Acetyl Tetrapeptide-5 (Eyeseryl): Eye Peptide

The skin around your eyes is thinner than anywhere else on your body. It's the first place to show signs of aging, fluid retention, and lack of sleep. Under-eye puffiness and dark circles can make you look tired even when you're not. This is where acetyl tetrapeptide-5 comes in.

Sold under the trade name Eyeseryl®, this synthetic four-amino-acid peptide was designed specifically to target the periorbital area. It works by reducing vascular permeability and inhibiting protein glycation—two mechanisms that directly address fluid accumulation and tissue degradation around the eyes. Unlike many cosmetic ingredients that promise results but deliver modest effects, acetyl tetrapeptide-5 has measurable clinical data showing reduction in under-eye puffiness within two weeks.

This article breaks down what acetyl tetrapeptide-5 is, how it works, what the research shows, and whether it's worth adding to your skincare routine.

Quick Facts
What Is Acetyl Tetrapeptide-5?
How Acetyl Tetrapeptide-5 Works
The Research on Acetyl Tetrapeptide-5
How to Use Acetyl Tetrapeptide-5
Safety and Side Effects
Frequently Asked Questions
Bottom Line
References

Quick Facts

Property	Details
INCI Name	Acetyl Tetrapeptide-5
Trade Name	Eyeseryl®
Developer	Lipotec (now Lubrizol)
Structure	Four-amino-acid peptide: Ac-βAla-His-Ser-His
Primary Mechanism	Reduces vascular permeability, inhibits ACE, prevents glycation
Target Area	Periorbital (under-eye) region
Key Benefits	Reduces puffiness, decreases fluid accumulation, improves elasticity
Typical Concentration	1-10% in skincare products (0.01-0.1% pure peptide)
Form	Water-soluble liquid solution

What Is Acetyl Tetrapeptide-5?

Acetyl tetrapeptide-5 is a synthetic peptide—a short chain of four amino acids linked together. Its sequence is acetyl-beta-alanine-histidine-serine-histidine (Ac-βAla-His-Ser-His). The "acetyl" group at the beginning stabilizes the peptide and helps it penetrate the skin barrier more effectively than unmodified peptides.

The peptide was developed by Lipotec, a Barcelona-based company acquired by Lubrizol in 2012. Lipotec specialized in creating cosmetic active ingredients, and Eyeseryl® was one of their breakthrough products, receiving the New Technology Award in 2005 at the Health & Beauty America Conference & Exhibition.

Unlike many cosmetic peptides that aim to stimulate collagen production or mimic Botox, acetyl tetrapeptide-5 was designed with a specific goal: reduce periorbital edema (under-eye puffiness). The periorbital area is prone to fluid accumulation because the skin is thin, the tissue is loose, and lymphatic drainage can be sluggish. This peptide targets multiple mechanisms that contribute to that swelling.

Acetyl tetrapeptide-5 is not a pharmaceutical. It's a cosmetic ingredient found in eye creams, serums, and gels. It doesn't require a prescription, and it's generally recognized as safe for topical use.

How Acetyl Tetrapeptide-5 Works

The peptide operates through three main mechanisms: reducing vascular permeability, inhibiting angiotensin-converting enzyme (ACE), and preventing glycation. Together, these actions address both the immediate fluid accumulation that causes puffiness and the long-term structural damage that leads to sagging and dark circles.

Reducing Vascular Permeability

Vascular permeability refers to how easily fluids leak from blood vessels into surrounding tissue. When blood vessels become "leaky," fluid accumulates in the interstitial space—the area between cells. In the under-eye region, this shows up as puffiness or bags.

In vitro studies using endothelial cell monolayers (the cells that line blood vessels) have shown that acetyl tetrapeptide-5 can inhibit vascular permeability in a dose-dependent manner. At a concentration of 1 mg/ml, the peptide achieved 50% inhibition compared to control conditions.

By strengthening the endothelial barrier and reducing fluid leakage, acetyl tetrapeptide-5 directly addresses one of the root causes of under-eye bags. Less fluid in the tissue means less visible swelling.

ACE Inhibition

Angiotensin-converting enzyme (ACE) is best known for its role in regulating blood pressure. It converts angiotensin I into angiotensin II, a potent vasoconstrictor that increases blood pressure and affects fluid balance. In the context of skin, ACE activity can influence local vascular tone and permeability.

Acetyl tetrapeptide-5 has been shown to inhibit ACE at a local level. By blocking this enzyme, the peptide may help modulate blood vessel tone and improve fluid clearance in the periorbital area. This mechanism is similar to how pharmaceutical ACE inhibitors work for blood pressure control, but the effect here is localized to the skin rather than systemic.

Research has found that the optimal concentration for acetyl tetrapeptide-5 to inhibit ACE-1 activity is 100 μg/mL. This suggests that the peptide's ability to regulate vascular function is a key part of its anti-puffiness effect.

It's worth noting that systemic ACE inhibitors (like lisinopril or enalapril) can cause angioedema—severe swelling, often around the face and eyes—as a side effect. This happens because blocking ACE prevents the breakdown of bradykinin, a peptide that promotes swelling. However, topical application of acetyl tetrapeptide-5 at cosmetic concentrations does not appear to cause the same issue. The effect is localized and aimed at improving drainage, not creating systemic bradykinin accumulation.

Anti-Glycation Activity

Glycation is a non-enzymatic reaction where sugar molecules bind to proteins, forming cross-links that stiffen and degrade the protein structure. This process generates advanced glycation end products (AGEs), which accumulate in tissues over time and contribute to aging.

In the skin, glycation affects collagen and elastin—the structural proteins that keep skin firm and elastic. Glycated collagen becomes brittle and less functional. In the eye area, this leads to sagging, wrinkles, and reduced resilience.

Acetyl tetrapeptide-5 has demonstrated anti-glycation activity in lab studies. It inhibits glycation of enzymes like superoxide dismutase (SOD), protecting their activity and preventing glycation-induced collagen degradation. By reducing AGE formation, the peptide helps preserve the structural integrity of the periorbital tissue.

This mechanism has long-term benefits. While the anti-edema effects of acetyl tetrapeptide-5 can be seen in weeks, the anti-glycation benefits accumulate over time, helping maintain skin elasticity and prevent the formation of deep under-eye hollows.

The Research on Acetyl Tetrapeptide-5

Most of the published research on acetyl tetrapeptide-5 comes from the manufacturer (Lipotec/Lubrizol) or studies that include it as part of a peptide blend. Independent, peer-reviewed clinical trials specifically testing acetyl tetrapeptide-5 alone are limited. That said, the data that exists is promising, and the mechanisms are biologically plausible.

Clinical Studies on Puffiness

The most frequently cited study involved 20 female volunteers aged 18 to 65 who applied a cream containing 0.01% acetyl tetrapeptide-5 (from a 10% Eyeseryl® solution) to the under-eye area twice daily for 60 days. Results were measured using digital photography and volumetric analysis of under-eye puffiness.

By day 15, 70% of participants showed a ≥30% reduction in puffiness.
By day 60, 95% of participants showed improvement.
Under-eye puffiness volume decreased by up to 29.7% after 28 days.
Skin elasticity around the eyes increased by 30% over 30 days.
Dark circles decreased significantly after 28 days of use.

These results are substantial, especially considering the low concentration of the active peptide (0.01%). However, it's important to note that this study was sponsored by the manufacturer and has not been independently replicated in a published, peer-reviewed journal.

A separate open-label clinical trial evaluated an eye contour cream containing multiple bioactive peptides, including acetyl tetrapeptide-5, in 20 healthy female volunteers aged 45-60 years. Almost all patients reported improvements in puffiness, with 62% reporting medium to very marked improvement.

Another study published in 2023 examined a multi-peptide anti-aging eye serum that included acetyl tetrapeptide-5 among other peptides. The formulation showed clinical efficacy in improving periocular skin appearance, though it's impossible to isolate the contribution of acetyl tetrapeptide-5 specifically.

In Vitro Studies

Laboratory studies provide mechanistic support for acetyl tetrapeptide-5's effects:

Vascular permeability: In endothelial cell monolayer assays, acetyl tetrapeptide-5 reduced vascular permeability by 50% at a concentration of 1 mg/ml.
ACE inhibition: The peptide inhibits ACE-1 activity at concentrations as low as 100 μg/mL.
Glycation inhibition: In vitro models showed that acetyl tetrapeptide-5 protects enzymes like superoxide dismutase from glycation-induced damage.

A 2021 study published in Molecules tested five cosmeceutical peptide mixtures on hydrogen peroxide-induced senescence in human skin fibroblasts. One mixture containing carnosine, acetyl tetrapeptide-5, hexapeptide-11, and acetyl hexapeptide-3 significantly reduced intracellular malondialdehyde and hydroxyl free radicals while increasing hydroxyproline and elastin content. This suggests that acetyl tetrapeptide-5, as part of a blend, has antioxidant and anti-aging effects at the cellular level.

Limitations of Current Research

While the data on acetyl tetrapeptide-5 is encouraging, there are important caveats:

Manufacturer-sponsored studies: Most clinical data comes from Lipotec/Lubrizol. A 2017 review published in Cosmetics noted that they were unable to find robust, independent clinical trials supporting the topical use of acetyl tetrapeptide-5.
Small sample sizes: The clinical studies involved 20 participants, which is a small cohort. Larger, randomized, placebo-controlled trials are needed.
Blended formulations: Many studies use acetyl tetrapeptide-5 in combination with other peptides or active ingredients, making it difficult to isolate its specific contribution.
Subjective endpoints: Some outcomes (like visible improvement in dark circles) rely on participant self-assessment or visual grading, which can be subjective.

That said, the in vitro data on vascular permeability, ACE inhibition, and glycation is mechanistically sound and aligns with what we know about under-eye puffiness.

How to Use Acetyl Tetrapeptide-5

Acetyl tetrapeptide-5 is typically found in eye creams, serums, and gels at concentrations ranging from 1-10% of the Eyeseryl® solution, which translates to 0.01-0.1% of pure peptide. Products are designed for topical application to the periorbital area.

Application:

Cleanse your face and pat the skin dry.
Apply a small amount (a pea-sized amount is usually sufficient) to the under-eye area using your ring finger, which applies the least pressure.
Gently tap or press the product into the skin. Avoid rubbing, which can irritate the delicate eye area.
Use twice daily—morning and evening—for best results. Clinical studies showing significant improvement used twice-daily application.
Be patient. Results typically appear within 15-30 days, but optimal effects may take 60 days or longer.

Formulation considerations:

Acetyl tetrapeptide-5 is water-soluble and stable in aqueous formulations.
It should be incorporated into the water phase of cosmetic products at temperatures below 40°C to preserve bioactivity.
It's compatible with other cosmetic peptides like argireline, Matrixyl, and palmitoyl tripeptide-1, which can provide complementary benefits.

What to pair it with:

Caffeine: Boosts lymphatic drainage and vasoconstriction, which can improve the decongestant effect.
Hyaluronic acid: Hydrates the under-eye area and plumps the skin, reducing the appearance of fine lines.
Niacinamide: Reduces inflammation and improves skin barrier function, which may boost penetration of peptides.
Copper peptides like GHK-Cu: Stimulate collagen synthesis and tissue repair, addressing structural causes of under-eye aging.

Safety and Side Effects

Acetyl tetrapeptide-5 is generally considered safe for topical use in cosmetic products. It has been dermatologically tested and is well-tolerated by most skin types, including sensitive skin.

Safety profile:

Non-toxic: No reports of systemic toxicity from topical application at cosmetic concentrations.
Non-irritating: The peptide does not typically cause irritation, redness, or burning when applied to the eye area.
Low risk of sensitization: Allergic reactions are rare.

Potential side effects:

While rare, some users may experience:

Mild irritation: Slight stinging or redness, especially if the product contains other active ingredients or preservatives.
Milia: Tiny white bumps can form if the product is too heavy for the delicate eye area. This is usually related to the formulation base (oils, occlusives) rather than the peptide itself.

Who should avoid it:

Individuals with known hypersensitivity to any component of the product.
People with active eye infections or inflammation should consult a dermatologist before use.

Pregnancy and breastfeeding:

There is limited data on the safety of acetyl tetrapeptide-5 during pregnancy or breastfeeding. While topical peptides are unlikely to be absorbed systemically in significant amounts, it's best to consult a healthcare provider before using any new cosmetic product during these periods.

Important note on ACE inhibition:

Pharmaceutical ACE inhibitors used for blood pressure control can cause angioedema (severe facial swelling) as a side effect. This occurs because systemic ACE inhibition prevents the breakdown of bradykinin, a peptide that promotes swelling. However, acetyl tetrapeptide-5 is applied topically at low concentrations and is not systemically absorbed. There are no reports of angioedema or similar swelling from cosmetic use of acetyl tetrapeptide-5.

Frequently Asked Questions

Q: How long does it take to see results from acetyl tetrapeptide-5?

Clinical studies show that 70% of users see a reduction in puffiness within 15 days of twice-daily use, with 95% showing improvement by 60 days. For best results, use the product consistently for at least 8 weeks.

Q: Can I use acetyl tetrapeptide-5 if I have dark circles?

Yes. While the peptide's primary action is reducing puffiness, studies show it can also improve dark circles by boosting blood circulation and reducing fluid accumulation, which can cast shadows under the eyes. However, dark circles have multiple causes (pigmentation, thinning skin, blood vessel visibility), so results vary.

Q: Is acetyl tetrapeptide-5 the same as retinol?

No. Retinol is a vitamin A derivative that increases cell turnover and stimulates collagen production. Acetyl tetrapeptide-5 is a peptide that reduces vascular permeability and inhibits glycation. They work through different mechanisms and can be used together, though it's best to apply retinol at night and peptides in the morning to avoid potential irritation.

Q: Can I use acetyl tetrapeptide-5 with other peptides?

Yes. Acetyl tetrapeptide-5 is commonly formulated with other peptides like argireline (for expression lines), Matrixyl (for collagen synthesis), palmitoyl tripeptide-1 (for firmness), Leuphasyl (for wrinkle reduction), and Snap-8 (for deep lines). Combining peptides can provide multi-targeted benefits.

Q: Does acetyl tetrapeptide-5 work for everyone?

No cosmetic ingredient works for 100% of users. In clinical studies, 95% of participants saw improvement by 60 days, meaning 5% did not. Results depend on the underlying cause of puffiness, product formulation, consistency of use, and individual skin biology.

Q: Is Eyeseryl® the same as acetyl tetrapeptide-5?

Yes. Eyeseryl® is the trade name for acetyl tetrapeptide-5 developed by Lipotec (now Lubrizol). When you see "Eyeseryl®" on a product label, it means the product contains acetyl tetrapeptide-5.

Q: Can acetyl tetrapeptide-5 prevent under-eye bags from forming?

It may help. The peptide's anti-glycation activity can slow structural degradation of collagen and elastin, which contributes to long-term sagging. Its effects on vascular permeability and fluid drainage may also reduce the tendency for puffiness to develop. However, under-eye bags are influenced by genetics, aging, sleep quality, diet, and fluid retention, so no single ingredient can completely prevent them.

Q: How does acetyl tetrapeptide-5 compare to caffeine for under-eye puffiness?

Both work, but through different mechanisms. Caffeine is a vasoconstrictor that temporarily tightens blood vessels and boosts lymphatic drainage, providing quick but short-lived effects. Acetyl tetrapeptide-5 reduces vascular permeability and inhibits glycation, offering longer-lasting structural improvements. Using both together can provide immediate and sustained benefits.

Q: Should I apply acetyl tetrapeptide-5 morning or night?

Both. Clinical studies showing significant improvement used twice-daily application—once in the morning and once at night. Consistent use is key to achieving results.

Bottom Line

Acetyl tetrapeptide-5 is a well-designed cosmetic peptide with a clear target: reducing under-eye puffiness and improving the appearance of the periorbital area. It works by reducing vascular permeability, inhibiting ACE, and preventing glycation—three mechanisms that directly address fluid accumulation, inflammation, and structural degradation.

Clinical data shows that most users see measurable improvement in puffiness within 15 to 60 days of consistent use. The peptide also appears to improve skin elasticity and reduce dark circles, though results vary depending on the underlying cause.

The main limitation is the lack of large-scale, independent, peer-reviewed studies. Most of the clinical data comes from the manufacturer, and while the in vitro research is solid, more rigorous human trials would strengthen the evidence base.

That said, acetyl tetrapeptide-5 has a strong safety profile, is well-tolerated, and is biologically plausible based on what we know about vascular physiology and glycation. If you're dealing with under-eye puffiness and looking for a non-invasive, topical option, products containing acetyl tetrapeptide-5 (marketed as Eyeseryl®) are worth considering.

As with any cosmetic ingredient, results take time. Don't expect overnight changes. Use the product consistently for at least 8 weeks before evaluating whether it's working for you.

Disclaimer: This article is for educational purposes only and does not constitute medical advice. Acetyl tetrapeptide-5 is a cosmetic ingredient, not a pharmaceutical drug. It is not intended to diagnose, treat, cure, or prevent any disease. If you have persistent under-eye puffiness, dark circles, or other concerns, consult a dermatologist or healthcare provider to rule out underlying medical conditions. Individual results may vary.

References

Lubrizol. Eyeseryl® peptide solution G. UL Prospector. Accessed February 15, 2026.
Beautiful With Brains. Can Acetyl Tetrapeptide-5 (Eyeseryl) Really Reduce Puffy Eyes? BeautifulWithBrains.com. Accessed February 15, 2026.
Personal Care Magazine. Lipotec's Eyeseryl wins award. PersonalCareMagazine.com. Accessed February 15, 2026.
Cosmetics Business. Lipotec confirms efficacy of EYESERYL peptide against baggy eyes in men. CosmeticsBusiness.com. Accessed February 15, 2026.
Cosmetic Ingredients Guide. Acetyl Tetrapeptide-5 | EyeSeryl®. CI.guide. Accessed February 15, 2026.
PubMed. Protective and Anti-Aging Effects of 5 Cosmeceutical Peptide Mixtures on Hydrogen Peroxide-Induced Premature Senescence in Human Skin Fibroblasts. PMID: 33849044. Accessed February 15, 2026.
PubMed. Topical Administration of a Novel Acetylated Tetrapeptide Suppresses Vascular Permeability and Immune Responses and Alleviates Atopic Dermatitis in a Murine Model. PMID: 36362286. Accessed February 15, 2026.
PubMed. Clinical evidence of the efficacy and safety of a new multi-peptide anti-aging topical eye serum. PMID: 37335808. Accessed February 15, 2026.
PubMed Central. The Clinical Evidence-Based Paradigm of Topical Anti-Aging Skincare Formulations Enriched with Bio-Active Peptide SA1-III (KP1) as Collagen Modulator: From Bench to Bedside. PMC9760069. Accessed February 15, 2026.
PubMed. Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study. PMID: 37245058. Accessed February 15, 2026.
PubMed. The effects of advanced glycation end-products on skin and potential anti-glycation strategies. PMID: 38563644. Accessed February 15, 2026.
PubMed. Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors. PMID: 36364850. Accessed February 15, 2026.
PubMed. ACE Inhibitor-Induced Angioedema: a Review. PMID: 29884969. Accessed February 15, 2026.
PubMed Central. ACE-I induced angioedema: a case report and review of literature. PMC2740143. Accessed February 15, 2026.
PubMed. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. PMID: 17531305. Accessed February 15, 2026.
PubMed Central. Instrumental evaluation of anti-aging effects of cosmetic formulations containing palmitoyl peptides, Silybum marianum seed oil, vitamin E and other functional ingredients on aged human skin. PMC4950680. Accessed February 15, 2026.
PubMed Central. A Randomized, Double-blind, Placebo-controlled Clinical Study Investigating the Efficacy and Tolerability of a Peptide Serum Targeting Expression Lines. PMC8211334. Accessed February 15, 2026.
PubMed Central. Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. PMC8400021. Accessed February 15, 2026.
MDPI. Topical Peptide Treatments with Effective Anti-Aging Results. MDPI.com. Accessed February 15, 2026.
PubChem. Acetyl tetrapeptide-5 | C20H28N8O7 | CID 11620163. PubChem. Accessed February 15, 2026.

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