Peptide education
Palmitoyl Pentapeptide-4 (Pal-KTTKS)
Pal-KTTKS
This page focuses on pal-KTTKS, a fatty-acid-linked five-amino-acid peptide used in cosmetic moisturizers. Palmitoyl pentapeptide-4 is an ingredient name that also covers a different sequence, pal-KTSKS.
A controlled split-face trial found that a moisturizer with 3 ppm pal-KTTKS improved fine-line and wrinkle measures more than its vehicle. A smaller eye-area trial reported nonsignificant instrument results, so the evidence remains limited.
Overview
Quick answer
The larger split-face study tested pal-KTTKS. Matrixyl is a trade-name mixture containing pal-KTTKS, not the pure peptide. Matrixyl 3000 is a different blend containing palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7.
What was tested?
In a split-face study, 93 women used a moisturizer containing 3 ppm pal-KTTKS on one side and the same moisturizer without it on the other for 12 weeks.
What changed?
Image analysis and expert grading found greater fine-line and wrinkle improvement on the peptide-treated side. The result applies to that formulation and group.
Did every trial show the same result?
No. A separate trial with seven participants per group reported no significant differences in its hydration, water-loss, and elasticity instrument measures.
Is the ingredient the same as Matrixyl 3000?
No. Matrixyl is a trade-name mixture containing pal-KTTKS. Matrixyl 3000 combines different peptides, palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7.
Evidence
Evidence snapshot
A 3 ppm pal-KTTKS moisturizer performed better than the same vehicle for fine-line and wrinkle measurements over 12 weeks.
The reported instrument comparisons were not statistically significant. Seven participants received each cream.
KTTKS increased matrix-protein production in cell culture. That experiment did not test a finished cosmetic or prove the mechanism in living skin.
The cosmetic safety panel assessed KTTKS and KTSKS forms under specified conditions of use and concentration.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| It reduces the appearance of wrinkles. | The larger split-face trial found improved wrinkle and fine-line measures for its pal-KTTKS moisturizer compared with vehicle. A smaller eye-area trial had nonsignificant instrument results. | There is controlled evidence for an appearance effect in one moisturizer, with limited and mixed results across the studies described. | |
| A peptide added to skin necessarily rebuilds collagen. | The split-face study measured appearance, not proof that a finished product increased collagen through the cell-culture mechanism. | The KTTKS sequence stimulated collagen and fibronectin production in cultured cells. It was not the palmitoylated material applied to skin. | A cell response is a biological lead, not proof of collagen rebuilding in a person using a cosmetic. |
Bottom line
Main takeaway
A studied moisturizer improved fine-line measures, but that does not guarantee the same result from every product.
Check the sequence, concentration, and vehicle before comparing a product with the studied formula.
Separate the controlled split-face result from the smaller trial and the unmodified-peptide cell study.
Identity
What it is
Palmitoyl pentapeptide-4 is a cosmetic ingredient name for a fatty-acid-linked pentapeptide. The safety assessment discusses both KTTKS and KTSKS forms.
The KTTKS sequence is related to the carboxyl-terminal propeptide of type I procollagen. The cell study used KTTKS without the attached fatty acid.
Matrixyl is a trade-name mixture containing pal-KTTKS. It is not a synonym for the isolated peptide or for Matrixyl 3000, which contains two other peptides.
Use context
Routes, doses, and cycle patterns
The study schedules describe the products and participants tested, not a standard concentration or schedule for all cosmetics.
Human studies and product labels
Split-face moisturizer trial
- Purpose
- Fine-line and wrinkle appearance
- Context
- Randomized comparison with moisturizer vehicle
- Route
- Topical, one side of the face
- Amount
- 3 ppm pal-KTTKS in the moisturizer
- Frequency
- Twice daily
- Duration
- 12 weeks
The concentration describes the ingredient in the tested moisturizer, not a dose of pure peptide per application.
Eye-area cream trial
- Purpose
- Appearance and skin measurements around the eyes
- Context
- Randomized three-arm comparison
- Route
- Topical cream
- Amount
- Approximately 0.5 g of cream per application
- Frequency
- Twice daily
- Duration
- 8 weeks
The reported cream amount is not the amount of peptide; the paper did not specify a peptide concentration.
Research
Research evidence
A 93-person split-face study found a vehicle-controlled improvement in wrinkle measures for a 3 ppm pal-KTTKS moisturizer. A smaller three-arm study reported nonsignificant instrument results. Neither establishes equivalence among products.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Pal-KTTKS split-face moisturizer study | 93 Caucasian women aged 35 to 55 | Double-blind, randomized, vehicle-controlled split-face trial | Moisturizer containing 3 ppm pal-KTTKS versus the same vehicle | Fine-line and wrinkle measures improved more on the peptide-treated side by image analysis and expert grading. | The trial covered one formulation for 12 weeks and was conducted by cosmetics-company researchers. | Limited controlled human cosmetic evidence |
| Three-arm eye-area cream trial | 21 Indonesian women, seven per group | Double-blind randomized comparison with another peptide cream and placebo | Palmitoyl pentapeptide-4 cream applied around the eyes | The reported hydration, water-loss, and elasticity instrument comparisons were not statistically significant. | Each group was small, and the study lasted eight weeks. The authors' favorable conclusion should be read alongside the reported results. | Small controlled human cosmetic study |
Cautions
Safety and unknowns
- The cosmetic safety panel found the assessed KTTKS and KTSKS forms safe under the uses and concentrations in its report. The report noted missing reproductive, developmental, and carcinogenicity data.
- In the larger trial the tested moisturizer was reported as well tolerated. A person may still react to a particular formulation or another ingredient in it.
- The smaller trial recorded no complaints in its seven-person pentapeptide group; that sample cannot exclude uncommon reactions.
Product quality
Product identity and quality
A product's peptide sequence and full formulation matter when comparing it with a study.
Sequence
Palmitoyl pentapeptide-4 can refer to KTTKS or KTSKS, while the larger trial tested pal-KTTKS.
Concentration
A percentage of a supplied ingredient blend is not necessarily the percentage of pure peptide.
Vehicle and other ingredients
Different creams and serums may deliver different amounts to skin and have different tolerability.
Mechanism
How it is proposed to work
KTTKS is a small piece of a procollagen precursor. Researchers found that the unmodified sequence affected matrix production in cultured cells.
KTTKS increased collagen and fibronectin production in the tested cell systems. That experiment did not use the finished moisturizer from the clinical study.
Attaching palmitic acid changes the molecule. Skin delivery and clinical effects depend on the resulting peptide and formulation, not cell findings alone.
Details
Technical details
Sources
References
- 1.
PubMed. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin
doi:10.1111/j.1467-2494.2005.00261.x PMID:18492182
Randomized split-face trial of a 3 ppm pal-KTTKS moisturizer against the same moisturizer without peptide.
- 2.
PubMed Central. Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet
PMID:36909866
Small three-arm study; the reported instrument measurements were not statistically significant.
- 3.
PubMed. A pentapeptide from type I procollagen promotes extracellular matrix production
PMID:8486721
Cell experiments on unpalmitoylated KTTKS, not a clinical test of a topical cosmetic.
- 4.
Cosmetic Ingredient Review. Safety Assessment of Myristoyl Pentapeptide-4, Palmitoyl Pentapeptide-4, and Pentapeptide-4 as Used in Cosmetics
Final cosmetic assessment addresses the KTTKS and KTSKS sequences and the specified practices of use.
- 5.
FDA. Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?)
US guidance on the regulatory significance of a product's intended use.
- 6.
Cosmetic Ingredient Review. Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics
Describes Matrixyl 3000 as a mixture of palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7.