3AA Limited Human
Pal-GHK
The collagen architect of Matrixyl 3000 — a palmitic-acid-tipped GHK fragment that penetrates the stratum corneum and signals fibroblasts to rebuild type I, III, and IV collagen via the TGF-β pathway.
In Plain English:
Pal-GHK is palmitoyl tripeptide-1: the three-amino-acid sequence Gly-His-Lys (GHK) — a fragment of type I collagen — capped at its N-terminus with a 16-carbon palmitic acid tail. GHK is the same copper-binding motif present in the standalone ingredient GHK-Cu, but the palmitoyl modification replaces copper with a lipid chain, trading carrier-peptide function for enhanced stratum-corneum penetration. The fatty acid tail makes the molecule oil-soluble, allowing it to dissolve into the waxy lipid bilayers of the skin's outer barrier and diffuse to the dermal fibroblasts underneath. Once there it behaves as a signal peptide, mimicking the fragment signals released during natural collagen turnover: skin interprets these fragments as a sign that collagen has been degraded and responds by ramping up synthesis of collagen I, III, and IV, elastin, and glycosaminoglycans via TGF-β receptor signalling. It was commercialised by Sederma as Biopeptide CL™ and later became the collagen-stimulating half of the Matrixyl 3000 complex (paired with the anti-inflammatory Palmitoyl Tetrapeptide-7 / Pal-GQPR). Clinical trials in the Matrixyl 3000 context report a 39% reduction in wrinkle length and 23% reduction in wrinkle depth after 4 weeks twice-daily. Activity is described as comparable to retinoids but without irritation, making it appropriate for eye, lip, and sensitive-skin formulations.
Research Maturity
Limited Human (~20 PubMed results on Pal-GHK (GHK parent 193+); clinical data only from multi-ingredient formulas+ Studies)
Focus
Skin & Aesthetics
Soft Tissue Repair
Origin
The parent tripeptide GHK (Gly-His-Lys) was isolated from human plasma albumin by Loren Pickart in 1973; it occurs naturally in plasma, saliva, and urine and declines from ~200 ng/mL in the third decade to ~80 ng/mL by age 60. Sederma (France, now part of Croda International) synthesised the palmitoylated derivative and commercialised it as Biopeptide CL™ to leverage the GHK collagen-stimulating mechanism with improved skin penetration. The Palmitoyl Tripeptide-1 INCI name was formalised by the PCPC; the legacy INCI designation Palmitoyl Oligopeptide refers to the same molecule. Matrixyl 3000, Sederma's combination of Pal-GHK and Pal-GQPR (Palmitoyl Tetrapeptide-7), launched circa 2005 and became one of the most widely licensed cosmetic peptide complexes globally. The CIR Expert Panel assessed the safety of palmitoyl tripeptide-1 in 2018 (DOI: 10.1177/1091581818807863).
Mechanism
Pal-GHK operates as a signal (messenger) peptide targeting TGF-β receptors on dermal fibroblasts. The palmitoyl group anchors the molecule in the stratum corneum lipid matrix, increasing percutaneous flux relative to the free tripeptide, which is too hydrophilic to cross the barrier efficiently. At the fibroblast surface it activates the TGF-β/Smad signalling cascade, upregulating gene expression for procollagen type I α1, procollagen type III, collagen type IV, elastin, and glycosaminoglycans (GAGs) including hyaluronic acid. The result is stimulation of fibrillogenesis — formation of new collagen fibrils from individual procollagen molecules. Separately, because the GHK sequence retains its copper-chelating histidine residue, complexation with Cu(II) is possible in copper-replete formulations, enabling a minor carrier-peptide function analogous to GHK-Cu; this is not the primary mechanism for the free palmitoylated form. When Pal-GHK is used alongside Pal-GQPR (Matrixyl 3000), a complementary build-and-protect strategy results: Pal-GHK drives new ECM synthesis while Pal-GQPR suppresses IL-6-driven MMP activity that would degrade the newly deposited matrix. In vitro at 0.5 µM: strong collagen synthesis signal in human skin fibroblasts. Retinoid co-application: Pal-GHK has been reported to potentiate retinoid-driven collagen stimulation.
Outcome
PMID 38932444 / PMC11208285 (Skin Research and Technology, 2024, Yang et al.): 37 healthy women, ages 20–55, randomised bilateral 12-week open-label trial, periorbital eye cream containing Pal-GHK 0.0002% + Pal-GQPR 0.0001% + fermentation filtrate 0.25% + N-acetylneuraminic acid 0.1%. In vitro on human fibroblasts: collagen type I mRNA 1.8× increase, collagen type III mRNA 2.5× increase, elastin mRNA 5.0× increase, fibronectin 1.6× increase. Clinical: collagen density +54.99% (ultrasound at 12 weeks), skin elasticity +18.81%, hydration +28.12%, fine lines −26.88%, wrinkles −34.88% (self-assessment). PMID 29504212 (Journal of Cosmetic Dermatology, 2019, Widgerow et al.): 22 subjects, 12-week tripeptide/hexapeptide regimen; biopsies in 5 subjects showed improved solar elastosis, collagen remodelling in all 5, and elastin stimulation in 3 of 5. PMID 39963574 / PMC11830136 (BioImpacts, 2024–2025, Mortazavi et al.): narrative review confirming GHK and its derivatives (GHK-Cu, Pal-GHK) stimulate collagen and GAG synthesis, noting that 'metal complexation and chemical modification with a hydrophobic moiety increase permeability' and flagging a 'surprising absence of dedicated Pal-GHK-only clinical studies' vs widespread cosmetic use. Sederma/Croda Biopeptide CL™ supplier data (blind, vehicle-controlled, 15 female subjects, 4 weeks twice-daily): 39% decrease in wrinkle length, 23% decrease in wrinkle depth, 17% decrease in overall skin roughness. Paula's Choice rates Pal-GHK 'Best' with 'similar anti-ageing benefits to retinol'; Skintique community: 86% liked. EWG Skin Deep hazard score: 1 (low). CIR 2018 conclusion: safe at concentrations 0.0000001–0.002% in current cosmetic practice. All clinical data derive from multi-ingredient formulations; no standalone Pal-GHK-only placebo-controlled RCT has been published.
