Acetyl tetrapeptide-5 is the peptide most often printed on eye creams sold for puffiness. Its trade name is Eyeseryl, and the claim on the shelf is specific: less swelling under the eye.
The research record is very small, and most of what exists is about injectable gels, not creams. This entry sets out what the record contains.
The molecule
Ac-β-Ala-His-Ser-His-OH: beta-alanine, histidine, serine, histidine, with an acetyl cap on the front end. PubChem CID 11620163, formula C20H28N8O7, molecular weight 492.5, CAS 820959-17-9. PubChem lists "Eyeseryl" as a synonym of the same record, so the trade name and the INCI name are one compound.
Two features are worth knowing. The first residue is beta-alanine, not the ordinary alanine in proteins. The two histidines make it chemically close to carnosine (beta-alanyl-histidine), a dipeptide found in muscle and studied as an anti-glycation agent. That family resemblance is a plausible reason the peptide was designed this way. It is not evidence about what the peptide does on a face.
At 492.5 daltons it sits just under the 500-dalton line often used as a rough limit for passive skin penetration. It has no fatty tail, unlike palmitoyl tetrapeptide-7 and the other palmitoylated actives that add one to get through the barrier.
What PubMed holds
Searched 5 October 2026:
| Search | Records |
|---|---|
| "acetyl tetrapeptide-5" in title or abstract | 1 |
| "acetyl tetrapeptide 5" as a quoted phrase | 0 (phrase not found; PubMed's unquoted fallback returns 116 unrelated records) |
| Eyeseryl | 0 |
| "acetyl tetrapeptide" (any number) in title or abstract | 7 |
The fallback is a trap worth stating. Typed without the hyphen, the phrase is not indexed, so PubMed splits it into separate words and returns over a hundred papers about acetyl groups and unrelated tetrapeptides. Counting those would inflate the evidence a hundredfold.
The one record is Wu and colleagues, Skin Pharmacology and Physiology 2021 (PMID 33849044). They tested five cosmetic peptides in cultured human skin fibroblasts, one at a time and then in mixtures. For acetyl tetrapeptide-5 the abstract reports 100 µg/mL as the optimal concentration for angiotensin-converting enzyme 1 (ACE-1) activity. ACE-1 is the enzyme that produces angiotensin II, which narrows blood vessels and promotes fluid retention. A puffiness ingredient tested in an ACE-1 assay shows which mechanism its makers had in mind.
The best-performing mixture combined carnosine, acetyl tetrapeptide-5, hexapeptide-11 and acetyl hexapeptide-3 (Argireline). It reduced oxidative-damage markers and raised hydroxyproline and elastin in cells stressed with hydrogen peroxide. That is a four-peptide mixture in a dish. It does not isolate this peptide, and it measured nothing on a person.
A Europe PMC full-text search returns 11 papers that mention the name somewhere in their text. By title, they are reviews of cosmetic actives, studies of multi-ingredient products, and the two injectable studies below. None is a trial of the peptide on its own.
No registered trial
ClinicalTrials.gov returned no study naming acetyl tetrapeptide-5 or Eyeseryl on 5 October 2026. The supplier's product page refused an automated read (a Cloudflare challenge), so its own test data could not be opened for this entry and is not quoted here.
This is the usual position for an eye-area peptide. The peptide eye cream census found that the best-controlled single-peptide eye trial in the literature was for Argireline, not this ingredient.
The second life: under-eye injectables
The human data that do mention acetyl tetrapeptide-5 come from an unexpected place: injectable gels from Professional Derma SA, a Swiss company that makes the Jalupro line.
Jalupro Young Eye, 40 women. Kutlubay and colleagues, Cureus 2026 (PMC13283013). The paper describes the product as a CE Class III device whose 1 mL syringe holds 12 mg of non-cross-linked hyaluronic acid, seven amino acids "and the EyeSeryl (acetyl tetrapeptide-5) complex". Forty women had two sessions three weeks apart, 0.5 mL per under-eye area. Ultrasound three months after the first treatment reported lower-eyelid skin thickness rising from 1.34 to 2.05 mm, and elasticity on shear-wave imaging from 3.96 to 4.99 kPa. Thirty-four of the 40 (85%) were satisfied. The authors declared no funding.
Jalupro Superhydro, 43 participants. Poleva, Journal of Cosmetic Dermatology 2025 (PMC11724232). Here the gel combines high- and low-molecular-weight hyaluronic acid, seven amino acids and three peptides: acetyl decapeptide-3, oligopeptide-24 and acetyl tetrapeptide-5. Three monthly sessions were injected deep, near the facial retaining ligaments, and assessed on the Global Aesthetic Improvement Scale and 3D photography. The paper states the product was provided by Professional Derma SA.
What these two studies cannot show:
- Neither had a control group. Both are single-arm, so there is no comparison against untreated skin, saline, or the same gel without the peptide.
- The peptide is one ingredient among many. Injected hyaluronic acid adds volume and water by itself, and the earlier under-eye polynucleotide census found the same problem of mixtures.
- Injection is not application. A peptide placed in the dermis by needle skips the barrier entirely. Nothing in either paper speaks to an eye cream.
What labels say and what this record supports
On a cream label, acetyl tetrapeptide-5 is usually listed well below the water, glycols and emollients, and its amount is not declared. Reading a peptide ingredient list explains why position is all a buyer can infer.
The record supports these statements, and no stronger ones:
- The compound is real, well characterised and correctly named on labels.
- One cell-culture study tested it, mostly in mixtures, and reported an ACE-1 assay result.
- No controlled human trial of the peptide alone, in any format, is in PubMed or registered.
- Two uncontrolled injectable studies list it as one ingredient in a hyaluronic-acid gel.
It does not support saying that the peptide reduces puffiness, that it lightens dark circles, or that it works in eye cream, and the absence of such a trial is the main finding of this entry.
For the related hair-care peptide with a similar name, see acetyl tetrapeptide-3. For the eye-area category as a whole, see peptide eye patches.
Sources
- PubChem, CID 11620163 (acetyl tetrapeptide-5; synonyms incl. Eyeseryl, CAS 820959-17-9), read 2026-10-05.
- PubMed E-utilities searches as tabled, run 2026-10-05, with the
quotedphrasesnotfoundcheck; no record carries the Retracted Publication type. - Wu Y et al., Skin Pharmacol Physiol 2021;34(4):194-202 (PMID 33849044), abstract read 2026-10-05.
- Kutlubay Z et al., Cureus 2026 (PMC13283013), full text read 2026-10-05.
- Poleva I, J Cosmet Dermatol 2025 (PMC11724232), full text read 2026-10-05.
- Europe PMC full-text search "acetyl tetrapeptide-5", 11 results, read 2026-10-05.
- ClinicalTrials.gov API v2 searches "acetyl tetrapeptide-5" and "eyeseryl", 0 results, 2026-10-05.