'Holy Grail' Prescription Formula - Input Welcome from HairLossTalk!

[TurboFixer]

would it be possible to offer a solution that contains finasteride and another than doesn't?

 

[Derelict]

I have no experience with topical 5ari but i have heard dutasteride because of its molecular weight has less sides than topical finasteride. i think you should have a 5ari in your topical, you are in an uphill battle without it.

 

[Dr.]

would it be possible to offer a solution that contains finasteride and another than doesn't?
- Possibly. Though it would be at 0.01% to minimize possibility of systemic DHT supression.

You should really consider adding Methyl Vanillate 0.2%. Cheap, natural and can increase WNT levels with ~30%.
- Good suggestion

when/where/how can this be purchased
- 2-3 months? I'll post the link when we go live with it.

I have no experience with topical 5ari but i have heard dutasteride because of its molecular weight has less sides than topical finasteride. i think you should have a 5ari in your topical, you are in an uphill battle without it.
- I'd like to see data that topical dutasteride doesn't lower serum DHT levels. Someone earlier also posted that daily use may build up over time, so its not optimal for daily use.

 

[nick123]

Wanted to provide an update and get feedback on the latest formula:

- Decided to forgo the finasteride (even at 0.01%) because if it scares consumers away from using it, then that's no good.
- I've seen azalaic acid concentrations from 0.025-12.5% used (mostly between 1.5-5%), so it's hard to tell what dose is optimal.
- Any strong feelings/anecdotes about Cetirizine 1%, Diclofenac, or Resveratrol, which were previously mentioned?
- Reluctant about adding coritcosteroids (Betamethasone 0.01%) long-term, or Ketozonazole at 2% due to possible systemic absorption

• Rx Ingredients:
  • Latanoprost 0.1%
  • Minoxidil 8%
  • Tretinoin 0.01%
• OTC Ingredients:
  • Melatonin 0.0033%
  • Sandalore 0.1%
  • Azelaic Acid 5%
  • Zinc Sulfate 0.25%
  • Vitamin B6 (P5P) 0.25%

Sandalore was used at 1% not a 0.1% concentration, many on this forum including myself have used it at 1% with moderate-good short term success but long term (> 3 months) any gains made quickly faded, I don't know of anyone still using it.

I've seen melatonin used at 0.1% so you may want to explore that, triple hairs upcoming TH16 comprises of 0.1% melatonin and 5% resveratrol.

 

[Norwoody]

If RU came in a foam that would be amazing.

 

[Norwoody]

Something like hydrocortisone might be good for the itch too.

 

[GRme11]

would it be possible to offer a solution that contains finasteride and another than doesn't?
- Possibly. Though it would be at 0.01% to minimize possibility of systemic DHT supression.

You should really consider adding Methyl Vanillate 0.2%. Cheap, natural and can increase WNT levels with ~30%.
- Good suggestion

when/where/how can this be purchased
- 2-3 months? I'll post the link when we go live with it.

I have no experience with topical 5ari but i have heard dutasteride because of its molecular weight has less sides than topical finasteride. i think you should have a 5ari in your topical, you are in an uphill battle without it.
- I'd like to see data that topical dutasteride doesn't lower serum DHT levels. Someone earlier also posted that daily use may build up over time, so its not optimal for daily use.

Methyl Vanillate could be a good cheap alternative for WNT-Beta Catenin Pathway. I posted this into the Pegasus success story thread:

What about Methyl Vanillate as a cheap alternative for WNT-Beta Catenin Activation?
1)https://www.forhair.com/images/stor..._activator_JOCD_12225_Final_Revised_Proof.pdf

Background: Activation of the WNT/b-catenin pathway has emerged as a potential therapeutic target in androgenetic alopecia (Androgenetic Alopecia). Methyl vanillate (MV) a safe plant-derived ingredient – has been recently shown to activate the WNT/b-catenin signaling.

Objectives: Two distinct substudies were conducted. First, we designed a 6-month, uncontrolled, open-label clinical study to investigate whether topically applied MV may increase hair count and hair mass index (HMI) in female Androgenetic Alopecia. Second, we conducted a molecular study on the effect of MV on WNT10B mRNA expression in scalp biopsies of women with Androgenetic Alopecia.

Methods: A total of 20 Caucasian women (age range: 2557 years) with Androgenetic Alopecia (Sinclair grade 12) were included. The research product was an alcohol-free formulation supplied in the form of a spray containing 0.2% MV as the active ingredient. (Application was 2ml Every Other Day. So, 4mg/ml in total when the product applied)

Results: In the clinical study, hair count and HMI were found to increase at 6 months by 6% (P < 0.01) and 12% (P < 0.001), respectively, compared with baseline. No participant discontinued treatment due to adverse effects, and the overall patient satisfaction was good. At the molecular level, the topical application of the research product resulted in a 32% increase in WNT10B mRNA expression levels in the temporal scalp area (P < 0.001).

Conclusion: Our pilot data suggest that topical MV can increase hair count and HMI by inducing WNT10B expression in the scalp, potentially serving as a novel treatment strategy for female Androgenetic Alopecia.

2) https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2230.2011.04019.x

Background: Wnt10b (wingless-related mouse mammary tumour virus integration site 10b) plays various roles in a wide range of biological actions, including hair-follicle development.

Aim: To assess the roles that Wnt10b plays in postnatal hair-follicle growth.

Methods: Adenovirus vectors AdWnt10b, AdGFP, AdGFP plus AdRFP, AdWnt10b plus AdFrzB, and AdWnt10b plus AdSimBC were co-cultured separately with vibrissae. In situ protein expression of Wnt10b, β-catenin and Lef1 was determined by immunohistochemistry, and the proliferation status of the hair follicle was detected by 5-bromo-2-deoxyuridine (BrdU) labelling. The presence of Wnt signalling molecules in the three stages of hair-follicle growth was detected by PCR-based microarray.

Results: AdWnt10b-infected cells were able to secrete bioactive Wnt10b, and when this was added into the basal medium, the vibrissae grew faster than in control medium or in medium containing canonical Wnt signalling antagonists. The in situ protein expression of Wnt10b was consistent with that of β-catenin and Lef1. The expression locus of Wnt10b was almost the same as the proliferating cells labelled by BrdU in the anagen hair follicle.

Conclusions: Wnt10b may promote hair-follicle growth by inducing the switch from telogen to anagen via a canonical Wnt signalling pathway to promote the proliferation of matrix cells.

3) https://portlandpress.com/bioscirep...10b-promotes-hair-follicles-growth-and-dermal (recent study in Rabbits though)

Abstract​

Wnt signaling plays an important role in the growth and development of hair follicles (HFs). Among the signaling molecules, Wnt10b was shown to promote the differentiation of primary skin epithelial cells toward the hair shaft and inner root sheath of the HF cells in mice in vitro. Whisker HFs were isolated from Rex rabbits and cultured in vitro to measure hair shaft growth. Meanwhile, dermal papilla cells (DPCs) were isolated and cultured in vitro. Treatment with AdWnt10b or the Wnt/β-Catenin Pathway inhibitor, XAV939, assessed the DPCs proliferation by CCK-8 assay. And the cell cycle was also analyzed by flow cytometry. We found that Wnt10b could promote elongation of the hair shaft, whereas XAV-939 treatment could eliminated this phenomenon. AdWnt10b treatment promoted the proliferation and induced G1/S transition of DPCs. AdWnt10b stimulation up-regulated β-Catenin protein in DPCs. Inhibition of Wnt/β-Catenin signaling by XAV-939 could decreased the basal and Wnt10b-enhanced proliferation of DPCs. And could also suppress the cell cycle progression in DPCs. In summary, our study demonstrates that Wnt10b could promote HFs growth and proliferation of DPCs via the Wnt/β-Catenin signaling pathway in Rex rabbits.

4)

Targeting Wnt/β-Catenin Pathway for Developing Therapies for Hair Loss

Persistent hair loss is a major cause of psychological distress and compromised quality of life in millions of people worldwide. Remarkable progress has been made in understanding the molecular basis of hair loss and identifying valid intracellular targets ...

www.ncbi.nlm.nih.gov

(Recent good study for the WNT beta Catenin Pathway in General)
From the study above:
View attachment 157160
My "concerns":

Vanillic Acid: Vanillic acid (4-hydroxy-3-methoxybenzoic acid) is a dihydroxybenzoic acid derivative used as a flavoring agent. It is an oxidized form of vanillin. It is also an intermediate in the production of vanillin from ferulic acid.

Methyl Vanillate: Methyl vanillate is a benzoate ester that is the methyl ester of vanillic acid. It has a role as an antioxidant and a plant metabolite. It is a benzoate ester, a member of phenols and an aromatic ether. It derives from a vanillic acid.

http://www.biomolther.org/journal/view.html?volume=28&number=4&spage=354 ( Vanillic Acid Stimulates Anagen Signaling via the PI3K/Akt/ β-Catenin Pathway in Dermal Papilla Cells->Decent effects)

(Vanillic acid restores DHT-downregulated β-catenin level in DPCs​

Dihydrotestosterone, implicated in the development of Androgenetic Alopecia, suppresses the cell-cycle progression and Wnt/β-catenin pathway in DPCs (Kang et al., 2015). To determine whether vanillic acid could restore the downregulation of β-catenin by DHT, DPCs were treated with DHT (100 nM) in the absence or presence of vanillic acid (10 μg/mL) for 24 h. The decreased levels of β-catenin and Cox-2, a target gene of β-catenin, observed in the DHT treated cells were restored by vanillic acid (Fig. 4A). Confocal microscopy data showed that DHT decreased the level of β-catenin, but pretreatment with vanillic acid attenuated the DHT-induced decrease of β-catenin level (Fig. 4B). These results suggest that vanillic acid can restore the DHT-induced downregulation of the Wnt/β-catenin pathway.)




Although,
To examine whether vanillic acid activates the Wnt/β-catenin pathway, DPCs were stimulated with vanillic acid (10 μg/mL) for 0-120 min. As shown in Fig. 3A, vanillic acid increased the levels of phospho(ser9)-GSK3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin after 15-120 min. Confocal microscopy data showed that vanillic acid increased the levels of phospho(ser552)-β-catenin and phospho(ser675)-β-catenin in the cytoplasm and nucleus (Fig. 3B, 3C). The phosphorylation of β-catenin by minoxidil was increased similarly to that by the vanillic acid (Fig. 3B, 3C). These results indicate that vanillic acid could increase the levels of active β-catenins via the regulation of GSK3β. GSK3β is a downstream target of PI3K/Akt, which in turn regulates the expression of β-catenin (Monick et al., 2001). To evaluate the mechanism underlying the activation of the Wnt/β-catenin pathway by vanillic acid via PI3K/Akt, we examined the levels of phospho(ser675)-β-catenin, β-catenin, and Cox-2, a target gene of β-catenin, following a 24 h treatment with vanillic acid in the presence or absence of wortmannin. As shown in Fig. 3D, vanillic acid increased the levels of phospho(ser675)-β-catenin, β-catenin, Cox-2, and cyclin D1, and the increased levels of these proteins were attenuated by wortmannin (Fig. 3D). These results suggest that the activation of the Akt pathway by vanillic acid contributes to the activation of the Wnt/β-catenin pathway.

From Conclusions:

(As shown in Fig. 3D, vanillic acid also upregulated the levels of Cox-2 and cyclin D1, which are the target genes of β-catenin, and the level of β-catenin. These changes were attenuated by wortmannin, indicating that the vanillic acid-mediated proliferation in DPCs is regulated by the PI3K/Akt/Wnt/β-catenin pathway. Consistent with this notion, minoxidil prolongs the duration of the anagen phase, possibly, due to the activation of the Wnt/β-catenin pathway by altering the PKA and Akt pathways in human DPCs (Kwack et al., 2011). Therefore, based on the above mechanism, vanillic acid could activate the anagen phase and promote hair growth.

DHT, a potent androgen, plays a crucial role in the pathogenesis of Androgenetic Alopecia (Sinclair, 1998). Our previous study partially supports the DHT-mediated Androgenetic Alopecia development, demonstrating that DHT can attenuate the cell cycle progression by inhibiting translocation of β-catenin into the nucleus in DPCs (Kang et al., 2015). In this study, we demonstrated that vanillic acid exhibits a protective effect on the downregulation of β-catenin by DHT (Fig. 4). In addition, we investigated the effects of vanillic acid on the levels of growth factors, the opening of KATP channels, and the inhibition of the TGF-β pathway related to the regulation of the hair growth (Guo et al., 1996; Suzuki et al., 2000; Yano et al., 2001; Soma et al., 2002; Shorter et al., 2008). However, we observed that vanillic acid does not affect the levels of VEGF, FGF-7, and FGF-10 mRNA, the opening of KATP channels, or the phosphorylation of smad2/3, a mediator of the TGF-β pathway (data not shown).
In conclusion, we evaluated the effects of vanillic acid on the proliferation of DPCs and verified that vanillic acid selectively regulates the PI3K/Akt/Wnt/β-catenin pathway. These findings suggest that vanillic acid could stimulate the anagen phase by activating the PI3K/Akt/Wnt/β-catenin pathway and potentially alleviate hair loss.)


So, if I understand correctly they are to 2 negative factors here from the Vanillic Acid but the positive effects, they seem very very good as well. The "negatives" : Regulation of GSK3β and the increased levels of Cox-2.
If I am not wrong, we need to inhibit GSK3β and the increment to the Cox-2, it will lead to an increment to PGE2 but PGD2 as well??

BUT Pegasus mentioned this:

PGE2 regulates wnt activity by direct phosphorylation of β-catenin and GSK3β

Our work shows that PGE2 acts via cAMP/PKA signaling to directly modify β-catenin stability and emphasizes the functional importance and evolutionary conservation of these interactions in organ development and regeneration. PGE2-mediated regulation of Wnt signaling was previously demonstrated in cell lines. The proposed biochemical mechanisms mediating the interaction are remarkably diverse and may depend on the particular cell line studied (Clevers, 2006). Castellone et al. used colon cancer cell lines to demonstrate PGE2/PI3K-mediated activation of Akt, leading to dissociation of Axin1 from the destruction complex (Castellone et al., 2005). While we cannot exclude the existence of this biochemical interaction in vivo, our studies suggest that activation of PKA is the functionally significant effector downstream of PGE2 in HSCs. Likewise, both phosphorylation of GSK3β and β-catenin by PGE2-based activation of PKA have been implicated in Wnt signaling regulation in vitro. (vanillic acid increased the levels of phospho(ser9)-GSK3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin after 15-120 min) Fujino et al. used the transformed HEK293 cell line and showed that both PKA and PI3K could function downstream of PGE2 to phosphorylate GSK3β (Fujino et al., 2002). However, PGE1-induced activation of PKA and phosphorylation of β-catenin at S675 was cell-line dependent (Hino et al., 2005). While we found both phosphorylation events occur in the presence of PGE2 in vivo, it remains to be determined if phosphorylation of β-catenin and GSK3β each play a significant role in the regulation of wnt activity by PGE2 in HSCs, especially given a recently proposed functional redundancy of GSK3β with GSK3α (Doble et al., 2007).

PGE2 may have co-evolved with Wnt as a mechanism to rapidly upregulate cellular proliferation to foster organ repair. In this setting, PGE2 - which is produced locally in response to tissue damage - is required for and can enhance the proliferative effects initiated by wnt activitation.

Evolutionarily, what was greatly beneficial for wound healing – the coordinated pro-proliferative, anti-apoptotic effects of wnt and PGE2, may be detrimental in cases of chronic inflammation or constitutive pathway activation and lead to tumor initiation and growth.

All these are by the Vanillic Acid. Although, I couldn't find any other properties for Methyl Vanillate (MV) but I believe that since it is derived from Vanillic Acid, as en ester, probably it will act the same way. (Both Vanillic Acid and MV are pretty cheap)

So, If have understood correctly, these regulations of GSK3β and Cox-2, provided only positive effects rather than negative effects??


If you want more info about Methyl Vanillate you can check this post. Thank you

 

[Dr.]

Sandalore was used at 1% not a 0.1% concentration, many on this forum including myself have used it at 1% with moderate-good short term success but long term (> 3 months) any gains made quickly faded, I don't know of anyone still using it.

I've seen melatonin used at 0.1% so you may want to explore that, triple hairs upcoming TH16 comprises of 0.1% melatonin and 5% resveratrol.

The original study used 500µM Sandalore. This is how you convert it:
500µM is short for 500µMol/L, the molaric mass of Sandalore is ~210 g/Mol
So 500µMol/L * 210g/Mol = 105000 µg/L = 105 mg/L = 0.105 g/L = 0.105 mg/ml, which is a concentration of only 0.01%.

The patent however cites 0.1-10%, which is 10X+ that for whatever reason, and I used 0.1%.

The concern with melatonin is that it may influence endogenous production and/or serum level, and regulates sleep-wake cycles (it makes people more likely to wake up when exposed to sunlight when they want to sleep in), so I want to keep it at the minimum effective dosage.

Any research or anecdotal reports on resveratrol?

 

[Pls_NW-1]

Something like hydrocortisone might be good for the itch too.

I think anti-histaminas might be a good addition to mixed topicals.

 

[Dr.]

We can't use ingredients like RU that are not FDA-approved for at least some purpose, or are GRAS/supplements.
I'm a bit concerned about using corticosteroids like hydrocoritsone in terms of what they do like skin atrophy.
Will see if we can use Methyl Vanillate 0.2%.

 

[Dr.]

I think anti-histaminas might be a good addition to mixed topicals.

Cetirizine 1% was mentioned twice. I've only seen one study on it, which was positive, but methologically problematic.
Any positive anecdotal results from users?

Is there any indication it can go systemic? 1% is 10mg, which is the same as the oral dose to control allergies.

 

[Isneezedsohard]

would it be possible to offer a solution that contains finasteride and another than doesn't?
- Possibly. Though it would be at 0.01% to minimize possibility of systemic DHT supression.

You should really consider adding Methyl Vanillate 0.2%. Cheap, natural and can increase WNT levels with ~30%.
- Good suggestion

when/where/how can this be purchased
- 2-3 months? I'll post the link when we go live with it.

I have no experience with topical 5ari but i have heard dutasteride because of its molecular weight has less sides than topical finasteride. i think you should have a 5ari in your topical, you are in an uphill battle without it.
- I'd like to see data that topical dutasteride doesn't lower serum DHT levels. Someone earlier also posted that daily use may build up over time, so its not optimal for daily use.

Looking forward to it!!!

 

[Pls_NW-1]

Cetirizine 1% was mentioned twice. I've only seen one study on it, which was positive, but methologically problematic.
Any positive anecdotal results from users?

Is there any indication it can go systemic? 1% is 10mg, which is the same as the oral dose to control allergies.

IdealForehead, a past user, used Desloratadin. He used, how he describes it, "the ultimate hair loss stack".

 

[Norwoody]

Question is, how much is this going to cost? Also, what carrier?

 

[Isneezedsohard]

Question is, how much is this going to cost? Also, what carrier?

I would also request no Propylene Glycol.

 

[TurboFixer]

would it be possible to offer a solution that contains finasteride and another than doesn't?
- Possibly. Though it would be at 0.01% to minimize possibility of systemic DHT supression.

You should really consider adding Methyl Vanillate 0.2%. Cheap, natural and can increase WNT levels with ~30%.
- Good suggestion

when/where/how can this be purchased
- 2-3 months? I'll post the link when we go live with it.

I have no experience with topical 5ari but i have heard dutasteride because of its molecular weight has less sides than topical finasteride. i think you should have a 5ari in your topical, you are in an uphill battle without it.
- I'd like to see data that topical dutasteride doesn't lower serum DHT levels. Someone earlier also posted that daily use may build up over time, so its not optimal for daily use.

what regions will you be able to ship to?

USA?
EU?
Oceania?
South America?

 

[Norwoody]

Could probably use something like CB too

 

[TurboFixer]

I would also request no Propylene Glycol.

100% seconding this suggestion

so many people report nasty reactions to it

 

[TurboFixer]

Could probably use something like CB too

true!

as of recently its FDA approved after all

 

[Norwoody]

finasteride/dutasteride+CB+minoxidil+keto is probably all you need. Of course it doesn't hurt to have some of the other stuff in there too. How about castor oil? Fluridil uses grapeseed oil + alcohol as a carrier.