Matrixyl (Palmitoyl Pentapeptide-4)

Also known as: Palmitoyl Pentapeptide-4, Palmitoyl Pentapeptide-3, Pal-KTTKS, Matrixyl

Evidence: Clinical

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Overview

Palmitoylated KTTKS, a fragment of the type I procollagen propeptide, applied topically; a 12-week split-face placebo-controlled trial (n=93) at 3 ppm found fewer fine lines and wrinkles.

KTTKS (residues 212 to 216 of the type I procollagen C-propeptide) was identified as the minimum sequence that stimulated collagen I, collagen III and fibronectin in fibroblasts (Katayama et al., 1993). The palmitoylated form (Matrixyl, by Sederma) was designed for skin penetration. In a 12-week, double-blind, split-face trial run by Procter & Gamble in 93 women, a moisturizer with 3 ppm pal-KTTKS reduced wrinkles and fine lines versus the same moisturizer alone (Robinson et al., 2005). Larger figures quoted in marketing (for example '68% wrinkle reduction') come from manufacturer data, not peer-reviewed trials. A 2011 review noted few clinical studies and little penetration data (Abu Samah and Heard, 2011).

Benefits

Fine line and wrinkle reduction (human RCT, n=93), collagen I, III and fibronectin stimulation by the KTTKS parent (in vitro)

Dosing reference

Research dose: Topical, 3 ppm pal-KTTKS in the published single-ingredient RCT; commercial palmitoyl peptides are typically used under 10 ppm. No oral or injectable dose exists.

Topical moisturizer or serum. The RCT ran 12 weeks; the multi-ingredient studies applied 0.5 g twice daily for 4 weeks. Trade solutions are far more dilute than the active peptide, so labels quoting a few percent of Matrixyl correspond to a few ppm of peptide.

Mechanism

Proposed matrikine signalling. The unmodified KTTKS fragment stimulated collagen I, collagen III and fibronectin production in fibroblasts and other mesenchymal cells without changing total protein synthesis (Katayama et al., 1993). The palmitoyl chain improves stability and skin entry: in hairless mouse skin pal-KTTKS reached the stratum corneum, epidermis and dermis, while KTTKS was not detected in any layer (Choi et al., 2014). Collagen IV induction, TGF-beta activation and a 'wound-repair' signal are not shown in primary sources for this compound.

Evidence

Clinical: at least one published human trial or an approved drug

KTTKS was the minimal procollagen fragment that stimulated collagen I, III and fibronectin in fibroblasts (Katayama et al., 1993)
12-week double-blind split-face RCT, 93 women aged 35 to 55: 3 ppm pal-KTTKS reduced wrinkles and fine lines vs placebo moisturizer by image analysis (Robinson et al., 2005)
Two split-face RCTs (n=42 and n=35) of multi-ingredient products containing pal-KTTKS improved periorbital roughness in 4 weeks; the peptide's share is not separable (Kaczvinsky et al., 2009)
Pal-KTTKS, unlike KTTKS, reached epidermis and dermis in hairless mouse skin in vitro (Choi et al., 2014)
Human-trial status: one single-ingredient RCT, run by a commercial user (Procter & Gamble); other human data are multi-ingredient or manufacturer figures

References

Side effects

Well tolerated in the 93-person 12-week RCT (Robinson et al., 2005). No other safety study of pal-KTTKS has been published. Commonly reported (anecdotal): mild irritation or redness. Labels quoting trade-solution percentages and papers quoting ppm of active peptide differ by roughly a hundredfold.

Storage

Storage: Room temperature, away from light
Lyophilized: 2 years at room temp
Reconstituted: N/A (ready to use)

Pharmacology

Half-life: No published pharmacokinetic data; pal-KTTKS was degraded in hairless mouse skin extracts, more slowly than KTTKS
Bioavailability: Topical (hairless mouse skin in vitro): 4.2, 2.8 and 0.3 ug/cm2 in stratum corneum, epidermis and dermis; none crossed full-thickness skin
Molecular weight: 802.05 Da
Sequence: Palmitoyl-Lys-Thr-Thr-Lys-Ser (pal-KTTKS)