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GHK-Cu

A naturally occurring copper-binding tripeptide, glycyl-L-histidyl-L-lysine complexed with copper(II), studied for collagen synthesis, tissue remodelling, wound repair and broad modulation of the human transcriptome.

What it is

GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine (sequence Gly-His-Lys), formed when the peptide binds a single copper ion in a 1:1 stoichiometry. The peptide was first isolated from human plasma by Loren Pickart in the 1970s, where it was identified as a factor that helped older liver tissue behave more like younger tissue in culture. It is classed as a copper-binding matrikine, a small signalling peptide that carries and delivers copper to cells and influences the extracellular matrix.

The molecule occurs naturally in blood, saliva and urine. Its plasma concentration is age-dependent: it averages around 200 ng/mL at age 20 and falls to roughly 80 ng/mL by age 60, a decline that has made it a recurring subject in regeneration, skin-biology and ageing research (Dou et al., 2020). Supplied strictly for laboratory research use only, not for human or veterinary use.

How it works

GHK has a very high affinity for copper(II) and can carry copper between compartments, delivering it to cells and enzymes that require it. Through this copper-shuttling and direct signalling, GHK-Cu is studied as a stimulator of collagen, elastin and glycosaminoglycan synthesis in dermal fibroblasts, and as a regulator of the matrix-remodelling balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). In fibroblast and ex-vivo skin work it raised expression of both MMP-1/MMP-2 and TIMP-1, shifting the TIMP-to-MMP ratio toward net collagen and elastin accumulation (J Aging Sci).

Beyond the matrix, gene-expression profiling using the Broad Institute Connectivity Map indicates GHK acts as a broad transcriptional modulator. It has been reported to change the expression of a large fraction of human genes, resetting an age-shifted expression pattern toward a healthier profile, and to engage antioxidant (Nrf2), DNA-repair, ubiquitin-proteasome and anti-inflammatory (reduced NF-kB and TNF-alpha) pathways (Pickart & Margolina, 2018). At low nanomolar concentration it also raised vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in dermal fibroblasts, consistent with a role in angiogenesis during repair.

What the research shows

The GHK-Cu literature spans classic in-vitro and in-vivo collagen work by Pickart and Maquart, controlled topical studies on photoaged skin, and modern transcriptomic analyses by Pickart and Margolina. The headline quantitative findings below are drawn from peer-reviewed sources; every figure carries its source link. Because most controlled human work has used topical formulations, injectable and systemic outcomes remain a research question rather than an established result.

~4,000
Human genes modulated
31.2% changed by ≥50%
70%
Subjects with raised collagen
vs 50% vitamin C, 40% retinoic acid
-55.8%
Facial wrinkle volume
8-week topical trial, p<0.001
~50%
ROS reduction
Caco-2 cells, 10 µM GHK
MetricResultModel or studySource
Human genes modulated ~4,000 genes affected; 31.2% changed by ≥50% (about 59% up, 41% down) Connectivity Map transcriptome analysis Pickart & Margolina, 2018
Collagen production (topical) Increased in 70% of treated women, vs 50% for vitamin C and 40% for retinoic acid 12-week thigh-skin biopsy comparison Pickart & Margolina, 2018
Facial wrinkle volume Reduced 55.8% (p<0.001); wrinkle depth reduced 32.8% (p=0.012) Randomised double-blind trial, n=40, 8 weeks topical J Aging Sci
MMP / TIMP and matrix output Raised MMP-1/MMP-2 and TIMP-1 expression; increased collagen and elastin production at all tested doses Fibroblast and ex-vivo skin J Aging Sci
Antioxidant (ROS) ~50% ROS reduction in Caco-2 cells at 10 µM; ~60% of control in H2O2-stressed WI-38 cells Cell-culture oxidative-stress models Dou et al., 2020
Angiogenic growth factors Increased VEGF and bFGF expression at 1 nM Irradiated human dermal fibroblasts Dou et al., 2020
Serum GHK with age ~200 ng/mL at age 20, declining to ~80 ng/mL by age 60 Human plasma measurement Dou et al., 2020
In-vivo connective tissue Stimulated connective-tissue accumulation and matrix deposition Rat experimental wound chambers (Maquart) Dou et al., 2020
Read the topical vs systemic distinction

The strongest controlled human data come from topical skin studies. Wound-healing and gene-modulation findings from cell and animal models are mechanistic, and do not translate directly to systemic dosing outcomes.

Side Effects

Almost all human safety data for GHK-Cu comes from topical and cosmetic dermatology, where it is generally well tolerated, with reactions usually limited to mild, transient redness or irritation at the application site. Reviews by Pickart and colleagues describe decades of cosmetic and wound-care use without reported adverse effects, and the peptide is active at very low nanomolar concentrations. It is important to note that GHK-Cu is a copper-carrying peptide, and there are no controlled human safety trials for injected or otherwise systemic use. Effects reported below come from the scientific literature and are not medical or dosing guidance.

Reported effect or concernFrequency or contextSource
Mild, transient skin redness or irritation Topical cosmetic use, usually resolves without intervention Pickart 2015
Generally well tolerated, no adverse effects on record Decades of topical and wound-care use reviewed Pickart & Margolina 2018
Contact dermatitis or copper sensitization Uncommon; copper allergy exists but is rarely documented for GHK-Cu formulations Pickart 2015
Copper permeates and forms a depot in skin tissue In vitro human skin study; the peptide delivers copper into and through skin Hostynek et al. 2010
Copper accumulation and hepatic or systemic toxicity Theoretical concern for excessive or systemic copper load; established for copper excess generally, not studied for GHK-Cu injection Copper exposure review
No controlled human safety data for injected use Authors note human dosing and delivery are not yet established Pickart 2015

The favorable tolerability record applies to low-concentration topical products, where copper stays largely in the skin and total exposure is small. It does not transfer to injected or systemic use, for which controlled human safety data do not exist and where copper delivery raises unresolved questions about accumulation.

At a glance

ClassCopper-binding tripeptide / matrikine (Gly-His-Lys·Cu)
Molecular weight403.9 g/mol (Cu complex); 340.4 g/mol free peptide
CAS89030-95-5 (Cu complex); 49557-75-7 (free peptide)
Vial50 mg lyophilized

Dosing

GHK-Cu (copper tripeptide-1) has no approved injectable or systemic human dose. The documented figures come from two places: topical cosmetic use on skin and in-vitro cell work, where concentrations are given as percentages or in the nanomolar to micromolar range. GHK also occurs naturally in human plasma, where its level declines with age. The numbers below are study and formulation concentrations reported in the literature, not injection instructions.

Context or regimenConcentration or doseRoute and frequencySource
Endogenous plasma level, age 20 About 200 ng/mL Naturally present in blood, not administered Pickart & Margolina 2018
Endogenous plasma level, age 60 Declines to about 80 ng/mL Naturally present in blood, not administered Pickart et al. 2015
In-vitro dermal fibroblast work 0.01, 1 and 100 nM (nanomolar) Added to cultured cells in the lab Pickart & Margolina 2018
In-vitro stem cell and cancer cell studies 1 to 10 nM up to about 1 µM (micromolar) Added to cultured cells in the lab Pickart et al. 2015
Collagen synthesis in skin fibroblasts Picomolar to nanomolar concentrations Applied to cells or skin in study conditions GHK-Cu overview
Photoaging cosmetic cream trial Percentage not disclosed in the review; twice daily for 12 weeks Topical, applied to face and around eyes Pickart & Margolina 2018 (PubMed)

There is no established injectable or systemic human dose for GHK-Cu, and the primary reviews do not publish a single agreed topical percentage. These values describe concentrations used in cell experiments and cosmetic study creams, plus the naturally occurring plasma range, and are provided for laboratory research use only.

Preparing it

The vial ships as a lyophilized powder and is reconstituted with bacteriostatic water (or sterile water for single-session work) before use. Copper peptides are typically a deep blue in solution, and the vial should be swirled gently, never shaken, and drawn down the side of the glass until fully dissolved. Choose a diluent volume that gives a concentration convenient to read on a U-100 syringe. See reconstitution for the method and the concentration formula for working out the diluent. Store reconstituted material cold at 2-8 C and protected from light.

Where to go next

Available now

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Research-grade GHK-Cu, third-party tested to high purity and shipped with a certificate of analysis. Strictly for laboratory research use.

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