GHK

Overview

GHK is the parent tripeptide Gly-His-Lys, originally isolated from human plasma by Loren Pickart (1973) as an activity that caused aged hepatocytes to synthesize proteins like younger tissue. It is DISTINCT from GHK-Cu, the 1:1 copper(II) complex tracked as a separate entry — but GHK binds copper readily in vivo, so in physiological environments the bare peptide rapidly associates with available Cu(II). Not FDA-approved for any indication; used in cosmetic and research contexts only.

Mechanism of Action

GHK is a high-affinity ligand for copper(II), forming the GHK-Cu complex that mediates most of its documented biology. Via the copper-bound form, GHK is proposed to modulate expression of a large number of human genes (microarray and Broad Institute Connectivity Map analyses from Pickart's group), including pathways related to extracellular matrix remodeling, antioxidant response element induction, angiogenesis, and DNA repair. Reported in vitro and preclinical effects include stimulation of fibroblast collagen and glycosaminoglycan synthesis and acceleration of wound healing. The bare (non-copper) peptide is typically weaker than GHK-Cu in these assays and is generally assumed to acquire copper in serum-containing environments.

Research Summary

The overwhelming majority of GHK research uses the GHK-Cu complex; direct studies of copper-free GHK are limited. Pickart (J Biomater Sci Polym Ed, 2008, PMID 18644225) reviewed GHK's role in tissue remodeling and wound healing. Pickart et al. (Oxid Med Cell Longev, 2012, PMID 22666519) reviewed GHK-Cu in oxidative stress and cognitive aging. Pickart, Vasquez-Soltero & Margolina (BioMed Res Int, 2014, PMID 25302294; 'GHK and DNA: Resetting the Human Genome to Health') summarized microarray data indicating GHK modulates expression of thousands of human genes. No human clinical trials exist for injected bare GHK; cosmetic formulations typically use topical GHK or GHK-Cu at ~50–200 ppm.

Dosing Information

Reported Side Effects

• Skin irritation, erythema, or contact dermatitis at topical application sites
• Very limited human safety data for injected use
• Theoretical contact sensitization to copper once the peptide binds Cu(II) in vivo

Research References

• The human tri-peptide GHK and tissue remodeling (Pickart, J Biomater Sci Polym Ed) (2008)
• The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health (Pickart et al., Oxid Med Cell Longev) (2012)
• GHK and DNA: resetting the human genome to health (Pickart et al., BioMed Res Int) (2014)