Rapamycin for Hair Growth and Pigmentation, Skin Anti-aging

This is a research paper from earlier this year that hasn’t gotten much attention. It seems like people may want to try topical rapamycin as a way to encourage hair regrowth and repigmentation.

Our preliminary data suggest that Rapamycin treatment can even partially restimulate pigmentation in some greying scalp HFs ex vivo . In contrast, TSC2 silencing ex vivo induced hyperactivation of mTORC1 and reduced human scalp HF melanogenesis.

In summary, we provide the first evidence that mTOR activity is an important, previously unappreciated physiological regulator of human hair growth and pigmentation. Thus, inhibiting intrafollicular mTORC1 activity by Rapa and rapalogs may become an attractive novel intervention strategy in the future management of greying, and alopecia.

Research Paper Overview here:

mTORC1 activity controls human scalp hair follicle pigmentation and growth
https://www.jidonline.org/article/S0022-202X(21)00855-1/fulltext#

It would be quite easy to create a topical “serum” with rapamycin powder.

If you have any friends who are chemists / biologists and have access to reagent suppliers, you can order rapamycin powder from suppliers like LC Laboratories. I’ve heard that some people crush up their sirolimus tablets to make rapamycin cream, which can result in a “chunkier” cream than is ideal. Lower purity rapamycin powder (e.g. from China) may also work in this application and be ok because the rapamycin skin study showed that topically applied rapamycin does not get into the blood stream, so you don’t have to worry about contaminants in lower quality rapamycin powder getting into your body.

Here is the best paper I’ve found that has detailed instructions on making a topical rapamycin cream. I imagine we could just use the Transcutol and rapamycin (mixed with a blender) in a formulation with a dropper to put it on the scalp for the “hair tonic” approach.

For topical / serum applications I used Transcutol to dissolve the rapamycin in. [I tried rapamycin cream for skin for 6 months, it works to reduce fine wrinkles but it wasn’t a huge benefit and new research came out later (see bottom of this post) that suggests that it may do some negative things to the skin also].

Where you can order Transcutol from Laballey.com:
https://www.laballey.com/…/diethylene-glycol-monoethyl…

The mTOR/Rapamycin/Hair research was previously identified by Matt Kaeberlein and Peter Attia:

On a related topic, there has been some research that suggests that rapamycin can be helpful for aging skin:

But there is also research that suggests rapamycin may not be that good for the skin, increasing inflammatory markers (which is not a good sign), and triggering a breakdown of the extracellular matrix:

"Rapamycin is a long studied molecule affecting mTOR/nutrient signaling and has recently been shown to decrease P16 levels of aging skin21, therefore it was chosen as a positive control of senotherapeutic effect in aging skin models. " … “Rapamycin induced a significant increase in P16 expression, a trend towards increased expression of inflammatory markers (IL6 and IL8), and a significant decrease in Keratin 1 gene expression levels (Fig. 3B). In the dermis, peptide 14 treatment promoted a significant reduction in B2M gene expression, a pro-aging factor, as well as in the expression ofIL8. Rapamycin treatment induced no significant changes in these markers and increased Matrix Metalloproteinase-1 (MMP1) gene expression, indicative of breakdown of the extracellular matrix (Fig. 3C).”

Source:
https://www.biorxiv.org/…/10.1101/2020.10.30.362822v2.full

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For two months, I’ve been using Dr. Green’s recipe, and I’ve noticed a slight darkening and very slight thickening of the hair at the hairline. No noticeable change to my skin. Since I’ve also been taking rapa orally during that same time, it’s impossible to know if it’s the cream. On his website, search the homepage for “The direction are add 1 capsule, 3 mg sirolimus, to 3.5 0z of Aquaphor Ointment. 3.5 Oz”

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Are you rubbing this on your head as well as your skin?

Details from Dr. Green’s website:

The direction are add 1 capsule, 3 mg sirolimus, to 3.5 0z of Aquaphor Ointment. 3.5 Oz is 99 gm or 99,000 mg. When add 3 mg to jar of 99,000 mg preparation is .003%. I use a much stronger preparation (15 capsules in 3.5 Oz to make a 0.045% ointment for age related and solar related lesions on my scalp with good effect. Since the powder is red, can see that it is well dispersed in the white ointment

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on the thinning front hairline and crown as well as my face and hands

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I’ve heard that higher concentration may inhibit hair growth
So I began with lower concentration, 1 mg sirolimus in 400g Aquaphor cream, and applied it on scalp, but no big change.
Hence I decided to try 16 mg sirolimus in 400g Aquaphor cream
And this time it worked, definitely worked, my hair became very thick and dense!

I am sure it’s not a placebo effect for me, because my hair is short, the hair density is easy to detect, and every friends notice my hair change

However, I also used this cream on my face and body, but I got itchy rash, so I stopped it on body.
I only use it on scalp now, and the result is satisfying

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I used 3mg for my 3.5oz Aquaphor cream. I’ll try higher concentration for my next batch.

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16mg in 400mg Aquafor? Did you mean 400 grams of Aquafor, or some other amount? Thanks!

Sorry that’s a typo, it’s 400 grams of Aquafor for sure

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I read the link suggesting rapamycin may not be that good for the skin last week and skimmed through it again today. Correct me if I am wrong, but it appears to have been for only 5 days with ex-vivo skin samples, and the funding was by a company with vested interests in having their product appear to be the best option. Their conclusions may be valid, but I am skeptical.

The study was funded by OneSkin, Inc., and supported by the Brazilian agencies FAPESP (2017/22057-5 e 2017/01184-9), CAPES, FAPDF, FUNDECT and CNPq.

Yes, I am skeptical.

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Skepticism is always appropriate when it comes to corporate-funded research.

However, given that rapamycin is the most well-known anti-aging molecule, but there is no commercial skin cream with rapamycin that they would be competing against (and only the really extreme geeks would know that topical rapamycin has even even been tried)… it doesn’t seem to me that lying or cheating on this type of analysis is going to be of much value. Its not like most people are comparing a non-prescription peptide cream to a rapamycin cream - so there is not much incentive to scam us on this…

The specific results:

“Rapamycin induced a significant increase in P16 expression, a trend towards increased expression of inflammatory markers (IL6 and IL8), and a significant decrease in Keratin 1 gene expression levels (Fig. 3B).

Are ultimately pretty easy to validate for anyone who has a lab, it seems.

I did try rapamycin cream I made for 6 months - saw a small improvement, but not sure if its worth it , even if it was not harming the skin via inflammation, and decreasing keratin 1 gene expression…

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@LeeJohn How long have you been using topical ramapycin on your scalp? Also, have you noticed your hair get curlier? At least with oral rapamycin, that’s been the case for me, although it may just be an instance of me being primed by Blagosklonny’s tweet where he mentioned something like that.

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Hair became curlier? That sounds cool
It has been roughly 6 months, I didn’t notice hair get curlier, but it has become denser then before definitely

However topical rapmycin didn’t turn my gray hair to black, I am still experimenting the concentration to see if topical rapmycin has any effect on follicular melanogenesis

You may want to try combining your regimen with microneedling to improve absorption.

I do this once in a while (combination of tretinoin + rapamycin). However my topical has dmso which is unpleasant for upto 30 minutes after application.

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I asked the microneedling with my dermatologist years before, but she thought it’s risky to use it at home without supervision, so I am cautious with it

Combination of tretinoin + rapamycin is a great idea, I have used tretinoin 0.1% on face&body for many years, It’s good to try it on scalp

I use a dermapen and I’m careful about having my scalp & hair, and the needles be clean and sanitized. I also only use fresh towels. But there may be other reasons to be careful too. Some folks who use microneedling complain of skin pigmentation that develops at the spot. Perhaps that happens when the needling is too frequent or too deep.

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I read through my comments and see your points. No implication of lying or cheating was meant. I have no doubt their results could easily be verified by other researchers. My skepticism is strongly related to how good a 5 day trial with ex-vivo skin samples can be. I would prefer a 6 months to 12 months trial using the skin cream on a large group of living humans, preferably not sponsored by any special interests. Is that likely? Well, probably not.

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Yes - sadly, not much gov’t funded cosmetic dermatology research… so we have to take what we have…

I’d trust the study performed with an actual rapamycin cream formulation, done over a period of 8 months, in humans, placebo controlled and blinded, showing positive anti-aging effects way more than the negative study, which was in vitro using cells from cadavers and looking at 100 nM concentration of rapamycin over a 5 day period. There’s just no comparison, IMO.

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I’ve been using the higher concentration of 16mg rapamycin in 3.5oz Aquaphor for almost three months, and I’ve continued to notice a slight creeping forward of my previously-receding hairline (< 1/2"), a little higher hair density, perhaps slight darkening, and a little kinkiness to the hair when there was none before. No dramatic effects, but it seems to be adding up over time.

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