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Acetyl tetrapeptide-5

Also known as Eyeseryl, Ac-Ala-His-Ser-His-NH2, CAS 820959-17-9

The dominant 'eye bag' cosmetic peptide; its evidence is one manufacturer trial of about twenty people.

preclinical Skin & cosmetic cosmetic ingredient

At a glance

Category
Skin & cosmetic
Status
cosmetic ingredient
Route
topical, to the periorbital skin
Half-life
Not applicable to topical use; systemic absorption is negligible. A 2026 safety-evaluation framework for cosmetic peptides concludes that topically applied peptides of this class are not expected to reach the bloodstream or lymphatic fluid at all 3
Onset
The supplier's dossier describes change from about 15 days of twice-daily use; no independently published timeline exists
Molecular weight
approximately 490 g/mol
Sequence
Acetyl-Ala-His-Ser-His-NH2 (Ac-AHSH-NH2)

A registered cosmetic ingredient, sold under the trade name Eyeseryl and present in a large share of eye creams and eye serums that make a puffiness claim 2. It is not a medicine, has no registered indication, and no medicines authority has assessed its efficacy. It is applied topically only.

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.

This is a short entry. There is little or no published research on this compound, so there is correspondingly little to report. Empty dosing or reconstitution sections mean no credible figures exist — not that they were left out.

Mechanism of action

The proposition is different from most cosmetic peptides: rather than building collagen or relaxing muscle, acetyl tetrapeptide-5 is aimed at periorbital oedema — the fluid component of an under-eye bag. The stated mechanism is inhibition of angiotensin-converting enzyme, reducing local fluid retention and vascular permeability, with a secondary anti-glycation effect claimed to protect the elasticity of the surrounding tissue. The ACE-inhibitory activity is at least measurable: an independent in-vitro study of cosmeceutical peptides identified an optimal concentration of 100 micrograms per millilitre for the ACE-1 activity of this peptide, testing it alongside carnosine, GHK, hexapeptide-11 and acetyl hexapeptide-3 1.

What that does not establish is the step that matters. An under-eye bag is largely a matter of orbital fat herniation and of skin laxity, with fluid contributing variably from person to person and from morning to evening. Inhibiting ACE in a cell assay does not demonstrate that a peptide applied to the skin surface reaches the periorbital microvasculature, nor that reducing local fluid changes the appearance of a bag whose main component is fat. Neither point has been addressed in a published study.

What the research shows

The evidence for acetyl tetrapeptide-5 as an eye-bag treatment is a single manufacturer panel study of roughly twenty subjects. It has not been published in a peer-reviewed journal, its protocol and blinding cannot be inspected, and it was run by the company selling the ingredient. A 2026 systematic review and meta-analysis of peptides for skin ageing found only two topical peptide trials of adequate quality across the whole field, and neither concerned this peptide 4.

Research in humans

No independent randomised, placebo-controlled trial of this peptide has been published. What circulates everywhere the ingredient is described is a single supplier study: approximately twenty women applying a cream containing about 0.01 percent of the peptide to the under-eye area twice daily for 60 days, with a majority reported to show improvement in eye bags by day 15 and nearly all by day 60. PeptideX has not been able to retrieve that study in any peer-reviewed or independently published form, and cites it here as what it is — an unpublished in-house panel study by the party selling the ingredient, of a size and design that would not support a conclusion even if it had been published. It is repeated verbatim across retail and formulator material, which is a measure of how effectively a single dossier can propagate, not of how well the ingredient works.

Animal and lab research

No relevant animal studies. Mechanistic support is in-vitro: measured ACE-1 inhibitory activity in a peptide screening study 1, at concentrations that cannot be assumed to occur in periorbital tissue after topical application.

Caveats. One unpublished manufacturer study in about twenty people is the entire clinical case. The endpoint — visible improvement in an under-eye bag — is subjective, highly sensitive to hydration, sleep, salt intake, time of day and photographic conditions, and unusually responsive to any occlusive moisturiser, which makes an unblinded uncontrolled panel study close to uninterpretable. The mechanism targets the fluid component of a feature that is often predominantly fat. There is no dose-response data, no long-term data, and no comparison against a plain eye cream.

What it is used for

  • Topical eye creams, gels and serums claiming to reduce under-eye puffiness and bags 2
  • Combined with caffeine, hyaluronic acid and other peptides in the same formulation, which prevents any effect being attributed to it 2
  • Investigated in vitro as one component of anti-ageing peptide mixtures, where its measured activity was ACE-1 inhibition rather than collagen stimulation 1

Dosing

Dose
The supplier's own panel study used a cream containing approximately 0.01 percent of the peptide, corresponding to 10 percent of the trade solution
Frequency
Twice daily to the periorbital area
Route
topical — a cosmetic ingredient, not an injectable peptide
Duration
60 days in the supplier study; any effect stops when use stops
  • This concentration comes from the ingredient supplier's unpublished panel study and its formulation guidance, not from independent dose-finding research. No dose-response study has been published.
  • A label claiming a percentage of Eyeseryl refers to the trade solution, not to the peptide, whose actual content is roughly a hundredth of that figure.
  • This is not an injectable, and the periorbital area is the worst possible place to experiment: cosmetic trade solutions are not sterile and not pyrogen-free, and the vascular anatomy around the eye makes injection injuries there disproportionately serious.
  • Under-eye puffiness that is caused by orbital fat herniation will not respond to a topical anti-oedema agent, and no product can distinguish the two on a reader's behalf.

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

Reconstitution

Solvent
water or the aqueous phase of an emulsion; not bacteriostatic water for injection
Storage
Raw material cool and dark, preferably 2-8 °C. A finished aqueous product requires a sound preservative system.

Added to the cooled water phase below roughly 40 °C, pH approximately 5 to 6.

Safety

Side effects

  • Generally well tolerated topically; cosmetic peptides as a class perform well in standard skin and eye irritation testing 3
  • Mild redness, stinging or tightness, more noticeable on periorbital skin, which is the thinnest on the body
  • Irritation if applied too close to the eyelid margin or if the product migrates into the eye
  • Contact allergy is rare — peptides are typically not electrophilic and lack the reactivity that drives delayed-type hypersensitivity 3; reactions are more often to preservatives or fragrance in the same product
  • No independently collected side effect profile exists for this peptide, because no independent trial of it has been published

Do not use if

  • Known hypersensitivity to the ingredient or the formulation
  • Active eyelid dermatitis, blepharitis or conjunctivitis
  • Damaged, inflamed or freshly treated skin around the eye
  • Do not apply to the eyelid margin, the inner canthus or into the eye
  • Injecting this ingredient has never been studied in humans, and cosmetic trade solutions are not sterile or pyrogen-free — a concrete infection risk, and periorbital injection injuries are among the most serious in aesthetics
  • Pregnancy and breastfeeding: no specific research, although systemic exposure from topical use is negligible 3

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. Within a formulation the peptide is sensitive to extreme pH. Concurrent use with retinoids or exfoliating acids around the eye raises the chance of irritation without any demonstrated change in the peptide's action.

Sources