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Acetyl tetrapeptide-3

Also known as Ac-KGHK-NH2, Component of Capixyl, CAS 827306-88-7

Topical tetrapeptide used mainly in hair and scalp products, marketed for follicle anchoring and matrix support.

preclinical Skin & cosmetic cosmetic ingredient

At a glance

Category
Skin & cosmetic
Status
cosmetic ingredient
Route
topical, to the scalp or skin, in a serum, lotion or emulsion
Half-life
Not applicable for topical use; systemic absorption is negligible and has not been measured. A 2026 safety-evaluation framework for cosmetic peptides concludes that topically applied peptides of this kind are not expected to reach the bloodstream or lymphatic fluid at all 3
Onset
Trials of blends containing it measured change after 16 to 24 weeks; the one published randomised trial ran 24 weeks 1
Molecular weight
approximately 510 g/mol (C22H39N9O5)
Sequence
Ac-Lys-Gly-His-Lys-NH2 (acetylated and C-terminally amidated KGHK)

Registered as a cosmetic ingredient under the INCI name acetyl tetrapeptide-3 2. It is not a medicine and has no registered indication; unlike minoxidil, it has not been assessed or approved by a medicines authority for hair loss. It is applied topically only. It is best known as one half of the trade blend Capixyl, in which it is combined with a red clover extract standardised for the isoflavone biochanin A 1.

Doping status: Not listed by WADA

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Acetyl tetrapeptide-3 is a short synthetic peptide built around the GHK motif — the same glycyl-histidyl-lysine core found in the endogenous matrikine GHK and in palmitoyl tripeptide-1 — extended with an additional lysine and capped at both ends. Acetylation of the N-terminus and amidation of the C-terminus remove the charged ends, which improves stability against exopeptidases in the skin.

The claimed mechanism is matrix signalling rather than hormonal action. In cell culture the peptide has been reported to raise type III collagen and laminin levels in human fibroblasts at micromolar concentrations. Applied to the scalp, the stated rationale is that a better-built extracellular matrix in and around the dermal papilla improves follicle anchoring and follicle size, thereby reducing shedding. This is a plausible narrative but a different kind of claim from that made for minoxidil or finasteride, which act on follicular blood flow and on androgen metabolism respectively.

In the Capixyl blend the peptide is paired with biochanin A from red clover, an isoflavone with reported 5-alpha-reductase inhibiting activity in vitro. The two components therefore have different intended targets, and any clinical result obtained with the blend cannot be attributed to the peptide alone.

What the research shows

Better than most cosmetic peptides, but still weak, and almost none of it isolates the peptide. There is one genuinely published, peer-reviewed randomised controlled trial in androgenetic alopecia, but it tested a combination product against minoxidil in 32 subjects. The in-vitro figures behind the marketing come from the raw material supplier. No trial has tested acetyl tetrapeptide-3 on its own.

Research in humans

A 24-week prospective, randomised, triple-blind controlled trial published in the Journal of Clinical and Aesthetic Dermatology in 2020 compared a topical combination of biochanin A, acetyl tetrapeptide-3 and ginseng extract against 3 percent minoxidil solution in 32 subjects with mild to moderate androgenetic alopecia 1. Terminal hair count rose 8.3 percent with the herbal combination and 8.68 percent with minoxidil, a difference that was not statistically significant, and the herbal group reported no adverse reactions 1. That is a real, independently published result, but it is a small non-inferiority comparison in which the peptide is one of three actives, there is no placebo arm, and non-inferiority to 3 percent minoxidil is a modest benchmark. Supplier-reported studies of 5 percent Capixyl over four months report larger effects on hair density; those have not been peer-reviewed. For facial skin, as opposed to scalp, no controlled clinical trial of this peptide has been published.

Animal and lab research

No relevant animal studies. The mechanistic basis is human fibroblast and dermal papilla cell culture work, largely generated by the raw material supplier, reporting increases in type III collagen and laminin at around 1 micromolar.

Caveats. The published trial cannot separate the peptide from biochanin A and ginseng extract, and n = 32 over 24 weeks is small for a hair-growth endpoint with high natural variability. The cell culture data are supplier-generated, and micromolar culture concentrations cannot be assumed to occur in the dermal papilla after topical application. Whether the peptide penetrates to the follicle at all in a relevant amount has not been demonstrated. There is no long-term data, and no evidence of effect in non-androgenetic hair loss beyond small uncontrolled series.

What it is used for

  • Topical scalp serums and lotions for thinning hair, usually as part of the Capixyl blend with red clover extract; the only published randomised trial tested such a combination in androgenetic alopecia 1
  • Often stacked in commercial products with redensyl and procapil, combinations for which independent comparative data are thin
  • Occasionally included in facial skincare on the strength of the collagen and laminin culture data, where the clinical evidence is weaker still
  • Shares the GHK core with palmitoyl tripeptide-1 and GHK-Cu; the three are related in structure but have separate evidence bases and should not be treated as interchangeable

Dosing

Dose
In finished scalp products the Capixyl blend is typically used at around 5 percent of the formulation, which corresponds to a far lower content of pure peptide; the published trial used a proprietary combination whose exact peptide concentration was not stated
Frequency
Applied once daily to the scalp, usually left on rather than rinsed off
Route
topical — this is a cosmetic ingredient, not an injectable peptide
Duration
At least 16 to 24 weeks before assessing any effect, matching the published trial. Any benefit stops when use stops
  • This is emphatically not an injectable. Injecting a cosmetic peptide solution has never been studied in humans, and cosmetic trade solutions are not sterile and not pyrogen-free. This matters more than usual here, because scalp mesotherapy with unlicensed preparations is something people actually attempt.
  • The stated use levels come from supplier formulation guidance, not from published dose-finding research.
  • A claim of '5% Capixyl' refers to the trade blend, which is mostly solvent, not to peptide content.
  • Anyone considering this for androgenetic alopecia should know that minoxidil and finasteride are the interventions with an actual regulatory evidence base; this ingredient has one small comparative trial as part of a combination, in which terminal hair count rose 8.3 percent against 8.68 percent for 3 percent minoxidil over 24 weeks in 32 subjects, with no placebo arm 1.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

24-week herbal combination trial in androgenetic alopecia

published trial

Source: Journal of Clinical and Aesthetic Dermatology, 2020 - randomised, triple-blind, n = 32

Weeks 1-24, twice daily1 mL of a topical combination of biochanin A, acetyl tetrapeptide-3 and ginseng extract, applied to the scalp
Comparator arm, weeks 1-24, twice daily1 mL of 3% minoxidil solution

This schedule tested a three-ingredient combination, not the peptide alone, and the peptide concentration in the product was not stated. There was no placebo arm: the finding is non-inferiority to 3% minoxidil in 32 people, with terminal hair counts rising 8.3% and 8.7% respectively. Nothing here establishes a dose for acetyl tetrapeptide-3 itself.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
Trade form: an aqueous or hydroalcoholic solution supplied in bulk to formulators, usually as part of a blend; loose powder is also sold
Solvent
water or the aqueous phase of a formulation; not bacteriostatic water for injection — this ingredient is not reconstituted for injection
Storage
Store the raw material cool and dark, preferably 2-8 °C. A finished aqueous or hydroalcoholic product requires an adequate preservative system.

Worked example

For a scalp serum the trade blend is added at roughly 5 percent of total weight to the cooled water phase, with the pH set to approximately 5 to 6.

Add below approximately 40 °C. The acetyl and amide caps improve stability against peptidases but do not protect against extremes of pH; stay within roughly pH 4 to 7.

Safety

Side effects

  • Generally well tolerated topically; no adverse reactions were reported in the herbal combination arm of the published 24-week trial 1, and cosmetic peptides as a class perform well in standard skin and eye irritation testing 3
  • Mild scalp redness, itching or a tight feeling
  • Contact dermatitis is uncommon — peptides are typically not electrophilic and so lack the reactivity that drives delayed-type hypersensitivity 3 — and is more often attributable to the solvent, preservative or fragrance in a scalp product than to the peptide
  • Irritation if it runs into the eyes during application
  • No systematic data on use beyond about six months

Do not use if

  • Known hypersensitivity to the ingredient or to the formulation
  • Damaged, inflamed or freshly treated skin or scalp, for example after a peel, laser treatment or microneedling
  • Do not apply to mucous membranes or in the eyes
  • Injecting this ingredient, including as scalp mesotherapy, has never been studied in humans, and cosmetic trade solutions are not sterile or pyrogen-free — a real infection and pyrogen risk, not a theoretical one
  • Pregnancy and breastfeeding: no specific research on the peptide, although topically applied cosmetic peptides are not expected to reach the bloodstream or lymphatic fluid 3. Note that the Capixyl blend also contains a red clover isoflavone extract 1, for which caution in pregnancy is conventionally advised

Interactions

No systemic drug interactions are expected with topical use, because a topically applied cosmetic peptide is not expected to reach the systemic circulation at all 3; this has not been measured for this ingredient specifically. Within a formulation the peptide is sensitive to extreme pH. Applied together with minoxidil or with alcohol-heavy scalp products, the chance of scalp irritation rises without any demonstrated change in the peptide's activity; no study has examined whether the combination is additive.

Sources