Acetyl tetrapeptide-5

Acetyl tetrapeptide-5 (INCI name; trade name Eyeseryl) is a synthetic acetylated tetrapeptide (Ac-βAla-His-Ser-His) developed by Lipotec/Lubrizol specifically for periorbital cosmetic use. Its proposed mechanisms — reducing vascular permeability via angiotensin-converting enzyme (ACE) inhibition and inhibiting non-enzymatic protein glycation — target fluid accumulation and tissue stiffening under the eyes. A manufacturer-sponsored open-label study of 20 volunteers using a formulation described as 10% Eyeseryl solution reported improvement in under-eye puffiness in 70% of subjects by day 15 and 95% by day 60. Evidence is limited to this single small, uncontrolled study. The ACE-inhibitory mechanism is plausible based on in vitro binding data but has not been confirmed in vivo after topical application.

Acetyl tetrapeptide-5 is proposed to reduce periorbital edema by inhibiting angiotensin-converting enzyme (ACE), thereby reducing vascular permeability and fluid accumulation in the periorbital tissues. It also inhibits non-enzymatic glycation of dermal proteins (anti-glycation activity). The manufacturer reports that the peptide binds to the active site of ACE in vitro. The histidine residues in the sequence are thought to coordinate the zinc ion at the ACE active site, similar to known ACE-inhibitory peptides derived from food proteins. The anti-glycation mechanism has been demonstrated in model systems but not in human skin in vivo with clinically relevant endpoints. The dual-mechanism claim (ACE inhibition + anti-glycation) has not been independently replicated for the topical cosmetic use case.

Approved labeled regimen

Acetyl tetrapeptide-5 is a cosmetic ingredient, not an approved drug. No established or recommended human dose.

Studied regimens (not recommendations)

One manufacturer-sponsored study described a formulation containing 10% Eyeseryl solution applied periorbitally twice daily for 60 days. This is a descriptive study exposure, not a recommended regimen, and the study did not independently establish the concentration of active acetyl tetrapeptide-5.

What is not established

No established or recommended human dose.

Established label risks

Not applicable.

Human-study signals

The manufacturer dossier does not describe a clear adverse-event signal in the 20-volunteer report. That absence of reporting is not evidence of safety and no independent controlled tolerability study was identified.

Unknowns and product-quality risks

• Not established for injection or internal use

• ACE-inhibitory activity raises theoretical concern if systemically absorbed or injected, but topical application at cosmetic concentrations is not expected to produce systemic blood-pressure effects

• No chronic-dermal-exposure data beyond 60 days

• No irritation/sensitization data in controlled patch tests published in peer-reviewed literature

• No known interactions from topical use

• No pregnancy/lactation safety data

• EU CosIng: listed in the cosmetic ingredient inventory (INCI entry; does not constitute regulatory approval)

• US: regulated as a cosmetic ingredient; no FDA drug approval

• WADA: acetyl tetrapeptide-5 was not identified by exact name in the 2026 Prohibited List, and this review did not identify a matching prohibited class for the topical cosmetic use described here. Absence of an exact-name entry is not blanket permission; athletes should check the exact product, route, and current List with their anti-doping organisation.

• Often sold in "research peptide" catalogs labelled as Eyeseryl; any injection or parenteral use would be outside the assessed safety and efficacy profile

• No independent clinical trials; single manufacturer-sponsored study only

• No studies comparing to established treatments for periorbital edema (e.g., caffeine-based creams, cold compresses)

• ACE-inhibitory activity in vivo after topical application not characterized

• Anti-glycation efficacy in human skin not demonstrated

• Formulation-dependent activity: efficacy data from 10% Eyeseryl solution cannot be generalized to other formulations

• No peer-reviewed, PubMed-indexed clinical trial identified as of searched date

• Databases and registries: PubMed, EU CosIng, PubChem, FDA UNII, CAS Common Chemistry, Cosmetic Ingredient Review ingredient/publication search

• Search terms: "acetyl tetrapeptide-5", "Eyeseryl", "Ac-βAla-His-Ser-His", "acetyl-β-alanyl-histidyl-seryl-histidine"

• Last searched: 2026-08-06

• Inclusion emphasis: regulatory status, identity records, safety profile, clinical evidence

• PubMed search 2026-08-06: no results for "acetyl tetrapeptide-5 clinical trial" or "Eyeseryl clinical trial" in indexed peer-reviewed journals

1. EU CosIng. Acetyl Tetrapeptide-5 (ref 54142). https://ec.europa.eu/growth/tools-databases/cosing/

2. UNII Y1DFQ308G8. https://precision.fda.gov/uniisearch/srs/unii/Y1DFQ308G8

3. Lubrizol. Eyeseryl peptide solution G product information. https://www.lubrizol.com/solutions/products/beauty/detail-pages/eyeseryl-peptide-solution-g

4. World Anti-Doping Agency. 2026 Prohibited List. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf

5. CAS Common Chemistry. Acetyl tetrapeptide-5 (CAS 820959-17-9). https://commonchemistry.cas.org/detail?cas_rn=820959-17-9

6. FDA UNII Y1DFQ308G8. https://precision.fda.gov/uniisearch/srs/unii/Y1DFQ308G8

7. EU CosIng ingredient database (ref 54142). https://ec.europa.eu/growth/tools-databases/cosing/