Reverse Gray Hair, Hair Repigmentation

Many people like the idea of reversing gray hair, and regaining their youthful hair color and thickness, or preventing gray hair entirely before it starts. The topical drug treatment program outlined below was developed by RiverTown Therapeutics and has some reasonable clinical data and photographs that demonstrate some significant results (scroll down to see images). So, I’ve pulled this post out from the “Rapamycin for Hair and Skin” thread, to make it easier to see, and because I found some additional information on the compounds used in the related studies.

The drugs mentioned in the research below; Tacrolimus, and Cyclosporin (and Tofacitinib mentioned in the twitter thread below), are generic drugs that are easily and inexpensively available at the reliable Indian pharmacies without prescription, just email them for price quotes and see our section on importing medicines. Another compound mentioned (below), called RT175, is a drug/compound first identified by Guilford Pharmaceuticals (for a different application) and called GPI 1485, and while not FDA approved for anything yet, it is available from lab supply companies and probably china-based suppliers (but it may not be needed). David Sinclair in the video below is suggesting that Tacrolimus is basically the same as GPI 1485, so just use that instead.

DIY RiverTown Anti-Gray Hair Serum

It is relatively easy for anyone to create this formulation at home by using the off-the-shelf minoxidil solution as the starting point and add the different compounds (powdered and mixed, very similar to how people are creating their own rapamycin skin cream. For convenience, I’ve also written up instructions on how you could make this topical anti-gray hair serum here, but I recommend you read the full DIY rapamycin skin cream thread which includes a list of additional things you may want to buy.

The startup company behind this research; “Rivertown Therapeutics”, never gained the funding it needed, and was shut down a year or two ago, so the product is not going to be developed as a commercial product anytime soon. But, the research and commentary below may be of interest to people who want to leverage the knowledge for their personal use and benefit. Below in some twitter posts are some additional comments on the idea that alopecia may be, in part, a low grade auto-immune disorder, thus perhaps a rationale for why topical rapamycin seems to help (and why topical tacrolimus and cyclosporin also seem to promote hair growth).

An interesting biohacker test would be to try this formulation in two different scenarios:

  1. Preventing the ongoing development of gray hair; ideal for any people here who are just starting to get gray hair,
  2. Reversing Gray Hair: For those who have a moderate to substantial amount of gray hair.

If you try this, please take pre and post photos of your hair, and report back any results. And if you want to go all in on hair growth, you could use the other compounds that have significant evidence for hair growth, and use micro needling, as people in our forums are doing already: Rapamycin-Loaded Microneedles Reverse Hair Loss in Mice , and Minoxidil Tablet, not lotion, for Hair Growth

Harvard Genetics / Longevity researcher David Sinclair talks about the Rivertown research on reversing gray hair in a recent podcast episode. He specifically brings up the Tacrolimus + CyclosporinA + Minoxidil research paper we link to below, out of the University of Alabama. The Video is queued up at the correct time below for this discussion:

Rivertown Therapeutics was started by Dr. David Weinstein:

Weinstein is a neuroscientist specializing in spinal-cord injuries and nerve regeneration. Working in his lab, in his spare time, he developed a drug compound he called RT1640.

Then Weinstein began experimenting on himself. “I didn’t tell anybody I was doing this, including my wife. And, after a couple of weeks, I said, ‘Look at my head.’ And she said, ‘Your hair is growing. Why?’ ”

Weinstein has big dark eyebrows and a kind face. Kind of an Elliott Gould vibe. I looked at his head. There was a spotty, thatchy outcropping of gray-black hair. Not exactly an overflowing abundance, but hair, to be sure. “I had nothing on top,” Weinstein said. “You can see—I grew my hair back! And it grew back more or less the color I had when I was young.” (source: New Yorker article)

Examples of Grey Hair Reversal and Growth Results from RiverTown


Topical RT1640 treatment effectively reverses gray hair and stem cell loss in a mouse model of radiation-induced canities

One potential combination therapeutic is RT1640, which is comprised of two drugs that are known to stimulate hair growth (cyclosporine A [CsA] and minoxidil), along with RT175, a non-immunosuppressive immunophilin ligand that is implicated in tissue regeneration. Using the ionizing radiation-induced acute mouse model of hair graying, we demonstrate that RT1640, over CsA alone, promotes regeneration of the hair pigment system during and following treatment. In non-irradiated mice, RT1640 is also physiologically active and successfully speeds hair growth and expands the McSC pool. It appears that this effect relies on the combined activities of the three drugs within RT1640 to simultaneously activate hair growth and McSCs as RT175 alone was insufficient to induce hair cycling in vivo, yet sufficient to drive the upregulation of the melanogenic program in vitro. This study sets the stage for further investigation into RT1640 and its components in McSC biology and, ultimately, melanocyte hypopigmentary disorders associated with disease and aging.

RT1640 consists of three drugs, cyclosporine A (CsA), minoxidil and RT175 (an immunophilin ligand). RT175 is a derivative of the immunosuppressant FK506 (also known clinically as Tacrolimus). Historically, FK506 was shown to have both immunomodulatory and regenerative properties that function through independent mechanisms. The non-immunosuppressive immunophilins ligands, like RT175, were developed to capitalize on the regenerative aspects of FK506 while avoiding the negative side effects associated with the immune role of this drug

Topical application of drugs to the skin
The composition of RT1640 is cyclosporin A (1.2mg/ml; Medisca NDC # 38779-0660-01), minoxidil (5 mg/ml; Medisca NDC # 38779-0574-05), and RT175 (120 ng/ml; manufactured for RiverTown Therapeutics, Inc. by Hovione FarmaCiencia SA, Lisbon, Portugal) diluted in 50:30:20 propylene glycol:ethanol:H2O. The Accepted Article composition of CsA is cyclosporin A (1.2mg/ml) diluted in 50:30:20 propylene glycol:ethanol:H2O. Gray-IR mice were gently shaved along their lower back and treated twice daily with the indicated solutions by smearing 150 l topically onto the lower back for 21 days. Both RT1640 and CsA induced hair cycling, and after treatment the mice were photographed to record visual changes in pigmentation of the newly grown hairs. These hairs were plucked an additional time to quantify the portion of pigmented and non-pigmented hairs and to initiate an additional round of hair cycling. Skins from these mice were harvested 7 days after the last hair plucking. Necropsy of these mice was also performed. Skin, lung, lymph, and brain was inspected for microscopic pigmented nevi that would be indicative of melanoma tumor formation. None were observed in any of the mice treated.

Full Research Paper (PDF) at link below:

Topical RT1640 treatment effectively reverses gray hair and stem cell loss in a mouse model of radiation-induced canities

http://sci-hub.wf/10.1111/pcmr.12913

Patents related to the compound RT175 mentioned in the paper above:

It seems that the startup company never got the necessary funding, and closed up shop in 2019 or 2020. Their website at rivertowntherapeutics.com is now gone, and their web domain is for sale.

Older write-ups on this topic:

There was some twitter discussion on RiverTown when it first started getting some press coverage:

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This is great stuff…but what a HORRIBLY done study.

“While our in vitro data suggests that RT175 is sufficient to enhance melanogenic gene expression directly, our in vivo data suggests that the success of RT1640 in promoting hair repigmentation lies in the fact that this combination therapy, above any of its individual components, addresses the reactivation requirements of the hair follicle and pigment system simultaneously. While these studies cannot distinguish whether reversal of gray hair in our IR mouse model is due to the RT175 OR minoxidil component of RT1640, our in vitro data supports a direct role for RT175 in regulation of melanogenesis”

There is NO MINOXIDIL control mouse cohort!! It would have taken nothing to do a minoxodil control. This seems seriously fishy to me in the promotion of Tacromilus!

This is similar to Agetron and his miraculous hair revival brew (which includes Minoxidil)…what’s doing the hair growth? He may be a super minoxodil hyper responder.

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At least tacromlimus and cyclosporin are already available as a reasonably cheap ointments… (as well as pimecrolimus)

I would suggest that someone with a graying beard tries one half of the face with one of these ointments

I could try but I haven’t used rapamycin for that long and I want to observe its effects first. Price for the 3 substances seems to be around 10-15 euros for 10-15g of ointments with a dose of 0.3-1mg/g

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Has anyone noticed any differences to their hair texture, shedding rate, color or growth since starting oral rapamycin?

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I have noticed no effects whatsoever except for slight side effects of the rapamycin initially so far but I only started in June

3 weeks ago, I added scalp topical rapamycin dissolved in ethanol. Not a huge fan of using DMSO because it increases permeability all over the body. Might try scalp microneedllng. Super interested in following this.

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I generally use Transcutol… for example, that is the base I used for my rapamycin skin cream.

Details below:

Note: Transcutol has a number of different chemical names/identifiers. Here is a list: 2-(2-Ethoxyethoxy)ethanol: Ethoxydiglycol, 3,6-dioxa-1-octanol, DEGEE, diethylene glycol monoethyl ether, Carbitol, Carbitol Cellosolve, Transcutol, Dioxitol, Polysolv DE, Dowanal DE

Chemical Identifier: CAS Number 111-90-0

Where you can order / buy Transcutol from:
LotionCrafters: Transcutol / Ethoxydiglycol
Laballey.com: Transcutol / Diethylene Glycol Monoethyl Ether

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Yes - they are available as cheap ointments, but personally I’d prefer to get the tablets, crush/grind them into powders, dissolve the powder in transcutol, and then apply the serum via dropper onto the skin. Seems easier to me. The issue is that Minoxidil comes in liquid, foam or tablet form. And the others in tablet or ointment form. Mixing the gels and ointments and foam/liquid minoxidil (with their different consistencies, etc.), or applying them on scalp one at a time, seems more potentially problematic and a hassle (to me at least).

cyclophil-50-mg-500x500
tacrograf-2-500x500
tacrolimus-ointment-500x500
visiocare-ointment-500x500

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I’m 35 taking 6mg/wk. I definitely have fewer gray hairs.

I’m also taking glycine 3g and NAC 2g daily so that may be a factor.

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One person replied to me as follows:

There may be something here… my father had a bone marrow transplant, and was taking serolimus & tacrolimus as anti-rejection drugs for several months. His eyebrows changed color from gray to dark brown. It didn’t affect any other areas, though.

I have a few greys here and there, but not much for 57 yo male compared to my peers. With the new high dosing rapamycin protocol (confirmed AUC), you’d think I’d be a good n=1 signal for rapamycin impact. I will attempt to track and report back. Will take some pics at various angles to capture density of greys and do followup few months.

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Update:

I gave David Weinstein, the founder of Rivertown (now at Apellis Pharmaceuticals), a call to talk about what happened at Rivertown. He’s a very genial and talkative fellow and was happy to answer my questions and very enjoyable to discuss this with. (we ended up going on a long tangent discussing rapamycin).

He said the key issue was that it is very hard to get funding around a combination product (with generic drugs as key parts of the combination) in the cosmeceutical market space. I suspect that behind this may be the issue of how defensible any patent would be in this area, and of course the cost of large clinical trials is very significant to get FDA approval.

He said there is ongoing research with these compounds he is involved in (he is the PI) at the University Alabama which is also focused on hair color reversal, and he remains very confident about the results of this formulation.

David said that they had tested it with 40 to 50 people during the course of his efforts with Rivertown the past few years, and there were very high rates of efficacy. Anytime you stimulate the renewed hair cycle he said, you will get return of the hair color. Only if you have had a completely bald head for a significant period of time does he think it will not work at all.

The medical name for the process of hair going gray is, David informed me, achromotrichia. Put simply, ‘achromotrichia’ is defined as the absence or loss of pigmentation in the hair.

I discussed with David Weinstein the differences between the compound which he had identified in the lab (which only later did he discover had also been identified by Guilford Pharmaceuticals independently) and tacrolimus.

Tacrolimus, he said is very similar to GPI 1485 (GPI 1485 is actually derived of tacrolimus), but GPI 1485 is not an immunosuppressant. David said he was apprehensive around the idea of ongoing use of an immunosupressant even in topical form. (though in the study of topical rapamycin cream for skin aging, there was no systemic take-up of topically applied rapamycin, so I think his concern may be overblown).

David commented on how the research behind GPI 1485 (and what he saw) is that its very effective in increasing speed of wound healing. He commented on how tacrolimus, as an immunosuppressant, likely slows wound healing. So, he suggested while tacrolimus may have some of the same effects as GPI 1485, it also has some risks and downsides. So, in an ideal world, you probably want to use GPI 1485, if you can get it.

For people looking for this chemical, here are the identifiers:

GPI-1485

CAS No. : 186268-78-0

More on the molecule:

And David Weinstein’s research that led him, accidentally, to the hair formulation:

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Did ITP ever test pulsed tacromlimus, cyclosporin or any other calcineurine inhibitors?

No - you can see the list of tested compounds here:

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I wonder if there is a synergistic effect. You know what I’ll get a tube of tacromlimus ointment and apply it to half my face and see what happens

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RapAdmin, So, you used crushed pills and Transcutol only in your skin cream? I thought pure Transcutol on the skin would be too harsh, but maybe not. Do you mind sharing your exact formula of rapamycin pills and Transcutol in terms of milligrams of rapamycin and grams or ounces of Transcutol? And, you apply with a dropper. Does it spread smoothly? Do you wash your hands afterward. Yes, it does seem less complicated, but do you see any good results? Thanks for any response.

Oh no - I started with raw rapamycin power from a lab supply house, then mixed it with Transcutol (I forget exactly how much - a small amount, perhaps 20 or 30 ml). Blended that for a while in a metal bowl with my blender. Then added Cetaphil (or something similar) to the mixture - a large tub, approx. 500 grams), and blended that together in the same metal bowl for about 5 minutes to get it fully mixed.
When I was using the rapamycin skin cream - I’d apply it typically morning and evening, just like any moisturizer. It definitely has an effect - but its not life-changing (perhaps similar in effect size to retin-A creams).

I was just referring to the general technique more broadly.

Gray Hair Reversal Recipe

For the RiverTown anti-gray hair serum it will start the same (but I’m going to use tablets this time, not the lab-supply powder). Something like the following (I’m still working on this, will do a full writeup in the next week):

For a 100 gram (3.5 oz) batch of the formulation I think I’ll use something like:

  • 120 mg cyclosporin (approx. 5 of the 25mg tablets, powdered)
  • 500 mg of minoxidil (approx. 50 of the 10mg tablets, powdered)
  • 100 mg of tacrolimus (approx. 50 of the 2mg tablets, powdered)

mix up in 20ml or so of transcutol, then add the other liquids to dilute it.
In the Rivertown formula they use the ratio: 50:30:20 of propylene glycol : ethanol : H2O.

I’ve had problems in the past with the topical minoxidil liquid mix causing scalp rash problems (not sure if it is the propylene glycol or the ethanol that is the issue) - so I’m evaluating other options and would appreciate any input here that people might have.

I might try just transcutol and see how it works on my skin as a first effort.

What might be some reasonable other options for mixing into the formulation? please comment if you have any ideas, and provide links to the literature that have made you think these other compounds might be good to replace the propylene glycol or ethanol for the hair serum.

General Hair Growth Serum Compounds

If you are very interested in the hair growth aspect (more so than just the gray hair reversal aspect) then you probably want to look at the minoxidil tablet successes that have been covered in The NY Times (Minoxidil Pills, An Old Medicine Grows New Hair for Pennies Per Day) and elsewhere recently.

And there are many other compounds that could be added to a hair growth serum that look like the have potential (and that have been discussed in depth in the "Rapamycin for Hair / Pigmentation / Skin anti-aging thread). These compounds for topical use include:

  • Rapamycin
  • Dutasteride or finasteride
  • Metformin
  • Tofacitinib
  • Ketoconazole
  • bimatoprost
  • ECGC
  • Rapamycin
  • valproic acid

Tretinoin (topical Mixture - Gel form) - this is a little more complex because I can only seem to find tretinoin gel that would work, not something I can readily mix with the rest of the compounds, so perhaps this needs to be a separate step / application layer.

And if you want to get really fancy, you could also do micro-needling to your scalp (with appropriate precautions). Micro-needling info here: Rapamycin-Loaded Microneedles Reverse Hair Loss in Mice

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I have not done enough research to know about other options at this time. Will post if I find something.

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Looking forward to your post after you formulate your batch. Which pharmacy do you prefer when your order is many disparate products along with your (preferably Zydus) rapamycin (I have a large order coming up with at least 10 different drugs for myself and family- many I have lazily just ordered from alldaychemist in the past, but their prices on many things are 2-4x what you’d get direct)?

You (and @Agetron too!) should really do a youtube video of your process making your concoction. You could film just the counter with your hands to preserve anonymity. For many of us (hand raised), watching somebody do this is infinitely more helpful/motivating than reading about it. Often I’ll read something and think “wow, this sounds complicated and difficult”. Then I’ll find a youtube video and it’s “that’s way easier than I thought- hell, I can do that”.

And, yes- the propylene glycol in the Kirkland (and all) topical minoxidil causes problems for a lot of people. There are people that sell minoxidil at 5x the price who compound it with something else for just that reason. Derek, the moreplatesmoredates bro-science entrepreneur sells it, among others.

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I don’t have any preferred pharmacy, in fact quite the opposite, I spread my orders across all the different reliable online pharmacies so I get a feel for the different prices, and service level of the vendors. So far, they all seem pretty similar but prices vary significantly (but they seem to price based on perceived demand and supply).

Interesting idea about the video. I’ll consider it. I don’t have a video camera, so it would just be the cell phone - and I’m not sure that would be very good quality for a YouTube video. But, I’ll try when I do make the formula.

Regarding the replacement for the propylene glycol … good to know I’m not the only one who doesn’t like that. I’ve heard from others beside you also on this issue.

Alternative Excipients (to replace propylene glycol)

I’m going to look around and see what other groups use. I notice that the Formulation 82M that was mentioned in The NY Times article about Minoxidil tablets, has this formulation:

82M is a customized compounded prescription solution that contains the FDA-approved hair growth medication Minoxidil 5%, Tretinoin 0.01% for enhanced penetration and hair growth effect, the anti-inflammatory Fluocinolone 0.01%, an organic anti-androgen Oleanolic Acid and a sophisticated blend of powerful antioxidants, scalp conditioners and hair conditioners in a non-irritating propylene glycol-free base.

Source: Formula 82M - Compounded Minoxidil Formula - 3 Month Supply — Bauman Medical

I think I saw somewhere that this formula uses a product called “Trichosol” - but I may have seen it in another product. I’m looking at it as a potential replacement for the propylene glycol. See website here: TrichoConcept™ - Uni-Chem

I saw this comment on another forum:

Another option is Minoxidil in Trichosol, sold by Farmacia Andorra.

Trichosol is non-alcoholic solvent for hair medications, and it doesn’t have PG but it’s indeed minimally greasy due to essential oils. I apply trichosol with syringe or pipette directly onto the scalp and it’s cosmetically acceptable.

Formula 82F is similar:

82F is a topical compounded prescription solution containing the FDA-approved hair growth medications finasteride 0.25% and minoxidil 5%, as well as retinoic acid for enhanced penetration of minoxidil and sebum reduction, a mild low-dose anti-inflammatory, oleanolic acid—a mild anti-androgen, and other beneficial ingredients such as powerful antioxidant algae extracts without any propylene glycol (a common irritant) at a neutral pH. Finasteride is the active ingredient in the FDA-approved drug Propecia.

The website notes:

Why Compounded Minoxidil Formula 82M?

Unfortunately, despite the hair growth properties of minoxidil, the over-the-counter Rogaine, Rogaine Foam or generic versions can often come with unwanted side effects like itchy scalp, scalp irritation, sticky and oily or greasy residues that interfere with hairstyling and more.

How is Minoxidil Formula 82M applied?

Dr. Bauman recommends that at least 20-30 drops of Formula 82M should be applied twice daily to the entire scalp, focusing primarily in the areas of concern. For maximum effect, minoxidil should be spread evenly and allowed to absorb for at least three hours before showering, swimming or participating in heavy physical activity. A special ‘droptainer’ bottle allows for the accurate application of Formula 82M directly where you need it… on the scalp, not on your hair.

Formula 82M is a topical product that deeply penetrates the scalp with a blend of 5% minoxidil, vitamin E, biotin, retinoic acid, a 5-alpha reductase inhibitor, and several other active ingredients not found in over-the-counter formulas. This powerful blend of ingredients is capable of slowing hair loss and thickening hair.

The combination of minoxidil and tretinoin has been proven to increase the efficacy of minoxidil by increasing percutaneous absorption threefold. One study showed that tretinoin alone increased hair growth by 58%, while the combination of minoxidil and tretinoin increased hair growth in 66% of individuals.

Here is another formulation:

follikle formula

  • Finasteride 0.25%
  • Minoxidil 8%
  • Retinoic Acid 0.01%
  • Hydrocortisone 1%

Other compound ideas I’m coming across as I search the web: (Alternatives to propylene glycol) from the /Tressless subreddit:

ell-cranell, it has propanol, glycerol and myo-inositol in addition to alfatradiol.

My guess is that any kind of cosmetic solvent would do the trick and the solvent doesn’t react with finasteride chemically. How about glycerine or hyaluronic acid? I am guessing water would be too viscous.

KB solution or stemoxydine.

Minoxidilmax sells premixed RU solution without propylene glycol. Haven’t tried it yet but you might consider it

minoxidil and finasteride with trichosol in a compounding pharmacy is by far the best option in the world

you can check this formulation l, has PEG, but only at 5%.
https://www.reddit.com/r/tressless/comments/uj78ay/a_topical_finasteride_solution_for_those_with/?utm_medium=android_app&utm_source=share

Humectants by their very nature will make hair greasy. Glycerin will be somewhat less greasy than PG though

DMSO might be a little bit too effective without something like a humectant or oleic acid to keep the drug in the dermis a little longer. Speaking of, oleic acid might be of interest to you:
Oleic Acid: Its Effects on Stratum Corneum in Relation to (Trans)Dermal Drug Delivery | SpringerLink