Acetyl Tetrapeptide-5 vs Pentapeptide-18
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: Leuphasyl, Tyr-Ala-Gly-Phe-Leu
Pentapeptide-18 is Lipotec's Leuphasyl, a 'Botox-like' cosmetic peptide modeled on enkephalins, the body's own calming neuropeptides. It is mostly sold alongside Argireline, with the claim that the two relax expression lines better together. It is a cosmetic ingredient, and the evidence is small and mostly manufacturer-run.
Key Comparison Insights
- Both peptides belong to the Skin & Hair category, suggesting similar primary applications.
Detailed Comparison
| Attribute | Acetyl Tetrapeptide-5 | Pentapeptide-18 |
|---|---|---|
| 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. | Pentapeptide-18 is Tyr-Ala-Gly-Phe-Leu, a close copy of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) with one amino acid swapped. The theory is that it binds enkephalin receptors on nerve endings, which dampens nerve activity and lowers acetylcholine release at the junction with facial muscles. Argireline works at a different step (the SNARE complex inside the nerve ending), which is why the two get marketed as a combo. The same big caveat as Argireline applies: it is sold on a nerve-to-muscle mechanism, but nobody has shown in living skin that a topical cream delivers enough peptide to the muscle to do this. |
| Common Dosing | 1% of the Eyeseryl solution in an eye cream Twice daily | About 2-5% of the commercial solution 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 | 28 days to 2 months 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 most quoted numbers come from a Lipotec study: about 11% wrinkle reduction with 5% Leuphasyl alone over 28 days in a small panel, and about 25% with 5% Leuphasyl plus 5% Argireline. The company calls that synergy, but on its own figures the combination roughly equals the two effects added together, so 'synergistic' is a stretch. The one journal paper we found is Dragomirescu and colleagues (2014, Cosmetics, MDPI), which tested 0.5%, 1% and 2% emulsions around the eyebrows and eyes for efficacy and safety. Trade summaries say only the 2% cream gave a significant improvement after two months in about 20 volunteers; we could not read the full paper to confirm the numbers. A 2020 review of cosmetic peptides lists it among the neurotransmitter-inhibitor peptides and notes that much of the support comes from the manufacturer. Bottom line: safe enough as a skincare ingredient and plausible on paper, but expect subtle softening at most, not anything close to an injection. |
Frequently Asked Questions: Acetyl Tetrapeptide-5 vs Pentapeptide-18
What is the difference between Acetyl Tetrapeptide-5 and Pentapeptide-18?
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. Pentapeptide-18 is a skin & hair peptide that pentapeptide-18 is lipotec's leuphasyl, a 'botox-like' cosmetic peptide modeled on enkephalins, the body's own calming neuropeptides. it is mostly sold alongside argireline, with the claim that the two relax expression lines better together. it is a cosmetic ingredient, and the evidence is small and mostly manufacturer-run. The main differences lie in their mechanisms of action and clinical applications.
Which is better, Acetyl Tetrapeptide-5 or Pentapeptide-18?
Neither is universally "better" - the choice depends on your specific goals. Acetyl Tetrapeptide-5 is typically used for skin & hair purposes, while Pentapeptide-18 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 Pentapeptide-18 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Acetyl Tetrapeptide-5 and Pentapeptide-18 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.