Published findings, in context.

Systematic review of 20 studies (18 preclinical, 2 randomized controlled trials) of GHK-Cu as a standalone intervention

“The Regenerative Potential of GHK-Cu in Aesthetic Medicine.”

Mokhtar J, Mohamed B, Haddad J, et al.·Aesthetic Surgery Journal·2026·PMID 42619529 (opens PubMed in a new tab)·DOI 10.1093/asj/sjag169 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Systematic review (PubMed, Embase and Cochrane CENTRAL from inception through March 2026, following PRISMA) of studies of GHK-Cu as a standalone intervention

Twenty studies were included: 18 preclinical studies and 2 randomized controlled trials. The authors synthesize preclinical data on extracellular matrix synthesis (matrix proteins and glycosaminoglycans), metalloproteinase activity, cell proliferation, inflammatory markers and delivery systems. Their conclusions about the two human trials are not summarized in this profile, and not every included study is listed here.

Mouse experimental silicosis model and RAW 264.7 macrophages: lung histology, fibrosis, oxidative stress and PRDX6 binding

Bian Y, Deng M, Liu J, et al.·Redox Biology·2024·PMID 38879894 (opens PubMed in a new tab)Title on PubMed·DOI 10.1016/j.redox.2024.103237 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Murine model of experimental silicosis induced by crystalline silica; in vitro experiments with the murine macrophage line RAW 264.7, used by the authors as an alveolar macrophage model

Exposure

GHK-Cu vs silica-only controls (mice and macrophage cultures)

Comparator

Silica-exposed animals without GHK-Cu

In a murine model of experimental silicosis, pulmonary inflammatory changes and fibrosis were assessed with and without GHK-Cu; their direction is not summarized in this profile. Peroxiredoxin 6 (PRDX6) was identified as a protein bound by GHK-Cu, and the authors attributed the effects in part to inhibition of silica-induced oxidative stress in macrophages (RAW 264.7 cells, used as an alveolar macrophage model).

Narrative review of gene-expression (Connectivity Map) data on GHK and earlier preclinical studies

“Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data”

Pickart L, Margolina A·International Journal of Molecular Sciences·2018·PMID 29986520 (opens PubMed in a new tab)·DOI 10.3390/ijms19071987 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Narrative review focused on gene-profiling data (Connectivity Map) and earlier preclinical studies

Narrative review that compiles the available gene-expression data for GHK and relates them to actions described in skin, pulmonary connective tissue, bone, liver and gastric mucosa in experimental models, as well as antioxidant effects, effects on inflammatory markers and effects on the proteasome system. The authors interpret the gene data as a possible explanation for the diversity of effects; most of the proposed pathways have not been validated in controlled human studies.

Mouse scald burn model and HUVEC: liposome-encapsulated vs free GHK-Cu, vessel counts and proliferation markers

Wang X, Liu B, Xu Q, et al.·2017·PMID 28370978 (opens PubMed in a new tab)Full record on PubMed·DOI 10.1111/wrr.12520 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Murine scald burn model; in vitro experiments in HUVEC with nanoscale liposomes encapsulating GHK-Cu

Exposure

Liposome-encapsulated GHK-Cu vs free GHK-Cu (mice and HUVEC cultures)

Comparator

Free (non-encapsulated) GHK-Cu

In HUVEC, GHK-Cu liposomes increased the proliferation rate (by 33.1%), with higher expression of VEGF, FGF-2, CDK4 and cyclin D1. In a murine scald burn model, liposome-encapsulated and free GHK-Cu were compared on vessel counts and on CD31 and Ki67 staining (endothelial and proliferation markers) in the burned skin, and the size of the scald area was followed over time; the direction and size of these endpoints are not summarized in this profile. The results refer to a specific liposomal formulation.

Mouse LPS-induced acute lung damage model and RAW 264.7 macrophages: cytokines, oxidative stress and lung histology

Park JR, Lee H, Kim SI, et al.·Oncotarget·2016·PMID 27517151 (opens PubMed in a new tab)Title on PubMed·DOI 10.18632/oncotarget.11168 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Murine model of lipopolysaccharide (LPS)-induced acute lung damage; complementary experiments in LPS-stimulated RAW 264.7 macrophages

Exposure

GHK-Cu vs LPS-only controls (mice and macrophage cultures)

Comparator

LPS-exposed animals and cultures without GHK-Cu

In macrophages and in the murine model, GHK-Cu was associated with lower production of reactive oxygen species, higher superoxide dismutase activity and lower TNF-α and IL-6 production, with suppression of NF-κB p65 and p38 MAPK signaling. Pulmonary histological changes and the infiltration of inflammatory cells into the lung parenchyma were also assessed in the mice; their direction is not summarized in this profile. The findings are limited to this acute murine model and a macrophage cell line and have not been examined in humans.

Narrative review of in vitro, animal and gene-expression data on GHK by company-affiliated authors

Pickart L, Vasquez-Soltero JM, Margolina A·BioMed Research International·2015·PMID 26236730 (opens PubMed in a new tab)Title on PubMed·DOI 10.1155/2015/648108 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Narrative review of in vitro and animal studies, observations in humans and gene-expression data

Narrative review proposing a role for GHK, as a copper complex, in tissue remodeling through effects on the synthesis and breakdown of glycosaminoglycans, metalloproteinases and their inhibitors, decorin, and the attraction of immune and endothelial cells; it also summarizes animal lesion models and observations in humans. It states that, according to database analyses, GHK changes the expression of thousands of human genes. The authors declare an affiliation with a company that sells GHK-Cu products.

Rat ACL reconstruction model: knee laxity, graft stiffness, maximum load, gait and histology

Fu SC, Cheuk YC, Chiu WY, et al.·Journal of Orthopaedic Research·2015·PMID 25731775 (opens PubMed in a new tab)Title on PubMed·DOI 10.1002/jor.22831 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Rat model of unilateral ACL reconstruction; randomization to saline or one of two GHK-Cu groups (24 animals per group)

Sample size

72

Exposure

GHK-Cu vs saline

Comparator

Saline

Knee laxity (side-to-side difference), stiffness of the graft complex, maximum load, gait parameters and histology were compared between the GHK-Cu and saline groups at 6 and 12 weeks. Differences in knee laxity and, in one GHK-Cu group, in graft stiffness were seen at 6 weeks but not at 12 weeks, and there were no differences in maximum load, gait parameters or histological scores; the authors described the effect as transient and not lasting after exposure ended. The direction of the 6-week differences is not summarized in this profile.

Human lung tissue gene-expression profiling, a Connectivity Map query and cultured lung fibroblasts exposed to GHK

“A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK”

Campbell JD, McDonough JE, Zeskind JE, et al.·Genome Medicine·2012·PMID 22937864 (opens PubMed in a new tab)·DOI 10.1186/gm367 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Gene-expression profiling of 64 lung tissue samples from 8 lungs of smokers with COPD; computational query of the Connectivity Map; in vitro exposure of lung fibroblasts from individuals with COPD and from former smokers without COPD to the GHK tripeptide (without copper)

Exposure

GHK tripeptide vs unexposed lung fibroblast cultures

Comparator

Unexposed fibroblasts; TGF-β as positive control

The authors identified 127 genes associated with regional emphysema severity. Using the Connectivity Map, GHK was identified as a compound predicted to reverse that gene signature and to induce patterns consistent with activation of the TGF-β pathway. In human fibroblasts, GHK reproduced TGF-β-induced expression patterns, organized the actin cytoskeleton, increased integrin β1 and restored the capacity of fibroblasts derived from COPD lungs to contract and remodel a three-dimensional gel in culture. The authors emphasized the need for further studies on the mechanism and on COPD progression.

Randomized human trial of finished products with and without GHK-Cu: blinded objective assessments and a self-rated questionnaire

Miller TR, Wagner JD, Baack BR, et al.·Archives of Facial Plastic Surgery·2006·PMID 16847171 (opens PubMed in a new tab)Title on PubMed·DOI 10.1001/archfaci.8.4.252 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Randomized trial of finished products with or without GHK-Cu, assessed at 12 weeks by computer-assisted analysis, blinded evaluators and a self-rated questionnaire

Sample size

13

Exposure

Finished products containing GHK-Cu

Comparator

Finished products without GHK-Cu

Thirteen participants completed the study. Computer-assisted analysis and blinded evaluators found no differences between the groups on the trial's objective measures at 12 weeks; only a self-rated questionnaire showed a difference between the groups (p = 0.04). The trial used finished products, not research material.

Dermal fibroblast cultures: MMP-2, TIMP-1 and TIMP-2 with GHK-Cu, copper ions and copper-free GHK

Life Sciences·2000·PMID 11045606 (opens PubMed in a new tab)Full record on PubMed·DOI 10.1016/s0024-3205(00)00803-1 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Dermal fibroblast cultures; measurement of MMP-2, TIMP-1 and TIMP-2 in conditioned media

Exposure

GHK-Cu vs copper ions alone vs copper-free GHK tripeptide

Comparator

Control cultures; copper-free GHK; copper ions alone

GHK-Cu increased MMP-2 levels and MMP-2 mRNA in cultured fibroblasts and increased the secretion of TIMP-1 and TIMP-2. The effect on MMP-2 was reproduced by copper ions but not by the copper-free GHK tripeptide, pointing to a substantial contribution of the metal to the observed activity.

Rat implanted-chamber model: composition of the tissue formed inside the chamber

Maquart FX, Bellon G, Chaqour B, et al.·Journal of Clinical Investigation·1993·PMID 8227353 (opens PubMed in a new tab)Title on PubMed·DOI 10.1172/JCI116842 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Experimental chamber model (steel mesh cylinders implanted in rats)

Exposure

GHK-Cu vs saline or a control tripeptide

Comparator

Saline; control tripeptide L-glutamyl-L-histidyl-L-proline

The tissue formed inside chambers exposed to GHK-Cu, saline or a control tripeptide was analyzed for dry weight, DNA, total protein, glycosaminoglycans (including the relative proportion of dermatan sulfate), type I and type III procollagen mRNA and TGF-β mRNA. The direction and size of these endpoints are not summarized in this profile.

Normal human fibroblast cultures: synthesis of sulfated glycosaminoglycans and hyaluronic acid

“Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+”

Wegrowski Y, Maquart FX, Borel JP·Life Sciences·1992·PMID 1522753 (opens PubMed in a new tab)·DOI 10.1016/0024-3205(92)90504-i (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Normal human fibroblast cultures; labeling with tritiated glucosamine and 35S-sulfate to quantify glycosaminoglycans

Exposure

GHK-Cu vs no-GHK-Cu culture

Comparator

Control cultures without GHK-Cu

GHK-Cu induced a biphasic, concentration-dependent increase in total glycosaminoglycan synthesis, with a maximum in the nanomolar range; at higher concentrations, synthesis returned to control levels. It preferentially increased the synthesis of extracellular dermatan sulfate and cell-layer-associated heparan sulfate, without affecting hyaluronic acid synthesis.

Randomized, evaluator-blinded human trial: a finished tripeptide-copper formulation, an active comparator and an inert vehicle

Bishop JB, Phillips LG, Mustoe TA, et al.·Journal of Vascular Surgery·1992·PMID 1495150 (opens PubMed in a new tab)Title on PubMed·DOI 10.1067/mva.1992.37086 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Prospective, randomized, evaluator-blinded trial of three finished formulations

Sample size

86

Exposure

Finished formulation containing a tripeptide-copper complex

Comparator

Active comparator formulation; inert vehicle (placebo)

Among 86 evaluable participants, the active comparator outperformed both the tripeptide-copper formulation and the inert vehicle on the trial's primary measure, and no advantage of the tripeptide-copper formulation over the vehicle was reported. The trial used a finished formulation, not research material.

Fibroblast cultures: protein synthesis and cell number across GHK-Cu concentrations

Maquart FX, Pickart L, Laurent M, et al.·FEBS Letters·1988·PMID 3169264 (opens PubMed in a new tab)Title on PubMed·DOI 10.1016/0014-5793(88)80509-x (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Fibroblast cultures exposed to a range of GHK-Cu concentrations; measurement of protein synthesis and cell number

Exposure

GHK-Cu vs no-GHK-Cu culture

Comparator

Control cultures without GHK-Cu

Protein synthesis by cultured fibroblasts was measured across a range of GHK-Cu concentrations, from picomolar to nanomolar, together with cell number, which did not change. The protein measured and the direction of the result are described in the original record. The authors noted that the Gly-His-Lys sequence occurs in the α2(I) chain of type I procollagen and proposed it as a possible physiological origin of the peptide.

Normal and neoplastic liver cells in culture: survival and growth with a tripeptide from human serum

Pickart L, Thaler MM·Nature New Biology·1973·PMID 4349963 (opens PubMed in a new tab)Title on PubMed

Filed under GHK-Cu

Model

Normal and neoplastic liver cells in culture exposed to a tripeptide from human serum; design details are not available in the indexed record

Exposure

Tripeptide from human serum

Discovery work for the GHK tripeptide. The authors described a tripeptide in human serum that prolonged the survival of normal liver cells in culture and increased the growth of neoplastic liver cells. PubMed has no abstract for this record, so the cell source, design and quantitative details could not be verified.