GHK-Cu
GHK is the tripeptide glycyl-L-histidyl-L-lysine, first isolated from human plasma in 1977 as a growth-modulating serum factor. It binds Cu(II) with high affinity; solution spectroscopy indicates a mononuclear 1:1 complex at neutral pH in which copper is nitrogen-coordinated with participation of the histidyl imidazole ring. The sequence also occurs internally in the α2(I) chain of type I collagen, from which it has been proposed to be released proteolytically at sites of tissue injury.
Information on this page is provided for laboratory research reference. The compound is not a drug, supplement, or medical product, and is not for human or veterinary use, ingestion, or consumption.
- #171246 · 100 mg99.729%
Each result applies to the tested sample shown, not to every catalog strength or lot.
The proposed mechanism centres on GHK acting as a copper carrier rather than a classical receptor agonist: the peptide competes with albumin for Cu(II) and delivers it in a form fibroblasts and keratinocytes respond to. Reported effects in culture include increased collagen and sulfated glycosaminoglycan synthesis, and coordinated up-regulation of MMP-2 alongside its inhibitors TIMP-1 and TIMP-2 — read by investigators as matrix synthesis plus remodelling rather than synthesis alone. How much is the copper and how much the peptide is not settled: in the MMP-2 work, copper salt alone reproduced the effect and the uncomplexed tripeptide did not.3,4,5,6
Forms Cu(II) complexes across pH 3.5–10.6 and competes with albumin for copper; proposed to facilitate transfer from plasma to tissue2,3
Increased collagen synthesis in fibroblast culture and raised type I and III collagen mRNA in rat wound chambers, with collagen stimulated about twice as much as non-collagen protein4,7
Increased MMP-2 protein and mRNA plus TIMP-1 and TIMP-2 in fibroblast culture; copper alone reproduced the MMP-2 effect while the tripeptide alone did not5,8
Increased decorin and decreased biglycan mRNA in rat wounds — differential rather than uniform matrix upregulation6
Increased in keratinocyte monolayers and skin-equivalent models; interpreted as increased proliferative potential of basal keratinocytes9
Reported direct binding and activation, with reduced protein degradation and improved mitochondrial function in cigarette-smoke-exposed mouse muscle10
Increased expression alongside greater angiogenesis in mouse scald wounds, using a liposomal formulation11
Skin & matrix
In cultured fibroblasts, GHK-Cu stimulated collagen synthesis dose-dependently with a maximal effect near 10⁻⁹ M, reported as independent of cell proliferation.4
In fibroblast cultures, GHK-Cu increased MMP-2 protein and mRNA and also the inhibitors TIMP-1 and TIMP-2. Copper alone reproduced the MMP-2 effect whereas the uncomplexed tripeptide did not, so the active species differs by endpoint.5
In keratinocyte monolayers and reconstructed skin-equivalent models, copper-GHK increased keratinocyte proliferation, PCNA and p63 positivity, and integrin α6 and β1 expression, with basal cells becoming cuboidal in the skin equivalents.9
In the same rat wound model, GHK-Cu increased decorin mRNA while decreasing biglycan mRNA, which the authors described as differential rather than uniform regulation of matrix components across the healing time course.6
In patients randomised after circumoral CO₂ laser resurfacing, investigators reported no statistically significant difference between copper tripeptide products and standard care for resolution of erythema, wrinkle improvement or overall skin quality at 12 weeks, although patient-reported satisfaction was higher in the copper tripeptide group.12
Tissue repair
In a rat wound-chamber model, GHK-Cu produced concentration-dependent increases in chamber dry weight, DNA, total protein, collagen and glycosaminoglycan content, with type I and III collagen mRNA raised while TGF-β mRNA was unchanged.7
In mouse scald wounds, liposome-encapsulated GHK-Cu shortened time to healing to about 14 days with greater angiogenesis than free GHK-Cu, accompanied in vitro by a 33.1% increase in endothelial cell proliferation.11
In a transcriptome study of human lung tissue, investigators identified 127 genes whose expression correlated with regional emphysema severity and reported that GHK reversed this signature in vitro and increased collagen remodelling by fibroblasts derived from COPD patients.13
In a multicentre randomised evaluator-blinded placebo-controlled trial of topical GHK-Cu gel on diabetic neuropathic ulcers alongside debridement and offloading, investigators reported 98.5% median area closure versus 60.8% for vehicle, and infection in 7% versus 34% of vehicle-treated ulcers.14
In a prospective randomised evaluator-blinded trial in venous stasis ulcers, a 0.4% tripeptide copper complex cream did not differ from inert vehicle in ulcer size reduction, while 1% silver sulfadiazine was statistically superior to both.15
Mitochondrial function
In cigarette-smoke-exposed mice, GHK-Cu reduced muscle mass loss, increased fibre cross-sectional area and improved grip strength, which the authors attributed to SIRT1 binding and improved mitochondrial function.10
Longevity & cellular ageing
In a small plasma comparison, circulating GHK was lower in COPD patients than in healthy controls (70.27 ± 38.87 vs 133.0 ± 54.54 ng/mL).10
What investigators recorded alongside the results above, at the rates their papers state.
Skin-irritation biomarkers (IL-1α, IL-8, HSPA1A, FOSL1) were not significantly upregulated by GHK-Cu, whereas copper chloride and copper acetate at 58 and 580 µM were. The authors concluded chelated copper has low irritation potential. This is an in-vitro assay, not clinical safety data.16
No treatment-emergent adverse events reported after topical use on laser-resurfaced facial skin. Absence of reported events in a 13-patient study does not establish a safety profile.12
0 of 13 participants, as reported
Wound infection during topical treatment of diabetic neuropathic ulcers occurred in 7% of GHK-Cu-treated ulcers versus 34% of vehicle-treated ulcers. No other adverse events are itemised in the published record.14
7% vs 34% vehicle
No human sensitisation study and no systemic copper-toxicity dataset for this compound could be located in the indexed literature. All human evidence concerns material applied to skin or a wound bed; there is no systemic-exposure safety record.16
no data
- 1.Growth-modulating serum tripeptide is glycyl-histidyl-lysine · Experientia · 1977 · PMID 858356
- 2.Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution · Biochemistry · 1982 · PMID 6291585
- 3.The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma · The Biochemical Journal · 1981 · PMID 7340824
- 4.Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ · FEBS Letters · 1988 · PMID 3169264
- 5.The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures · Life Sciences · 2000 · PMID 11045606
- 6.Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+) · Journal of Investigative Dermatology · 2000 · PMID 11121126
- 7.In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds · Journal of Clinical Investigation · 1993 · PMID 8227353
- 8.Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ · Journal of Investigative Dermatology · 1999 · PMID 10383745
- 9.Copper-GHK increases integrin expression and p63 positivity by keratinocytes · Archives of Dermatological Research · 2009 · PMID 19319546
- 10.Glycyl-l-histidyl-l-lysine-Cu(2+) rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway · Journal of Cachexia, Sarcopenia and Muscle · 2023 · PMID 36905132
- 11.GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis · Wound Repair and Regeneration · 2017 · PMID 28370978
- 12.Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin · Archives of Facial Plastic Surgery · 2006 · PMID 16847171
- 13.A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK · Genome Medicine · 2012 · PMID 22937864
- 14.Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper · Wound Repair and Regeneration · 1994 · PMID 17147644
- 15.A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers · Journal of Vascular Surgery · 1992 · PMID 1495150
- 16.Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds · Scientific Reports · 2016 · PMID 27892491