Palmitoyl Tripeptide-38 vs Pentapeptide-18
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: 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 | Palmitoyl Tripeptide-38 | 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 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. | 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 | 2% of the commercial ingredient in a finished product Once or twice daily | About 2-5% of the commercial solution in a finished product Once or twice daily |
| Administration | Topical (serums, creams) | Topical (serums, creams) |
| Typical Duration | About 2 months in the manufacturer's study before changes were measured; ongoing use to keep any effect | 28 days to 2 months in studies; ongoing use to maintain any effect |
| Best Time to Take | Morning and/or evening, on clean skin before moisturizer | Morning and/or evening, on clean skin |
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. | 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: Palmitoyl Tripeptide-38 vs Pentapeptide-18
What is the difference between Palmitoyl Tripeptide-38 and Pentapeptide-18?
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. 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, Palmitoyl Tripeptide-38 or Pentapeptide-18?
Neither is universally "better" - the choice depends on your specific goals. Palmitoyl Tripeptide-38 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 Palmitoyl Tripeptide-38 and Pentapeptide-18 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Palmitoyl Tripeptide-38 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.