The Science Behind Hair+ Please

GHK is a naturally occurring human tripeptide, glycyl-L-histidyl-L-lysine. Every human study cited here applied it to skin.

TOPICAL, HUMAN SCALP. Lee WJ et al. 2016, Annals of Dermatology 28(4):438-443. Randomized, double-blind, 45 men aged 20 to 60 with male pattern hair loss, topical spray once daily to the frontal scalp for 6 months. Hair count within a 1 cm diameter circle rose by 52.6 hairs at 100 mg/mL (n=15) and 71.5 hairs at 50 mg/mL (n=14), versus 9.6 on placebo (n=14), p<0.05. No adverse events occurred in any arm. The agent was ALAVAX, a complex of 5-aminolevulinic acid and GHK peptide, so the result belongs to the complex.

TOPICAL, HUMAN SKIN. The standing review is Pickart and Margolina 2018, International Journal of Molecular Sciences 19(7):1987. It reports that plasma GHK falls from roughly 200 ng/mL at age 20 to about 80 ng/mL by age 60, and states directly that GHK-Cu penetrates the stratum corneum, which is why it is active in cosmetic formulations.

Leyden and colleagues presented a 12-week study at the 2002 American Academy of Dermatology annual meeting: a GHK-Cu facial cream applied to 71 women with mild to advanced photoaging increased skin density and thickness, reduced laxity, improved clarity, and reduced fine lines and wrinkle depth. A companion thigh-skin arm found improved collagen production in 70 percent of women treated with GHK-Cu, versus 50 percent treated with a vitamin C cream and 40 percent treated with retinoic acid. That is a responder rate - the proportion of women whose collagen production improved - and on it GHK-Cu outperformed both comparators.

EX VIVO, HUMAN FOLLICLES. Pyo HK et al. 2007, Archives of Pharmacal Research. Human hair follicle organ culture. The peptide tested was AHK-Cu, a related but different tripeptide-copper complex, not GHK-Cu. At 10^-12 to 10^-9 M it elongated human follicles and increased dermal papilla cell proliferation, raised VEGF output, lowered TGF-beta1 and reduced dermal papilla apoptosis.

ANIMAL STUDY. Uno H, Kurata S 1993, Journal of Investigative Dermatology. Topical copper-binding peptide in stumptail macaques and fuzzy rats enlarged anagen follicles from vellus toward terminal type, assessed by phototrichogram and folliculogram.

The lipidosterolic extract of Serenoa repens berries is dominated by free fatty acids - lauric, oleic, myristic and linoleic - together with phytosterols such as beta-sitosterol. These fatty acids inhibit 5-alpha-reductase, the enzyme converting testosterone to dihydrotestosterone, the androgen implicated in follicular miniaturisation in pattern hair loss. That is the same enzyme finasteride targets, though saw palmetto is a botanical extract and not a prescription 5-alpha-reductase inhibitor.

TOPICAL, HUMAN. Wessagowit V et al. 2016, Australasian Journal of Dermatology 57(3):e76-e82. In an open, within-subject study, 50 male volunteers aged 20 to 50 with androgenetic alopecia applied topical products containing Serenoa repens extract for 24 weeks. Terminal hair count rose by 74.1 percent from baseline at week 24 and vellus hair count fell by about 25 percent, with mean severity shifting from Norwood-Hamilton stage 4 toward stage 3.

ORAL, HUMAN. Prager N, Bickett K, French N, Marcovici G 2002, Journal of Alternative and Complementary Medicine 8(2):143-152. Randomized, double-blind, placebo-controlled pilot of an oral botanical 5-alpha-reductase inhibitor blend containing saw palmetto and beta-sitosterol. 6 of 10 men in the active arm (60 percent) were rated improved by blinded investigators at the final visit, against roughly 11 percent on placebo.

A 16-week randomized, placebo-controlled study published in 2023 in Clinical, Cosmetic and Investigational Dermatology tested a standardized saw palmetto oil administered both orally and topically and reported reduced hair fall and improved hair growth in androgenetic alopecia subjects.

The direction of effect is consistent across studies, the topical route is the route this patch uses, and the mechanism is plausible and well characterised.

Procyanidin B2 is a dimeric flavan-3-ol, a proanthocyanidin, concentrated in apple peel and immature apple juice. Preclinical work showed growth-promoting activity in cultured mouse hair epithelial cells and anagen induction in murine models, and that is what led Takahashi and colleagues to take it to human scalp.

TOPICAL, HUMAN - the pivotal trial. Takahashi T et al. 2001, Phytotherapy Research 15(4):331-336, titled 'The first clinical trial of topical application of procyanidin B-2 to investigate its potential as a hair growing agent'. Double-blind design, 29 men: 19 applied a 1 percent procyanidin B-2 tonic and 10 applied placebo, used sequentially for 4 months in the primary analysis with follow-up to 6 months.

Result: 78.9 percent of the procyanidin B-2 group showed an increase in mean hair diameter, versus 30.0 percent of the placebo group. That difference was significant at p<0.02 by Fisher's exact probability test. Over the full 6-month period, the increase in the number of terminal hairs - defined as hairs more than 60 micrometres in diameter - within the designated scalp area was significantly greater in the procyanidin B-2 group than in placebo. No adverse side effects were observed in either group.

An earlier report by the same group in Phytomedicine investigated topical procyanidin B-2 from apple in the same context. A later randomized, double-blind, placebo-controlled study of topical procyanidin B2 in men with androgenetic alopecia was published in the Turkish Journal of Dermatology in 2022, extending the evidence base beyond the original trial.

Procyanidin B2's mechanism is understood to be independent of 5-alpha-reductase inhibition, which is why it sits alongside saw palmetto and rosemary in this formula rather than duplicating them.

Biotin is a water-soluble B vitamin and an essential cofactor for five carboxylase enzymes involved in fatty acid synthesis, gluconeogenesis and amino acid catabolism. Keratin production depends on those pathways, which is the biological reason biotin is associated with hair and nails.

The documented clinical finding is specific and consistent. Patel DP, Swink SM, Castelo-Soccio L 2017, Skin Appendage Disorders 3(3):166-169, systematically searched PubMed for case reports and randomized clinical trials of biotin for hair and nail growth. They identified 18 reported cases of biotin use associated with hair or nail changes. In every one of those cases the patient had an underlying pathology causing poor hair or nail growth - inherited or acquired biotin deficiency, biotinidase deficiency, brittle nail syndrome or uncombable hair syndrome - and in every one there was clinical improvement after supplementation.

That is where biotin's evidence sits: correction of a deficiency or of a defined pathology, documented in every reported case. Biotin is in this formula on that cofactor rationale. Route studied: ORAL.

One safety point is well documented and clinically important. High-dose biotin interferes with streptavidin-biotin immunoassays, and the US Food and Drug Administration has issued a safety communication on this. Interference can produce falsely low troponin results, which risks a missed heart attack diagnosis, and can distort thyroid function tests, parathyroid hormone and several hormone assays. Anyone taking biotin should tell the laboratory before blood tests.

TOPICAL, HUMAN - the head-to-head trial. Panahi Y, Taghizadeh M, et al. 2015, SKINmed 13(1):15-21. A randomized active-comparator trial in patients with androgenetic alopecia: rosemary oil (n=50) versus minoxidil 2 percent (n=50), applied for 6 months, with standardized professional microphotographic assessment at baseline, 3 months and 6 months.

Result: both groups showed negligible change at 3 months and a statistically significant increase in hair count from baseline at 6 months. The difference between rosemary oil and minoxidil 2 percent was not statistically significant. Scalp itching was significantly more frequent in the minoxidil group than in the rosemary group.

MECHANISM. Murata K et al. 2013, Phytotherapy Research, used activity-guided fractionation to identify 12-methoxycarnosic acid as the constituent of Rosmarinus officinalis leaf extract responsible for 5-alpha-reductase inhibition. The extract inhibited 5-alpha-reductase by 82.4 percent at 200 micrograms per millilitre and 94.6 percent at 500 micrograms per millilitre. Rosemary extract and 12-methoxycarnosic acid inhibited androgen-dependent proliferation of LNCaP cells by 64.5 percent and 66.7 percent respectively, suggesting interference with dihydrotestosterone binding at the androgen receptor. The extract also promoted proliferation of human dermal papilla cells in vitro and promoted hair growth in mouse models.

Rosemary therefore has both a characterised mechanism and a 6-month human trial with an active comparator, applied to scalp skin - an unusually strong position for a botanical, and the same route this patch uses.

ORAL, HUMAN - the route is stated first because it matters. Cho YH et al. 2014, Evidence-Based Complementary and Alternative Medicine 2014:549721. A randomized, double-blind, placebo-controlled trial. 90 men with mild to moderate androgenetic alopecia were enrolled and 76 completed (37 pumpkin seed oil, 39 placebo), taking 400 mg of pumpkin seed oil per day orally - two 100 mg capsules 30 minutes before breakfast and dinner - for 24 weeks.

Results: mean hair count increased 40 percent from baseline in the pumpkin seed oil group versus 10 percent in placebo at 24 weeks, a net difference of 30 percentage points, p<0.001. At 12 weeks the figures were 30 percent versus 5 percent, p<0.001. Self-rated improvement scores (p=0.013) and self-rated satisfaction scores (p=0.003) were significantly higher on pumpkin seed oil. Adverse effects were comparable between arms and the treatment was well tolerated.

By design quality this is the strongest single trial behind any ingredient in this formula: randomized, double-blind, placebo-controlled, 24 weeks, 76 completers, with a clear placebo-adjusted effect - at 400 mg per day taken orally.

MECHANISM. Pumpkin seed oil is rich in phytosterols, notably beta-sitosterol, along with delta-7-sterols, and these are proposed to inhibit 5-alpha-reductase and reduce conversion of testosterone to dihydrotestosterone. That is the same mechanistic family as saw palmetto, and beta-sitosterol at 414.7 g/mol sits below the 500-Dalton threshold.