Scientific Reference

GHK-Cu

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

GHK-Cu is glycyl-histidyl-lysine bound to copper(II), a combination originally purified from human blood plasma. The peptide alone grips copper tightly, and in cosmetic ingredient lists the complex goes by copper tripeptide-1. The evidence divides into three tiers: experiments on cultured fibroblasts and skin cells, wound and tissue studies in animals, and a handful of topical-product studies in volunteers. Those human studies are small and cosmetic in origin, not rigorous clinical trials. Statements that it changes the activity of huge numbers of genes derive mainly from re-analysing existing expression datasets from cell lines, which shows correlation instead of a proven tissue effect.

Mechanism of Action

Copper(II) is held by the glycine amino nitrogen, a deprotonated backbone nitrogen and the histidine imidazole, producing a complex stable near neutral pH. One idea is that it shuttles copper between plasma proteins and cells. Copper serves as cofactor for lysyl oxidase, which cross-links collagen and elastin, and fibroblast cultures have shown altered collagen and glycosaminoglycan production after exposure. Animal wound work has also followed vessel growth and inflammation markers. It is unresolved how much of the activity belongs to the peptide and how much to its copper.

Molecular Information

  • Type: Copper tripeptide complex
  • 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