Palmitoyl Tripeptide-38 vs Acetyl Tetrapeptide-5
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Matrixyl synthe'6, Matrixyl Synthe 6
Palmitoyl tripeptide-38 is the active in Sederma's Matrixyl synthe'6, a newer member of the Matrixyl family launched around 2011. It is a three-amino-acid fragment with a fatty acid tail, sold as a wrinkle 'filler from the inside' for forehead lines and crow's feet. It is a cosmetic ingredient, not a drug, and the honest picture is simple: the efficacy claims come almost entirely from the company that makes it.
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.
Key Comparison Insights
- Both peptides belong to the Skin & Hair category, suggesting similar primary applications.
Detailed Comparison
| Attribute | Palmitoyl Tripeptide-38 | Acetyl Tetrapeptide-5 |
|---|---|---|
| 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 Pal-Lys-Met(O2)-Lys: lysine, an oxidized methionine (methionine sulfone) and lysine, with a palmitic acid chain attached so it can get into the outer skin more easily. The sequence is taken from connective tissue proteins (collagen VI and laminin), and the idea is the classic 'matrikine' story: small fragments of broken-down matrix proteins act as a signal telling skin cells to make more matrix. Sederma claims it boosts six components in lab tests, which is where the 'synthe'6' name comes from: collagen I, III and IV, fibronectin, hyaluronic acid and laminin-5. That is a plausible signaling mechanism, but it rests on cell culture work by the manufacturer. Whether enough peptide reaches the dermis in real skin to make a measurable difference has not been independently shown. | 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. |
| Common Dosing | 2% of the commercial ingredient in a finished product Once or twice daily | 1% of the Eyeseryl solution in an eye cream Twice daily |
| Administration | Topical (serums, creams) | Topical (eye creams, gels, serums) |
| Typical Duration | About 2 months in the manufacturer's study before changes were measured; ongoing use to keep any effect | 28-60 days in manufacturer studies; ongoing use to maintain any effect |
| Best Time to Take | Morning and/or evening, on clean skin before moisturizer | Morning and evening, gently patted under the eyes |
Possible Side Effects May vary by individual |
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| Research Summary | There is no independent, peer-reviewed clinical trial of palmitoyl tripeptide-38 on its own that we could find. The main human data is the manufacturer's: a placebo-controlled study in 25 women aged 42 to 70 with forehead lines and crow's feet, using 2% of the Matrixyl synthe'6 ingredient for two months, with reported reductions in wrinkle measures that ranged widely between people. Sederma's launch material in 2011 described visibly smoother forehead and crow's feet wrinkles after two months but gave no published sample sizes or numbers. Where the peptide shows up in published journals, it is usually as one ingredient in a multi-ingredient serum, which cannot isolate its effect. Broader reviews of cosmetic peptides make the same point about this whole category: results are often small, short and unpublished outside company brochures. A 2026 meta-analysis of randomized peptide trials found that topical peptides overall did not produce a significant wrinkle improvement in pooled data. Bottom line: a reasonable, well-tolerated ingredient with a plausible mechanism, but expect mild changes at best and treat the percentage claims as marketing until someone outside the company repeats them. | 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. |
Frequently Asked Questions: Palmitoyl Tripeptide-38 vs Acetyl Tetrapeptide-5
What is the difference between Palmitoyl Tripeptide-38 and Acetyl Tetrapeptide-5?
Palmitoyl Tripeptide-38 is a skin & hair peptide that palmitoyl tripeptide-38 is the active in sederma's matrixyl synthe'6, a newer member of the matrixyl family launched around 2011. it is a three-amino-acid fragment with a fatty acid tail, sold as a wrinkle 'filler from the inside' for forehead lines and crow's feet. it is a cosmetic ingredient, not a drug, and the honest picture is simple: the efficacy claims come almost entirely from the company that makes it. 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. The main differences lie in their mechanisms of action and clinical applications.
Which is better, Palmitoyl Tripeptide-38 or Acetyl Tetrapeptide-5?
Neither is universally "better" - the choice depends on your specific goals. Palmitoyl Tripeptide-38 is typically used for skin & hair purposes, while Acetyl Tetrapeptide-5 is used for skin & hair. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can Palmitoyl Tripeptide-38 and Acetyl Tetrapeptide-5 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Palmitoyl Tripeptide-38 and Acetyl Tetrapeptide-5 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.