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Matrixyl

Also known as Palmitoyl pentapeptide-4, Pal-KTTKS, Palmitoyl pentapeptide-3, Matrixyl 3000 (combination product)

Topical matrikine peptide with a fatty acid tail said to stimulate collagen and extracellular matrix.

early-clinical Skin & cosmetic cosmetic ingredient

At a glance

Category
Skin & cosmetic
Status
cosmetic ingredient
Route
topical, in a cream, emulsion or serum
Half-life
Not applicable for topical use; systemic absorption is negligible. A 2026 safety-evaluation framework for cosmetic peptides concludes that topically applied peptides of this kind are not expected to reach the bloodstream or lymphatic fluid at all 4
Onset
Studies measured improvement after 8 to 12 weeks of daily use; the pivotal published trial ran 12 weeks 1
Molecular weight
approximately 802 g/mol
Sequence
Palmitoyl-Lys-Thr-Thr-Lys-Ser (Pal-KTTKS)

Registered as a cosmetic ingredient under the INCI name palmitoyl pentapeptide-4 2. Not a medicine and with no registered indication; efficacy has not been assessed by any medicines authority. Applied topically only. 'Matrixyl 3000' is a trade name for a combination of other palmitoyl peptides — palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7, the latter being the single most-used peptide in marketed anti-ageing cosmetics 5 — and does not necessarily contain pal-KTTKS.

Doping status: Not listed by WADA

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

KTTKS is a pentapeptide fragment from the propeptide end of type I collagen. When collagen is broken down, fragments like this are released; they act as matrikines — signalling molecules that prompt fibroblasts to produce new matrix material 2. Applying KTTKS to the skin is therefore essentially an attempt to present the body with a repair signal.

The palmitoyl group was added because KTTKS on its own is too hydrophilic to cross the skin barrier. The fatty acid tail raises lipophilicity and with it penetration through the stratum corneum considerably; this is the main reason pal-KTTKS performs better in practice than the bare pentapeptide 2.

In cell culture, pal-KTTKS stimulates the synthesis of collagen types I and III, and of fibronectin and glycosaminoglycans. The extent to which those effects translate in vivo into measurable change in the dermal matrix is less well established than the number of marketing claims would suggest.

Unlike argireline and SNAP-8, matrixyl does not act on muscle contraction but on the build-up of the skin itself; the two categories are therefore often combined in a single formulation.

What the research shows

Among the common cosmetic peptides, matrixyl is one of the better studied, with at least one soundly designed randomised trial. The measured effect is modest, however, and the research comes largely from industry. There is no comparative research placing matrixyl against an established agent such as tretinoin.

Research in humans

The most cited study (Robinson et al., International Journal of Cosmetic Science, 2005) was a 12-week, double-blind, placebo-controlled split-face study in 93 women aged 35 to 55. A moisturizer containing 3 ppm pal-KTTKS produced a significant reduction in wrinkles and fine lines compared with the control, assessed by both image analysis and expert grading, and was well tolerated 12. It is worth noting that a 2026 systematic review and meta-analysis of randomised trials of peptides in skin ageing, searching MEDLINE, CENTRAL and Web of Science to February 2025, did not capture this study among its 19 included trials — of which only two were topical 3; that reflects the indexing of the cosmetic-science literature as much as the quality of the trial. Data from the raw material supplier at 5 ppm report a reduction in wrinkle depth of roughly 18% and in wrinkle volume of roughly 37% over 28 days; those figures have not been independently published.

Animal and lab research

Not relevant: the research rests on human fibroblast cultures and on clinical skin measurements. In cell culture, increases in type I collagen synthesis of well over 100% have been reported, but cell culture concentrations cannot be compared with what reaches the dermis after topical application.

Caveats. The favourable research is largely industry-funded or supplier-generated and not always peer-reviewed. Effect sizes are small and close to what a good moisturizer can achieve through hydration alone — the split-face design partly, but not fully, controls for that. There are no long-term data and no head-to-head comparisons with retinoids.

What it is used for

  • Topical skincare products aimed at fine lines, skin texture and firmness 1
  • Often combined with argireline or SNAP-8, and with niacinamide or hyaluronic acid; the number of distinct peptide combinations in marketed anti-ageing products rose by 88.5% between 2011 and 2018 5
  • Positioned as a milder alternative to retinoids for people who cannot tolerate them — without comparative research to support that positioning

Dosing

Dose
3-8 ppm pure pal-KTTKS in the finished product; the commercial solution (typically around 100 ppm) is used at 3-8% of the formulation to achieve this
Frequency
Applied once to twice daily
Route
topical — this is a cosmetic ingredient, not an injectable peptide
Duration
At least 8-12 weeks before an effect can be expected; the effect disappears after stopping
  • This is emphatically not an injectable agent. No dosing protocol exists for subcutaneous or intradermal administration.
  • The effective concentrations are strikingly low: the clinical study used 3 parts per million 1. More is not demonstrably better; there is no dose-response research supporting higher concentrations.
  • Percentages on product packaging usually refer to the commercial solution, not to pure peptide. A claim of '5% Matrixyl' therefore says little about the actual pal-KTTKS content.
  • These figures come from published research and from supplier documentation for formulators, not from a medicines registration.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Reconstitution

Vial sizes
Commercial form: an aqueous glycerine solution of the peptide, usually around 100 ppm, supplied to formulators
Solvent
water or the aqueous phase of an emulsion; not bacteriostatic water for injection — this ingredient is not reconstituted for injection
Storage
Store cool and dark, preferably 2-8 °C for the raw material. A finished aqueous product needs a sound preservative system.

Worked example

For a final concentration of roughly 3-4 ppm, the 100 ppm commercial solution is added at 3-4% of the total formulation to the cooled water phase.

Add at a temperature below about 40 °C, after the emulsion has formed. The peptide is reasonably stable at a pH of 4 to 7; large deviations from that are not advised.

Safety

Side effects

  • Generally well tolerated with topical use; no relevant skin reactions were reported in the published 12-week trial 1, and cosmetic peptides as a class perform well in standard skin and eye irritation testing 4
  • Mild redness or tingling at the application site
  • Contact allergy is rare — peptides are typically not electrophilic and so lack the reactivity that drives delayed-type hypersensitivity 4; reactions are more often attributable to preservatives, fragrance or other ingredients of the product
  • Irritation can occur if applied too close to the eyelid

Do not use if

  • Known hypersensitivity to the ingredient or to the formulation
  • Damaged, inflamed or freshly treated skin
  • Do not apply to mucous membranes or in the eyes
  • Injecting this ingredient has never been studied and cosmetic commercial solutions are not sterile or pyrogen-free
  • Pregnancy and breastfeeding: no specific research, although systemic exposure with topical use is negligible — topically applied cosmetic peptides are not expected to reach the bloodstream or lymphatic fluid 4

Interactions

No systemic drug interactions are expected with topical use, because a topically applied cosmetic peptide is not expected to reach the systemic circulation at all 4. Within the formulation, a strongly acidic environment, such as with high-concentration ascorbic acid, can reduce stability; suppliers therefore advise applying them separately. Combining with retinoids or alpha hydroxy acids can increase the chance of irritation, without demonstrably changing the peptide's action.

Sources