Scientific Reference

GHK-Cu (Copper Tripeptide-1)

Evidence profile: Predominantly in-vitro and preclinical; the controlled human trials identified reported no benefit over control

GHK-Cu is the copper(II) complex of glycyl-L-histidyl-L-lysine, a tripeptide first isolated from human plasma. The free peptide binds copper with high affinity, and the complex is also known by the ingredient name copper tripeptide-1. Published work falls into three groups: cell-culture studies with fibroblasts and other skin-derived cells, wound and tissue models in animals, and a smaller number of studies of topical preparations in human volunteers. The human studies are mostly small and come from cosmetic research rather than controlled clinical trials. Reports that it alters the expression of large numbers of genes rest largely on reanalysis of gene-expression data from cultured cell lines, which shows association rather than a demonstrated effect in tissue.

Mechanism of Action

GHK holds copper(II) through the amino nitrogen of glycine, a deprotonated backbone nitrogen and the imidazole ring of histidine, giving a complex that is stable at neutral pH. One proposed role is as a carrier that moves copper between plasma proteins and cells. Copper is a cofactor for lysyl oxidase, the enzyme that cross-links collagen and elastin, and fibroblast culture studies have reported changes in collagen and glycosaminoglycan synthesis on exposure to the complex. Animal wound studies have also looked at blood-vessel formation and inflammatory markers. How much of the reported activity belongs to the peptide and how much to the copper it carries has not been settled.

Molecular Information

  • Type: Copper tripeptide complex
  • Length: 3 amino acids
  • Molecular weight: 400.90 g/mol
  • Molecular formula: C14H21CuN6O4-

Published Research

  • Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin

    Miller TR et al. · Archives of facial plastic surgery · 2006 · Clinical

    PMID 16847171 — View on PubMed
  • A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers

    Bishop JB et al. · Journal of vascular surgery · 1992 · Clinical

    PMID 1495150 — View on PubMed
  • Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+)

    Siméon A et al. · The Journal of investigative dermatology · 2000 · Preclinical

    PMID 11121126 — View on PubMed
  • Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+

    Maquart FX et al. · FEBS letters · 1988 · Preclinical

    PMID 3169264 — View on PubMed
  • Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

    Li H et al. · Scientific reports · 2016 · Preclinical

    PMID 27892491 — View on PubMed
  • Human skin penetration of a copper tripeptide in vitro as a function of skin layer

    Hostynek JJ et al. · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2011 · Preclinical

    PMID 20721598 — View on PubMed