EvoMuse Virile Mane writeup

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    EvoMuse Virile Mane writeup


    As you can probably figure, we have had our hands full here at EvoMuse, with our release pace picking up speed. As promised a while ago, here is the meat of the VM Writeup.

    I'm sure you don't care right now about the marketing paragraphs in the beginning and end, so let's get to it and I will edit those in later.

    There is also an illustration here that I will upload to photobucket and try to get into the correct spot.

    Virile Mane Write Up


    Ingredients & Function
    Baicalin

    As seen in the above below, the dermal papillae (DP) are little bumps sitting on top of the dermis, surrounding individual hair follicles like a ring. These cells are crucial components in nourishing hair and allowing for growth. They also contain androgen receptors, that when stimulated by the presence of dihidrotestosterone (DHT), will translocate to the cell membrane and allow for binding.

    Excessive DHT binding at the papillae cells can be catastrophic for hair growth. Baicalin interferes with this process, stopping the translocation of the androgen receptor so DHT has no place to bind. In addition, baicalin has also been shown to upregulate DP cell proliferation which encourages new hair growth (1).

    Baicalin has also been shown to promote angiogenesis (growth of new blood vessels) through activating a specific estrogen related receptor (ERRa), which causes production of vascular endothelial growth factor (VEGF) (2).

    Finally, It has been observed that all three PPAR subtypes are expressed in hair follicle cells, and that specific activation and inhibition of specific PPAR subtypes increases hair follicle survival (3). Baicalin has been shown to downregulate PPARy in multiple studies, which could aid in slowing hair loss.

    [IMG]file:///C:\Users\Anthony\AppData\Local \Temp\ksohtml\wps_clip_image-2838.png[/IMG]

    L-Carnitine L-Tartrate (LCLT)

    According to work from Foitzik et al., LCLT downregulates certain inflammatory cytokines (TGF-beta, caspase-3, caspase-7) in cultured hair follicles. These cytokines are responsible for the initial phase of hair follicle apoptosis, or cell death. LCLT also upregulates proliferation of keratinocytes (see image below), and increases the energy supply to follicles in the anagen phase (4,5).

    [IMG]file:///C:\Users\Anthony\AppData\Local \Temp\ksohtml\wps_clip_image-14707.png[/IMG]


    6-Gingerol

    6-Gingerol is included in the Virile Mane formula due to its potent interaction with the transient receptor potential vanilloid 1 (TRPV1). TRPV1 functions as an integrator of endogenous and exogenous nociceptive stimuli. The painful response from the consumption of hot peppers, for example, is the result of TRPV1 activation.

    TRPV1 exists all over the body, including skin tissue. The most researched ligand of this receptor is capsaicin, however, too potent of an activation depletes sensory nerves of a compound called Substance P. The same way that Capsaicin is used in Nociception (pain relief) is by depletion of Substance P. What we find in skin and hair follicles is that it is most desirable to activate the TRPV1 receptor without depleting Substance P completely.

    Research has shown that a judicious amount of local TRPV1 activation can encourage hair growth (too much and we see a paradoxical effect) (6). 6-Gingerol does this by increasing the release of something called calcitonin gene-related peptide (CGRP) from sensory neurons, which then increases local IGF-1 levels, encouraging growth of new hair (7,8).

    As an added benefit, Gingerols inhibit expression of the COX-2 enzyme, by inhibiting expression of Interleukin-1b, thus resulting in reduced inflammatory response so detrimental to hair growth. (61)

    Beta Escin phosphatidylcholine complex

    Beta Escsin, aka, aescin, is the active component of Horse Chestnut and was chosen for its ability to enhance vascular microcirculation as well as act as an antioxidant. More blood flow to the scalp equals more nutrient delivery, and controlling oxidation reduce follicle damage to allow for more continuous turn over of the hair growth cycle (9–11). The phosphatidylcholine complex allows for better delivery to the target cells (12).

    Tocotrienols (from Palm Oil)

    Tocotrienols refer to four specific components of vitamin E found in high concentrations in palm oil. They have gained quite a bit of popularity in recent years due largely to the success of self-experimentation in various online hair loss support circles. The main mechanism of action is likely related to their unique and powerful antioxidant ability. They have been shown to increase the production of superoxide dismutase (SOD) and glutathione peroxidase, which typically decrease with age, encouraging hair loss due to unchecked oxidative stress.

    A recent study found that subjects supplementing with tocotrienols increased hair growth by almost 35% over the placebo group (13). While no published data exists yet, another common user report from tocotrienol supplementation is darkening of hair back to its original color in addition to the regrowth.

    DL Panthenol

    This a racemic blend of the B5 provitamin, panthenol, which is converted in the body to pantothenic acid. It is believed that hair can efficiently absorb pantothenic acid where it can repair damaged proteins, improving health of the existing hair. It also acts as a humectant, meaning it pulls water from the air and attracts it to the hair to keep it moisturized and give it a shiny look.

    Manganese-copper-zinc complex

    These three nutrients tend to decrease with age and are critical for formation of SOD. When SOD is inadequately produced, superoxide levels stay above optimal; which gives the hair the signal to stop growing and fall out.

    Anthocyanin (dragon fruit)

    Responsible for providing dark colored pigmentation, anthocyanins can be found in a variety of fruit skins. The inclusion in Virile Mane is simply to increase blood flow to the scalp through a nitric oxide mediated mechanism, thereby improving nutrient delivery and oxygen to hair follicles (14,15).

    Coconut Oil

    Coconut oil has numerous benefits for hair and scalp health. The primary fatty acid in coconut oil, Lauric Acid, can penetrate the hair shaft allowing for protection against protein loss and moisture regulation, unlike mineral oils (16–19).

    Cholecalciferol

    Cholecalciferol, or Vitamin D3, is an important vitamin for maintaining hair growth, as evidenced by the appearance of vitamin D receptors in the dermal papilla (20,21). Vitamin D deficiencies are increasingly common, and without adequate D3 the hair loss/growth cycle is tipped very unfavorably. Recent research has shown Vitamin D3 and its analogues to regulate differentiation and proliferation of hair follicles, and help to kick-start the hair growing cycle (22–25).

    Menthol

    In the early 2000's, something called the TRPM8 protein was discovered in sensory neurons, which can be thought of as somewhat of a cousin to the TRPV1 receptor. Menthol binds to this receptor; which is what gives it the cooling property normally experienced only with actual temperature reduction (26). In Virile Mane, menthol has been included to soothe the scalp, improve blood flow, and enhance the delivery of other ingredients.

    Green Tea Catechins

    Catechins are considered a procyanidin, which are a form of flavonols found in various plants. Green Tea and its catechins have quite a bit of data backing their use for preventing hair loss and encouraging growth. Research shows an anti-apoptotic effect on the dermal pappilae under various conditions, including testosterone induced apoptosis, and has been shown to be effective for reversal of androgenic alopecia (27–30). It appears one of the main ways green tea catechins do this is by strongly binding to keratin and reducing oxidative stress that normally disrupts the hair turnover cycle (31).

    Apple Polyphenols

    Apple Polyphenols are another source of procyanidins, and in particular, a highly effective oligomer called Procyanidin B-2, which even as a standalone treatment has been said by researchers to show "potential as a promising cure for male pattern baldness" (32). Numerous studies under various parameters have demonstrated exceptional results for inducing the anagen cycle in humans, animals, in vitro and in vivo (33–36).

    In one study, Procyanidin B-2 was about 220% more effective than Procyanidin C-1 at promoting growth in epithelial cells in vitro, and about equally effective as Procyanidin B-1 and Procyanidin B-3, which themselves were more effective than Minoxidil (37). In addition, Procyandin B-2's stimulation of cAMP and inhibition of PKC (which is a potent inducer of inflammation) are effective at stimulating Anagen phase. Virile Mane uses a potent Apple Polyphenol extract standardized for a high amount of Procyanidin B-2.

    Daphne Feddei (Daphne Factor F-3)

    Daphne Factor F-3, from the Daphne Feddei plant has several unique characteristics in regards to hair growth. A protein called Neurotrophin-4 (NT-4) works in conjunction with DHT to start the catagen cycle, and in alopecia this can become far too dominant, encouraging excessive hair loss. The NT-4/DHT effect on hair loss is accelerated by androgens, and effectively curbed by Daphne Factor F-3 (38).

    Dieckol (ecklonia cava)/Aconiti Ciliare Tuber extract

    Dieckol is found in the edible seaweed ecklonia cava, and demonstrates anti-inflammatory and anti-oxidative properties. A brand new study published in the Journal of Experimental Dermatology showed that dieckol was able to cause significant hair growth by stimulating both dermal papilla cells and outer root sheath cells (39). In addition to this, a previous study showed a positive effect from Dieckol on inhibiting the 5-ar enzyme, which is responsible for converting testosterone to DHT (40).

    Aconiti Ciliare Tuber (ACT) extract is the first ingredient in the formula to target something called the Wnt/b-catenin pathway for hair growth. Recent research has shown ACT "has the potential to promote the induction of hair growth via activation of the stem cell activity of the dermal papilla cells" (41).

    Honokiol

    Honokiol is a lignan isolated from Magnolia, with proven research behind its ability to stimulate hair growth. Like some of the other ingredients in Virile Mane, honokiol suppresses factors that promote follicular apoptosis, in this case, the cytokine TNF-a (42). Another study showed that honokiol was able to stimulate hair growth on par with Minoxidil (43). And finally, it has also been shown to be another inhibitor of the 5-ar enzyme thereby reducing the loss of hair by limiting the conversion of testosterone to DHT (44).

    Sophora Flavescens extract

    Sephora Flavescens extract has been shown to stimulate growth factors like IGF-1 and KGF in papilla cells, while also inhibiting 5-ar activity, giving it another multi-angled attack at hair growth promotion (45). Another potential mechanism for Sophora Flavescens to reduce hair loss & promote growth, is by reducing the production of AGE's (the damaging binding of proteins to glucose) that tend to wreak havoc all over the body and accelerate various factors with aging (46).

    Polygonum multiflorum (PM)

    In the past few years, a couple of promising studies have been published showing great potential for Polygonum multiflorum for hair growth. One specific compound found in PM showed that it was able to outperform Minoxidil in the parameters tested (47). A second study showed PM to be effective at promoting hair growth in mice by initiating the anagen phase (48).
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    Crataegus pinnatifida (CP)
    Crataegus pinnatifida is typically used in traditional oriental medicine for improving digestion and circulation, but is now being looked at for its potential to stimulate hair growth. A 2013 study showed CP promoted hair growth by inducing the anagen phase, and accelerated proliferation of Dermal Papilla Cells (49). While the data is still limited and this study was conducted in mice, we believe it is promising enough to include in the Virile Mane formula and expect to see human data in the near future.

    Cinnamic acid
    Cinnamic acid was included in Virile Mane for its beneficial effect on scalp health, and it may even be able to combat and reverse issues with dandruff (50).

    Melatonin
    A review published in 2012 noted that "five clinical studies showed positive effects of a topical melatonin solution in the treatment of AGA (androgenic alopecia) in men and women while showing good tolerability" (51). Melatonin is considered to have a pivotal role in hair physiology, and has been shown to be anti-apoptotic in hair follicles by reducing oxidative stress (52).

    4-methylcatechol (4-MC)
    4-MC has been shown to promote the synthesis of something called Nerve Growth Factor (NGF), which causes a protective cascade against hair loss (53). In addition to this, rapid local elevations of NGF (as would happen with topical application of Virile Mane) have been shown to promote keratinocyte growth and induce and progress the anagen hair cycling phase (54).

    Astragali Radix and Rehmanniae Radix
    This specific combination of Astragali and Rehmannie Radix has been shown in research to upregulate the synthesis of both TGF-b1 and BMP-6, which, as it turns out, are very important for the regulation of the triphasic hair growth cycle (55). BMP, or bone morphogenetic protein, has recently been elucidated as a key factor in the multi-faceted cellular cross-talk for hair turnover and normal dermal papillae function (56). It turns out that, like many of the processes in hair turnover, not enough of a cellular signal is detrimental just as too much of it is. Astragali and Rehmanniae radix, help regulate proliferation, differentiation, and apoptosis of hair follicle stem cells encouraging normal hair growth (57).

    Palmitoylethanolamide
    Palmitoylethanolamide is included in the Virile Mane formula to tackle hair loss from two distinct angles. The first being PPAR activation (baicalin does this as well) (58). The second angle involves prostaglandin manipulation. Data exists pointing to inflammation and autoimmunity from mast cell activation to be a potential causative factor in male pattern baldness (59). When these mast cells are triggered, a prostaglandin known as PGD2 is created, which can encourage hair loss. POA is used here to inhibit PGD2 production (60).




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    48. Park H-J, Zhang N, Park DK. Topical application of Polygonum multiflorum extract induces hair growth of resting hair follicles through upregulating Shh and β-catenin expression in C57BL/6 mice. J Ethnopharmacol [Internet]. 2011 May 17 [cited 2014 Feb 28];135(2):369–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21419834
    49. Shin H-S, Lee J-M, Park S-Y, Yang J-E, Kim J-H, Yi T-H. Hair growth activity of Crataegus pinnatifida on C57BL/6 mouse model. Phytother Res [Internet]. 2013 Sep [cited 2014 Feb 28];27(9):1352–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23148028
    50. Baroni A, De Rosa R, De Rosa A, Donnarumma G, Catalanotti P. New strategies in dandruff treatment: growth control of Malassezia ovalis. Dermatology [Internet]. 2000 Jan [cited 2014 Mar 4];201(4):332–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11146344
    51. Fischer TW, Trüeb RM, Hänggi G, Innocenti M, Elsner P. Topical melatonin for treatment of androgenetic alopecia. Int J Trichology [Internet]. 2012 Oct [cited 2014 Feb 28];4(4):236–45. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    52. Zhang J, Hu D-H, Chen G, Bai X-Z, Tang C-W. [Protective effect of melatonin on oxidative stress inducing hair follicle injury in scald rat]. Zhonghua Shao Shang Za Zhi [Internet]. 2009 Apr [cited 2014 Feb 28];25(2):129–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19799039
    53. Kimura N, Nishizaki K, Orita Y, Masuda Y. 4-methylcatechol, a potent inducer of nerve growth factor synthesis, protects spiral ganglion neurons from aminoglycoside ototoxicity--preliminary report. Acta Otolaryngol Suppl [Internet]. 1999 Jan [cited 2013 Dec 28];540:12–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10445072
    54. Zhou Z, Kawana S, Aoki E, Katayama M, Nagano M, Suzuki H. Dynamic changes in nerve growth factor and substance P in the murine hair cycle induced by depilation. J Dermatol [Internet]. 2006 Dec [cited 2014 Mar 5];33(12):833–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17169085
    55. Zhang Q, Fong CC, Yu WK, Chen Y, Wei F, Koon CM, et al. Herbal formula Astragali Radix and Rehmanniae Radix exerted wound healing effect on human skin fibroblast cell line Hs27 via the activation of transformation growth factor (TGF-β) pathway and promoting extracellular matrix (ECM) deposition. Phytomedicine [Internet]. 2012 Dec 15 [cited 2014 Mar 5];20(1):9–16. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23083814
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    1. Kim A-R, Kim S-N, Jung I-K, Kim H-H, Park Y-H, Park W-S. The Inhibitory Effect of Scutellaria baicalensis Extract and Its Active Compound, Baicalin, on the Translocation of the Androgen Receptor with Implications for Preventing Androgenetic Alopecia. Planta Med [Internet]. 2014 Feb [cited 2014 Feb 25];80(2-3):153–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24496985
    2. Zhang K, Lu J, Mori T, Smith-Powell L, Synold TW, Chen S, et al. Baicalin increases VEGF expression and angiogenesis by activating the ERR{alpha}/PGC-1{alpha} pathway. Cardiovasc Res [Internet]. 2011 Feb 1 [cited 2014 Feb 25];89(2):426–35. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    3. Billoni N, Buan B, Gautier B, Collin C, Gaillard O, Mahé YF, et al. Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPAR alpha involvement in hair growth. Acta Derm Venereol [Internet]. [cited 2014 Mar 5];80(5):329–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11200828
    4. Foitzik K, Hoting E, Förster T, Pertile P, Paus R. L-carnitine-L-tartrate promotes human hair growth in vitro. Exp Dermatol [Internet]. 2007 Nov [cited 2010 Dec 28];16(11):936–45. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17927577
    5. Foitzik K, Hoting E, Heinrich U, Tronnier H, Paus R. Indications that topical L-carnitin-L-tartrate promotes human hair growth in vivo. J Dermatol Sci [Internet]. 2007 Nov [cited 2014 Feb 14];48(2):141–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17804203
    6. Bodó E, Bíró T, Telek A, Czifra G, Griger Z, Tóth BI, et al. A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Am J Pathol [Internet]. 2005 Apr [cited 2014 Feb 25];166(4):985–98. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    7. Harada N, Okajima K, Arai M, Kurihara H, Nakagata N. Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in mice and in humans with alopecia. Growth Horm IGF Res [Internet]. 2007 Oct [cited 2014 Feb 25];17(5):408–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17569567
    8. Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans. Growth Horm IGF Res [Internet]. 2008 Aug [cited 2014 Feb 25];18(4):335–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18321745
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    13. Beoy LA, Woei WJ, Hay YK. Effects of tocotrienol supplementation on hair growth in human volunteers. Trop life Sci Res [Internet]. 2010 Dec [cited 2014 Mar 1];21(2):91–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24575202
    14. Matsumoto H, Takenami E, Iwasaki-Kurashige K, Osada T, Katsumura T, Hamaoka T. Effects of blackcurrant anthocyanin intake on peripheral muscle circulation during typing work in humans. Eur J Appl Physiol [Internet]. 2005 May [cited 2014 Jan 29];94(1-2):36–45. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15605279
    15. Zhu Y, Xia M, Yang Y, Liu F, Li Z, Hao Y, et al. Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin Chem [Internet]. 2011 Nov [cited 2014 Mar 1];57(11):1524–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21926181
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    19. Ruetsch SB, Kamath YK, Rele AS, Mohile RB. Secondary ion mass spectrometric investigation of penetration of coconut and mineral oils into human hair fibers: relevance to hair damage. J Cosmet Sci [Internet]. [cited 2014 Mar 1];52(3):169–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11413497
    20. Reichrath J, Schilli M, Kerber A, Bahmer FA, Czarnetzki BM, Paus R. Hair follicle expression of 1,25-dihydroxyvitamin D3 receptors during the murine hair cycle. Br J Dermatol [Internet]. 1994 Oct [cited 2014 Feb 27];131(4):477–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7947199
    21. Billoni N, Gautier B, Mahé YF, Bernard BA. Expression of retinoid nuclear receptor superfamily members in human hair follicles and its implication in hair growth. Acta Derm Venereol [Internet]. 1997 Sep [cited 2014 Feb 27];77(5):350–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9298126
    22. Aoi N, Inoue K, Chikanishi T, Fujiki R, Yamamoto H, Kato H, et al. 1α,25-dihydroxyvitamin D3 modulates the hair-inductive capacity of dermal papilla cells: therapeutic potential for hair regeneration. Stem Cells Transl Med [Internet]. 2012 Aug [cited 2014 Feb 27];1(8):615–26. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    23. Kim DH, Lee JW, Kim IS, Choi SY, Lim YY, Kim HM, et al. Successful treatment of alopecia areata with topical calcipotriol. Ann Dermatol [Internet]. 2012 Aug [cited 2014 Feb 27];24(3):341–4. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    24. Vegesna V, O’Kelly J, Uskokovic M, Said J, Lemp N, Saitoh T, et al. Vitamin D3 analogs stimulate hair growth in nude mice. Endocrinology [Internet]. 2002 Nov [cited 2014 Feb 27];143(11):4389–96. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12399436
    25. Hu L, Bikle DD, Oda Y. Reciprocal role of vitamin D receptor on β-catenin regulated keratinocyte proliferation and differentiation. J Steroid Biochem Mol Biol [Internet]. 2013 Nov 12 [cited 2014 Feb 27]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/24239508
    26. Patel T, Ishiuji Y, Yosipovitch G. Menthol: a refreshing look at this ancient compound. J Am Acad Dermatol [Internet]. 2007 Nov [cited 2014 Feb 27];57(5):873–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17498839
    27. Kwon OS, Han JH, Yoo HG, Chung JH, Cho KH, Eun HC, et al. Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine [Internet]. 2007 Aug [cited 2014 Feb 27];14(7-8):551–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17092697
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    29. Esfandiari A, Kelly AP. The effects of tea polyphenolic compounds on hair loss among rodents. J Natl Med Assoc [Internet]. 2005 Aug [cited 2014 Mar 4];97(8):1165–9. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    30. Kim YY, Up No S, Kim MH, Kim HS, Kang H, Kim HO, et al. Effects of topical application of EGCG on testosterone-induced hair loss in a mouse model. Exp Dermatol [Internet]. 2011 Dec [cited 2014 Feb 27];20(12):1015–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21951062
    31. Kim M-M. Effect of procyandin oligomers on oxidative hair damage. Skin Res Technol [Internet]. 2011 Feb [cited 2014 Feb 28];17(1):108–18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21226878
    32. Takahashi T, Kamimura A, Yokoo Y, Honda S, Watanabe Y. The first clinical trial of topical application of procyanidin B-2 to investigate its potential as a hair growing agent. Phytother Res [Internet]. 2001 Jun [cited 2014 Feb 28];15(4):331–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11406858
    33. Takahashi T, Kamimura A, Kagoura M, Toyoda M, Morohashi M. Investigation of the topical application of procyanidin oligomers from apples to identify their potential use as a hair-growing agent. J Cosmet Dermatol [Internet]. 2005 Dec [cited 2014 Mar 4];4(4):245–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17168871
    34. Kamimura A, Takahashi T. Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study. Br J Dermatol [Internet]. 2002 Jan [cited 2014 Feb 28];146(1):41–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11841365
    35. Kamimura A, Takahashi T, Morohashi M, Takano Y. Procyanidin oligomers counteract TGF-beta1- and TGF-beta2-induced apoptosis in hair epithelial cells: an insight into their mechanisms. Skin Pharmacol Physiol [Internet]. 2006 Jan [cited 2014 Mar 4];19(5):259–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16778458
    36. Takahashi T, Kamimura A, Shirai A, Yokoo Y. Several selective protein kinase C inhibitors including procyanidins promote hair growth. Skin Pharmacol Appl Skin Physiol [Internet]. [cited 2014 Feb 28];13(3-4):133–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10859531
    37. Takahashi T, Kamiya T, Hasegawa A, Yokoo Y. Procyanidin oligomers selectively and intensively promote proliferation of mouse hair epithelial cells in vitro and activate hair follicle growth in vivo. J Invest Dermatol [Internet]. 1999 Mar [cited 2014 Feb 28];112(3):310–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10084307
    38. Uchiyama C, Ishida K, Tsutsui T, Naito A, Kurita K, Hanihara H, et al. Effects of Hura crepitans and its active ingredient, daphne factor F3, on dihydrotestosterone-induced neurotrophin-4 activation and hair retardation. Biol Pharm Bull [Internet]. 2012 Jan [cited 2014 Mar 4];35(1):42–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22223335
    39. Bak SS, Ahn BN, Kim JA, Shin SH, Kim JC, Kim MK, et al. Ecklonia cava promotes hair growth. Clin Exp Dermatol [Internet]. 2013 Dec [cited 2014 Feb 28];38(8):904–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24252083
    40. Kang J-I, Kim S-C, Kim M-K, Boo H-J, Jeon Y-J, Koh Y-S, et al. Effect of Dieckol, a Component of Ecklonia cava, on the Promotion of Hair Growth. Int J Mol Sci [Internet]. 2012 Jan [cited 2014 Feb 28];13(5):6407–23. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    41. Park P-J, Moon B-S, Lee S-H, Kim S-N, Kim A-R, Kim H-J, et al. Hair growth-promoting effect of Aconiti Ciliare Tuber extract mediated by the activation of Wnt/β-catenin signaling. Life Sci [Internet]. 2012 Nov 2 [cited 2014 Feb 28];91(19-20):935–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23000887
    42. Byeon SE, Lee YG, Kim J-C, Han JG, Lee HY, Cho JY. Hinokitiol, a natural tropolone derivative, inhibits TNF-alpha production in LPS-activated macrophages via suppression of NF-kappaB. Planta Med [Internet]. 2008 Jun [cited 2014 Feb 25];74(8):828–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18537078
    43. Hwang SL, Kim JC. In vivo hair growth promotion effects of cosmetic preparations containing hinokitiol-loaded poly(epsilon-caprolacton) nanocapsules. J Microencapsul [Internet]. 2008 Aug [cited 2014 Feb 28];25(5):351–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18465297
    44. Bernard P, Scior T, Do QT. Modulating testosterone pathway: a new strategy to tackle male skin aging? Clin Interv Aging [Internet]. 2012 Jan [cited 2014 Mar 4];7:351–61. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    45. Roh S-S, Kim CD, Lee M-H, Hwang S-L, Rang M-J, Yoon Y-K. The hair growth promoting effect of Sophora flavescens extract and its molecular regulation. J Dermatol Sci [Internet]. 2002 Oct [cited 2014 Feb 28];30(1):43–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12354419
    46. Jung HA, Yoon NY, Kang SS, Kim YS, Choi JS. Inhibitory activities of prenylated flavonoids from Sophora flavescens against aldose reductase and generation of advanced glycation endproducts. J Pharm Pharmacol [Internet]. 2008 Sep [cited 2014 Feb 28];60(9):1227–36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18718128
    47. Sun YN, Cui L, Li W, Yan XT, Yang SY, Kang J Il, et al. Promotion effect of constituents from the root of Polygonum multiflorum on hair growth. Bioorg Med Chem Lett [Internet]. 2013 Sep 1 [cited 2014 Feb 25];23(17):4801–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23896496
    48. Park H-J, Zhang N, Park DK. Topical application of Polygonum multiflorum extract induces hair growth of resting hair follicles through upregulating Shh and β-catenin expression in C57BL/6 mice. J Ethnopharmacol [Internet]. 2011 May 17 [cited 2014 Feb 28];135(2):369–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21419834
    49. Shin H-S, Lee J-M, Park S-Y, Yang J-E, Kim J-H, Yi T-H. Hair growth activity of Crataegus pinnatifida on C57BL/6 mouse model. Phytother Res [Internet]. 2013 Sep [cited 2014 Feb 28];27(9):1352–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23148028
    50. Baroni A, De Rosa R, De Rosa A, Donnarumma G, Catalanotti P. New strategies in dandruff treatment: growth control of Malassezia ovalis. Dermatology [Internet]. 2000 Jan [cited 2014 Mar 4];201(4):332–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11146344
    51. Fischer TW, Trüeb RM, Hänggi G, Innocenti M, Elsner P. Topical melatonin for treatment of androgenetic alopecia. Int J Trichology [Internet]. 2012 Oct [cited 2014 Feb 28];4(4):236–45. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    52. Zhang J, Hu D-H, Chen G, Bai X-Z, Tang C-W. [Protective effect of melatonin on oxidative stress inducing hair follicle injury in scald rat]. Zhonghua Shao Shang Za Zhi [Internet]. 2009 Apr [cited 2014 Feb 28];25(2):129–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19799039
    53. Kimura N, Nishizaki K, Orita Y, Masuda Y. 4-methylcatechol, a potent inducer of nerve growth factor synthesis, protects spiral ganglion neurons from aminoglycoside ototoxicity--preliminary report. Acta Otolaryngol Suppl [Internet]. 1999 Jan [cited 2013 Dec 28];540:12–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10445072
    54. Zhou Z, Kawana S, Aoki E, Katayama M, Nagano M, Suzuki H. Dynamic changes in nerve growth factor and substance P in the murine hair cycle induced by depilation. J Dermatol [Internet]. 2006 Dec [cited 2014 Mar 5];33(12):833–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17169085
    55. Zhang Q, Fong CC, Yu WK, Chen Y, Wei F, Koon CM, et al. Herbal formula Astragali Radix and Rehmanniae Radix exerted wound healing effect on human skin fibroblast cell line Hs27 via the activation of transformation growth factor (TGF-β) pathway and promoting extracellular matrix (ECM) deposition. Phytomedicine [Internet]. 2012 Dec 15 [cited 2014 Mar 5];20(1):9–16. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23083814
    56. Rendl M, Polak L, Fuchs E. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. Genes Dev [Internet]. 2008 Feb 15 [cited 2014 Feb 25];22(4):543–57. Available from: http://genesdev.cshlp.org/content/22/4/543.long
    57. Lin H-Y, Yang L-T. Differential response of epithelial stem cell populations in hair follicles to TGF-β signaling. Dev Biol [Internet]. 2013 Jan 15 [cited 2014 Jan 24];373(2):394–406. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23103542
    58. Paterniti I, Impellizzeri D, Crupi R, Morabito R, Campolo M, Esposito E, et al. Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma. J Neuroinflammation [Internet]. 2013 Jan [cited 2014 Mar 6];10:20. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract
    59. Won CH, Kwon OS, Kim YK, Kang YJ, Kim BJ, Choi CW, et al. Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells. Arch Dermatol Res [Internet]. 2008 Mar [cited 2014 Jan 26];300(3):147–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18286292
    60. Cerrato S, Brazis P, della Valle MF, Miolo A, Puigdemont A. Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells. Vet Immunol Immunopathol [Internet]. 2010 Jan 15 [cited 2014 Mar 6];133(1):9–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19625089
    61 Evid Based Complement Alternat Med.2013;2013:146142. doi: 10.1155/2013/146142. Epub 2013 Jun 16.
        Attenuation of Proinflammatory Responses by S-[6]-Gingerol via Inhibition of ROS/NF-Kappa B/COX2 Activation in HuH7 Cells.
        Li XH1, McGrath KC, Tran VH, Li YM, Duke CC, Roufogalis BD, Heather AK.
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    Thanks for the write-up. Very interesting compilation of ingredients.

    What are your thoughts on this study?

    6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.
    ncbi.nlm.nih.gov/pmc/articles/PMC3578824/
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    That's a pretty comprehensive formulation. I like that you have focused heavily on managing inflammation and apoptosis. Something most treatments don't do. Is it available yet?
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    Quote Originally Posted by CF2 View Post
    Thanks for the write-up. Very interesting compilation of ingredients.

    What are your thoughts on this study?

    6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.
    ncbi.nlm.nih.gov/pmc/articles/PMC3578824/
    INteresting find...let me take a thorough look at it.
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    Wow, I am shocked you actually included 6-gingerol! That's something I'd always thought would work well for hair loss topically. I can tell you have done some serious ****ing research, would love to try this when it's available
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    I'm excited. Coop you suffer from hair loss? Mine is pretty severe which I've managed over the years to a combination of finasteride, minoxidil and hair transplants. I'm not off fin and have been a while, but need something to maintain. What are your thoughts on Revivogen? I'm really excited about Virile Mane though.
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    It is available I believe internally. I've been on it for 3-4 weeks now. I forgot exactly how long lol.

    Haven't seen anything yet though. :-(

    Great write up and formula. Should work. Probably takes a while.
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    Quote Originally Posted by halfhuman View Post
    It is available I believe internally. I've been on it for 3-4 weeks now. I forgot exactly how long lol.

    Haven't seen anything yet though. :-(

    Great write up and formula. Should work. Probably takes a while.
    Pretty much immediately I started getting really wild hairs (especially in the front). Have you gotten anything like that?
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    Quote Originally Posted by dsade View Post
    Pretty much immediately I started getting really wild hairs (especially in the front). Have you gotten anything like that?
    Really? I cut my hair shorter just so it can apply much better and I can see a difference quicker.

    Later I'm going to shower again and look closely.

    I'm applying once in the AM and again in the PM before bed. I only apply on the hair line.
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    Quote Originally Posted by saggy321 View Post
    I'm excited. Coop you suffer from hair loss? Mine is pretty severe which I've managed over the years to a combination of finasteride, minoxidil and hair transplants. I'm not off fin and have been a while, but need something to maintain. What are your thoughts on Revivogen? I'm really excited about Virile Mane though.
    Mildly yeah, I have a full family history (everyone!) so I'm trying to stop it early. I only use nizoral 2%, 3% salicylic acid shampoo! and n2 shampoo + some s5 cream. Haven't made the leap into fin or minoxidil due to the lifelong commitment.

    How did hair transplants work for you and how costly were they? How about the rest of the stuff you used?

    Quote Originally Posted by dsade View Post
    Pretty much immediately I started getting really wild hairs (especially in the front). Have you gotten anything like that?
    Where can I get some?
    http://pescience.com/
    http://selectprotein.com/
    The above is my own opinion and does not reflect the opinion of PES
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    Quote Originally Posted by saggy321 View Post
    I'm excited. Coop you suffer from hair loss? Mine is pretty severe which I've managed over the years to a combination of finasteride, minoxidil and hair transplants. I'm not off fin and have been a while, but need something to maintain. What are your thoughts on Revivogen? I'm really excited about Virile Mane though.
    Mildly yeah, I have a full family history (everyone!) so I'm trying to stop it early. I only use nizoral 2%, 3% salicylic acid shampoo! and n2 shampoo + some s5 cream. Haven't made the leap into fin or minoxidil due to the lifelong commitment.

    How did hair transplants work for you and how costly were they? How about the rest of the stuff you used?

    Quote Originally Posted by dsade View Post
    Pretty much immediately I started getting really wild hairs (especially in the front). Have you gotten anything like that?
    Where can I get some?
    http://pescience.com/
    http://selectprotein.com/
    The above is my own opinion and does not reflect the opinion of PES
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    Quote Originally Posted by mr.cooper69 View Post
    Mildly yeah, I have a full family history (everyone!) so I'm trying to stop it early. I only use nizoral 2%, 3% salicylic acid shampoo! and n2 shampoo + some s5 cream. Haven't made the leap into fin or minoxidil due to the lifelong commitment.

    How did hair transplants work for you and how costly were they? How about the rest of the stuff you used?



    Where can I get some?
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    Dsade. Can you ship oversees if I pay for postage.

    Coop fin worked well but I after while I wasnt willing to live with the side effects so I dropped it a couple of years ago. I'm on revivogen, S5, minoxidil and Nizoral at the moment. It's working OK but I've still lost over the past couple of years. The transplants have been awesome, but you need to find a good surgeon there are a lot of charlatans out there. Cost depends on number of grafts, but on average each session had cost me around 6000 to 7000 usd.
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    Quote Originally Posted by dsade View Post
    shoot me your address.
    Will post feedback soon

    Quote Originally Posted by saggy321 View Post
    Dsade. Can you ship oversees if I pay for postage.

    Coop fin worked well but I after while I wasnt willing to live with the side effects so I dropped it a couple of years ago. I'm on revivogen, S5, minoxidil and Nizoral at the moment. It's working OK but I've still lost over the past couple of years. The transplants have been awesome, but you need to find a good surgeon there are a lot of charlatans out there. Cost depends on number of grafts, but on average each session had cost me around 6000 to 7000 usd.
    Hmmm, I've been considering fin but two things that push me away from it are:

    A. The infamous "shed" that many people get a few months in
    B. The fact that if you come off it, you shed like never before

    Did you experience either of those? I realize not everyone gets these effects, but at present it's enough for me to put it off.

    Revivogen honestly doesn't look terribly effective, but I like the premise. You'd probably enjoy Regenepure more, and it can replace your nizoral.

    S5 really does work well, it's just a biotch to apply.

    And as for transplants...at that price, maybe 20 years from now lol
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    The shed is pretty normal, as you go from Telogen back to Anagen phase. The dormant hairs have to be booted from the matrix. I know it freaked me out pretty bad, but the mistake most people make is seeing the shedding, freaking out, and stopping treatment - resulting in the perception that they have made the problem worse.
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    Quote Originally Posted by saggy321 View Post
    Dsade. Can you ship oversees if I pay for postage.

    Coop fin worked well but I after while I wasnt willing to live with the side effects so I dropped it a couple of years ago. I'm on revivogen, S5, minoxidil and Nizoral at the moment. It's working OK but I've still lost over the past couple of years. The transplants have been awesome, but you need to find a good surgeon there are a lot of charlatans out there. Cost depends on number of grafts, but on average each session had cost me around 6000 to 7000 usd.
    Yeah, I can absolutely ship overseas for you.
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    Would a dermaroller help w/ virile mane effectiveness?
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    Quote Originally Posted by dsade View Post

    Yeah, I can absolutely ship overseas for you.
    Thanks man! Can you shoot me the details. Cost per bottle and shipping. Also need to know how I can make payment.
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    Quote Originally Posted by mr.cooper69 View Post
    Will post feedback soon



    Hmmm, I've been considering fin but two things that push me away from it are:

    A. The infamous "shed" that many people get a few months in
    B. The fact that if you come off it, you shed like never before

    Did you experience either of those? I realize not everyone gets these effects, but at present it's enough for me to put it off.

    Revivogen honestly doesn't look terribly effective, but I like the premise. You'd probably enjoy Regenepure more, and it can replace your nizoral.

    S5 really does work well, it's just a biotch to apply.

    And as for transplants...at that price, maybe 20 years from now lol
    finasteride has been awesome for me and finally 7-8 months later has been so good at stopping shedding that I been able to stop using minoxidil (minxodil was the best at decreasing shedding for me, I used it for 2 years straight). when I stop being lazy im going to throw minoxidil back in and hope to get some minor growth on the temples back. Point being , idk what your hair situation is but if its mild and still not that noticeable then get on while you can to mantain it like I did.

    very interested in this formula, No doubt if it wasnt for nizoral + fina + minoxidil Id have been close to a NW3 by now while now Im still mantaining better than a NW2. If this can help even more then count me in
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    Quote Originally Posted by Younglifter16 View Post

    finasteride has been awesome for me and finally 7-8 months later has been so good at stopping shedding that I been able to stop using minoxidil (minxodil was the best at decreasing shedding for me, I used it for 2 years straight). when I stop being lazy im going to throw minoxidil back in and hope to get some minor growth on the temples back. Point being , idk what your hair situation is but if its mild and still not that noticeable then get on while you can to mantain it like I did.

    very interested in this formula, No doubt if it wasnt for nizoral + fina + minoxidil Id have been close to a NW3 by now while now Im still mantaining better than a NW2. If this can help even more then count me in
    It was for me, bit over the years the site effects worsened and for me became intolerable so I had to quit. So glad I did though.
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    Quote Originally Posted by Younglifter16 View Post
    finasteride has been awesome for me and finally 7-8 months later has been so good at stopping shedding that I been able to stop using minoxidil (minxodil was the best at decreasing shedding for me, I used it for 2 years straight). when I stop being lazy im going to throw minoxidil back in and hope to get some minor growth on the temples back. Point being , idk what your hair situation is but if its mild and still not that noticeable then get on while you can to mantain it like I did.

    very interested in this formula, No doubt if it wasnt for nizoral + fina + minoxidil Id have been close to a NW3 by now while now Im still mantaining better than a NW2. If this can help even more then count me in
    Good to know, I'm an NW2 atm. Interesting that you DCed minoxidil without a shed. Usually, the hairs gained on minoxidil are lost when the product is discontinued

    Quote Originally Posted by saggy321 View Post
    It was for me, bit over the years the site effects worsened and for me became intolerable so I had to quit. So glad I did though.
    That's also odd. The clinical trials showed that with time, the side effects actually decreased to less than 0.3% of users
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    is this available for purchase?
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    Big bump to this!

    Quote Originally Posted by Urban Monk View Post
    Would a dermaroller help w/ virile mane effectiveness?
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    Where can you get this?
  

  
 

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