C tier · mixed
Two double-blind placebo-controlled topical trials exist and they disagree: a 93-subject 12-week study run by the ingredient's commercial developer reported significant fine-line improvement, while the only independent replication (21 women, seven per arm, 8 weeks) found every instrumental endpoint non-significant (p>0.05) and no separation from placebo. Real matrikine mechanism, thin and inconsistent human data, and zero registered trials on ClinicalTrials.gov.
matrixyl
Palmitoyl pentapeptide-4 is a synthetic lipopeptide in which the collagen-derived pentapeptide KTTKS is joined to a palmitic acid tail. It carries the INCI name Palmitoyl Pentapeptide-4, has been sold as the Sederma/Croda cosmetic active Matrixyl since the late 1990s, and is lawfully used in leave-on skincare across the UK and EU. KTTKS itself is a genuine fragment of the C-terminal propeptide of type I procollagen that stimulates collagen and fibronectin production in cultured mesenchymal cells.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade C above is our own and is not adjusted because we stock it.
the explanation
Matrixyl is a small piece of collagen with a fatty tail attached so that it can get into the outer layers of skin. It is an ordinary, legal skincare ingredient that has been in face creams for around twenty-five years, and it has more human testing behind it than almost anything else in this index. That testing is still small and mixed: the biggest study was run by the company that developed the ingredient, and the one independent study found no measurable difference from a plain cream.
regulatory status
Regulated cosmetic ingredient in the UK and EU; not a licensed medicine anywhere
Palmitoyl Pentapeptide-4 is a listed INCI cosmetic ingredient and is lawfully used in leave-on skincare in Great Britain under the retained UK cosmetics regime and in the EU and Northern Ireland under Regulation (EC) No 1223/2009, which requires a qualified safety assessor's Cosmetic Product Safety Report and a Product Information File before a finished product is placed on the market. That is a product-safety clearance for topical use on intact skin, not a marketing authorisation: there is no MHRA, EMA or FDA approval of the peptide as a medicine, and the cosmetics framework expressly excludes anything intended for ingestion, inhalation, injection or implantation, while MHRA Guidance Note 8 treats product form (capsule, tablet, injection) as part of deciding whether something is a medicinal product. The US Cosmetic Ingredient Review Expert Panel had only a draft report on Palmitoyl Pentapeptide-4 as of September 2023 and had not issued a final safety conclusion. The peptide is not named anywhere on the current WADA Prohibited List, although the S0 non-approved-substances catch-all would capture any substance without regulatory approval for human therapeutic use if it were presented for systemic use; it is not a documented lawful dietary-supplement ingredient in the UK or US.
how it works · proposed mechanism
KTTKS is not an invented sequence. It is residues 212-216 of the carboxy-terminal propeptide of type I procollagen, released during procollagen processing, and Katayama and colleagues showed in 1993 that it is the minimal fragment able to stimulate matrix synthesis in mesenchymal cells. Matrixyl attaches a palmitic acid chain to that fragment so that it survives peptidases longer and partitions into the stratum corneum.
KTTKS is a genuine procollagen matrikine
Katayama et al. (J Biol Chem, 1993) identified Lys-Thr-Thr-Lys-Ser as the minimal sequence from the type I procollagen C-terminal propeptide able to increase production of collagen I, collagen III and fibronectin in cultured mesenchymal cells, in a concentration- and time-dependent way without altering total protein synthesis. The proposed physiology is feedback from matrix turnover rather than a growth-factor effect. This is one of the better-characterised matrikine claims in cosmetic chemistry.
Palmitoylation is a delivery and stability strategy
Free KTTKS is hydrophilic and rapidly cleaved by skin and plasma peptidases. Adding a C16 acyl chain produces an amphiphile that is more proteolytically stable and lipophilic enough to partition into the stratum corneum; a 2019 Molecules study of KTTKS analogues found the palmitoyl derivatives were the most active plasmin inhibitors and were non-toxic to fibroblasts. Nothing about palmitoylation alters receptor-level pharmacology - it alters where the peptide can go.
Fibroblast-level readouts, not tissue-level readouts
The supporting biology is collagen and fibronectin production in fibroblast culture; the supporting clinical readouts are expert grading of fine lines and subject self-assessment. Neither published controlled trial measured dermal collagen content, dermal thickness or histology. The chain from culture-dish matrix synthesis to visible wrinkle change is inferred rather than demonstrated.
Penetration is shallow and formulation-dependent
In vitro data summarised by the Cosmetic Ingredient Review indicate palmitoylated peptides diffuse into epidermis and dermis but do not penetrate beyond the dermis, with essentially no transcutaneous passage. An LC-MS/MS survey of six marketed anti-wrinkle creams found intact pal-KTTKS ranging from close to the expected label value down to under a quarter of it, so what actually reaches skin varies enormously between products.
what’s reported
evidence shape
7 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Every piece of human evidence for this molecule is a face cream applied to intact skin, and the two controlled trials disagree. Robinson 2005 was designed, funded and published by Procter & Gamble, used a split-face design in 93 women aged 35-55 over 12 weeks, and reported significance only on wrinkle and fine-line grading plus self-assessment, with no histology and no collagen measurement. The single independent attempt (Aruan 2023, 21 Indonesian women, seven per arm, 8 weeks, university-funded) found corneometry, transepidermal water loss and cutometry all non-significant (p>0.05) and could not separate palmitoyl pentapeptide-4 from placebo, which the authors attributed to being underpowered. A 2026 systematic review and meta-analysis of 19 peptide RCTs in 1,341 participants found only a modest pooled wrinkle effect for peptides as a class (MD 0.27, p=0.04). None of this transfers to a lyophilised vial for reconstitution: there is no human pharmacokinetic, systemic or injection data for pal-KTTKS at all, and the very cosmetics framework that makes the ingredient lawful excludes products intended for injection.
key published findings
- Robinson 2005 (Int J Cosmet Sci, Procter & Gamble): 93 Caucasian women aged 35-55, 12 weeks, double-blind split-face against a control moisturiser; pal-KTTKS was well tolerated and gave significant improvement versus placebo for reduction in wrinkles and fine lines, supported by subject self-assessment.
- Aruan 2023 (J Clin Aesthet Dermatol): 21 Indonesian women in three arms of seven (acetylhexapeptide-3, palmitoyl pentapeptide-4, placebo) over 8 weeks; corneometer, tewameter and cutometer results were all non-significant (p>0.05) and the two actives did not differ from one another.
- In that independent trial the Crow's Feet Grading Scale fell by 0.86 points for palmitoyl pentapeptide-4 on both static and dynamic scoring at week 8 versus baseline - an improvement the authors could not distinguish statistically from placebo.
- Katayama 1993 (J Biol Chem): KTTKS corresponds to residues 212-216 of the type I procollagen C-terminal propeptide and is the minimal fragment stimulating collagen I, collagen III and fibronectin production in mesenchymal cells.
- Nukaly 2026 (Front Med) meta-analysis of 19 randomised trials and 1,341 participants: peptides improved hydration and brightness with a modest pooled wrinkle effect (MD 0.27, p=0.04), and oral polypeptides outperformed topical ones (MD 1.5, p=0.01).
- ClinicalTrials.gov returns zero registered studies for Matrixyl, palmitoyl pentapeptide, KTTKS or pentapeptide-4 searched as terms or as interventions.
limitations of the evidence
- The larger positive trial was designed, funded and published by the ingredient's commercial developer, and the only independent replication attempt was null on every instrumental measure.
- Both trials relied on surface endpoints - expert grading, self-assessment, corneometry, cutometry; no human study has measured dermal collagen content, dermal thickness or histology after pal-KTTKS.
- The independent trial randomised seven subjects per arm over 8 weeks and its authors described it as having an insufficient sample and too short a duration, so it cannot exclude a real modest effect.
- Matrixyl is a trademark, not a molecule: Matrixyl 3000 is palmitoyl tripeptide-1 plus palmitoyl tetrapeptide-7 and Matrixyl synthe'6 is a different peptide again, so trial evidence for pal-KTTKS does not support claims made for those blends, and their supplier data do not support claims for pal-KTTKS.
- Delivered content in finished products is unreliable: LC-MS/MS of six marketed creams found intact peptide from near-label down to under a quarter of the expected value.
- No published human pharmacokinetic, absorption, distribution, metabolism or safety data exist for any route other than topical application to intact skin.
documented safety signals
- Topical tolerability is the best-documented aspect of this ingredient: no skin irritation was reported in the 93-subject trial, guinea-pig sensitisation testing was negative, and human repeated insult patch testing in the CIR record showed no sensitisation.
- Slight erythema has been observed in some studies, classified overall as non-irritant.
- The Cosmetic Ingredient Review Expert Panel had only a draft report as of September 2023 and had not issued a final safety conclusion for palmitoyl pentapeptide-4.
- There are no safety data of any kind for injection, ingestion or inhalation; the absence of reported harm by those routes reflects the complete absence of study, not evidence of safety.
identity
| full name | Palmitoyl pentapeptide-4 (palmitoyl-Lys-Thr-Thr-Lys-Ser, pal-KTTKS), the cosmetic active trademarked as Matrixyl |
| category | Cosmetic |
| modality | peptide |
| formula | C39H75N7O10 |
| molar mass | 802.1 g/mol |
| cas | 214047-00-4 |
| sequence | Palmitoyl-Lys-Thr-Thr-Lys-Ser |
laboratory handling
| storage | Lyophilised powder is stored desiccated at -20 °C, protected from light and moisture. Palmitoylated peptides are surface-active and prone to adsorption losses, so laboratory preparations are handled in low-binding vessels. Handling information only. |
| solubility | Amphiphilic: poorly soluble in water alone, and laboratory preparations typically use a small proportion of a co-solvent before dilution into aqueous buffer. |
| co-studied with | Routinely formulated alongside other matrikine peptides (palmitoyl tripeptide-1, palmitoyl tetrapeptide-7) and with retinoids or ascorbic acid derivatives, but no controlled trial has compared any of those combinations against pal-KTTKS alone, so additive claims made for multi-peptide blends are unevidenced. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
7 citedCosmetic Ingredient Review Expert Panel · 2023 · official
Medicines and Healthcare products Regulatory Agency · 2025 · official
International Journal of Cosmetic Science · 2005 · randomized
Journal of Clinical and Aesthetic Dermatology · 2023 · randomized
Journal of Biological Chemistry · 1993 · preclinical
Frontiers in Medicine · 2026 · systematic review
PubChem, National Library of Medicine · 2026 · reference
others in Cosmetic