Skincare
Acetyl tetrapeptide-5
Also known as Eyeseryl · Acetyl Tetrapeptide-5 (INCI)
No real evidence at all
1 of 51 peptides sit at this level
- Category
- Skincare
- Doping status
- Not banned in sport
- Sources
- 16
Acetyl tetrapeptide-5 is a peptide four amino acids long — amino acids are the small units proteins are built from. Cosmetic makers buy it under the trade name Eyeseryl and put it in eye creams to make bags under the eye look smaller. No published study has tested a cream containing it against a dummy cream on anybody's eyes; the figures that circulate come from the ingredient maker's own material. The only measurements in living people come from three studies of injected mixtures, in which nobody separated this peptide from the other ingredients. It is a cosmetic ingredient, not a medicine, and it is not approved to treat anything.
Acetyl tetrapeptide-5What it is
What it is
A four-amino-acid peptide listed on labels as Acetyl Tetrapeptide-5 and sold under the trade name Eyeseryl, meant for the skin around the eye. It appears in several serums sold in Sweden, usually mixed with other peptides.
How it is sold, and whether it is legal
- Sold as
- Applied to the skin (eye serum, eye cream)
- Legal status in the EU
- A cosmetic ingredient under EU Regulation 1223/2009. That an ingredient is legal says nothing about whether it works — the regulation requires no proof of effect before sale, only that the responsible person can show "adequate and verifiable evidence" for the claims actually made, under article 20 and the annex to Regulation 655/2013. The Swedish Medical Products Agency supervises the market but does not approve cosmetics in advance.
What it does in your body
4 parts of the body · 1 from one small study, 1 only seen in a dish, 2 claimed but never tested
According to PubChem the molecule is an acetylated beta-alanine followed by histidine, serine and histidine (C20H28N8O7, 492.5 g/mol). The mechanism given in marketing — less fluid build-up and less sugar damage to collagen around the eye — could not be traced to any peer-reviewed publication in this review.
- Under-eye tissue, when it is injected in a mixture
- The only measurements of this molecule inside living people come from clinics injecting it under the eye as one ingredient in a mixture. Three months after two injection sessions, ultrasound scans showed thicker skin and stiffer tissue than before. The same syringe also held hyaluronic acid and seven amino acids, so nothing in the study separates one ingredient from another.
- Measured in 40 women aged 23 to 53, 80 eyelids, two injection sessions three weeks apart and three months of follow-up. There was no untreated group and no dummy injection to compare against.
- One small study
- Source [06]
- Skin cells in a dish
- The selling claim is that this peptide blocks an enzyme called ACE, so that less fluid leaks into the tissue under the eye. A 2021 laboratory study tested five cosmetic peptides on human skin cells damaged with hydrogen peroxide, using 100 micrograms of this one per millilitre of fluid to measure that enzyme's activity. Cells in a dish are not an eye — no skin, no blood vessel and no person was involved.
- Measured in human skin cells grown in a dish. The full text sits behind a paywall, so only what the abstract states is reported here, and the abstract does not say by how much the enzyme was blocked.
- Only seen in a dish, not in a body
- Source [07]
- Puffiness under the eye
- This is what the ingredient is sold to do. The claim is that by blocking that enzyme it stops fluid seeping out of tiny blood vessels into the tissue under the eye, so the area drains instead of swelling. A 2022 paper on a peptide skincare range lists that claim in one line of a table, with no trial cited beside it.
- Never measured in a published study. The often-quoted figures — 20 people, a cream with 0.01% of the peptide, twice a day for 60 days, 95% improved — trace only to the ingredient maker's own material. A 2021 analysis of 88 facial cosmetics found that this is where efficacy data for cosmetic peptides normally lives: not in peer-reviewed journals but in patents and supplier brochures.
- Claimed, never tested
- Source [02]Source [08]Source [09]
- The skin's outer layer
- A cream has to get past the dead outer layer of skin before it can reach anything underneath. Nobody has published a measurement of whether this peptide does. The two cosmetic peptides measured this way barely moved. Of acetyl hexapeptide-8, 99.7% washed straight off and 0.22% stayed in the dead outer layer; 0.01% reached the living layer beneath it, and none at all reached the deeper skin or the fluid below. Carnosine, a peptide only two amino acids long, did not get past the very first layer.
- Not measured for this peptide. The figures above come from laboratory tests on donated human skin using two other cosmetic peptides, reported in a 2026 review of how peptide safety in cosmetics is assessed.
- Claimed, never tested
- Source [10]
What changed when it was measured
4 findings · all from one small study
We found no peer-reviewed, published clinical study of acetyl tetrapeptide-5. The figures that circulate — 20 subjects, 0.01%, 60 days, less puffiness in 95% — trace only to the ingredient supplier's own marketing material and to retailer pages, never to an original source anyone can check. The sequence field is deliberately left empty: PubChem's chemical name shows the first amino acid is beta-alanine, which has no letter in the standard one-letter code, so writing "AHSH" would describe a different molecule. A systematic review in Frontiers in Medicine (2026) found only 2 topical randomised studies among 19 included, and does not cover this ingredient.
For a cream, nothing is published. No cream containing this peptide has been tested against a dummy cream, so there is no measurement of how long anything takes. In the only published study of the eye area, the scans were taken three months after the second of two injection sessions, so nothing is known about what happened in between. In the facial injection study the largest change was recorded one month after the last of four monthly sessions, and it had partly faded four months later.
- Thickness of the skin under the eye, on ultrasound
- 1.34 mm before treatment and 2.05 mm three months after — a rise of about 53%, compared only against the same women's own before-measurement. There was no untreated group and no dummy injection. The muscle under the skin went from 0.95 mm to 1.33 mm on the same comparison.
- 40 women aged 23 to 53, 80 eyelids, two injection sessions three weeks apart, three months of follow-up. Open-label: everyone knew what they were getting.
- One small study
- Source [06]
- Stiffness of the tissue under the eye
- Stiffness is reported in kilopascals, the unit used for how hard tissue is to squash. It went from 3.96 to 4.99 in the skin and from 4.39 to 5.36 in the muscle beneath it, three months after treatment. Both figures are against the same women's own before-measurement only. The authors write that the changes "cannot be attributed exclusively to the intervention".
- The same 40 women and 80 eyelids, two injection sessions three weeks apart, three months of follow-up.
- One small study
- Source [06]
- Water content and springiness of facial skin
- Water content up 25.9% one month after the last injection and still up 15.9% four months after. Springiness up 29.2% then 20.7%. A scan measure of collagen density up 20.3% then 16.7%. Every figure is against the same women before their first injection — the study had no comparison group at all.
- 28 women aged 25 to 65, four injection sessions one month apart, then four months of follow-up. Open-label and not randomised.
- One small study
- Source [11]
- How much the face was lifted, on 3D photographs
- An average lift of 1.6 mm at the final check, three months after the last of three monthly injection sessions. It was measured against each person's own before-photograph. There was no comparison group, and the records were pulled together and read after the treatments had already happened.
- 43 people (42 women, 1 man) aged 35 to 65, three monthly injection sessions and three months of follow-up. The manufacturer supplied the product.
- One small study
- Source [12]
What can go wrong
4 effects
We found no public expert toxicology assessment specific to acetyl tetrapeptide-5, and no serious side effects have been reported. An absence of reported problems is not the same thing as documented safety. Products used close to the eye should be treated carefully by anyone with a known contact allergy.
- Bruising and swelling where the needle went in
- Both papers describe it as mild and short-lived, settling on its own without treatment. This is what a needle does to thin skin, and it says nothing about the peptide itself.
- In the under-eye injection study, swelling in 5 of the 80 treated eyelids and bruising in 3 of 80. In the facial injection study, bruising in 3 of 28 women.
- Source [06]Source [11]
- Pain during the injection
- Described as mild and limited to the moment of injection. The needle goes into the thin skin below the eye, in small blebs.
- Reported for all 80 treated eyelids in the under-eye study — that is, by every one of the 40 women.
- Source [06]
- Anything at all from a cream or a serum
- No published study has recorded the side effects of a leave-on product whose active ingredient is acetyl tetrapeptide-5. The 2026 review that pooled 19 randomised peptide skincare trials in 1,341 people, lasting 4 to 12 weeks, contains no trial of this ingredient to draw on.
- Not measured.
- Source [02]
- Serious harm — the kind that needs a hospital
- 111 people over a few months is far too few, for far too short a time, to establish that a rare or slow problem does not exist. No expert safety assessment of this specific ingredient was found in this review — neither a US Cosmetic Ingredient Review report nor an EU scientific committee opinion.
- None reported. The three published studies of products containing this peptide cover 111 people between them, followed for three to four months after the last injection.
- Source [06]Source [11]Source [12]
Who it is known to be dangerous for
Nobody has established this. No expert safety assessment of acetyl tetrapeptide-5 turned up in this review: no US Cosmetic Ingredient Review report and no EU scientific committee opinion covers it. Several related cosmetic peptides have been assessed, but not this one. The three published studies of products containing it enrolled adults only and almost entirely women: 1 man against 110 women, with minimum ages of 18, 25 and 35. Nothing has been published on use in pregnancy, on children, or on skin that is already inflamed or broken.
The amounts the studies used
2 amounts
These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.
- Cureus 2026 — changes in the tissue under the eye, measured by ultrasound (product: Jalupro Young Eye)
- 1 mL of solution per session, 0.5 mL into each side, injected as small blebs into the deeper layer of the skin through a 13 mm, 32-gauge needle. The solution held 12 mg of non-cross-linked hyaluronic acid, seven amino acids and the EyeSeryl (acetyl tetrapeptide-5) complex. The paper does not state how much of the peptide itself was in it.
- Two sessions three weeks apart, then three months of follow-up.
- Source [06]
- Journal of Cosmetic Dermatology 2025 — skin water content and springiness (product: Jalupro Super Hydro)
- 2.5 mL of solution per session, injected under the skin. The solution held sodium hyaluronate, seven amino acids and three peptides, one of which was acetyl tetrapeptide-5. The paper does not state how much of the peptide the solution contained.
- Four sessions, one a month, then four months of follow-up after the last one.
- Source [11]
What people report
What follows is what people say online. It is not evidence, it is not graded, and it is not checked by anyone. People who had a bad time and people who are selling something both post more than people for whom nothing happened. It is here because you would go and read it anyway, and knowing who is talking is better than not.
The morning puffiness looks better, but nobody can tell which ingredient did it
In threads about The Ordinary's Multi-Peptide Eye Serum — the product most people meet this ingredient in — posters describe waking up less puffy and the eye area feeling firmer. Others in the same threads say the effect did not last, and regulars openly accuse the most glowing posts of being fake. The bottle also holds caffeine and three other peptides, and the comparison people actually make is against the plain caffeine serum, not against nothing.
Read in r/30PlusSkinCare, the thread "Anyone tried The Ordinary's Multi-Peptide Eye Serum?", and r/TheOrdinarySkincare threads comparing it with the caffeine solution
What the published studies say
No published study has compared this peptide against the caffeine and the other peptides sold beside it, or against a dummy cream, on anyone's eyes.
Two months, no difference, not buying it again
The other half of the same threads. One poster used it for two whole months, saw nothing worth repurchasing for, and went back to their ordinary face moisturiser around the eye. Another came back a month in and wrote that they did not know whether they had seen much difference.
Read in r/30PlusSkinCare, the thread "What are your experiences with The Ordinary Multi-Peptide Eye Serum?"
It stings — and so does the caffeine one
Several posters in the same thread say the serum burns or tingles on the skin under the eye. Most of them were applying it straight after washing their face. At least one reports the same trouble from The Ordinary's caffeine eye solution, and nobody there can say which of the bottle's ingredients is responsible.
Read in r/30PlusSkinCare, the thread "Anyone tried The Ordinary's Multi-Peptide Eye Serum?"
What the published studies say
No published study has recorded the side effects of any leave-on product whose active ingredient is this peptide.
The dark circles turned out not to be about the eye area at all
A widely-read post describes a year of new dark circles in someone's mid-twenties, several eye creams and The Ordinary's caffeine solution, and no result from any of them. The cause the thread settled on was iron deficiency. Other posters replied that their own circles improved whenever they restarted iron supplements. None of this was measured, and none of it involves this peptide.
Read in r/SkincareAddiction, the thread "[PSA] TIL dark circles under eyes can be caused by iron deficiency"
What the published studies say
The only thing this ingredient is claimed to move is fluid leaking from small blood vessels, and even that has never been tested in a published study.
Where to read it yourself
- r/SkincareAddiction
Reddit community
One of the largest general skincare communities on Reddit. It describes itself as science-based, and it carries a long archive of threads on dark circles and under-eye bags.
Its rules ban blog spam, product spam and referral codes, but people arrive when something is wrong, so unhappy posts outnumber contented ones. Nobody there measures anything — the outcome is always what someone sees in a mirror.
- r/30PlusSkinCare
Reddit community
A Reddit community for people over 30 comparing what they use; posts from under-30s are removed. It carries most of the discussion of peptide eye serums and of under-eye puffiness.
Recommendations are passed on as personal experience and repeated until they read as consensus. Posters routinely change several products at once and rarely take before-photographs. Regulars in the main eye-serum thread accuse the most enthusiastic reviews there of being fake.
- r/TheOrdinarySkincare
Reddit community
A Reddit community about one brand's products, including the Multi-Peptide Eye Serum that lists acetyl tetrapeptide-5 on its label.
A single-brand community draws both loyalists and people arriving specifically to complain. It discusses finished products, never ingredients, so this peptide is never separated from the caffeine and the three other peptides in the same bottle.
- FDA Adverse Event Monitoring System (AEMS) public dashboard for cosmetic products
Official side-effect reports
The US regulator's public, searchable record of side-effect reports for cosmetic products. Since the Modernization of Cosmetics Regulation Act of 2022, the company named on a cosmetic label must report a serious adverse event to the FDA within 15 business days.
The dashboard is organised by product and brand, not by ingredient, so no entry in it can be pinned to this peptide. A report is not proof the product caused anything, and most reactions are never reported at all.
What nobody has measured
9 unknowns
- Whether the peptide crosses the dead outer layer of human skin at all — no penetration study of this molecule has been published.
- Whether a cream containing it does anything a dummy cream does not; that comparison has never been made in a published study.
- What the peptide contributed in the three injection studies, since none of them separated it from the hyaluronic acid, the amino acids and the other peptides in the same syringe.
- Whether the claimed anti-glycation effect — less sugar damage to collagen around the eye — happens at all; no published measurement of it was found.
- Whether it does anything for dark circles caused by shape, thin skin or pigment rather than by fluid.
- How often it irritates or sensitises the skin around the eye, and at what concentration — no expert safety assessment of this ingredient was found.
- Whether anything measured in the injection studies lasts beyond the three to four months they followed people for.
- Whether men respond the same way; the published studies enrolled 1 man against 110 women.
- What repeated use around the eye does over years — every published study of a product containing it ran for months, not years.
Questions people ask
6 questions
- Is there a study showing it gets rid of bags under the eye?
- No. The numbers that circulate — 20 people, a cream with 0.01% of the peptide, twice a day for 60 days, 95% improved — trace to the ingredient maker's own material. There is nothing published that a reader can go and check. A 2026 systematic review pooled 19 randomised peptide trials in 1,341 people, lasting 4 to 12 weeks, and contains no trial of this ingredient at all. That review also found that only 2 of the 19 trials tested anything applied to the skin, and that the measurable benefit came mostly from peptides swallowed as a supplement.
- Source [02]Source [09]
- Has anyone registered a trial of it?
- No. ClinicalTrials.gov is the public US register where studies are recorded before they start. It returns zero records for acetyl tetrapeptide-5 and zero for the trade name Eyeseryl. Not a completed trial, not one that is running, not even a registered plan.
- Source [13]
- How can it be sold if nobody has tested whether it works?
- Because a cosmetic is not a medicine. Under EU Regulation 1223/2009 no proof of effect is needed before a cosmetic goes on sale. What is required is that the company whose name is on the label holds evidence for the claims it actually prints. That duty comes from the common criteria in Regulation 655/2013, which say claims must be supported by "adequate and verifiable evidence". Nobody inspects that file before the jar reaches a shelf.
- Source [14]Source [15]
- Does it even get through the skin?
- Nobody has published a measurement for this peptide. Two other cosmetic peptides were tested on donated human skin in a laboratory, and almost all of it washed off. Of acetyl hexapeptide-8, 0.22% stayed in the dead outer layer, 0.01% reached the living layer under it, and none reached the deeper skin or the fluid beneath. The authors of that 2026 review concluded that peptides like these would not be expected to reach the bloodstream. That is also why a side effect somewhere else in the body is not expected from a cream.
- Source [10]
- A clinic offered me an injection with this in it. Is that the same as the cream?
- No. Every measurement of this molecule inside living people comes from injections rather than creams. In every one of them it was a minor ingredient in a mixture with hyaluronic acid and amino acids. None of those studies — 40 people, 28 people and 43 people — had a group that did not get the injection. So none of them can say what the peptide contributed, or whether it contributed anything.
- Source [06]Source [11]Source [12]
- Where can I look up reports of things going wrong?
- The US Food and Drug Administration runs a public dashboard of side-effect reports for cosmetic products. Since the Modernization of Cosmetics Regulation Act of 2022, the company named on a cosmetic label must report a serious adverse event within 15 business days. The law's definition of serious includes serious and persistent rashes and a persistent or significant change in appearance. The dashboard is organised by product, not by ingredient, so it cannot answer a question about this peptide on its own.
- Source [16]
Sources
16 sources
- [01]PubChem: Acetyl tetrapeptide-5 – C20H28N8O7, 492.5 g/mol, chemical name showing acetylated beta-alanine followed by His, Ser and His
- [02]Nukaly HY m.fl. Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials. Front Med 2026;13:1618306 (2026)
- [03]Regulation (EC) No 1223/2009 on cosmetic products (EUR-Lex, CELEX 32009R1223) (2009)
- [04]Commission Regulation (EU) No 655/2013 on common criteria for claims made about cosmetic products (EUR-Lex, CELEX 32013R0655) (2013)
- [05]WADA: World Anti-Doping Code International Standard – Prohibited List 2026 (i kraft 1 januari 2026) (2026)
- [06]Kutlubay Z, Zengin M, Kargın A, Salt V, Hamid R. Quantitative ultrasonographic and shear wave elastographic assessment of infraorbital tissue changes after non-cross-linked hyaluronic acid and amino acid therapy. Cureus 2026;18(5):e109369 — 40 women, product contained the EyeSeryl (acetyl tetrapeptide-5) complex (2026)
- [07]Wu Y, Cao K, Zhang W, Zhang G, Zhou M. Protective and anti-aging effects of 5 cosmeceutical peptide mixtures on hydrogen peroxide-induced premature senescence in human skin fibroblasts. Skin Pharmacol Physiol 2021;34(4):194–202 (2021)
- [08]Rovero P, Malgapo DMH, Sparavigna A, Beilin G, Wong V, Lao MP. The clinical evidence-based paradigm of topical anti-aging skincare formulations enriched with bio-active peptide SA1-III (KP1) as collagen modulator. Clin Cosmet Investig Dermatol 2022;15:2693–2703 — Table 1 lists "Acetyl Tetrapeptide-5 (Eyeseryl): inhibits angiotensin-converting enzyme; reduces eye edema and dark circles", with no reference attached (2022)
- [09]Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, Almeida IF. Usage of synthetic peptides in cosmetics for sensitive skin. Pharmaceuticals (Basel) 2021;14:702 — 88 facial cosmetics analysed; "Most of the available information regarding these ingredients is not reported in peer-reviewed scientific journals, but rather in patents and supplier brochures" (2021)
- [10]Bjerke DL, Li J, Gao Y, Hu P, Lintner K, Hakozaki T. A framework for the safety evaluation of peptides in cosmetics. Curr Res Toxicol 2026;10:100291 — acetyl hexapeptide-8 on human cadaver skin: 99.7% in the skin washes, 0.22% stratum corneum, 0.01% viable epidermis, none in dermis or receptor fluid (2026)
- [11]Shelemba E, Olshanska O, Benoit AG, Rumyantseva E. Safety and efficacy of an injectable solution enriched with sodium hyaluronate, amino acids and peptides. J Cosmet Dermatol 2025;24(1):e16586 — the three peptides include acetyl tetrapeptide-5 (2025)
- [12]Poleva I. Novel gel formulation and deep injection techniques for lifting effects in cosmetic dermatology. J Cosmet Dermatol 2025;24(1):e16789 — retrospective, no control group; polypeptides listed include acetyl tetrapeptide-5; product supplied by Professional Derma SA (2025)
- [13]ClinicalTrials.gov search for "acetyl tetrapeptide-5" — 0 studies, and 0 for "Eyeseryl" (totalCount 0 from the registry's own data endpoint, checked 2026-08-02) (2026)
- [14]Regulation (EC) No 1223/2009 on cosmetic products (EUR-Lex, CELEX 32009R1223) (2009)
- [15]Commission Regulation (EU) No 655/2013 laying down common criteria for the justification of claims used in relation to cosmetic products (EUR-Lex, CELEX 32013R0655) — section 3, evidential support (2013)
- [16]FDA: Modernization of Cosmetics Regulation Act of 2022 (MoCRA) — serious adverse event reporting within 15 business days, and the AEMS public dashboard for cosmetic products (2022)
Skin
12 peptides · strongest evidence first
- Approved medicinePT-141Approved for low sexual desire that causes distress, in women who have not been through the menopause.Therapeutic13 sources
- Approved medicineSetmelanotideApproved for obesity caused by hypothalamic damage, Bardet-Biedl syndrome or three named gene faults — not for ordinary obesity.Therapeutic14 sources
- Tested in people, but barelyAcetyl hexapeptide-8Sold in skincare for expression lines and wrinkles.Skincare8 sources
- Tested in people, but barelyCollagen peptides (hydrolysed collagen)Sold as a supplement for skin, hair, bones and joints.Supplement4 sources
- Tested in people, but barelyGHK-Cu (copper tripeptide-1)Sold in skincare for wrinkles, skin repair and hair growth.Skincare6 sources
- Tested in people, but barelyLL-37Sold online for infections, wound healing and gut problems; a peptide the body makes itself.Gray market17 sources
- Tested in people, but barelyMelanotan IISold online as a tanning injection, and separately as something that produces erections.Gray market21 sources
- Tested in people, but barelyPalmitoyl pentapeptide-4Sold in anti-wrinkle skincare.Skincare5 sources
- Tested in people, but barelyPalmitoyl tetrapeptide-7Sold in skincare blends for wrinkles and irritated-looking skin.Skincare4 sources
- Tested in people, but barelyPalmitoyl tripeptide-1Sold in skincare to support collagen and soften wrinkles.Skincare4 sources
- Only tested on animalsKPVSold for gut inflammation, skin conditions and wound healing.Gray market12 sources
- No real evidence at allAcetyl tetrapeptide-5This oneSold in eye creams for puffiness and dark circles.Skincare5 sources