Description
GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring human tripeptide with the sequence Gly-His-Lys.
It was first isolated in the 1970s from human plasma by Loren Pickart. Plasma levels are higher in young adults (around 200 ng/mL) and decline with age. GHK is released during tissue remodeling from the extracellular matrix protein SPARC and functions as a signaling matrikine.
Research indicates that free GHK can influence gene expression, support tissue repair processes, modulate inflammation, and affect cellular activity related to regeneration and extracellular matrix components. It is studied primarily in the contexts of wound healing, skin biology, and regenerative signaling, and is used in some cosmetic and research applications as the copper-free form (also called Tripeptide-1).
GHK vs. GHK-Cu
| Aspect | GHK (free peptide) | GHK-Cu (copper complex) |
|---|---|---|
| Structure | Tripeptide only: Gly-His-Lys | Same tripeptide bound 1:1 to a copper(II) ion |
| Natural form | Exists free in plasma, but readily binds copper | Predominant biologically active form under physiological conditions |
| Primary activity | Residual gene-modulation and signaling activity | Substantially stronger regenerative, collagen-stimulating, antioxidant, and anti-inflammatory effects |
| Key biological role | Matrikine signaling peptide released during tissue remodeling | Copper delivery + enhanced peptide signaling; activates lysyl oxidase and other copper-dependent enzymes involved in collagen/elastin cross-linking |
| Gene expression | Can modulate thousands of genes on its own | More potent and broader modulation (often cited as the main driver of the well-known gene-expression profile) |
| Evidence strength | More limited standalone studies | Far more extensive research, especially in wound healing, skin remodeling, and cosmetic applications |
| Typical use | Research / occasional cosmetic (Tripeptide-1) | Widely used in topical skincare and research protocols for tissue repair and anti-aging |
| Relative potency | Weaker overall | Stronger across nearly all measured endpoints (collagen synthesis, wound closure, antioxidant activity, etc.) |
Summary
GHK is the copper-free tripeptide backbone. GHK-Cu is the same peptide complexed with copper. While free GHK retains some biological activity (gene regulation and signaling), the copper-bound form is significantly more potent and is responsible for most of the well-documented regenerative, matrix-remodeling, and protective effects associated with this peptide family. In practice, the vast majority of research and commercial applications refer to GHK-Cu.
