to convince me that it is significantly better than oral Minoxidil (OM). Very few of my patients on low-dose OM for hair loss discontinue the medication due to side-effects. The other consideration is cost. OM it is an inexpensive, generic drug, that is covered by medical benefits.”

Update: March 2021 — An excellent video presentation on sublingual Minoxidil from Dr. Bevin Bhoyrul from Sinclair Dermatology:

Update: July 2020 — Also from Sinclair Dermatology comes a case series report of 64 patients taking sublingual Minoxidil (0.45 mg per day) for pattern hair loss.

April 9, 2018

Sinclair Dermatology

Sublingual Minoxidil Delivery
Sublingual Minoxidil Delivery.

Earlier today, a reader named Chris posted a very interesting video about a new hair loss treatment from Australia that entails putting some kind of dissolvable listerine-style strip underneath the tongue. Chris asked me for my opinion about this treatment.

At first, I thought that this seemed like an obvious scam since the title of the video includes the word “breakthrough” in it. Moreover, the video does not even mention what ingredients are in the sublingual strip or patch itself.

However, since the famous Australian dermatologist Dr. Rodney Sinclair appears in the video, I decided to conduct further research. Dr. Sinclair (associated with “The Hairy Pill“) is an extremely well respected researcher in the hair loss world. In the above video, he is honest and clearly says that this treatment will not bring back hair in totally bald scalps.

Having said that, so far it seems that the results from this treatment on people who have moderate levels of balding have been very positive. And this got me curious about what magic concoction was in the strip itself?

Clinical Trial for Sublingual Minoxidil

I did not have to conduct much further research to figure out what this new potential breakthrough hair loss cure entailed. On Dr. Sinclair’s blog, the latest post from today discusses a new clinical trial they are conducting that is recruiting both men and women. Volunteers will be treated with low-dose oral Minoxidil that will be given as a sublingual tablet (which will dissolve under the tongue).

I would not be surprised if the tablet is actually the strip/patch that was shown in the video I posted earlier. It would be very uncomfortable to put an actual tablet underneath the tongue and wait for it to dissolve, unless the dissolution happened very rapidly. On the other hand, a strip would be much easier to keep in place underneath the tongue for a longer period of time.

I discussed oral Minoxidil for hair loss in detail last year. While I often use topical Minoxidil foam, I would not take the oral version as I do not want more body hair as a potential side effect. However, oral Minoxidil clearly seems to be a superior option to topical Minoxidil when it comes to hair growth benefits. Partly due to the sulfotransferase issue.

If you live in Australia or in the nearby vicinity, perhaps it is worth volunteering for these trials. Today I finally learnt the definition of “sublingual”.

Also make sure to read my post on extra strength Minoxidil 15 percent for other alternatives to regular dosage store-bought Minoxidil foam.

The Arrector Pili Muscle (aka Goosebump Muscle)

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.