# GHK-Cu: Copper Tripeptide-1, Indexed From the Research Record

> GHK-Cu, the copper(II) chelate of glycyl-histidyl-lysine, drives fibroblast collagen synthesis at picomolar doses and shifts roughly 31% of human gene expression toward repair. A cited herbarium of the literature.

A medicinal-botany herbarium of the copper-tripeptide literature: the mechanism, the dose-response data, the skin and hair record, the neuroprotective gene work, and the open questions. Every quantitative claim is pinned to its source.

## What the GHK-Cu record establishes

GHK-Cu is the glycyl-L-histidyl-L-lysine copper(II) complex, a copper-binding tripeptide first isolated from human plasma in 1973. Molecular weight: 402.92 Da. CAS: 89030-95-5. INCI name: Copper Tripeptide-1. It is a research peptide and a legal cosmetic ingredient, not an approved drug by any route.

The sequence is not foreign to the body. GHK occurs within the alpha-2(I) chain of type I collagen and in SPARC/osteonectin, and circulates in plasma, saliva and urine. Plasma levels fall from about 200 ng/mL at age 20 to about 80 ng/mL by age 60 [3]. That decline is what frames the compound as restorative in the literature — replacing a signal the body sheds with age, rather than introducing something new.

The data has a consistent shape. In human fibroblast cultures GHK-Cu raised collagen synthesis dose-dependently, with onset between 10⁻¹² and 10⁻¹¹ M, a peak near 10⁻⁹ M, and no change in cell number — marking a specific metabolic effect rather than a growth artifact [1]. A Connectivity Map analysis reports that GHK shifts expression of roughly 31.2% of human genes at a 50%-or-greater threshold: 59% up, 41% down, with strong stimulation of ubiquitin-proteasome, DNA-repair and antioxidant gene sets [2]. The widely repeated "~4,000 genes" figure is an extrapolation; the verified threshold table reports on the order of 2,100 genes [2].

This herbarium catalogues what the compound has been studied for, specimen by specimen, and is explicit about which tier of evidence each finding sits in. The strongest controlled human signals are topical and dermatologic; the broader systemic, neuroprotective and gene-level claims rest largely on in-vitro, bioinformatic and rodent work, much of it from a single research lineage [2][7]. Where a study used the free peptide GHK rather than the copper chelate, the distinction is flagged — copper coordination is required for most of the documented matrix activity [6].

The specimen plates that follow run from the copper-binding site to the cell to the whole organism: [copper peptide skin and collagen research](/skin-research), [copper peptide hair research](/hair-research), [GHK-Cu neuroprotective research](/research), and [GHK-Cu dosage in the research literature](/dosage).

## The GHK Copper Peptide: What It Is

The GHK copper peptide is the most-studied member of the copper-peptide class, and GHK-Cu is its canonical form. Its defining feature is copper coordination: the Cu(II) ion binds through the histidine imidazole nitrogen, the glycine alpha-amino nitrogen and the deprotonated glycine-histidine amide nitrogen, leaving the lysine side chain free. The complex carries a very high copper stability constant — log K of approximately 16.4 — far above free GHK, which limits pro-oxidant free-copper release.

That chelation is functional rather than incidental. Copper coordination enables lysyl-oxidase-mediated collagen and elastin cross-linking and superoxide-dismutase-like antioxidant chemistry, and the copper-free peptide does not reproduce MMP-2 stimulation in fibroblast cultures [6]. Across research models the GHK copper peptide stimulates synthesis of collagen, dermatan sulfate, chondroitin sulfate and the proteoglycan decorin [3], while broadly modulating the matrix-remodeling and tissue-repair gene programs catalogued on the [research](/research) plate.

## What a Copper Peptide Is

A copper peptide is a short amino-acid chain bound to a copper(II) ion. GHK-Cu — three amino acids and one copper atom — is the archetype. The peptide acts as both a carrier and a signal: it delivers copper to enzymes that require it, and in study models it instructs dermal fibroblasts to rebuild the extracellular matrix [6].

The class earns its research interest from breadth, not from a single lock-and-key target. In tissue-remodeling reviews GHK-Cu raises collagen, elastin, VEGF, FGF-2 and NGF while suppressing free radicals, thromboxane, TGF-beta-1 and TNF-alpha, and it chemoattracts the repair cells — macrophages, mast cells and capillary cells — that a wound recruits [6]. It is this radiating, many-pathway profile, rather than a narrow mechanism, that the copper-peptide literature keeps returning to.

## Copper Tripeptide-1: The INCI Name for GHK-Cu

Copper Tripeptide-1 is the INCI (International Nomenclature of Cosmetic Ingredients) name for GHK-Cu — the label term used to declare copper-peptide content in skincare. The two names refer to the same molecule: glycyl-histidyl-lysine chelated 1:1 to copper(II), molecular weight 402.92 Da, CAS 89030-95-5.

The naming matters for reading the evidence. Under "Copper Tripeptide-1" the compound appears in a long cosmetic safety record and in placebo-controlled facial-cream trials; under "GHK-Cu" or "GHK" it appears in mechanistic, gene-expression and rodent literature. They are one compound described by two communities, and this herbarium pins both labels to the same specimen.

## What GHK-Cu Has Been Studied For

### Copper Peptide Benefits in the Research Record

The documented copper peptide benefits in the research record cluster into four areas, each with its own specimen plate in this herbarium. None is a promise of effect — each is a record of what was measured, in which model, at which dose.

**Skin and matrix.** GHK-Cu stimulates fibroblast synthesis of collagen, elastin, glycosaminoglycans and decorin [1][3], and topical GHK-Cu raised collagen production in 70% of treated women versus 50% for vitamin C and 40% for retinoic acid in placebo-controlled work [3]. Catalogued on the [copper peptide skin and collagen research](/skin-research) plate.

**Hair.** In a 6-month trial of 45 men with androgenetic alopecia, a topical 5-aminolevulinic-acid + GHK complex (ALAVAX) increased hair count by 52.6 and 71.5 versus 9.6 for placebo, with no adverse events [4] — the strongest controlled human hair signal for a GHK-containing topical. Catalogued on the [copper peptide hair research](/hair-research) plate.

**Wound and tissue repair.** GHK-Cu accelerates wound healing across numerous animal and human models, raising collagen, elastin, VEGF, FGF-2 and NGF while suppressing free radicals and TGF-beta-1 [6].

**Genes and the nervous system.** GHK shifts expression of roughly 31% of human genes toward repair, DNA-fidelity and antioxidant programs [2], including 408 upregulated neuron-associated genes [7] — the basis for the rodent neuroprotection work on the [GHK-Cu neuroprotective research](/research) plate. These are research findings, not promises of benefit; the herbarium frames each as what was measured, in which model, at which dose.

## Questions Readers Bring to GHK-Cu

### What does a GHK-Cu peptide do?

GHK-Cu is a naturally occurring copper-binding tripeptide studied for stimulating fibroblast collagen synthesis [1] and for broad tissue-remodeling activity — increasing collagen, elastin, VEGF, FGF-2 and antioxidant defenses while suppressing inflammatory and free-radical signals [6] — across in-vitro and animal models. It is a cosmetic ingredient and a research peptide, not an approved therapeutic.

### What is GHK-Cu and how does it work?

GHK-Cu is the glycyl-histidyl-lysine copper(II) complex, a tripeptide present in human plasma that acts as both a copper chaperone and a signaling molecule. It stimulates matrix synthesis at picomolar-to-nanomolar concentrations [1] and broadly modulates tissue-repair gene programs [2][6]. The copper ion is not decorative: it is required for most of the documented matrix-remodeling activity.

### What is the difference between GHK and GHK-Cu?

GHK is the free tripeptide (MW 340.38, CAS 49557-75-7); GHK-Cu is its copper(II) chelate (MW 402.92, CAS 89030-95-5). Copper coordination is required for most documented tissue-repair activities — the free peptide does not reproduce MMP-2 stimulation in fibroblasts [6] — so [the difference between GHK and GHK-Cu](/) governs how each study should be read.

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A night-herbarium of the GHK-Cu literature — each copper-tripeptide study pressed, labeled, and pinned to its source, with no clinic behind the specimen sheet and nothing here for sale.