Palmitoyl Pentapeptide-4
Also known as Palmitoyl Pentapeptide-4, Pal-KTTKS, Matrixyl, Palmitoyl Pentapeptide-3
“CIR Expert Panel says: safe as used in cosmetics.”
Palmitoyl Pentapeptide-4 (Pal-KTTKS, trade name Matrixyl) is a synthetic lipopeptide comprising palmitic acid conjugated to the pentapeptide Lys-Thr-Thr-Lys-Ser, a matrikine subfragment of type I collagen propeptide. The CIR Expert Panel for Cosmetic Ingredient Safety issued a dedicated Final Report (released November 18, 2024; panel meeting September 30–October 1, 2024) covering Myristoyl Pentapeptide-4, Palmitoyl Pentapeptide-4, and Pentapeptide-4 (KTTKS and KTSKS sequences), concluding all three are safe in cosmetics in the present practices of use and concentration. The ingredient is not restricted under EU cosmetics regulations. Palmitoyl Pentapeptide-4 is the most-used ingredient in this class, reported in 239 VCRP-registered formulations (2023), predominantly leave-on products (223 of 239) at concentrations up to 0.0012% in face/neck and eye lotions and up to 0.0035% in hair conditioners. Two published clinical studies directly evaluated Pal-KTTKS: Robinson et al. (2005, PMID 18492182) conducted a 12-week double-blind, split-face, placebo-controlled trial (n=93 women, 35–55 years) finding significant improvement in fine lines and wrinkles with a moisturizer containing 3 ppm Pal-KTTKS, with the compound well tolerated; Aruan et al. (2023, PMID 36909866) conducted an 8-week double-blind randomized trial (n=21 Indonesian women) comparing palmitoyl pentapeptide-4 cream against acetylhexapeptide-3 and placebo for crow's feet, finding PPP-4 demonstrated superior outcomes and was well tolerated. Genotoxicity testing (Ames test, micronucleus) returned negative results; irritation studies at 0.01–0.12% concentrations rated the ingredient as non-irritating to at most slightly irritating; sensitization testing showed no sensitizing potential.
Matrikine signal peptide: Pal-KTTKS (KTTKS sequence) is a subfragment of type I collagen propeptide that stimulates fibroblast production of collagen, elastin, and fibronectin, supporting extracellular matrix renewal
Anti-aging efficacy: 12-week placebo-controlled RCT (Robinson et al., PMID 18492182) demonstrated significant reduction in fine lines and wrinkles at 3 ppm in a leave-on moisturizer
Widely adopted: most-used palmitoyl pentapeptide in cosmetics globally (239 VCRP formulations as of 2023), spanning face/neck, eye, hair, and body products
Lipophilic delivery: palmitic acid conjugation renders the otherwise hydrophilic KTTKS peptide more skin-penetrant through the stratum corneum lipid barrier
Favorable tolerability profile: non-sensitizing in guinea pig maximization test, guinea pig local tolerance study, and human HRIPT (106-subject study with 0.018% Palmitoyl Pentapeptide-4 found no irritation or sensitization)
- · No significant safety concerns identified at cosmetic use concentrations; the CIR Expert Panel issued an unqualified Safe finding with no conditions
- · Ingredient-specific published clinical data is limited to two small trials; most safety data submitted to CIR was from unpublished industry studies
One HET-CAM assay on a trade-name mixture containing 0.01% Palmitoyl Pentapeptide-4 classified the mixture as moderately irritating, though this result reflects the full formulation rather than the ingredient alone; in-vitro corneal epithelial model testing at 0.036% effective concentration returned a not-irritating result
Safety Assessment of Myristoyl Pentapeptide-4, Palmitoyl Pentapeptide-4, and Pentapeptide-4 as Used in Cosmetics — CIR Final Report (Rele…
“The Expert Panel for Cosmetic Ingredient Safety concluded that Myristoyl Pentapeptide-4, Palmitoyl Pentapeptide-4, and Pentapeptide-4 (KTTKS and KTSKS sequences) are safe in cosmetics in the present practices of use and concentration described in this safety assessment.”— FR_Pentapeptides_092024.pdf, p. 11