Updates on Research into the Activation of the Wnt/β-catenin Pathway

I have discussed the Wnt/β-catenin pathway and Wnt signaling numerous times on this blog in the past. This avenue of research is one of the most exciting ones out there in the hair loss world. It does not involve any kind of complicated cell multiplication and implantation related procedure. If realized, the cure or treatment for hair loss that will arise from activating the Wnt signaling pathway (and subsequently maintaining the epithelial β-catenin signaling) will likely come from a topical product.

Of note, defects in the workings of the Wnt pathway are implicated in numerous diseases and medical conditions. Therefore, there are numerous scientists around the world who are studying this important subject matter for non-alopecia related reasons.

Wnt Signaling and Hair Loss: Updates

  • By far the most well known company that is currently working on a topical hair loss drug to activate this pathway is Samumed. We are all eagerly awaiting their publication of final Phase II clinical trial results and subsequent commencement of Phase III trials. Several people recently noted that Samumed just completed Phase II trials, but I think that those were completed last year per this official government source. However, detailed published results are still not final. In any case, perhaps the pipeline page’s bar for the SM04554 hair loss product did move forward a bit recently per one commentator implication? I am on the company’s mailing list, but have received no recent email updates regarding the hair loss product. I am hoping it will happen any day now. Worth monitoring their Twitter account.
  • In my last post, I mentioned that Dr. Antonella Tosti is presenting a paper titled “A new topical Wnt/beta-catenin activator in the treatment of men with male pattern hair loss”. I wondered what topical this would be, and commentator “Bob Ross’s Hair” hypothesized that is was methyl vanillate based on this study from 2016 in which Dr. Tosti is a co-author.
  • Related to the above, Dr. John Cole’s staff recently wrote a blog post on their new WNT Act product for sale in the US. This product contains methyl vanillate. Dr. Cole has collaborated with Dr. Tosti (and various other Italian scientists) many times in the past and mentioned this in his interview on this blog. It seems like the Deltacrin WNT product sold in Italy is the exact same thing as the WNT Act product being sold in the US. On the US product’s Amazon page, they claim a 7% increase in hair density and a 10% increase in hair diameter.
  • Commentator “Donitello” who often posts nonsense did surprise me and found a gem early last week that all my google alerts missed. A South Korean company named JW Pharmaceutical (in partnership with the University of Pennsylvania and Dr. George Cotsarelis) is developing a topical Wnt signal activating product to tackle hair loss. The product is currently known as CWL08006, and the company aims to start pre-clinical trials in 2019 and certain types of human testing in 2018. Apparently JW Pharma has been conducting research on the Wnt pathway since the early 2000s, and currently holds numerous patents and rights to proprietary compounds in this area.

50 thoughts on “Updates on Research into the Activation of the Wnt/β-catenin Pathway”

  1. even a broken clock is right twice a day 🙂

    jokes aside, I dont believe WNT would be a solution for our hopes. we need something at least improve few NWs..
    cure for me: improve 2-3 NWs e.g. NW5 to NW3

    1. You try propecia? Just asking. I was asked to train hard again in the gym….as this might lead to an opportunity for me. Tbh, I have a bottle of finasteride and nervous. Idk if blocking the conversion of test to dht also activates other areas via cortisol or brain. If it just suppressed dht and didn’t kill conversion reductase…I don’t think I would be as nervous. I think I am a NW 2-2.5. My hair was do to medication error.over a year later…haven’t lost more, but did not regain. Caused recession but the tissue is not scared over…so in recessed area technically still alive, according to a M.D. Dermatologist. My finasteride was prescribed by another doc…whom was willing to look at compound topical finasteride if I can give hi data or mechsnisms of how to write the script…AKA he didn’t know what could make it penetrate scalp and dose etc.

    2. Donitello, this is why I hate banning people, even repeat offenders. They can still come out with something unique and useful.

      BTW — many of your past links were already posted in comments (sometimes to the same post), so I am glad that this time you were the first one.

  2. Tbh right now topical finasteride that could penetrate quick with latanoprost and A. Acid is probably the best thing. Replicel I read has failed to deliver phase 2 with sheisedo…this was a month ago I read. Making their partnership merky. Although the Japan company can just do it themselves. Bodybuilders in particular are looking at compounded topical as above. Some claim ghrp 6 ….has stimulated hair. However one would need to be on that for awhile…and it wouldn’t be advised to do so.in 2k15 …2018 was suppose to be the year for hair loss treatments and that seems mute.When I see lebron James hair come back…then I believe lol. As funny as that sounds…many NBA athletes seek treatment post injury outside U.S.A and try things.

    1. I want to know too, if anyone has tried that product. How long does a bottle last and can you buy the active ingredients elsewhere since the price of the amazon product is sky high .

  3. Do you think that if there would be an ability to replace testosterone as the primary male hormone, with for example Trestolone (does not convert to DHT, completely inhibits LH and testosterone production), that could be potentially beneficial for hair loss sufferers?

  4. Something tells me there wasn’t much positive to report for the near future considering the only news being reported on forums is wnt research.smh

    1. We can only know the positivity versus negativity if we were there in person at the WCHR conference in Japan this past week. Otherwise all speculation.

      And Samumed was on the cover of Forbes magazine last year, so I would not take Wnt research lightly.

  5. I think the research collaboration with jwc and university Pennsylvania could be really good. Yes they plan on clinicAL trials in 2019 but they did mention trying to release a cosmetic wnt for hair loss in the next couple years. Maybe this will work better than Rogaine. I’ll take anything at this point. I hope SM comes out with good news soon. If they can achieve 20% regrowth and thickening of existing hair then that would be great. Something has to come out in the next 24 months.

  6. I almost ordered the Wnt product last night, but when i looked for pics there was a surprising (or maybe not so surprising) lack of photos. I decided against it because the two that i saw were extreme closeups and could have easily been faked

  7. Admin I certainly do not take WNT lightly. I do however regret that their isn’t and probaby won’t be a legit WNT product available for a while. Now many of the balding men on here will have children that will be happy about WNT for sure.

  8. Regarding methyl vanillate:

    – As far as I know, the idea of methyl vanillate comes from a 2014 South Korean study which looked at Wnt/B-catenin signalling for osteporosis (Cha, 2014, Hovenia dulcis Thunb Extract and Its Ingredient Methyl Vanillate Activate Wnt/β-Catenin Pathway and Increase Bone Mass in Growing or Ovariectomized Mice, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899039/).

    – In that 2014 Cha study, researchers examined 350 plants to find which might effectively and safely induce osteoblast differentiation to improve quality and quantity of mice bone. From this, they identified the extract from the Hovenia dulcis (the Japanese raisin tree, a tree native to eastern Asia which has been used in traditional medicines for treatment of liver diseases and for detoxification of alcohol poisoning -https://en.wikipedia.org/wiki/Hovenia_dulcis). They then examined 8 ingredients of the Hovenia extract, and concluded that methyl vanillate (MV) increased osteoblast differentiation with activation of the Wnt/β-catenin pathway. They also found that MV was beneficial when taken orally. Note that MV is used for flavoring in the food and beverage industry, and is considered safe for humans.

    – The 2016 Tosti study took the idea of methyl vanillate from the 2014 Cha osteoporosis study to examine any benefit in hair loss. They had n=20 Caucasian female patients (age range: 25-57 years) with AGA; n=10 patients were in Florida, USA, and n=10 were in unspecified “European private practices and dermatology clinics”. The woman used an alcohol-free spray with 0.2% methyl vanillate (vehicle unspecified), spraying 2mL every other day for 6 months on their scalp vertex and rubbing it throughout the area of hair loss.

    – Results: “The mean hair counts were 40.2 +/- 6.7 (range, 26–49) at baseline and 42.5 +/- 7.8 (range, 24–52) at 6 months. The mean increase in total hair count from baseline to 6 months was 2.3… The overall satisfaction with the topical spray was rated as excellent by seven patients (35%), good by eight patients (40%), average by three patients (15%), and poor by two patients (10%).”

    – Some obvious problems with the study: Only women, no men (!). Very small number of patients. No control group with placebo treatment. No comparison to other Wnt/β-catenin pathway-activating ingredients which have already been researched on hair, most obviously valproic acid (VPA). Different analysis methods were used for different subsets of the patients. Range of results is huge; for example, in examining the data, it seems that fully 20% of the patients experienced negative hair counts, i.e. hair loss, over the 6-month period. Vehicle is only specified as “an alcohol-free forumulation”.

    – The Italian pharmaceutical company Biodue S.p.A. (English info: http://www.pharcos.com/en/azienda/) pays research grants to the corresponding author of this study (Enzo Emanuele). Additionally, Biodue “partly” paid for this study. Biodue/Pharcos produces a hair-loss product line called Deltacrin which includes a food supplement with melatonin and extracts of soy and carthamus, a conditioning shampoo, a “strengthening and sebum balancing cosmetic adjuvant”, and the WNT spray, shampoo, and supplement (http://www.pharcos.com/en/lines/linea-deltacrin-en-en-en-it-it/, http://www.pharcos.com/en/products/endeltacrin-wnt-shampoo/).

    – The ingredients of the Deltacrin WNT product, as per the Pharcos website: “Aqua, Propylene Glycol, Trehalose, Panthenol, PEG-40 Hydrogenated Castor Oil, Methyl Vanillate, Wheat Amino Acids, Soy Amino Acids, Arginine HCl, Serine, Threonine, Niacinamide, Faex Extract, Aesculus Hippocastanum Extract, Ammonium Glycyrrhizate, Zinc Gluconate, Caffeine, Biotin, Manganese PCA, Disodium EDTA, Sodium Hydroxymetylglycinate, Lactic Acid, Parfum”. Some very interesting ingredients in addition to the methyl vanillate lol.

    – Dr. Cole’s forhair site says that Deltacrin WNT and WNT Act are the same product, where “Deltacrin WNT is sold in Italy exclusively and WNT Act is sold in the USA”.

    – The forhair site uses the Tosti 2016 study as the evidence for their claims – on Amazon and elsewhere – that with WNT Act, “patients achieve 10% increase in hair diameter and a 7% increase in hair density. Quite impressive, as no negative effects have been reported.” The forhair site adds: “WNT Act works separate from Rogaine or Propecia. This means that using this WNT Act increases density in addition to the benefits of whatever other hair treatments you use. It is now possible to increase hair density by 20%+ via treatments alone.”

    – Pictures on Dr. Cole’s forhair site show the “results” of WNT Act. There are no pictures in the 6-page 2016 Tosti study which I have. Instead, it seems that the pictures on Dr. Cole’s forhair site were taken – without attribution – from the site keratin.com (http://www.keratin.com/aa/aa014.shtml), where they are used to illustrate different hair densities. As far as I can tell, these pictures have been on the keratin.com website for many years prior to the release of the 2016 study or the Wnt Act/Deltacrin product. If that is correct, the pictures cannot have anything to do with methyl vanillate.

    – Not to be petty, and it’s really the least of all the issues here, but the Tosti study shows a mean increase of 5.7%. In the study abstract, that’s rounded up to 6%. However, in the WNT Act marketing, they claim a 7% increase in hair density, which as far as I can tell is this same 5.7% result from the Tosti study. Regarding the “10% increase in hair diameter” that WNT Act claims, I can’t find it in the 2016 Tosti study; in the research, they measured an increase of 11.6% in the “hair-mass index”, which is not defined but which I assume must be sq. mms of hair per sq. cm of skin (based on Cohen’s 2008 cross-section trichometer method https://www.ncbi.nlm.nih.gov/pubmed/18384368). There are lots of other imprecisions like these both in the study and in the marketing.

    Additional points:

    – The WNT Act product sells on Amazon for a price of US$80 for 2.4oz. I think that equates to 71mL, although ounce measurements can be confusing. The percentage of methyl vanillate in the product is not specified. Cole’s forhair site recommends daily use, so with 2mL per day, the WNT Act bottle would last about 1 month for that price of US$80. [Cole’s forhair staff suggest daily use rather than every-other-day; although they cite the Italian study, their blog indicates that they didn’t actually read it, so they weren’t aware that the patients in the study used the product every other day rather than every day. On the other hand, although I don’t think that they thought it through this much, but the 2014 Cha study does show that MV increases osteoblast formation in a dose-dependent manner, so more might actually be better in any event lol].

    – Unlike many chemicals used in DIY kitchen labs for AGA, the ingredient methyl vanillate is cheap and easy to buy (no problems with import restrictions, no worries about dodgy factories and middlemen… that’s very nice when compared to what you have to go through with many others of these products). Molecular weight 182, which is also nice. Even massively increasing the dosage amounts in the 2016 Tosti study, you could buy a few years’ worth of MV for less than US$50. Based on what I wrote above, I think Dr. Cole’s product isn’t worth it and his marketing is incorrect, imprecise, and likely fraudulent, but that does not mean that methyl vanillate itself is worthless. So if you want to try MV, just buy some and do it yourself.

    – Best research on Wnt/B pathway and hair which I’ve found is from a group of South Korean researchers, Dr. S.J. Jo in particular in 2013, 2014, 2015, plus Yonsei researchers in 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323655/, https://www.ncbi.nlm.nih.gov/pubmed/24533507, https://www.ncbi.nlm.nih.gov/pubmed/28595998

    – With all this, it’s interesting to think about DKK 1. Powerful Wnt antagonist and is upregulated in hair follicle dermal papilla. Maybe block ER-β? Anyone have any ideas?

    – I’ve seen several Wnt/B-catenin activators used for hair loss, like VPA, lithium, methyl vanillate, etc. Has anyone seen any research on these? Experiments comparing them on a DIY basis by kitchen-lab forum guys?

    – I’ve seen a few guys on different forums in the last years who had disappointing results from VPA alone. Personally, I’ve been using sodium valproate (epilepsy drug) for about 2 months. Cheap, stable, easy to apply. I’ve gotten vertex regrowth and was surprised very recently to see new dark vellus hairs popping out on temples, but I’m using so many products (incl. dermapenning) that it’s impossible to say what benefit is from VPA specifically.

    1. Thank you for that detailed description. I was on the fence of buying but now I’m definitely gonna pass on that especially since Ive done work with Dr Cole.

    2. Hi man!
      What please could you advice what kind of VPA source do you use ?
      I’ve tried liquid syrup with VPA (Convulex) and it cause skin shedding like after sunburn.

    3. This is the type of constructive, well thought out, objective comment that adds to all of the latest developments brought to us by Admin and others, and what keeps me tuned in to this blog. Even though long, it does not waste a bit of anyone’s time. Thanks!

  9. More and more people are aware that the current situation to treat androgenetic alopecia in men and women is so bad and current treatments are precarious. Improvements are expected shortly, that’s for sure.

  10. @guest99: if you don’t think like pheonix you don’t have mpb…you are a commercial or something like that…Current situation with mpb treatment is deplorable…

  11. Hey everyone, haven’t posted or even visited this page in a while. Just wanted to come back with an update on my hair. Ive been on fin for around 8-9 months now and WOW. I was a big fin hater my first go around if some of you remember my posts from over a year ago. Had awful sexual sides and it seemed to just make my hair worse. I decided to give it another go when my hairline tanked.

    Long story short, not quite a year on it, but these last couple months have been awesome for me. Hair is quite thick again, and seems to keep getting better. Temples look Alot better, and even hairline density got way better. I got scared at first because I lost alot wheb first starting fin again this time. It was see through about 4-5 months into fin. Now at almost month 9 it looks wayyyy better. Even if my hair is wet now it is hard to tell im balding.

    If anyone remembers, i also started taking grapeseed extract to battle fin libido sides. I have 0 problems in the bedroom now. It was a little iffy when I first started fin again, but in no time im back to normal. I take 1 a day with fin and two L-arginine tabs and thats it. Honestly I worried so much for over two years about how bad my hair was getting and this feels like its bought me quite a bit of time. I recommend if you are having hair worries! And I was a big anti fin guy over a year ago! Just saying.
    Sorry admin – I dont want to hijack this thread and turn it into a fin thread, but I wanted to let everyone know my progress! So happy!

    1. That’s awesome RancidMingo! Fin is a life saver for many. I always tell the young new hair loss sufferers to hop on Propecia 1mg. Ride out the first 6 months of possible sides and then a year into it your hair should be better. It’s the only treatment that tackles the real problem at the root.

    2. Hi Rancidmango, I have big sexual dysfunction because I took Prozac (including a drop of libido). Since 4 years I weaned Prozac, but the side effects persist. What your secret? Grapeseed extract? Where to find, how much, etc.? It is only to counter the effects of Finasteride or it’s effective when the libido has been severely destroyed sing a long time. Thanks! William

      1. William – I dont think grape seed extract would help your situation. From what I understand it works for my situation because it helps keep estrogen in check and fin seems to increase estrogen. Maybe the l arginine would work for you though. It seems to help bloodflow. You can get it at any grocery store or pharmacy.

    3. Fin is great for guys that want to maintain their hair & transition into a female. I just want the maintenance and i would prefer staying male. I work in a clinic that performs sex reassignment surgeries and finasteride is of immense importance when transitioning.

        1. @That Guy I’m just stating the facts. By no means scaremongering. I mean, It’s a win win for guys who are balding and want to be a woman. Another year on Finasteride and you’ll have to change your name your name to ‘That Girl’. Which is completely fine, I admire you.

        2. I’ve been taking Fin for 20 years switched to Dut two years ago. I kind of wish it did, it would solve a lot of problems for me. No more bitches driving me crazy (both in good and not so good ways) costing $$$. Probably would care less about hair. Give it up That Guy, I learned a long time ago you can’t argue or reason with stupid. 🙂

        1. @br1:LOL Girls? Who cares? The important thing is to feel better with yourself without ceasing to be a man…or neurological sides…you must have the androgenetic receptors destroyed. If you really take Finasteride. I doubt it. Accept it Finasteride is a thing of the past. Easy.

    4. theres def evidence grape seed extract can be good for circulation if the dose is high enough. Theres also a scientific study that showed improved erections from l-citruline supplementation. L-Citrulline increases arginine in the body more than taking arginine so you can make this switch.

    5. Well done and congrats!

      I’ve been on fin for over a year now and I can safely say it has improved both my hair and — by extension — life. It of course didn’t fix what receded from my hairline, but the rest of the hair is thick and essentially the way it was before I noticed it was thinning.

      I want to restore the hairline, but I don’t want to shell out for a transplant if Follica makes it to market in the next couple years.

  12. I had no sexual problems with finasteride. I am single, but I did the “shower test”. No problems and still on it.
    I find the best way to debunk anything like PRP, ACell, herbs, etc is to do an advanced search on YouTube for videos dated at least 2014 or older from suffering people claiming initial benefits of it then see where they are now. In all cases, still very bald. Real situations expose fake people.
    So where are these original WNT patients now?

      1. Changed your mind from this post?

        “In my experience, it is a maintenance tool that shows just enough thickening to let you know that it does in fact work. So the value is not so much in taking you forward, but in keeping you from going backward.”

  13. Yes William Fin will convert into Estrogen. Fin indirectly blocks DHT serum levels, but you all know why, it helps stop the conversion of Testosterone to DHT. Well, if testosterone cannot go into DHT, then it will possibly( most likely, but still an asterisk is needed because not 99.99% ) convert into estrogen. We see this with anabolic steroid abuse.

    Example, Metaphorical: Guy injects testosterone( abusive limits ), so his total test ( TT on blood work ) goes up. However, the body wants to be balanced, not hormone imbalanced. Well, the body can’t stop the synthetic testosterone people put into their bodies, so the body as a defense mechanism, lowers it’s own natural testosterone, it can’t on the synthetic. Basically the brain, after injection…goes, ” Hey we have to much testosterone up here, lets stop producing down there( your man berries- testes ).” So, the hormones in your brain and signal to produce testosterone drops. In science, we call this a negative feedback loop. So the L.H and F.S.H in the anterior pit. gland , housed in your brain get inhibited….doesn’t hormone inhibition sound familiar? Almost like I am foreshadowing?…….So that is why a body builder, ” Cycles”, off steroids. So they do not permanently shut down their production of natural testosterone for LIFE.

    Now With this extra testosterone, it will convert to DHT and Estrogen. Of course, in the above scenerio, Bodybuilders do not block DHT, they want to black Estrogen converting to avoid Gyno- Your man pecs, turning into female breasts. If you are sensitive to estrogen, there is a chance gyno can happen. Even the Rock, Dwayne Johnson….had Gyno. He admitted it.

    Now lets reverse engineer this….Your not pumping a hormone into you, you are inhibiting it. So, the opposite happens, a hormone elevates…..well it’s not DHT…so….what’s next? Yes that is right, Estrogen, you are the father( in Maury’s voice ). Although we all know Darth vader was Luke’s father( jokin ). So, simply put, it wouldn’t even shock me, if some claim their testosterone levels increased while on FInasteride, but also estrogen.

    P.S….Arginine, the amino acid is found in egg white protein. Also, most erection tabs…it is the main ingredient. Also, us weight trainers, use it to give us bigger pumps. Well in theory, if it can do that for muscle….it can work other places.

    I hope that helps. So yes, blocking estrogen while on Fin, would be good. As I look at my bottle of proscar and too nervous to take it Lol. True story. I am about a NW 2-2.5…if your were using, ” The Scale.”

    1. But if you blocked Estrogen while on Fin, you will not get a ggod result with fin, Estrogen have a positive effect on scalp follicles..

      1. @ balding mate.
        We are not blocking estrogen per say. We are preventing the extra free Testosterone from converting to estrogen. We have extra free T since it is not being turned into DHT and I am trying to prevent that from now turning into estrogen. And I actually thought the same way as you at first. But there is no question Fin has had a major effect on my hair for the better, and im not even on it a year yet, and I wouldn’t just say that because I am incredibly anal about my hair and how it looks.
        The only reason I started grape seed was to see if it helped with sexual sides that I got from my first go around w. Fin. And I did get noticeable sexual sides when starting fin roughly 8 months ago. They went away after starting larginine and grape seed complex. Pardon me if its too TMI, but im right back to going at it multiple times a day if I so choose, with or without a partner with no difference as before I started – other than semi watery semen.
        I feel so different than I did about 5 months ago. I was so depressed from baldin, especially after about month 3 when fin wrecked my hairline. I mean it was so bad and see through and felt dry and dead. I even made a post here about it a few months back at how bad it got. Now at almost 9 months, it has improved alottt.
        Seems darker, much more life to it, and seems to keep getting better. I still shed hairs, but they are usually small dead ones that I think are coming back stronger anyway. Even the temples are coming back nicely.

  14. Ive seen numerous posts, not so much here,but on other forums of people asking whether or not fin makes you lose hair before gaining anything back and getting better. I could never find responses to that question, only a ton of posts asking about it. So I figured id just come here and let everyone know my storyy. I searched for a long time trying to find that answer with no luck.
    But fin DEFINITELY sped up my hairloss at first. Bad. Hairline tanked quickest. But now at almost month 9 it improved above baseline and keeps getting better. 🙂

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