Palmitoyl Pentapeptide-4

Pal-KTTKS, commercially known as Matrixyl, has convincing anti-wrinkle benefits like the retinoids, but is gentler on the skin and does not damage the skin barrier, making it a viable alternative.


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments


Wrinkle treatment


Significantly improves wrinkle depth, roughness, volume and density by stimulating the production of collagen and glycosaminoglycans.


Smoother skin


Led to 2-fold reductions in bumpy texture after 8 weeks of treatment.


Skin lightening


Reduced age spots and evened out skin tone, as reported by subjects in one study.


Increased skin thickness


Increased skin thickness by 9% after 4 months in one study.

Looking to buy skin care products containing Palmitoyl Pentapeptide-4?

Buy from

Scientific Research

Caution: Please read's medical disclaimer.

Table of contents:

1. Sources

KTTKS is a pentapeptide subfragment of the propeptide of type I collagen. More specifically, it is the minimum sequence of this propeptide necessary to potently stimulate the production of collagen and fibronectin by human fibroblasts.[1] The addition of palmitic acid to KTTKS forms palmitoyl-KTTKS, or pal-KTTKS.[2]

Matrixyl, an active ingredient found in many anti-aging products, is a commercial solution containing 100 ppm of pal-KTTKS.[3]

2. Bioavailability

KTTKS is hydrophilic and has a relatively high molecular weight, making it a poor candidate for topical delivery. The attachment of a lipophilic group in palmitic acid, therefore, serves to improve the delivery of KTTKS across the epidermis by enabling it to penetrate the stratum corneum barrier. Indeed, the calculated permeability coefficient of pal-KTTKS is 17 times higher than the predicted value for KTTKS, as the effect of the increased lipophilicity dominates over that of the increase in molecular weight.[2]

Unfortunately, there is no available data on the permeation of pal-KTTKS into the skin. One study claimed to have confirmed the penetration of KTTKS into full-thickness human skin ex vivo, but no data were presented.[4] Typical concentrations used in cosmetic products are very low, purportedly on the order of 3 ppm. This makes detection difficult, and may explain the paucity of published permeation data.[2]

Upon delivery into the skin, it is thought that pal-KTTKS may act as a prodrug, releasing the peptide KTTKS by enzymatic cleavage.[5]

The recommended concentration of pal-KTTKS for cosmetic purposes is between 2-8 ppm, as pal-KTTKS is extremely potent.[2] However, the availability and stability of pal-KTTKS in anti-wrinkle creams is strongly influenced by the cosmetic formulation.[6]

3. Effects on the skin

3.1 Anti-wrinkle effect

There is strong evidence that pal-KTTKS is effective in decreasing facial wrinkles and roughness, in the form of several clinical studies.

Facial moisturizers containing pal-KTTKS have been shown to improve fine lines and wrinkles in 2 separate studies.[7][8] In the first study, 93 subjects applied a moisturizer containing 3 ppm pal-KTTKS to one side of the face and a moisturizer containing placebo control to the other.[7] The second was a double-blind, 8 week, split-face, randomized round robin study with 60 panelists per product. The women applied a serum-type moisturizer containing 3 ppm pal-KTTKS, niacinamide, panthenol and vitamin E, or a moisturizer base vehicle.[8] In both studies, digital image analysis and expert grading agreed that the the pal-KTTKS containing moisturizer significantly improved wrinkles and fine lines compared to the placebo.[7][8]

Another study in which 25 volunteers were treated with twice-daily applications of 3 ppm pal-KTTKS for 6 months, also revealed pronounced improvements in wrinkle depth (22%), roughness (16%), wrinkle volume (24%) and main lines density (47%).[9]

Higher concentrations of pal-KTTKS exhibit even stronger anti-wrinkle effects, as expected. In one double-blind, placebo-controlled study, 50 ppm pal-KTTKS was applied to the right eye area of female volunteers twice daily. After only 28 days, optical profilometry revealed that wrinkle depth, wrinkle density and skin rugosity decreased by 18%, 37% and 21%, respectively.[10]

Comparative studies have demonstrated that 3 ppm of pal-KTTKS is as effective as 700 ppm (0.07%) of retinol and more than twice as effective as B serrata extract in reducing wrinkle depth and length.[4][11]

Pal-KTTKS also seems to work well when combined with other cosmeceutical ingredients. 4 products containing niacinamide, pal-KT, pal-KTTKS and carnosine -- a daytime SPF 30 lotion also containing antioxidants, a night cream, an eye cream also containing caffeine, and a wrinkle treatment also containing retinyl propionate -- were tested for their efficacy in treating wrinkles around the eyes in one study. Results showed that 4 weeks of treatment with these products improved the smoothness of the skin and reduced the depth of larger wrinkles.[12]

Another study was later conducted to assess the clinical efficacy of a similar cosmetic moisturizer regimen versus a prescription regimen containing 0.02% tretinoin in improving facial fine lines and wrinkles. Products in the cosmetic regimen (Olay Professional Pro-X Age Repair Lotion, Olay Professional Pro-X Wrinkle Smoothing Cream and Olay Professional Pro-X Deep Wrinkle Treatment) contained combinations of pal-KTTKS, pal-KT, niacinamide and retinyl esters. This regimen was found to significantly improve the appearance of fine lines and wrinkles around the eyes after 8 weeks, and to deliver comparable benefits to the tretinoin regimen after 24 weeks while being better tolerated.[13]

The anti-wrinkle effect of pal-KTTKS is related to its ability to stimulate collagen I, III, VI and also fibronectin, elastin and glycosaminoglycan production.[14] Histologically, pal-KTTKS is also associated with increases in elastin fiber density, thickness and improved regulation of type IV collagen at the dermal-epidermal junction.[15]

Like 700 ppm of retinol, 3 ppm of pal-KTTKS increased the thickness of the skin by approximately 9% after 4 months of application in one study.[4]

Pal-KTTKS has also been shown to improve age-related hyperpigmented spots, according to subject self-assessments in another study.[7]

In a double-blind, vehicle-controlled study, both expert grading and self-assessments agreed that a facial moisturizer containing 3 ppm pal-KTTKS not only improved facial wrinkles but also led to 2-fold reduction in bumpy texture compared to the vehicle after 8 weeks of treatment. Participants in that study also noted that their skin tone had become more even.[11]

A daytime SPF 30 lotion, night cream and eye cream were also found to improve the skin barrier as measured by transepidermal water loss in one study, but this effect cannot be solely or clearly attributed to pal-KTTKS as these products also contained other active ingredients.[12]

4. Side Effects

Pal-KTTKS does not achieve its success in alleviating wrinkles at the expense of damage to the skin barrier.[4] 12 weeks of twice daily topical application of pal-KTTKS did not lead to significant differences in transepidermal water loss compared to treatment with the vehicle in one study, suggesting that pal-KTTKS is gentle on the skin barrier.[7]

Tests of oral and ocular irritation, mutagenicity and sensitization, using 100 ppm or higher concentrations of pal-KTTKS, have also demonstrated its safety.[4]

Scientific References

  1. Katayama K, et. al. A pentapeptide from type I procollagen promotes extracellular matrix production. J Biol Chem. (1993)
  2. Abu Samah NH, Heard CM. Topically applied KTTKS: a review. Int J Cosmet Sci. (2011)
  3. Huang CK, Miller TA. The truth about over-the-counter topical anti-aging products: a comprehensive review. Aesthet Surg J. (2007)
  4. Lintner K. Promoting production in the extracellular matrix without compromising barrier. Cutis. (2002)
  5. Palladino P, et. al. Conformation and self-association of peptide amphiphiles based on the KTTKS collagen sequence. Langmuir. (2012)
  6. Chirita RI, et. al. Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics. Anal Chim Acta. (2009)
  7. Robinson LR, et. al. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Int J Cosmet Sci. (2005)
  8. Mas-Chamberlin C, et. al. Relevance of antiwrinkle treatment of a peptide: 4 months clinical double blind study vs excipient. Poster presented at: 20th World Congress o Dermatology, Paris, France. (2002)
  9. Matrixyl: The messenger peptide for dermal matrix repairs. (2007)
  10. Lintner K. Cosmetic or dermopharmaceutical use of peptides for healing, hydrating and improving skin appearance during natural or induced ageing (heliodermia, pollution). US Patent 6620419 (2003)
  11. Osborne R, et. al. Use of a facial moisturizer containing palmitoyl pentapeptide improves the appearance of aging skin. J Am Acad Dermatol. (2005)
  12. Kaczvinsky JR, et. al. Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging. J Cosmet Dermatol. (2009)
  13. Ho ET, et. al. A randomized, double-blind, controlled comparative trial of the anti-aging properties of non-prescription tri-retinol 1.1% vs. prescription tretinoin 0.025%. J Drugs Dermatol. (2012)
  14. Gorouhi F, Maibach HI. Role of topical peptides in preventing or treating aged skin. Int J Cosmet Sci. (2009)
  15. Guttman C. Studies demonstrate value of procollagen fragment Pal-KTTKS. Dermatol Times. (2002)