Acetyl Tetrapeptide-5 vs Hexapeptide-9
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Eyeseryl, Ac-beta-Ala-His-Ser-His
Acetyl tetrapeptide-5 is a short synthetic peptide sold by Lipotec (now Lubrizol) as Eyeseryl, made for eye creams that target under-eye puffiness. The pitch is that it reduces fluid leaking into the tissue under the eyes. It is a cosmetic ingredient, and nearly all of the human data comes from the company that sells it.
Also: Collaxyl, Collaxyl IS
Hexapeptide-9 is a collagen-inspired signaling peptide sold as Collaxyl (originally from Vincience, now Ashland) for anti-wrinkle and firming skincare. The idea is that a small repeat of a collagen sequence nudges skin cells to rebuild the junction between the outer and inner skin. It is a cosmetic ingredient, and the evidence for the original peptide is mostly old, small and company-run, although a 2025 trial on a modified cyclic version is more interesting.
Key Comparison Insights
- Both peptides belong to the Skin & Hair category, suggesting similar primary applications.
Detailed Comparison
| Attribute | Acetyl Tetrapeptide-5 | Hexapeptide-9 |
|---|---|---|
| Category | Skin & Hair | Skin & Hair |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | The peptide is acetyl-beta-alanine-histidine-serine-histidine. The manufacturer's lab work claims three effects: it reduces vascular permeability (less fluid seeping out of small blood vessels, tested in an endothelial cell model), it inhibits glycation (sugar damage to proteins like collagen), and it has some ACE-inhibiting activity that is linked to fluid balance. All of that is in vitro and company-generated. An important reality check: under-eye bags have several causes, and a lot of them in older adults come from fat pads pushing forward and loose skin, not fluid. A peptide aimed at fluid cannot touch fat-pad bags, so even in the best case it fits morning puffiness better than structural eye bags. | Hexapeptide-9 is Gly-Pro-Gln-Gly-Pro-Gln, a repeat taken from collagen sequences. Ashland says the sequence is found in collagen IV and XVII and works as a matrikine, a matrix fragment that signals cells to make more matrix proteins. The claimed targets are the dermal-epidermal junction (collagen IV, laminin-5, integrins) and collagen production. The original patent describes it as designed to improve cell adhesion and possibly support matrix production. One weakness is stability: the linear peptide is easily broken down by collagen-digesting enzymes, which is why a Chinese group built a ring-shaped (cyclized) version to make it last longer in skin. |
| Common Dosing | 1% of the Eyeseryl solution in an eye cream Twice daily | Low single-digit percent of the ingredient in a finished product Once or twice daily |
| Administration | Topical (eye creams, gels, serums) | Topical (serums, creams) |
| Typical Duration | 28-60 days in manufacturer studies; ongoing use to maintain any effect | 4-8 weeks in studies; ongoing use to maintain any effect |
| Best Time to Take | Morning and evening, gently patted under the eyes | Morning and/or evening, on clean skin |
Possible Side Effects May vary by individual |
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| Research Summary | We could not find an independent, peer-reviewed clinical trial of acetyl tetrapeptide-5. The evidence is manufacturer data reported in trade publications. Lipotec's best-known study used a 1% Eyeseryl cream on one eye and placebo on the other in male volunteers aged 30 to 65, twice daily for 28 days, and reported about a 30% reduction in under-eye puffiness volume, with most volunteers rating it positively. Another supplier document describes a 60-day study in 20 women using a cream with a very low peptide level, scored from photos by a dermatologist. Other summaries quote different numbers (17% to 21%) from studies we could not trace to an original paper. The studies differ in concentration, sex, length and how puffiness was measured, so they cannot be pooled. Independent ingredient databases rate the evidence as limited for exactly this reason. Bottom line: plausible for mild fluid puffiness, cheap to try in an eye cream, but not a fix for true eye bags and not backed by independent trials. | The oldest human data is a 2004 study from Vincience, the lab behind Collaxyl: a double-blind, placebo-controlled test of a gel containing 3% of a 'collagen-like hexapeptide' plus a 1% booster ingredient, applied around the eyes of 20 women for four weeks. It reported fewer and shallower wrinkles on skin replicas, but the booster and the small size mean it cannot prove the peptide alone did the work. Supplier material cites other 28-day studies in about 20 volunteers that we could not trace to journals. The newest and best-designed study is a 2025 randomized, double-blind trial in the Journal of Cosmetic Dermatology (96 adults aged 30-55 in China) comparing a cyclized hexapeptide-9 serum at 0.002% with 0.002% retinol and a vehicle for 56 days. The cyclized peptide beat both on wrinkle, elasticity and hydration measures, with no treatment-related side effects. Two caveats: it tested a modified molecule, not the Collaxyl peptide in most products, and several authors are affiliated with cosmetic companies. Bottom line: the concept has some support, the cyclic version looks promising, but regular hexapeptide-9 in a store-bought cream rests on thin evidence. |
Frequently Asked Questions: Acetyl Tetrapeptide-5 vs Hexapeptide-9
What is the difference between Acetyl Tetrapeptide-5 and Hexapeptide-9?
Acetyl Tetrapeptide-5 is a skin & hair peptide that acetyl tetrapeptide-5 is a short synthetic peptide sold by lipotec (now lubrizol) as eyeseryl, made for eye creams that target under-eye puffiness. the pitch is that it reduces fluid leaking into the tissue under the eyes. it is a cosmetic ingredient, and nearly all of the human data comes from the company that sells it. Hexapeptide-9 is a skin & hair peptide that hexapeptide-9 is a collagen-inspired signaling peptide sold as collaxyl (originally from vincience, now ashland) for anti-wrinkle and firming skincare. the idea is that a small repeat of a collagen sequence nudges skin cells to rebuild the junction between the outer and inner skin. it is a cosmetic ingredient, and the evidence for the original peptide is mostly old, small and company-run, although a 2025 trial on a modified cyclic version is more interesting. The main differences lie in their mechanisms of action and clinical applications.
Which is better, Acetyl Tetrapeptide-5 or Hexapeptide-9?
Neither is universally "better" - the choice depends on your specific goals. Acetyl Tetrapeptide-5 is typically used for skin & hair purposes, while Hexapeptide-9 is used for skin & hair. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can Acetyl Tetrapeptide-5 and Hexapeptide-9 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Acetyl Tetrapeptide-5 and Hexapeptide-9 together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.