GHK-Cu Peptide

Research

GHK-Cu research studies database

Every indexed GHK-Cu record with model, route, what was measured, limitations and evidence grade. Search and filter by category, model or year.

By the GHK-Cu Peptide editorial team · Last reviewed · Editorial review: pending

Short answer

This database lists 81 verified GHK and GHK-Cu records: 3 randomised human trials (all topical) [Bishop 1992] [Mulder 1994] [Miller 2006], 7 other human studies, 10 animal studies, 21 cell and tissue studies, 24 chemistry and analytical studies, and 16 reviews. Each record states its model, route, test substance, what was measured, its limitations and its editorial review status.

GHK-Cu Scientific Evidence Explorer

Search and filter 81 PubMed-verified records. Filters are saved in the address bar, so a filtered view can be shared.

81 of 81 records

  • ChemistryEvidence grade DNo organism2026 · Eur J Pharm SciGHK without copper

    Glycyl-l-histidyl-l-lysine as a novel co-former in co-amorphous systems: Enhanced aqueous solubility and physical stability

    The study found that GHK fully amorphised three model compounds within 15 minutes of milling, whereas single amino-acid co-formers mostly left partly crystalline mixtures.

    Design, limitations and citation
    System
    Ball-milled co-amorphous mixtures
    Test substance
    GHK as co-former with three model compounds
    Route
    No organism
    Study design
    Solid-state characterisation (DSC, dissolution, stability)
    Sample size
    Not reported in the abstract
    Limitations
    GHK is used here as an excipient, not studied as an active substance.
    Citation
    Huang Q, Zou Z, Cheng D et al. (2026). Glycyl-l-histidyl-l-lysine as a novel co-former in co-amorphous systems: Enhanced aqueous solubility and physical stability. Eur J Pharm Sci. PubMed 41771428 · doi:10.1016/j.ejps.2026.107493
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2026 · Sports Med

    Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance

    The review covers regulatory status and safety data of peptides sold directly to the public, including GHK-Cu, and reports that rigorous human safety data for the unapproved peptides are scarce.

    Design, limitations and citation
    System
    Narrative review
    Test substance
    Approved and unapproved peptides, including GHK-Cu
    Route
    No organism
    Study design
    Narrative review (sports medicine)
    Sample size
    Not reported in the abstract
    Limitations
    Narrative review across many substances.
    Citation
    Mendias CL, Awan TM (2026). Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Sports Med. PubMed 41966639 · doi:10.1007/s40279-026-02437-0
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2026 · Curr Issues Mol BiolMulti-ingredient product

    Multi-Target Restoration of Dermal Elastic Fibers Through Elastin Upregulation, Elastase Suppression, and Scaffold Reinforcement

    The study measured elastin expression and secretion by dermal fibroblasts exposed to copper tripeptide-1, alongside two other ingredients tested for elastase and scaffold-gene effects.

    Design, limitations and citation
    System
    Dermal fibroblasts
    Test substance
    Copper tripeptide-1 within a three-ingredient combination
    Route
    Added to cell culture
    Study design
    Expression, secretion and enzyme assays
    Sample size
    Not reported in the abstract
    Limitations
    Cell culture; combination study.
    Citation
    Ye S, Kang S, Jeong ET et al. (2026). Multi-Target Restoration of Dermal Elastic Fibers Through Elastin Upregulation, Elastase Suppression, and Scaffold Reinforcement. Curr Issues Mol Biol. PubMed 42193036 · doi:10.3390/cimb48050431
    Editorial review
    pending
  • AnimalEvidence grade Cintraperitoneal and intranasal2026 · Res Sq

    Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs

    This preprint measured spatial-navigation escape latency and hippocampal gene expression and reported different, partly opposite, transcriptional programmes after intraperitoneal versus intranasal dosing.

    Design, limitations and citation
    System
    Aged C57BL/6J mice (20–21 months)
    Test substance
    GHK-Cu intraperitoneally for 5 days or intranasally for 8 weeks
    Route
    Intraperitoneal / intranasal (animal)
    Study design
    Behavioural task, immunohistochemistry and hippocampal RNA sequencing
    Sample size
    Not reported in the abstract
    Limitations
    Preprint, not peer reviewed; mice; the two routes also differed in duration.
    Citation
    Mazzola J, Rosenfeld M, Tucker M et al. (2026). Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs. Res Sq. PubMed 42245779 · doi:10.21203/rs.3.rs-9520102/v1
    Editorial review
    pending
  • ReviewEvidence grade Rtopical2026 · Aesthet Surg J

    The Regenerative Potential of GHK-Cu in Aesthetic Medicine

    The review included 18 preclinical studies and 2 randomised trials of GHK-Cu as a standalone aesthetic intervention and reported that findings were constrained by methodological variability and few clinical studies.

    Design, limitations and citation
    System
    Systematic review: 20 studies (18 preclinical, 2 RCTs)
    Test substance
    GHK-Cu as a standalone intervention
    Route
    Applied to skin
    Study design
    PRISMA systematic review
    Sample size
    Not reported in the abstract
    Limitations
    A published letter (Rahman and Webb, 2026) disputes how this review weighed mechanistic against clinical evidence.
    Citation
    Mokhtar J, Mohamad B, Haddad J et al. (2026). The Regenerative Potential of GHK-Cu in Aesthetic Medicine. Aesthet Surg J. PubMed 42619529 · doi:10.1093/asj/sjag169
    Editorial review
    pending
  • ReviewEvidence grade Rtopical2026 · Arch Intern Med Res

    A Systematic Review of the Mechanisms and Therapeutic Applications of GHK-Cu (Glycyl-L-Histidyl-L-Lysine-Copper Complex) in Topical Microneedle Delivery: A Case for Expanded Clinical Trials

    The review stratified 64 records by model and reports that microneedle-mediated GHK-Cu delivery has not been evaluated in a registered, adequately powered human randomised trial published in the peer-reviewed literature.

    Design, limitations and citation
    System
    Systematic review, 64 records retained
    Test substance
    GHK-Cu with microneedle delivery
    Route
    Applied to skin
    Study design
    PRISMA-mapped systematic review stratified by model
    Sample size
    Not reported in the abstract
    Limitations
    Review argues for more trials; abstract truncated in PubMed.
    Citation
    Najafi N, Maatouk H, Vardanyan KG et al. (2026). A Systematic Review of the Mechanisms and Therapeutic Applications of GHK-Cu (Glycyl-L-Histidyl-L-Lysine-Copper Complex) in Topical Microneedle Delivery: A Case for Expanded Clinical Trials. Arch Intern Med Res. PubMed 42787770 · doi:10.26502/aimr.0255
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2026 · Pharmaceutics

    GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap

    The review graded biological evidence and chemical/formulation quality separately and concluded that clinical evidence is sparse and does not meet contemporary active-entity quality standards; it notes that the 13-participant post-laser study was negative on objective measures.

    Design, limitations and citation
    System
    Structured evidence-mapping review to 12 Aug 2026
    Test substance
    GHK, GHK-Cu, GHK-derived and non-GHK copper peptides, kept separate
    Route
    No organism
    Study design
    Systematic evidence map with two-axis grading; no pooling
    Sample size
    Not reported in the abstract
    Limitations
    Author-defined grading framework.
    Citation
    Mateescu DM, Gavrilescu DM, Mincioaga RI et al. (2026). GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap. Pharmaceutics. PubMed 42797253 · doi:10.3390/pharmaceutics18091077
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2026 · J Chromatogr A

    Characterization of copper tripeptide-loaded lipid carriers and their stability in complex cosmetic matrices

    The study measured the stability of liposome-encapsulated GHK-Cu after incorporation into model emulsion and serum formulations.

    Design, limitations and citation
    System
    Oil-in-water emulsion and serum cosmetic matrices
    Test substance
    Liposome-encapsulated GHK-Cu
    Route
    No organism
    Study design
    Electromigration separation coupled to ICP-MS; stability study
    Sample size
    Not reported in the abstract
    Limitations
    Model formulations; abstract truncated in PubMed.
    Citation
    Ogórek K, Mierzwa M, Drozd M et al. (2026). Characterization of copper tripeptide-loaded lipid carriers and their stability in complex cosmetic matrices. J Chromatogr A. PubMed 42887096 · doi:10.1016/j.chroma.2026.467540
    Editorial review
    pending
  • ReviewEvidence grade Rtopical2026 · Life (Basel)

    Peptides in Aesthetic Dermatology: Classification, Fibroblast-Centered Mechanisms, Delivery Technologies, and Clinical Evidence

    The review states that many controlled peptide studies are limited by small samples, short follow-up, industry sponsorship or multi-ingredient formulations, and that evidence supports product-specific interpretation rather than interchangeability across peptide classes or administration routes.

    Design, limitations and citation
    System
    Critical narrative review
    Test substance
    Peptides used in aesthetic dermatology, by class
    Route
    Applied to skin
    Study design
    Narrative review
    Sample size
    Not reported in the abstract
    Limitations
    Covers many peptide classes, not only copper peptides.
    Citation
    Yi KH, Kim HS, Lee HE et al. (2026). Peptides in Aesthetic Dermatology: Classification, Fibroblast-Centered Mechanisms, Delivery Technologies, and Clinical Evidence. Life (Basel). PubMed 42942246 · doi:10.3390/life16101660
    Editorial review
    pending
  • ReviewEvidence grade Rtopical2026 · J Drugs DermatolMulti-ingredient product

    Peptides for Hair Growth and Treatment of Hair Loss and Alopecia: A Systematic Review

    The review included 14 human studies of peptide-containing hair formulations and assigned recommendation grades by formulation; GHK appears only as one component of combinations.

    Design, limitations and citation
    System
    Systematic review of human clinical studies (14 included)
    Test substance
    Peptide-containing hair formulations
    Route
    Applied to skin
    Study design
    PRISMA systematic review
    Sample size
    Not reported in the abstract
    Limitations
    Included formulations are mostly combinations; grading is by formulation, not by ingredient.
    Citation
    Joerg L, Zafar K, Jagdeo J (2026). Peptides for Hair Growth and Treatment of Hair Loss and Alopecia: A Systematic Review. J Drugs Dermatol. PubMed 42976838 · doi:10.36849/JDD.9736
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2026 · Aesthet Surg J

    Mechanistic Plausibility Should not be Conflated With Clinical Validation of Glycyl-L-Histidyl-L-Lysine-Copper

    A 2026 letter whose title states its position: mechanistic plausibility of GHK-Cu should not be conflated with clinical validation.

    Design, limitations and citation
    System
    Letter
    Test substance
    GHK-Cu
    Route
    No organism
    Study design
    Commentary
    Sample size
    Not reported in the abstract
    Limitations
    No abstract indexed; summarised from the title only.
    Citation
    Rahman E, Webb WR (2026). Mechanistic Plausibility Should not be Conflated With Clinical Validation of Glycyl-L-Histidyl-L-Lysine-Copper. Aesthet Surg J. PubMed 42981269 · doi:10.1093/asj/sjag227
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2026 · Aesthet Surg J

    Response to: Mechanistic Plausibility Should Not Be Conflated With Clinical Validation of GHK-Cu

    The review authors’ published response to the 2026 letter on mechanistic plausibility versus clinical validation.

    Design, limitations and citation
    System
    Author response
    Test substance
    GHK-Cu
    Route
    No organism
    Study design
    Commentary
    Sample size
    Not reported in the abstract
    Limitations
    No abstract indexed; summarised from the title only.
    Citation
    Mokhtar J, Lellouch AG (2026). Response to: Mechanistic Plausibility Should Not Be Conflated With Clinical Validation of GHK-Cu. Aesthet Surg J. PubMed 43006658 · doi:10.1093/asj/sjag248
    Editorial review
    pending
  • ReviewEvidence grade Rtopical2025 · Molecules

    Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?

    The review summarises methods for measuring skin permeation of free and liposome-encapsulated GHK-Cu and notes that transport of GHK-Cu liposomes has received little study.

    Design, limitations and citation
    System
    Literature review
    Test substance
    Free and liposomal GHK-Cu
    Route
    Applied to skin
    Study design
    Methods review
    Sample size
    Not reported in the abstract
    Limitations
    Narrative review.
    Citation
    Ogórek K, Nowak K, Wadych E et al. (2025). Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?. Molecules. PubMed 39795193 · doi:10.3390/molecules30010136
    Editorial review
    pending
  • ReviewEvidence grade Rtopical2025 · Bioimpacts

    Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective

    The review concludes that published information on skin permeability, effectiveness and physicochemical properties is insufficient and notes a "surprising absence" of clinical studies of GHK-Cu and palmitoyl-GHK.

    Design, limitations and citation
    System
    Literature review
    Test substance
    GHK, GHK-Cu, palmitoyl-GHK
    Route
    Applied to skin
    Study design
    Narrative review of topical use and permeation
    Sample size
    Not reported in the abstract
    Limitations
    Narrative review.
    Citation
    Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR (2025). Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective. Bioimpacts. PubMed 39963574 · doi:10.34172/bi.30071
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2025 · J Phys Chem B

    Intramolecular Charge Transfer-Induced Fluorescent Probe for the Sensitive Detection of Copper Tripeptide

    The study designed donor–acceptor fluorescent probes selective for Cu(II) over competing metal ions and applied them to detecting copper tripeptide.

    Design, limitations and citation
    System
    Solution
    Test substance
    Imidazopyridine fluorescent probes
    Route
    No organism
    Study design
    Probe synthesis, DFT and selectivity testing
    Sample size
    Not reported in the abstract
    Limitations
    Sensor chemistry; not a validated quality-control assay.
    Citation
    Dkhar B, Narayanan M, Venkatakrishnan P et al. (2025). Intramolecular Charge Transfer-Induced Fluorescent Probe for the Sensitive Detection of Copper Tripeptide. J Phys Chem B. PubMed 40359517 · doi:10.1021/acs.jpcb.5c01431
    Editorial review
    pending
  • HumanEvidence grade Btopical2025 · CureusMulti-ingredient product

    Efficacy and Safety Assessment of ThriveCo Scar Fader Gel With Scarcede™ in the Treatment of Skin Scars

    The study assessed visible scar change on the Manchester Scar Scale by a dermatologist with a multi-ingredient gel.

    Design, limitations and citation
    System
    Women with acne scars
    Test substance
    Gel with copper tripeptide-1 among four actives
    Route
    Applied to skin
    Study design
    Open-label prospective study
    Sample size
    Not reported in the abstract
    Limitations
    No control group; four actives in one gel, so no attribution to the copper peptide.
    Citation
    Patel MN, Patel N, Merja A et al. (2025). Efficacy and Safety Assessment of ThriveCo Scar Fader Gel With Scarcede™ in the Treatment of Skin Scars. Cureus. PubMed 41001334 · doi:10.7759/cureus.90934
    Editorial review
    pending
  • HumanEvidence grade Btopical2024 · CureusMulti-ingredient product

    An Assessment of the Safety, Efficacy, and Tolerability of a Novel Scalp Treatment Regimen Combining a Hydroxy Acid-Based Scrub and Copper Tripeptide Serum in the Management of Seborrheic Dermatitis in Adults

    The study measured adherent scalp flaking, scalp hydration, hair density and hair thickness over 15 days of a two-product regimen.

    Design, limitations and citation
    System
    Adults with mild-to-moderate scalp flaking
    Test substance
    Scalp scrub plus a serum with copper tripeptide-1 among five actives
    Route
    Applied to skin
    Study design
    Open-label single-centre study over 15 days
    Sample size
    Not reported in the abstract
    Limitations
    No control group; 15 days; two products and several actives, so no attribution to the copper peptide.
    Citation
    Patel MN, Patel N, Merja A et al. (2024). An Assessment of the Safety, Efficacy, and Tolerability of a Novel Scalp Treatment Regimen Combining a Hydroxy Acid-Based Scrub and Copper Tripeptide Serum in the Management of Seborrheic Dermatitis in Adults. Cureus. PubMed 39449909 · doi:10.7759/cureus.70108
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2024 · Electrophoresis

    Novel Applications of CE-ICP-MS/MS: Monitoring of Antiaging GHK-Cu Cosmetic Component Encapsulation in Liposomes

    The study used CE-ICP-MS/MS copper and phosphorus signals to confirm liposome formation and to measure the amount of GHK-Cu encapsulated.

    Design, limitations and citation
    System
    Liposome preparations
    Test substance
    GHK-Cu
    Route
    No organism
    Study design
    Capillary electrophoresis coupled to ICP-MS/MS
    Sample size
    Not reported in the abstract
    Limitations
    Method demonstration in model liposomes.
    Citation
    Zajda J, Wadych E, Ogórek K et al. (2024). Novel Applications of CE-ICP-MS/MS: Monitoring of Antiaging GHK-Cu Cosmetic Component Encapsulation in Liposomes. Electrophoresis. PubMed 39451062 · doi:10.1002/elps.202400047
    Editorial review
    pending
  • Ex vivoEvidence grade DCell culture2023 · J Cosmet DermatolMulti-ingredient product

    Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests

    The study measured collagen I, IV and VII expression across GHK-Cu and hyaluronic acid ratios and reported collagen IV increases of 25.4-fold in cells and 2.03-fold in ex vivo skin at a 1:9 ratio.

    Design, limitations and citation
    System
    Human dermal fibroblasts; ex vivo skin
    Test substance
    GHK-Cu with low-molecular-weight hyaluronic acid
    Route
    Added to cell culture
    Study design
    qRT-PCR screen of ratios then immunofluorescence in ex vivo skin
    Sample size
    Not reported in the abstract
    Limitations
    Combination with hyaluronic acid; mRNA in cells and staining in excised skin.
    Citation
    Jiang F, Wu Y, Liu Z et al. (2023). Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests. J Cosmet Dermatol. PubMed 37062921 · doi:10.1111/jocd.15763
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2023 · J Org Chem

    Phenothiazine-Based Cu(II)-Selective Fluorescent Sensor: GHK-Cu Sensing Applications

    The study reported a phenothiazine fluorescent sensor selective for Cu(II) over other transition-metal salts and applied it to GHK-Cu sensing.

    Design, limitations and citation
    System
    Methanol solution
    Test substance
    Phenothiazine-based Cu(II) sensor
    Route
    No organism
    Study design
    Fluorescent sensor development
    Sample size
    Not reported in the abstract
    Limitations
    Sensor chemistry; not a validated quality-control assay.
    Citation
    Sahu R, Yadav S, Gunturu KC et al. (2023). Phenothiazine-Based Cu(II)-Selective Fluorescent Sensor: GHK-Cu Sensing Applications. J Org Chem. PubMed 37830186 · doi:10.1021/acs.joc.3c01600
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2023 · Pharmaceutics

    Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application

    The study prepared anionic and cationic liposomes of about 100 nm and measured GHK-Cu encapsulation efficiencies of 31.7 ± 0.9% (cationic) and 20.0 ± 2.8% (anionic) for the selected formulations.

    Design, limitations and citation
    System
    Hydrogenated-lecithin liposomes
    Test substance
    GHK-Cu
    Route
    No organism
    Study design
    Formulation study: size, bilayer fluidity, encapsulation efficiency; enzyme assays
    Sample size
    Not reported in the abstract
    Limitations
    Formulation characterisation; enzyme-inhibition assays are cell-free.
    Citation
    Dymek M, Olechowska K, Hąc-Wydro K et al. (2023). Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application. Pharmaceutics. PubMed 37896245 · doi:10.3390/pharmaceutics15102485
    Editorial review
    pending
  • Ex vivoEvidence grade Dtopical2022 · Pharmaceutics

    Cutaneous Delivery of Cosmeceutical Peptides Enhanced by Picosecond- and Nanosecond-Domain Nd:YAG Lasers with Quick Recovery of the Skin Barrier Function: Comparison with Microsecond-Domain Ablative Lasers

    The study found that all tested laser modalities increased skin permeation of the peptides in vitro, with non-ablative lasers disrupting the stratum corneum ultrastructure.

    Design, limitations and citation
    System
    Pig and mouse skin in Franz diffusion cells
    Test substance
    Copper tripeptide-1 and two palmitoyl peptides after laser pre-treatment
    Route
    Applied to skin
    Study design
    Permeation comparison across laser types
    Sample size
    Not reported in the abstract
    Limitations
    Animal skin; delivery outcome only.
    Citation
    Lee WR, Hsiao CY, Chang ZY et al. (2022). Cutaneous Delivery of Cosmeceutical Peptides Enhanced by Picosecond- and Nanosecond-Domain Nd:YAG Lasers with Quick Recovery of the Skin Barrier Function: Comparison with Microsecond-Domain Ablative Lasers. Pharmaceutics. PubMed 35214181 · doi:10.3390/pharmaceutics14020450
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2021 · Inorg Chem

    Ternary Cu2+ Complexes of Human Serum Albumin and Glycyl-l-histidyl-l-lysine

    The study identified two ternary Cu(GHK)–albumin complexes formed through albumin histidine imidazoles, with His3 as one site (conditional constant 2,900 M⁻¹ at pH 7.4).

    Design, limitations and citation
    System
    Aqueous solution with human serum albumin
    Test substance
    Cu(II)–GHK with HSA
    Route
    No organism
    Study design
    Spectroscopic binding studies
    Sample size
    Not reported in the abstract
    Limitations
    The second site is assigned only as likely His128 or His510.
    Citation
    Bossak-Ahmad K, Bal W, Frączyk T et al. (2021). Ternary Cu2+ Complexes of Human Serum Albumin and Glycyl-l-histidyl-l-lysine. Inorg Chem. PubMed 34730942 · doi:10.1021/acs.inorgchem.1c03084
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2021 · Inorg Chem

    Intermediate Cu(II)-Thiolate Species in the Reduction of Cu(II)GHK by Glutathione: A Handy Chelate for Biological Cu(II) Reduction

    The study characterised a transient glutathione–Cu(II)–GHK intermediate in the reduction of Cu(II)–GHK by glutathione and measured how temperature, oxygen and ternary ligands changed the reduction rate.

    Design, limitations and citation
    System
    Aqueous solution
    Test substance
    Cu(II)–GHK with reduced glutathione
    Route
    No organism
    Study design
    UV-Vis, CD, EPR, NMR and cyclic voltammetry
    Sample size
    Not reported in the abstract
    Limitations
    Chemical reaction study; the biological role proposed by the authors is a hypothesis.
    Citation
    Ufnalska I, Drew SC, Zhukov I et al. (2021). Intermediate Cu(II)-Thiolate Species in the Reduction of Cu(II)GHK by Glutathione: A Handy Chelate for Biological Cu(II) Reduction. Inorg Chem. PubMed 34781677 · doi:10.1021/acs.inorgchem.1c02669
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2020 · J Pept SciDerivative or conjugate

    Effect of oligoarginine conjugation on the antiwrinkle activity and transdermal delivery of GHK peptide

    The study compared GHK with a tetra-arginine conjugate and found faster cellular penetration and higher in vitro collagen biosynthesis with the conjugate.

    Design, limitations and citation
    System
    Cell cultures and skin delivery models
    Test substance
    GHK and an oligoarginine conjugate (GHK-R4)
    Route
    Added to cell culture
    Study design
    Comparative delivery and collagen assays
    Sample size
    Not reported in the abstract
    Limitations
    Conjugate differs from GHK-Cu; the authors attribute part of the effect to the arginine tail itself.
    Citation
    Hur GH, Han SC, Ryu AR et al. (2020). Effect of oligoarginine conjugation on the antiwrinkle activity and transdermal delivery of GHK peptide. J Pept Sci. PubMed 31788907 · doi:10.1002/psc.3234
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2020 · Int J Mol Sci

    Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

    The study found that cis-urocanic acid also coordinates Cu(II) and that GHK, Cu(II) and cis-urocanic acid form a ternary complex.

    Design, limitations and citation
    System
    Aqueous solution
    Test substance
    Cu(II) with GHK and cis-urocanic acid
    Route
    No organism
    Study design
    Binding studies of binary and ternary complexes
    Sample size
    Not reported in the abstract
    Limitations
    The physiological relevance is inferred from published tissue concentrations, not measured in tissue.
    Citation
    Bossak-Ahmad K, Wiśniewska MD, Bal W et al. (2020). Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate. Int J Mol Sci. PubMed 32867146 · doi:10.3390/ijms21176190
    Editorial review
    pending
  • AnimalEvidence grade Cintradermal2020 · Plast Reconstr Surg Glob OpenMulti-ingredient product

    QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study

    The study measured cytotoxicity of each ingredient in keratinocyte and fibroblast assays and hair growth after intradermal injection of the full formulation in animals.

    Design, limitations and citation
    System
    Human keratinocyte and fibroblast assays; animal hair-growth model
    Test substance
    Multi-ingredient formulation including copper tripeptide-1 (or biomimetic peptides)
    Route
    Injected into skin
    Study design
    MTT cytotoxicity and intradermal animal study
    Sample size
    Not reported in the abstract
    Limitations
    Multi-ingredient; authors connected to the formulation; abstract truncated in PubMed.
    Citation
    Kapoor R, Shome D, Vadera S et al. (2020). QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study. Plast Reconstr Surg Glob Open. PubMed 32983753 · doi:10.1097/GOX.0000000000002843
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2020 · Aging Pathobiol Ther

    The potential of GHK as an anti-aging peptide

    Narrative review from a university comparative-medicine group; it cites serum GHK averaging 200 ng/mL at age 20 and 80 ng/mL by age 60.

    Design, limitations and citation
    System
    Literature review
    Test substance
    GHK and GHK-Cu
    Route
    No organism
    Study design
    Narrative review
    Sample size
    Not reported in the abstract
    Limitations
    Narrative review; the serum figures are cited from earlier work, not newly measured.
    Citation
    Dou Y, Lee A, Zhu L et al. (2020). The potential of GHK as an anti-aging peptide. Aging Pathobiol Ther. PubMed 35083444 · doi:10.31491/apt.2020.03.014
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2018 · Chemistry

    N-Terminal Cu-Binding Motifs (Xxx-Zzz-His, Xxx-His) and Their Derivatives: Chemistry, Biology and Medicinal Applications

    The review summarises the coordination chemistry of peptides whose N-terminal sequence binds Cu(II) with high affinity, a class that includes GHK and the albumin N-terminus.

    Design, limitations and citation
    System
    Literature review
    Test substance
    N-terminal Xxx-His and Xxx-Zzz-His copper-binding motifs
    Route
    No organism
    Study design
    Narrative review
    Sample size
    Not reported in the abstract
    Limitations
    Narrative review; GHK is one example among many motifs.
    Citation
    Gonzalez P, Bossak K, Stefaniak E et al. (2018). N-Terminal Cu-Binding Motifs (Xxx-Zzz-His, Xxx-His) and Their Derivatives: Chemistry, Biology and Medicinal Applications. Chemistry. PubMed 29336493 · doi:10.1002/chem.201705398
    Editorial review
    pending
  • HumanEvidence grade Bintradermal2018 · J Cosmet Laser TherMulti-ingredient product

    Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth - safety and efficacy evaluation in a first-in-man pilot clinical study

    The study assessed hair regrowth and adverse events after repeated intradermal scalp injections of a multi-ingredient formulation.

    Design, limitations and citation
    System
    Adults with hair loss
    Test substance
    Injectable formulation of several growth factors, thymosin β4 and copper tripeptide-1
    Route
    Injected into skin
    Study design
    Open-label single-arm pilot study
    Sample size
    1000
    Limitations
    No control group; at least six actives, so no effect or safety finding can be attributed to copper tripeptide-1.
    Citation
    Kapoor R, Shome D (2018). Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth - safety and efficacy evaluation in a first-in-man pilot clinical study. J Cosmet Laser Ther. PubMed 29482481 · doi:10.1080/14764172.2018.1439965
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2018 · Inorg Chem

    Measurement of Interpeptidic Cu(II) Exchange Rate Constants by Static Fluorescence Quenching of Tryptophan

    The study measured second-order rate constants for Cu(II) transfer from a tryptophan analogue complex to GHK of 1.6 × 10² M⁻¹ s⁻¹ and to DAHK of 5.0 × 10¹ M⁻¹ s⁻¹.

    Design, limitations and citation
    System
    Aqueous solution
    Test substance
    Cu(II) exchange between GHW and GHK or DAHK
    Route
    No organism
    Study design
    Static fluorescence quenching kinetics
    Sample size
    Not reported in the abstract
    Limitations
    Model exchange reaction using a substituted peptide as the copper donor.
    Citation
    Beuning CN, Mestre-Voegtlé B, Faller P et al. (2018). Measurement of Interpeptidic Cu(II) Exchange Rate Constants by Static Fluorescence Quenching of Tryptophan. Inorg Chem. PubMed 29648796 · doi:10.1021/acs.inorgchem.8b00182
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2018 · Int J Mol Sci

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

    Narrative review interpreting published gene-expression (connectivity map) data on GHK. Both authors list R&D Skin Biology as their affiliation and declare no conflict of interest.

    Design, limitations and citation
    System
    Literature review
    Test substance
    GHK and GHK-Cu
    Route
    No organism
    Study design
    Narrative review with gene-expression data mining
    Sample size
    Not reported in the abstract
    Limitations
    Gene-expression associations from cell-line databases are not outcome measurements; commercial affiliation.
    Citation
    Pickart L, Margolina A (2018). Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. PubMed 29986520 · doi:10.3390/ijms19071987
    Editorial review
    pending
  • HumanEvidence grade Bintradermal2018 · J Clin Aesthet DermatolMulti-ingredient product

    Androgenetic Alopecia Treatment in Asian Men

    The series assessed pre- and post-treatment photographs of men given a combination regimen in which copper tripeptide was one of many ingredients of one component.

    Design, limitations and citation
    System
    Men treated in one clinic, 2011–2017
    Test substance
    Combination regimen including oral and topical drugs plus an injected multi-ingredient solution containing copper tripeptide
    Route
    Injected into skin
    Study design
    Retrospective clinic series with photographs
    Sample size
    18,918 treated
    Limitations
    Uncontrolled; approved drugs in the same regimen; the copper peptide contribution cannot be separated.
    Citation
    Tanaka Y, Aso T, Ono J et al. (2018). Androgenetic Alopecia Treatment in Asian Men. J Clin Aesthet Dermatol. PubMed 30057663
    Editorial review
    pending
  • AnimalEvidence grade Ctopical2017 · Wound Repair Regen

    GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis

    The study measured a 33.1% higher endothelial-cell proliferation rate with GHK-Cu liposomes and compared CD31 and Ki67 staining and healing time in mice treated with liposomal versus free GHK-Cu.

    Design, limitations and citation
    System
    HUVEC cultures; mouse scald model
    Test substance
    GHK-Cu liposomes vs free GHK-Cu
    Route
    Applied to skin
    Study design
    Cell proliferation, Western blot; mouse comparison
    Sample size
    Not reported in the abstract
    Limitations
    Mice; liposomal formulation; abstract truncated in PubMed.
    Citation
    Wang X, Liu B, Xu Q et al. (2017). GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis. Wound Repair Regen. PubMed 28370978 · doi:10.1111/wrr.12520
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2016 · Pharm Dev Technol

    Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery

    The study measured hydrolytic degradation under basic and oxidative stress (less under acid), stability in water and pH 4.5–7.4 buffers for at least two weeks at 60 °C, and three degradation products by HPLC-MS, one being histidine.

    Design, limitations and citation
    System
    Aqueous buffers, octanol–PBS, stress conditions
    Test substance
    GHK-Cu
    Route
    No organism
    Study design
    Preformulation: solubility, log D, forced degradation, stability-indicating RP-HPLC with MS
    Sample size
    Not reported in the abstract
    Limitations
    Preformulation data for one material source; no product or shelf-life study.
    Citation
    Badenhorst T, Svirskis D, Wu Z (2016). Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery. Pharm Dev Technol. PubMed 25384620 · doi:10.3109/10837450.2014.979944
    Editorial review
    pending
  • HumanEvidence grade Btopical2016 · J Cosmet Laser TherMulti-ingredient product

    Significant improvement in crow's feet after treatment with Jet-M and a mixed solution of copper-GHK, oligo-hyaluronic acid, rhodiolar extract, tranexamic acid, and β-glucan (GHR formulation)

    The case report described photographs and biopsy staining (collagen, fibrillin-1, procollagen type 1) from treated and untreated areas in one person.

    Design, limitations and citation
    System
    One adult, periocular skin
    Test substance
    Multi-ingredient solution with copper-GHK applied with a microdroplet device
    Route
    Applied to skin
    Study design
    Single case report with biopsies
    Sample size
    1
    Limitations
    One person; five active ingredients plus a device; cannot attribute any finding to GHK-Cu.
    Citation
    Byun SY, Chae JB, Na JI et al. (2016). Significant improvement in crow's feet after treatment with Jet-M and a mixed solution of copper-GHK, oligo-hyaluronic acid, rhodiolar extract, tranexamic acid, and β-glucan (GHR formulation). J Cosmet Laser Ther. PubMed 27064823 · doi:10.3109/14764172.2016.1157367
    Editorial review
    pending
  • HumanEvidence grade Btopical2016 · Ann DermatolDerivative or conjugate

    Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth

    The study measured hair count, length and thickness at 1, 3 and 6 months; hair-count change differed from placebo in the lower-strength group, while length and thickness did not differ between groups.

    Design, limitations and citation
    System
    Men with pattern hair loss
    Test substance
    5-aminolevulinic acid–GHK complex at two strengths vs placebo
    Route
    Applied to skin
    Study design
    Placebo-controlled three-arm study over six months (randomisation not described in the abstract)
    Sample size
    45
    Limitations
    Copper-free GHK complexed with 5-ALA, so it is not a GHK-Cu study; small groups; single centre.
    Citation
    Lee WJ, Sim HB, Jang YH et al. (2016). Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth. Ann Dermatol. PubMed 27489425 · doi:10.5021/ad.2016.28.4.438
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2016 · Sci Rep

    Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

    The study compared irritation potential at the same concentrations and found GHK-Cu not cytotoxic and without significant change in the irritation markers measured, while the copper salts differed.

    Design, limitations and citation
    System
    Human keratinocyte model
    Test substance
    GHK-Cu vs copper chloride vs copper acetate
    Route
    Added to cell culture
    Study design
    Cytotoxicity (MTT, LDH) and irritation biomarkers by PCR and protein assays
    Sample size
    Not reported in the abstract
    Limitations
    Keratinocyte culture model; not a human patch test; tested concentrations are those of the paper.
    Citation
    Li H, Toh PZ, Tan JY et al. (2016). Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds. Sci Rep. PubMed 27892491 · doi:10.1038/srep37664
    Editorial review
    pending
  • Ex vivoEvidence grade Dtopical2015 · Pharm Res

    Microneedle-Mediated Delivery of Copper Peptide Through Skin

    The study found that microneedle depth depended on application force and measured 134 ± 12 nmol of peptide and 705 ± 84 nmol of copper permeating through microneedle-treated skin in 9 hours.

    Design, limitations and citation
    System
    Two in vitro skin models; cell and pig models for safety
    Test substance
    GHK-Cu after polymeric microneedle pre-treatment
    Route
    Applied to skin
    Study design
    Permeation, histology and confocal microscopy
    Sample size
    Not reported in the abstract
    Limitations
    Delivery study; does not measure any skin outcome in people.
    Citation
    Li H, Low YS, Chong HP et al. (2015). Microneedle-Mediated Delivery of Copper Peptide Through Skin. Pharm Res. PubMed 25690343 · doi:10.1007/s11095-015-1652-z
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2015 · Biomed Res Int

    GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration

    Narrative review of skin-related GHK literature, including gene-expression analyses. All three authors list Skin Biology (Research & Development Department) as their affiliation.

    Design, limitations and citation
    System
    Literature review
    Test substance
    GHK and GHK-Cu
    Route
    No organism
    Study design
    Narrative review
    Sample size
    Not reported in the abstract
    Limitations
    Not systematic; commercial affiliation; several statements are not tied to controlled human data.
    Citation
    Pickart L, Vasquez-Soltero JM, Margolina A (2015). GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. PubMed 26236730 · doi:10.1155/2015/648108
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2014 · Curr Med ChemDerivative or conjugate

    Developments in the synthesis and biological activity of glycyl-L-histydyl- L-lysine derivatives

    The review summarises solution-phase and solid-phase synthesis of Gly-His-Lys, protecting-group strategies and structural modifications of the tripeptide.

    Design, limitations and citation
    System
    Literature review
    Test substance
    GHK and synthetic derivatives
    Route
    No organism
    Study design
    Narrative review of synthesis
    Sample size
    Not reported in the abstract
    Limitations
    Narrative review.
    Citation
    Kukowska M, Dzierzbicka K (2014). Developments in the synthesis and biological activity of glycyl-L-histydyl- L-lysine derivatives. Curr Med Chem. PubMed 24350846 · doi:10.2174/0929867321666131218095056
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2014 · Acta Pol Pharm

    Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts

    The study measured IGF-2-dependent TGF-β1 secretion by dermal fibroblasts exposed to 1 nM GHK, GHK-Cu or copper chloride.

    Design, limitations and citation
    System
    Normal human dermal fibroblasts
    Test substance
    GHK, GHK-Cu and CuCl₂ at 1 nM
    Route
    Added to cell culture
    Study design
    ELISA of IGF-2-dependent TGF-β1 secretion
    Sample size
    Not reported in the abstract
    Limitations
    Abstract truncated in PubMed; single cell type.
    Citation
    Gruchlik A, Chodurek E, Dzierzewicz Z (2014). Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts. Acta Pol Pharm. PubMed 25745767
    Editorial review
    pending
  • AnimalEvidence grade Ctopical2013 · Otolaryngol Head Neck Surg

    Effects of topical copper tripeptide complex on wound healing in an irradiated rat model

    The study measured ischaemic flap area, caveolin-1 and VEGF staining; mean ischaemic area was 5.0 cm² with GHK-Cu gel and 3.8 cm² with the control ointment.

    Design, limitations and citation
    System
    Irradiated rat dorsal skin flaps
    Test substance
    GHK-Cu gel vs aquaphilic ointment, twice daily for 10 days
    Route
    Applied to skin
    Study design
    Controlled animal study with digital image and immunohistochemistry analysis
    Sample size
    23 (13 test, 10 control)
    Limitations
    Rats; the measured ischaemic area was larger in the GHK-Cu group.
    Citation
    Parker NP, Ardeshirpour F, Schmechel SC et al. (2013). Effects of topical copper tripeptide complex on wound healing in an irradiated rat model. Otolaryngol Head Neck Surg. PubMed 23744835 · doi:10.1177/0194599813492644
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2012 · J Biol Inorg Chem

    Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine

    The study measured predominantly 1:1 binding and a conditional dissociation constant at pH 7.4 of 7.0 × 10⁻¹⁴ M for GHK (2.6 × 10⁻¹⁴ M for DAHK), with the enthalpic and entropic contributions.

    Design, limitations and citation
    System
    Aqueous buffer, pH 7.4
    Test substance
    Cu(II) with GHK and DAHK
    Route
    No organism
    Study design
    Isothermal titration calorimetry with glycine competitor
    Sample size
    Not reported in the abstract
    Limitations
    Conditional constant: valid for the stated pH and with competitor and buffer contributions removed.
    Citation
    Trapaidze A, Hureau C, Bal W et al. (2012). Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine. J Biol Inorg Chem. PubMed 21898044 · doi:10.1007/s00775-011-0824-5
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2012 · J Pept SciGHK without copper

    Stem cell recovering effect of copper-free GHK in skin

    The study measured keratinocyte proliferation and staining for integrins α6 and β1, p63 and PCNA in skin equivalents cultured with copper-free GHK.

    Design, limitations and citation
    System
    Normal human keratinocytes; skin-equivalent models
    Test substance
    Copper-free GHK
    Route
    Added to cell culture
    Study design
    Cell proliferation and immunostaining
    Sample size
    Not reported in the abstract
    Limitations
    Cultured cells and engineered tissue.
    Citation
    Choi HR, Kang YA, Ryoo SJ et al. (2012). Stem cell recovering effect of copper-free GHK in skin. J Pept Sci. PubMed 23019153 · doi:10.1002/psc.2455
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2012 · Acta Pol Pharm

    Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts

    The study measured TNF-α-dependent IL-6 secretion and reported decreases with GHK, GGH, copper chloride and their copper complexes.

    Design, limitations and citation
    System
    Normal human dermal fibroblasts (NHDF)
    Test substance
    GHK, GGH, their copper complexes, CuCl₂
    Route
    Added to cell culture
    Study design
    ELISA of TNF-α-stimulated IL-6 secretion
    Sample size
    Not reported in the abstract
    Limitations
    Single cell type; copper chloride alone also changed the readout.
    Citation
    Gruchlik A, Jurzak M, Chodurek E et al. (2012). Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts. Acta Pol Pharm. PubMed 23285694
    Editorial review
    pending
  • Ex vivoEvidence grade Dtopical2011 · Inflamm Res

    Human skin penetration of a copper tripeptide in vitro as a function of skin layer

    The study reported the same permeability coefficient (2.43 ± 0.51 × 10⁻⁴ cm/h) and 136.2 µg/cm² copper permeated, with 97 µg/cm² retained in dermatomed skin.

    Design, limitations and citation
    System
    Human skin layers in flow-through diffusion cells
    Test substance
    GHK cuprate diacetate, 0.68% aqueous copper
    Route
    Applied to skin
    Study design
    Permeation and retention by ICP-MS over 48 h
    Sample size
    Not reported in the abstract
    Limitations
    Near-duplicate of the 2010 report by the same group with a different retained-copper figure; measures copper, not intact peptide.
    Citation
    Hostynek JJ, Dreher F, Maibach HI (2011). Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res. PubMed 20721598 · doi:10.1007/s00011-010-0238-9
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2011 · Chemistry

    X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties

    The study reported a dimeric Cu(II)–GHK structure in the solid state and a monomer in solution with three nitrogen ligands (glycine amine, deprotonated amide and histidine imidazole) and a labile oxygen in the fourth equatorial position.

    Design, limitations and citation
    System
    Single crystals and aqueous solution
    Test substance
    Cu(II)–GHK and Cu(II)–DAHK
    Route
    No organism
    Study design
    X-ray crystallography, EPR, HYSCORE, X-ray absorption, NMR, electrochemistry
    Sample size
    Not reported in the abstract
    Limitations
    No openly licensed copy of the coordinates was found (Crystallography Open Database searched 2026-11-11), so this site does not render them.
    Citation
    Hureau C, Eury H, Guillot R et al. (2011). X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties. Chemistry. PubMed 21780203 · doi:10.1002/chem.201100751
    Editorial review
    pending
  • Ex vivoEvidence grade Dtopical2010 · Inflamm Res

    Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy

    The study measured a permeability coefficient through dermatomed skin of 2.43 ± 0.51 × 10⁻⁴ cm/h, with 136.2 µg/cm² copper permeated over 48 h and 82 µg/cm² retained.

    Design, limitations and citation
    System
    Human skin layers in flow-through diffusion cells
    Test substance
    GHK cuprate diacetate, 0.68% aqueous copper
    Route
    Applied to skin
    Study design
    Permeation and retention by ICP-MS over 48 h
    Sample size
    Not reported in the abstract
    Limitations
    Measures copper, not intact peptide; infinite-dose conditions; excised skin.
    Citation
    Hostynek JJ, Dreher F, Maibach HI (2010). Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy. Inflamm Res. PubMed 20703511 · doi:10.1007/s00011-010-0214-4
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2009 · Anal Chim ActaDerivative or conjugate

    Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics

    The study validated an LC-MS/MS method (quantification limits, linearity, accuracy, precision) for palmitoyl peptides in creams, using palmitoyl-GHK as the internal standard.

    Design, limitations and citation
    System
    Cosmetic creams
    Test substance
    Palmitoyl peptides; pal-GHK as internal standard
    Route
    No organism
    Study design
    LC-MS/MS method development and validation
    Sample size
    Not reported in the abstract
    Limitations
    Pal-GHK is the internal standard, not the analyte.
    Citation
    Chirita RI, Chaimbault P, Archambault JC et al. (2009). Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics. Anal Chim Acta. PubMed 19393372 · doi:10.1016/j.aca.2009.03.015
    Editorial review
    pending
  • HumanEvidence grade Btopical2009 · J Clin Aesthet DermatolMulti-ingredient product

    Clinical assessment of a combination lip treatment to restore moisturization and fullness

    The study measured visual grading, corneometry, lip caliper dimensions and self-assessment over four weeks of a multi-ingredient lip product.

    Design, limitations and citation
    System
    Women 22–40 with mild-to-moderate lip dryness
    Test substance
    Two-step lip product including palmitoyl-GHK among many ingredients
    Route
    Applied to skin
    Study design
    Four-week single-centre open-label study
    Sample size
    32
    Limitations
    No control group; palmitoyl-GHK is one of many ingredients and not GHK-Cu, so no effect can be attributed to it.
    Citation
    Trookman NS, Rizer RL, Ford R et al. (2009). Clinical assessment of a combination lip treatment to restore moisturization and fullness. J Clin Aesthet Dermatol. PubMed 20725584
    Editorial review
    pending
  • Ex vivoEvidence grade Dtopical2008 · J Cosmet Sci

    Biological activities of selected peptides: skin penetration ability of copper complexes with peptides

    The study measured penetration of copper complexes of GHK and of glutathione through the stratum corneum in vitro.

    Design, limitations and citation
    System
    Skin barrier models
    Test substance
    GHK-Cu and glutathione–Cu complexes
    Route
    Applied to skin
    Study design
    In vitro penetration study
    Sample size
    Not reported in the abstract
    Limitations
    Abstract truncated in PubMed; in vitro barrier model.
    Citation
    Mazurowska L, Mojski M (2008). Biological activities of selected peptides: skin penetration ability of copper complexes with peptides. J Cosmet Sci. PubMed 18350235
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2008 · J Pharm Biomed AnalGHK without copper

    Acrolein sequestering ability of the endogenous tripeptide glycyl-histidyl-lysine (GHK): characterization of conjugation products by ESI-MSn and theoretical calculations

    The study characterised the products of GHK reacting with acrolein by ESI-MS/MS and found sequential addition of up to three acrolein molecules, including at the lysine ε-amine.

    Design, limitations and citation
    System
    Phosphate buffer, pH 7.4
    Test substance
    GHK with acrolein
    Route
    No organism
    Study design
    HPLC consumption and ESI-MSn product characterisation
    Sample size
    Not reported in the abstract
    Limitations
    Cell-free chemistry.
    Citation
    Beretta G, Arlandini E, Artali R et al. (2008). Acrolein sequestering ability of the endogenous tripeptide glycyl-histidyl-lysine (GHK): characterization of conjugation products by ESI-MSn and theoretical calculations. J Pharm Biomed Anal. PubMed 18378108 · doi:10.1016/j.jpba.2008.02.012
    Editorial review
    pending
  • ReviewEvidence grade RNo organism2008 · J Biomater Sci Polym Ed

    The human tri-peptide GHK and tissue remodeling

    Narrative review by the researcher who first characterised GHK, summarising reported effects on tissue remodelling. The listed affiliation is Skin Biology, a company.

    Design, limitations and citation
    System
    Literature review
    Test substance
    GHK and GHK-Cu
    Route
    No organism
    Study design
    Narrative review
    Sample size
    Not reported in the abstract
    Limitations
    Not systematic; no risk-of-bias assessment; author affiliated with a commercial skin-care company.
    Citation
    Pickart L (2008). The human tri-peptide GHK and tissue remodeling. J Biomater Sci Polym Ed. PubMed 18644225 · doi:10.1163/156856208784909435
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2007 · Photomed Laser Surg

    In vitro observations on the influence of copper peptide aids for the LED photoirradiation of fibroblast collagen synthesis

    The study measured fibroblast viability, procollagen type I C-peptide and bFGF with LED light alone or combined with Cu-GHK.

    Design, limitations and citation
    System
    Human fibroblast line HS68
    Test substance
    Cu-GHK combined with red LED irradiation
    Route
    Added to cell culture
    Study design
    Factorial: LED energy × Cu-GHK; viability, P1CP, bFGF
    Sample size
    Not reported in the abstract
    Limitations
    Cell line; combined with a light treatment; abstract truncated in PubMed.
    Citation
    Huang PJ, Huang YC, Su MF et al. (2007). In vitro observations on the influence of copper peptide aids for the LED photoirradiation of fibroblast collagen synthesis. Photomed Laser Surg. PubMed 17603859 · doi:10.1089/pho.2007.2062
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2007 · Chem Res ToxicolGHK without copper

    Glycyl-histidyl-lysine (GHK) is a quencher of alpha,beta-4-hydroxy-trans-2-nonenal: a comparison with carnosine. insights into the mechanism of reaction by electrospray ionization mass spectrometry, 1H NMR, and computational techniques

    The study measured HNE consumption in the presence of GHK, confirmed GHK–HNE adducts by mass spectrometry and NMR, and found GHK less potent than carnosine as an HNE quencher.

    Design, limitations and citation
    System
    Phosphate buffer, pH 7.4
    Test substance
    GHK with 4-hydroxy-2-nonenal (HNE)
    Route
    No organism
    Study design
    HPLC consumption assay, ESI-MS/MS, 1H NMR, computation
    Sample size
    Not reported in the abstract
    Limitations
    Cell-free chemistry at millimolar peptide concentration.
    Citation
    Beretta G, Artali R, Regazzoni L et al. (2007). Glycyl-histidyl-lysine (GHK) is a quencher of alpha,beta-4-hydroxy-trans-2-nonenal: a comparison with carnosine. insights into the mechanism of reaction by electrospray ionization mass spectrometry, 1H NMR, and computational techniques. Chem Res Toxicol. PubMed 17672515 · doi:10.1021/tx700185s
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2007 · Talanta

    ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum

    The study identified the copper complexes present at different pH by ESI-MS and measured permeability coefficients through a model stratum corneum membrane that increased with pH.

    Design, limitations and citation
    System
    Flynn diffusion cell with a liposome model membrane
    Test substance
    GHK, GHK-Cu and (GHK)₂-Cu
    Route
    No organism
    Study design
    ESI-MS speciation across pH and permeability measurement
    Sample size
    Not reported in the abstract
    Limitations
    Artificial membrane, not skin.
    Citation
    Mazurowska L, Mojski M (2007). ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum. Talanta. PubMed 19071668 · doi:10.1016/j.talanta.2006.11.034
    Editorial review
    pending
  • HumanEvidence grade Atopical2006 · Arch Facial Plast Surg

    Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin

    The trial found no significant difference in resolution of post-laser redness, wrinkles or overall skin quality on objective and blinded assessment; only patient-reported satisfaction differed (P = .04).

    Design, limitations and citation
    System
    Adults after circumoral CO₂ laser resurfacing
    Test substance
    Skin-care regimen with vs without GHK-Cu
    Route
    Applied to skin
    Study design
    Randomised trial with computer analysis and blinded evaluators
    Sample size
    13 completed
    Limitations
    13 completers; primary objective measures were null.
    Citation
    Miller TR, Wagner JD, Baack BR et al. (2006). Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg. PubMed 16847171 · doi:10.1001/archfaci.8.4.252
    Editorial review
    pending
  • AnimalEvidence grade Ctopical2006 · Vet Dermatol

    Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits

    The study measured unhealed wound area and contraction on days 7, 14 and 21; the copper-complex group had smaller unhealed areas than the untreated group at each time point.

    Design, limitations and citation
    System
    New Zealand rabbits, full-thickness dorsal wounds
    Test substance
    Tripeptide-copper complex vs zinc oxide vs no treatment, daily for 21 days
    Route
    Applied to skin
    Study design
    Randomised three-group animal study
    Sample size
    18
    Limitations
    Rabbits; small groups.
    Citation
    Cangul IT, Gul NY, Topal A et al. (2006). Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits. Vet Dermatol. PubMed 17083573 · doi:10.1111/j.1365-3164.2006.00551.x
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2005 · Arch Facial Plast Surg

    Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts

    The study measured faster population-doubling times in normal and irradiated fibroblasts exposed to GHK-Cu than in untreated controls, and their bFGF, TGF-β1 and VEGF output.

    Design, limitations and citation
    System
    Primary human dermal fibroblasts, normal and previously irradiated, serum-free
    Test substance
    GHK-Cu 1 nM
    Route
    Added to cell culture
    Study design
    Population-doubling and growth-factor ELISA
    Sample size
    Not reported in the abstract
    Limitations
    Cultured cells from surgical specimens.
    Citation
    Pollard JD, Quan S, Kang T et al. (2005). Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Arch Facial Plast Surg. PubMed 15655171 · doi:10.1001/archfaci.7.1.27
    Editorial review
    pending
  • AnimalEvidence grade Ctopical2003 · Vet Surg

    The effect of topical tripeptide-copper complex on healing of ischemic open wounds

    The study measured wound area daily for 13 days and TNF-α, MMP-2 and MMP-9 in biopsies; wound area decreased in the gel group but not the vehicle group compared with no treatment.

    Design, limitations and citation
    System
    Rat full-thickness wounds in an ischaemic skin flap
    Test substance
    Tripeptide-copper complex 2% gel vs vehicle vs no treatment
    Route
    Applied to skin
    Study design
    Three-group experimental study
    Sample size
    24
    Limitations
    Rats; abstract truncated in PubMed.
    Citation
    Canapp SO, Farese JP, Schultz GS et al. (2003). The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Vet Surg. PubMed 14648529 · doi:10.1111/j.1532-950x.2003.00515.x
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2001 · Arch Facial Plast Surg

    The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model

    The study measured fibroblast viability and secretion of basic FGF and TGF-β1 after copper tripeptide or tretinoin exposure.

    Design, limitations and citation
    System
    Primary human facial dermal fibroblasts (normal and keloid-derived), serum-free
    Test substance
    Copper tripeptide 1 nM vs tretinoin
    Route
    Added to cell culture
    Study design
    Cell counts and ELISA at 24, 72, 120 h
    Sample size
    Not reported in the abstract
    Limitations
    Primary cell lines from surgical samples; abstract truncated in PubMed.
    Citation
    McCormack MC, Nowak KC, Koch RJ (2001). The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model. Arch Facial Plast Surg. PubMed 11176716
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism2001 · Biochim Biophys Acta

    Copper complexes of glycyl-histidyl-lysine and two of its synthetic analogues: chemical behaviour and biological activity

    The study measured complex stoichiometries and stabilities, reported binuclear species, and concluded that the lysine side-chain amine joins the copper complex only at alkaline pH and stays protonated at physiological pH.

    Design, limitations and citation
    System
    Aqueous solution; human serum (stability)
    Test substance
    Cu(II) with GHK and two synthetic analogues
    Route
    No organism
    Study design
    Potentiometry, calorimetry, UV-Vis, circular dichroism, EPR; serum stability
    Sample size
    Not reported in the abstract
    Limitations
    The serum-stability measurement covered the synthetic analogues for 3 hours.
    Citation
    Conato C, Gavioli R, Guerrini R et al. (2001). Copper complexes of glycyl-histidyl-lysine and two of its synthetic analogues: chemical behaviour and biological activity. Biochim Biophys Acta. PubMed 11325542 · doi:10.1016/s0304-4165(01)00127-1
    Editorial review
    pending
  • In vitroEvidence grade DCell culture2000 · Life Sci

    The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures

    The study measured higher MMP-2, TIMP-1 and TIMP-2 secretion with GHK-Cu; copper ions reproduced the MMP-2 effect and GHK alone did not.

    Design, limitations and citation
    System
    Dermal fibroblast cultures
    Test substance
    GHK-Cu, GHK alone, copper ions
    Route
    Added to cell culture
    Study design
    Conditioned-media and mRNA measurement
    Sample size
    Not reported in the abstract
    Limitations
    Cultured cells; the copper-only result complicates attribution to the complex.
    Citation
    Siméon A, Emonard H, Hornebeck W et al. (2000). The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sci. PubMed 11045606 · doi:10.1016/s0024-3205(00)00803-1
    Editorial review
    pending
  • AnimalEvidence grade Cwound chamber2000 · J Invest Dermatol

    Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+)

    The study measured increased wound-tissue dry weight, protein, type I collagen and glycosaminoglycans with repeated GHK-Cu injections, with greater chondroitin and dermatan sulfate accumulation.

    Design, limitations and citation
    System
    Rat wound-chamber model and rat dermal fibroblasts
    Test substance
    GHK-Cu
    Route
    Into an implanted chamber (animal)
    Study design
    Comparison with saline; GAG and proteoglycan analysis
    Sample size
    Not reported in the abstract
    Limitations
    Rats; chamber delivery.
    Citation
    Siméon A, Wegrowski Y, Bontemps Y et al. (2000). Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol. PubMed 11121126 · doi:10.1046/j.1523-1747.2000.00166.x
    Editorial review
    pending
  • AnimalEvidence grade Cwound chamber1999 · J Invest Dermatol

    Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+

    The study measured matrix metalloproteinase expression and activation in wound fluid; GHK-Cu did not alter interstitial collagenase activity and changed MMP-2 and MMP-9 profiles.

    Design, limitations and citation
    System
    Rat wound-chamber model
    Test substance
    GHK-Cu, serial injections into the chamber
    Route
    Into an implanted chamber (animal)
    Study design
    Comparison with saline; MMP activity and expression
    Sample size
    Not reported in the abstract
    Limitations
    Rats; chamber delivery; abstract truncated in PubMed.
    Citation
    Siméon A, Monier F, Emonard H et al. (1999). Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. J Invest Dermatol. PubMed 10383745 · doi:10.1046/j.1523-1747.1999.00606.x
    Editorial review
    pending
  • ChemistryEvidence grade Dintravenous1997 · J Chromatogr B Biomed Sci ApplGHK without copper

    Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L-histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with post-column derivatization

    The method reached detection limits of 50 ng/mL (GHK) and 15 ng/mL (His-Lys) in rat plasma; in the applied rat study, intravenously given GHK was rapidly degraded to His-Lys, which was rapidly eliminated.

    Design, limitations and citation
    System
    Rat plasma
    Test substance
    GHK and its metabolite His-Lys
    Route
    Intravenous (animal)
    Study design
    HPLC method with solid-phase extraction and post-column OPA derivatisation; applied to a rat pharmacokinetic study
    Sample size
    Not reported in the abstract
    Limitations
    Rats only; copper-free peptide; the abstract gives no half-life values.
    Citation
    Endo T, Miyagi M, Ujiie A (1997). Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L-histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with post-column derivatization. J Chromatogr B Biomed Sci Appl. PubMed 9187381 · doi:10.1016/s0378-4347(96)00460-4
    Editorial review
    pending
  • In vitroEvidence grade DCell culture1995 · Biomaterials

    Effect of the tripeptide glycyl-L-histidyl-L-lysine on the proliferation and synthetic activity of chick embryo chondrocytes

    The study measured chondrocyte proliferation and synthesis of collagen types I, II and III with the copper-tripeptide supplement on plastic and collagen supports.

    Design, limitations and citation
    System
    Chick embryo chondrocytes on three supports
    Test substance
    (Gly-His-Lys)₂·Cu complex in medium
    Route
    Added to cell culture
    Study design
    Proliferation and collagen-type synthesis
    Sample size
    Not reported in the abstract
    Limitations
    Avian cells; biomaterials context; abstract truncated in PubMed.
    Citation
    Pesáková V, Novotná J, Adam M (1995). Effect of the tripeptide glycyl-L-histidyl-L-lysine on the proliferation and synthetic activity of chick embryo chondrocytes. Biomaterials. PubMed 8562779 · doi:10.1016/0142-9612(95)93115-t
    Editorial review
    pending
  • In vitroEvidence grade DCell culture1995 · Cell Mol Biol (Noisy-le-grand)

    Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype

    The study found that GHK-Cu and GHK coatings (10⁻¹⁰–10⁻⁸ M) did not change cell spreading but increased the attachment of rat and human osteoblastic cells.

    Design, limitations and citation
    System
    Rat calvaria cells, human trabecular osteoblasts, human marrow stromal cells
    Test substance
    GHK-Cu, GHK, collagen I, fibronectin coatings
    Route
    Added to cell culture
    Study design
    Spreading, attachment and phenotype markers
    Sample size
    Not reported in the abstract
    Limitations
    Cultured cells on coated surfaces.
    Citation
    Godet D, Marie PJ (1995). Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype. Cell Mol Biol (Noisy-le-grand). PubMed 8747089
    Editorial review
    pending
  • AnimalEvidence grade Ctopical1995 · Arch Int Pharmacodyn Ther

    Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts

    The study measured hydroxyproline, protein, DNA and amine-oxidase activity and observed slower skin reorganisation and delayed fibroblast activation with the copper-peptide complexes.

    Design, limitations and citation
    System
    Guinea-pig dorsal skin wounds; cultured fibroblasts
    Test substance
    GHK-Cu, three synthetic analogues, copper acetate
    Route
    Applied to skin
    Study design
    Biochemical and histological comparison
    Sample size
    Not reported in the abstract
    Limitations
    Guinea pigs; findings run opposite to several other animal reports.
    Citation
    Buffoni F, Pino R, Dal Pozzo A (1995). Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts. Arch Int Pharmacodyn Ther. PubMed 8836453
    Editorial review
    pending
  • HumanEvidence grade Atopical1994 · Wound Repair Regen

    Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper

    The trial reported median plantar-ulcer area closure of 98.5% with the gel vs 60.8% with vehicle (p < 0.05), a larger difference in ulcers over 100 mm², and fewer ulcer infections (7% vs 34%).

    Design, limitations and citation
    System
    Adults with neuropathic plantar ulcers
    Test substance
    GHK-Cu gel (Iamin), with standardised wound care
    Route
    Applied to skin
    Study design
    Multicentre randomised evaluator-blinded placebo-controlled trial
    Sample size
    Not reported in the abstract
    Limitations
    Sample size not given in the abstract; one 1994 topical gel; the authors note the effect depended on starting immediately after debridement. No independent replication is indexed.
    Citation
    Mulder GD, Patt LM, Sanders L et al. (1994). Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair Regen. PubMed 17147644 · doi:10.1046/j.1524-475X.1994.20406.x
    Editorial review
    pending
  • AnimalEvidence grade Cwound chamber1993 · J Clin Invest

    In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds

    The study measured concentration-dependent increases in dry weight and connective-tissue components (collagen, DNA, glycosaminoglycans) in GHK-Cu-injected wound chambers compared with saline.

    Design, limitations and citation
    System
    Rat wound-chamber model (mesh chamber implanted under the skin)
    Test substance
    GHK-Cu injected into the implanted chamber
    Route
    Into an implanted chamber (animal)
    Study design
    Controlled comparison with saline across concentrations
    Sample size
    Not reported in the abstract
    Limitations
    Rats; material delivered directly into an implanted chamber, which is not a route of administration to a person.
    Citation
    Maquart FX, Bellon G, Chaqour B et al. (1993). In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest. PubMed 8227353 · doi:10.1172/JCI116842
    Editorial review
    pending
  • HumanEvidence grade Atopical1992 · J Vasc Surg

    A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers

    The trial measured ulcer size: silver sulfadiazine reduced it more than the copper tripeptide cream or placebo, and there was no difference between the copper tripeptide cream and placebo.

    Design, limitations and citation
    System
    Adults with venous leg ulcers
    Test substance
    Tripeptide-copper complex 0.4% cream
    Route
    Applied to skin
    Study design
    Prospective randomised evaluator-blinded trial: copper tripeptide cream vs silver sulfadiazine 1% vs vehicle placebo
    Sample size
    86 evaluable
    Limitations
    Single trial of one 1992 topical formulation; the comparison with placebo was null.
    Citation
    Bishop JB, Phillips LG, Mustoe TA et al. (1992). A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. J Vasc Surg. PubMed 1495150 · doi:10.1067/mva.1992.37086
    Editorial review
    pending
  • In vitroEvidence grade DCell culture1992 · Life Sci

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

    The study measured a biphasic increase in glycosaminoglycan synthesis, maximal at 10⁻⁹–10⁻⁸ M and returning to control at higher concentrations, mainly dermatan sulfate and heparan sulfate.

    Design, limitations and citation
    System
    Normal human fibroblast cultures
    Test substance
    GHK-Cu
    Route
    Added to cell culture
    Study design
    Radiolabel incorporation into glycosaminoglycans
    Sample size
    Not reported in the abstract
    Limitations
    Cultured cells.
    Citation
    Wegrowski Y, Maquart FX, Borel JP (1992). Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Life Sci. PubMed 1522753 · doi:10.1016/0024-3205(92)90504-i
    Editorial review
    pending
  • In vitroEvidence grade DCell culture1988 · FEBS Lett

    Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+

    The study measured collagen synthesis in fibroblast cultures that rose from 10⁻¹²–10⁻¹¹ M GHK-Cu and peaked at 10⁻⁹ M, independent of cell number.

    Design, limitations and citation
    System
    Fibroblast cultures
    Test substance
    GHK-Cu
    Route
    Added to cell culture
    Study design
    Collagen synthesis assay across concentrations
    Sample size
    Not reported in the abstract
    Limitations
    Cultured cells; the wound-site liberation hypothesis is the authors’ suggestion.
    Citation
    Maquart FX, Pickart L, Laurent M et al. (1988). Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. PubMed 3169264 · doi:10.1016/0014-5793(88)80509-x
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism1983 · Biochem J

    N.m.r. and e.p.r. investigation of the interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma

    The EPR spectra between pH 6.0 and 9.6 showed seven-line nitrogen superhyperfine splitting, read by the authors as three nitrogen atoms coordinated to Cu(II); the study cautioned that NMR line broadening mainly reflected minor species.

    Design, limitations and citation
    System
    Aqueous solution
    Test substance
    Cu(II)–GHK
    Route
    No organism
    Study design
    13C and 1H NMR line broadening; EPR across pH
    Sample size
    Not reported in the abstract
    Limitations
    Spectroscopic inference; no crystal structure in this paper.
    Citation
    Laussac JP, Haran R, Sarkar B (1983). N.m.r. and e.p.r. investigation of the interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma. Biochem J. PubMed 6303307 · doi:10.1042/bj2090533
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism1982 · Biochemistry

    Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution

    The study found a mononuclear 1:1 complex at neutral pH with Cu(II) equatorially bound by two or three nitrogen atoms, one of them in the histidine imidazole ring, and transitions with apparent pK values of 3.6, 9.2 and 11.4.

    Design, limitations and citation
    System
    Aqueous solution
    Test substance
    Cu(II)–GHK
    Route
    No organism
    Study design
    Optical, EPR and electron spin-echo spectroscopy with pH titration
    Sample size
    Not reported in the abstract
    Limitations
    Solution structure inferred from spectroscopy; differs from the oxygen-bridged solid-state structure.
    Citation
    Freedman JH, Pickart L, Weinstein B et al. (1982). Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution. Biochemistry. PubMed 6291585 · doi:10.1021/bi00262a004
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism1981 · Biochem J

    The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma

    The study measured multiple Cu(II)–GHK species across pH 3.5–10.6, derived their stability constants, and found by equilibrium dialysis that GHK competed with albumin for Cu(II) at pH 7.5.

    Design, limitations and citation
    System
    Aqueous solution, 25 °C, 0.15 M NaCl
    Test substance
    Cu(II) with GHK, with and without L-histidine
    Route
    No organism
    Study design
    Potentiometric titration, visible absorption, equilibrium dialysis
    Sample size
    Not reported in the abstract
    Limitations
    Solution equilibria at fixed temperature and ionic strength; species assignments are proposed from the data.
    Citation
    Lau SJ, Sarkar B (1981). The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma. Biochem J. PubMed 7340824 · doi:10.1042/bj1990649
    Editorial review
    pending
  • In vitroEvidence grade DCell culture1980 · J Cell Physiol

    Growth-modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes

    The study reported that GHK in plasma was associated with copper and iron, and that at physiological pH in vitro it associated with several transition-metal ions but not with calcium, potassium or sodium.

    Design, limitations and citation
    System
    Human plasma fractions; rat hepatoma cell line (HTC4)
    Test substance
    GHK with Cu, Fe, Co, Zn and other ions
    Route
    Added to cell culture
    Study design
    Metal-association assays and cell culture
    Sample size
    Not reported in the abstract
    Limitations
    1980 methods; the cell-growth findings are in a single transformed cell line.
    Citation
    Pickart L, Thaler MM (1980). Growth-modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes. J Cell Physiol. PubMed 6246126 · doi:10.1002/jcp.1041020205
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism1977 · BiochemistryGHK without copper

    Determination of the microscopic and macroscopic acid dissociation constants of glycyl-L-histidyl-L-lysine and related histidine peptides

    The study measured the acid dissociation constants of the glycyl amine, histidyl imidazole and lysyl amine groups; the lysyl amine titrated over a much higher pH range than the other two groups.

    Design, limitations and citation
    System
    Aqueous solution, proton NMR
    Test substance
    Gly-His-Lys (free peptide)
    Route
    No organism
    Study design
    pH titration followed by NMR chemical shift
    Sample size
    Not reported in the abstract
    Limitations
    Copper-free peptide; solution chemistry only.
    Citation
    Rabenstein DL, Greenberg MS, Evans CA (1977). Determination of the microscopic and macroscopic acid dissociation constants of glycyl-L-histidyl-L-lysine and related histidine peptides. Biochemistry. PubMed 14668 · doi:10.1021/bi00624a026
    Editorial review
    pending
  • ChemistryEvidence grade DNo organism1977 · ExperientiaGHK without copper

    Growth-modulating serum tripeptide is glycyl-histidyl-lysine

    This 1977 report identified the growth-modulating tripeptide isolated from human serum as glycyl-histidyl-lysine.

    Design, limitations and citation
    System
    Human serum fraction
    Test substance
    Isolated serum tripeptide
    Route
    No organism
    Study design
    Isolation and sequence identification
    Sample size
    Not reported in the abstract
    Limitations
    No abstract is indexed; the identification is reported from the title and later citing work.
    Citation
    Schlesinger DH, Pickart L, Thaler MM (1977). Growth-modulating serum tripeptide is glycyl-histidyl-lysine. Experientia. PubMed 858356 · doi:10.1007/BF02002806
    Editorial review
    pending

By category

All primary studies

The table below is the same data as the explorer in a form that works without JavaScript. Reviews are listed in the explorer.

All primary GHK-Cu studies
StudyModel and routeWhat was measuredLimitationsGrade
Huang 2026
Eur J Pharm Sci
Chemical characterisation
ChemistryNo organism
Ball-milled co-amorphous mixtures
GHK without copper
The study found that GHK fully amorphised three model compounds within 15 minutes of milling, whereas single amino-acid co-formers mostly left partly crystalline mixtures.GHK is used here as an excipient, not studied as an active substance.Evidence grade D
Ye 2026
Curr Issues Mol Biol
Collagen and extracellular matrix · Skin research
In vitroCell culture
Dermal fibroblasts
Multi-ingredient product
The study measured elastin expression and secretion by dermal fibroblasts exposed to copper tripeptide-1, alongside two other ingredients tested for elastase and scaffold-gene effects.Cell culture; combination study.Evidence grade D
Mazzola 2026
Res Sq
Non-topical routes
Animalintraperitoneal and intranasal
Aged C57BL/6J mice (20–21 months)
GHK-Cu (copper complex)
This preprint measured spatial-navigation escape latency and hippocampal gene expression and reported different, partly opposite, transcriptional programmes after intraperitoneal versus intranasal dosing.Preprint, not peer reviewed; mice; the two routes also differed in duration.Evidence grade C
Ogórek 2026
J Chromatogr A
Laboratory analytical methods · Chemical characterisation
ChemistryNo organism
Oil-in-water emulsion and serum cosmetic matrices
GHK-Cu (copper complex)
The study measured the stability of liposome-encapsulated GHK-Cu after incorporation into model emulsion and serum formulations.Model formulations; abstract truncated in PubMed.Evidence grade D
Dkhar 2025
J Phys Chem B
Laboratory analytical methods
ChemistryNo organism
Solution
GHK-Cu (copper complex)
The study designed donor–acceptor fluorescent probes selective for Cu(II) over competing metal ions and applied them to detecting copper tripeptide.Sensor chemistry; not a validated quality-control assay.Evidence grade D
Patel 2025
Cureus
Skin research
Humantopical
Women with acne scars
Multi-ingredient product · n = Not reported in the abstract
The study assessed visible scar change on the Manchester Scar Scale by a dermatologist with a multi-ingredient gel.No control group; four actives in one gel, so no attribution to the copper peptide.Evidence grade B
Patel 2024
Cureus
Hair research · Skin research
Humantopical
Adults with mild-to-moderate scalp flaking
Multi-ingredient product · n = Not reported in the abstract
The study measured adherent scalp flaking, scalp hydration, hair density and hair thickness over 15 days of a two-product regimen.No control group; 15 days; two products and several actives, so no attribution to the copper peptide.Evidence grade B
Zajda 2024
Electrophoresis
Laboratory analytical methods
ChemistryNo organism
Liposome preparations
GHK-Cu (copper complex)
The study used CE-ICP-MS/MS copper and phosphorus signals to confirm liposome formation and to measure the amount of GHK-Cu encapsulated.Method demonstration in model liposomes.Evidence grade D
Jiang 2023
J Cosmet Dermatol
Collagen and extracellular matrix · Skin research
Ex vivoCell culture
Human dermal fibroblasts; ex vivo skin
Multi-ingredient product
The study measured collagen I, IV and VII expression across GHK-Cu and hyaluronic acid ratios and reported collagen IV increases of 25.4-fold in cells and 2.03-fold in ex vivo skin at a 1:9 ratio.Combination with hyaluronic acid; mRNA in cells and staining in excised skin.Evidence grade D
Sahu 2023
J Org Chem
Laboratory analytical methods
ChemistryNo organism
Methanol solution
GHK-Cu (copper complex)
The study reported a phenothiazine fluorescent sensor selective for Cu(II) over other transition-metal salts and applied it to GHK-Cu sensing.Sensor chemistry; not a validated quality-control assay.Evidence grade D
Dymek 2023
Pharmaceutics
Laboratory analytical methods · Chemical characterisation
ChemistryNo organism
Hydrogenated-lecithin liposomes
GHK-Cu (copper complex)
The study prepared anionic and cationic liposomes of about 100 nm and measured GHK-Cu encapsulation efficiencies of 31.7 ± 0.9% (cationic) and 20.0 ± 2.8% (anionic) for the selected formulations.Formulation characterisation; enzyme-inhibition assays are cell-free.Evidence grade D
Lee 2022
Pharmaceutics
Skin research
Ex vivotopical
Pig and mouse skin in Franz diffusion cells
GHK-Cu (copper complex)
The study found that all tested laser modalities increased skin permeation of the peptides in vitro, with non-ablative lasers disrupting the stratum corneum ultrastructure.Animal skin; delivery outcome only.Evidence grade D
Bossak-Ahmad 2021
Inorg Chem
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution with human serum albumin
GHK-Cu (copper complex)
The study identified two ternary Cu(GHK)–albumin complexes formed through albumin histidine imidazoles, with His3 as one site (conditional constant 2,900 M⁻¹ at pH 7.4).The second site is assigned only as likely His128 or His510.Evidence grade D
Ufnalska 2021
Inorg Chem
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution
GHK-Cu (copper complex)
The study characterised a transient glutathione–Cu(II)–GHK intermediate in the reduction of Cu(II)–GHK by glutathione and measured how temperature, oxygen and ternary ligands changed the reduction rate.Chemical reaction study; the biological role proposed by the authors is a hypothesis.Evidence grade D
Hur 2020
J Pept Sci
Skin research · Collagen and extracellular matrix
In vitroCell culture
Cell cultures and skin delivery models
Derivative or conjugate
The study compared GHK with a tetra-arginine conjugate and found faster cellular penetration and higher in vitro collagen biosynthesis with the conjugate.Conjugate differs from GHK-Cu; the authors attribute part of the effect to the arginine tail itself.Evidence grade D
Bossak-Ahmad 2020
Int J Mol Sci
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution
GHK-Cu (copper complex)
The study found that cis-urocanic acid also coordinates Cu(II) and that GHK, Cu(II) and cis-urocanic acid form a ternary complex.The physiological relevance is inferred from published tissue concentrations, not measured in tissue.Evidence grade D
Kapoor 2020
Plast Reconstr Surg Glob Open
Hair research · Safety and tolerability data · Non-topical routes
Animalintradermal
Human keratinocyte and fibroblast assays; animal hair-growth model
Multi-ingredient product
The study measured cytotoxicity of each ingredient in keratinocyte and fibroblast assays and hair growth after intradermal injection of the full formulation in animals.Multi-ingredient; authors connected to the formulation; abstract truncated in PubMed.Evidence grade C
Kapoor 2018
J Cosmet Laser Ther
Hair research · Non-topical routes
Humanintradermal
Adults with hair loss
Multi-ingredient product · n = 1000
The study assessed hair regrowth and adverse events after repeated intradermal scalp injections of a multi-ingredient formulation.No control group; at least six actives, so no effect or safety finding can be attributed to copper tripeptide-1.Evidence grade B
Beuning 2018
Inorg Chem
Copper binding · Laboratory analytical methods
ChemistryNo organism
Aqueous solution
GHK-Cu (copper complex)
The study measured second-order rate constants for Cu(II) transfer from a tryptophan analogue complex to GHK of 1.6 × 10² M⁻¹ s⁻¹ and to DAHK of 5.0 × 10¹ M⁻¹ s⁻¹.Model exchange reaction using a substituted peptide as the copper donor.Evidence grade D
Tanaka 2018
J Clin Aesthet Dermatol
Hair research · Non-topical routes
Humanintradermal
Men treated in one clinic, 2011–2017
Multi-ingredient product · n = 18,918 treated
The series assessed pre- and post-treatment photographs of men given a combination regimen in which copper tripeptide was one of many ingredients of one component.Uncontrolled; approved drugs in the same regimen; the copper peptide contribution cannot be separated.Evidence grade B
Wang 2017
Wound Repair Regen
Collagen and extracellular matrix · Skin research
Animaltopical
HUVEC cultures; mouse scald model
GHK-Cu (copper complex)
The study measured a 33.1% higher endothelial-cell proliferation rate with GHK-Cu liposomes and compared CD31 and Ki67 staining and healing time in mice treated with liposomal versus free GHK-Cu.Mice; liposomal formulation; abstract truncated in PubMed.Evidence grade C
Badenhorst 2016
Pharm Dev Technol
Chemical characterisation · Laboratory analytical methods
ChemistryNo organism
Aqueous buffers, octanol–PBS, stress conditions
GHK-Cu (copper complex)
The study measured hydrolytic degradation under basic and oxidative stress (less under acid), stability in water and pH 4.5–7.4 buffers for at least two weeks at 60 °C, and three degradation products by HPLC-MS, one being histidine.Preformulation data for one material source; no product or shelf-life study.Evidence grade D
Byun 2016
J Cosmet Laser Ther
Skin research · Collagen and extracellular matrix
Humantopical
One adult, periocular skin
Multi-ingredient product · n = 1
The case report described photographs and biopsy staining (collagen, fibrillin-1, procollagen type 1) from treated and untreated areas in one person.One person; five active ingredients plus a device; cannot attribute any finding to GHK-Cu.Evidence grade B
Lee 2016
Ann Dermatol
Hair research
Humantopical
Men with pattern hair loss
Derivative or conjugate · n = 45
The study measured hair count, length and thickness at 1, 3 and 6 months; hair-count change differed from placebo in the lower-strength group, while length and thickness did not differ between groups.Copper-free GHK complexed with 5-ALA, so it is not a GHK-Cu study; small groups; single centre.Evidence grade B
Li 2016
Sci Rep
Skin research · Safety and tolerability data
In vitroCell culture
Human keratinocyte model
GHK-Cu (copper complex)
The study compared irritation potential at the same concentrations and found GHK-Cu not cytotoxic and without significant change in the irritation markers measured, while the copper salts differed.Keratinocyte culture model; not a human patch test; tested concentrations are those of the paper.Evidence grade D
Li 2015
Pharm Res
Skin research · Safety and tolerability data
Ex vivotopical
Two in vitro skin models; cell and pig models for safety
GHK-Cu (copper complex)
The study found that microneedle depth depended on application force and measured 134 ± 12 nmol of peptide and 705 ± 84 nmol of copper permeating through microneedle-treated skin in 9 hours.Delivery study; does not measure any skin outcome in people.Evidence grade D
Gruchlik 2014
Acta Pol Pharm
Skin research
In vitroCell culture
Normal human dermal fibroblasts
GHK-Cu (copper complex)
The study measured IGF-2-dependent TGF-β1 secretion by dermal fibroblasts exposed to 1 nM GHK, GHK-Cu or copper chloride.Abstract truncated in PubMed; single cell type.Evidence grade D
Parker 2013
Otolaryngol Head Neck Surg
Collagen and extracellular matrix · Skin research
Animaltopical
Irradiated rat dorsal skin flaps
GHK-Cu (copper complex) · n = 23 (13 test, 10 control)
The study measured ischaemic flap area, caveolin-1 and VEGF staining; mean ischaemic area was 5.0 cm² with GHK-Cu gel and 3.8 cm² with the control ointment.Rats; the measured ischaemic area was larger in the GHK-Cu group.Evidence grade C
Trapaidze 2012
J Biol Inorg Chem
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous buffer, pH 7.4
GHK-Cu (copper complex)
The study measured predominantly 1:1 binding and a conditional dissociation constant at pH 7.4 of 7.0 × 10⁻¹⁴ M for GHK (2.6 × 10⁻¹⁴ M for DAHK), with the enthalpic and entropic contributions.Conditional constant: valid for the stated pH and with competitor and buffer contributions removed.Evidence grade D
Choi 2012
J Pept Sci
Skin research
In vitroCell culture
Normal human keratinocytes; skin-equivalent models
GHK without copper
The study measured keratinocyte proliferation and staining for integrins α6 and β1, p63 and PCNA in skin equivalents cultured with copper-free GHK.Cultured cells and engineered tissue.Evidence grade D
Gruchlik 2012
Acta Pol Pharm
Skin research
In vitroCell culture
Normal human dermal fibroblasts (NHDF)
GHK-Cu (copper complex)
The study measured TNF-α-dependent IL-6 secretion and reported decreases with GHK, GGH, copper chloride and their copper complexes.Single cell type; copper chloride alone also changed the readout.Evidence grade D
Hostynek 2011
Inflamm Res
Skin research · Laboratory analytical methods
Ex vivotopical
Human skin layers in flow-through diffusion cells
GHK-Cu (copper complex)
The study reported the same permeability coefficient (2.43 ± 0.51 × 10⁻⁴ cm/h) and 136.2 µg/cm² copper permeated, with 97 µg/cm² retained in dermatomed skin.Near-duplicate of the 2010 report by the same group with a different retained-copper figure; measures copper, not intact peptide.Evidence grade D
Hureau 2011
Chemistry
Copper binding · Chemical characterisation
ChemistryNo organism
Single crystals and aqueous solution
GHK-Cu (copper complex)
The study reported a dimeric Cu(II)–GHK structure in the solid state and a monomer in solution with three nitrogen ligands (glycine amine, deprotonated amide and histidine imidazole) and a labile oxygen in the fourth equatorial position.No openly licensed copy of the coordinates was found (Crystallography Open Database searched 2026-11-11), so this site does not render them.Evidence grade D
Hostynek 2010
Inflamm Res
Skin research · Laboratory analytical methods
Ex vivotopical
Human skin layers in flow-through diffusion cells
GHK-Cu (copper complex)
The study measured a permeability coefficient through dermatomed skin of 2.43 ± 0.51 × 10⁻⁴ cm/h, with 136.2 µg/cm² copper permeated over 48 h and 82 µg/cm² retained.Measures copper, not intact peptide; infinite-dose conditions; excised skin.Evidence grade D
Chirita 2009
Anal Chim Acta
Laboratory analytical methods
ChemistryNo organism
Cosmetic creams
Derivative or conjugate
The study validated an LC-MS/MS method (quantification limits, linearity, accuracy, precision) for palmitoyl peptides in creams, using palmitoyl-GHK as the internal standard.Pal-GHK is the internal standard, not the analyte.Evidence grade D
Trookman 2009
J Clin Aesthet Dermatol
Skin research
Humantopical
Women 22–40 with mild-to-moderate lip dryness
Multi-ingredient product · n = 32
The study measured visual grading, corneometry, lip caliper dimensions and self-assessment over four weeks of a multi-ingredient lip product.No control group; palmitoyl-GHK is one of many ingredients and not GHK-Cu, so no effect can be attributed to it.Evidence grade B
Mazurowska 2008
J Cosmet Sci
Skin research
Ex vivotopical
Skin barrier models
GHK-Cu (copper complex)
The study measured penetration of copper complexes of GHK and of glutathione through the stratum corneum in vitro.Abstract truncated in PubMed; in vitro barrier model.Evidence grade D
Beretta 2008
J Pharm Biomed Anal
Chemical characterisation · Laboratory analytical methods
ChemistryNo organism
Phosphate buffer, pH 7.4
GHK without copper
The study characterised the products of GHK reacting with acrolein by ESI-MS/MS and found sequential addition of up to three acrolein molecules, including at the lysine ε-amine.Cell-free chemistry.Evidence grade D
Huang 2007
Photomed Laser Surg
Collagen and extracellular matrix
In vitroCell culture
Human fibroblast line HS68
GHK-Cu (copper complex)
The study measured fibroblast viability, procollagen type I C-peptide and bFGF with LED light alone or combined with Cu-GHK.Cell line; combined with a light treatment; abstract truncated in PubMed.Evidence grade D
Beretta 2007
Chem Res Toxicol
Chemical characterisation
ChemistryNo organism
Phosphate buffer, pH 7.4
GHK without copper
The study measured HNE consumption in the presence of GHK, confirmed GHK–HNE adducts by mass spectrometry and NMR, and found GHK less potent than carnosine as an HNE quencher.Cell-free chemistry at millimolar peptide concentration.Evidence grade D
Mazurowska 2007
Talanta
Laboratory analytical methods · Skin research · Copper binding
ChemistryNo organism
Flynn diffusion cell with a liposome model membrane
GHK-Cu (copper complex)
The study identified the copper complexes present at different pH by ESI-MS and measured permeability coefficients through a model stratum corneum membrane that increased with pH.Artificial membrane, not skin.Evidence grade D
Miller 2006
Arch Facial Plast Surg
Skin research
Humantopical
Adults after circumoral CO₂ laser resurfacing
GHK-Cu (copper complex) · n = 13 completed
The trial found no significant difference in resolution of post-laser redness, wrinkles or overall skin quality on objective and blinded assessment; only patient-reported satisfaction differed (P = .04).13 completers; primary objective measures were null.Evidence grade A
Cangul 2006
Vet Dermatol
Collagen and extracellular matrix · Skin research
Animaltopical
New Zealand rabbits, full-thickness dorsal wounds
GHK-Cu (copper complex) · n = 18
The study measured unhealed wound area and contraction on days 7, 14 and 21; the copper-complex group had smaller unhealed areas than the untreated group at each time point.Rabbits; small groups.Evidence grade C
Pollard 2005
Arch Facial Plast Surg
Skin research
In vitroCell culture
Primary human dermal fibroblasts, normal and previously irradiated, serum-free
GHK-Cu (copper complex)
The study measured faster population-doubling times in normal and irradiated fibroblasts exposed to GHK-Cu than in untreated controls, and their bFGF, TGF-β1 and VEGF output.Cultured cells from surgical specimens.Evidence grade D
Canapp 2003
Vet Surg
Collagen and extracellular matrix · Skin research
Animaltopical
Rat full-thickness wounds in an ischaemic skin flap
GHK-Cu (copper complex) · n = 24
The study measured wound area daily for 13 days and TNF-α, MMP-2 and MMP-9 in biopsies; wound area decreased in the gel group but not the vehicle group compared with no treatment.Rats; abstract truncated in PubMed.Evidence grade C
McCormack 2001
Arch Facial Plast Surg
Skin research
In vitroCell culture
Primary human facial dermal fibroblasts (normal and keloid-derived), serum-free
GHK-Cu (copper complex)
The study measured fibroblast viability and secretion of basic FGF and TGF-β1 after copper tripeptide or tretinoin exposure.Primary cell lines from surgical samples; abstract truncated in PubMed.Evidence grade D
Conato 2001
Biochim Biophys Acta
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution; human serum (stability)
GHK-Cu (copper complex)
The study measured complex stoichiometries and stabilities, reported binuclear species, and concluded that the lysine side-chain amine joins the copper complex only at alkaline pH and stays protonated at physiological pH.The serum-stability measurement covered the synthetic analogues for 3 hours.Evidence grade D
Siméon 2000
Life Sci
Collagen and extracellular matrix
In vitroCell culture
Dermal fibroblast cultures
GHK-Cu (copper complex)
The study measured higher MMP-2, TIMP-1 and TIMP-2 secretion with GHK-Cu; copper ions reproduced the MMP-2 effect and GHK alone did not.Cultured cells; the copper-only result complicates attribution to the complex.Evidence grade D
Siméon 2000
J Invest Dermatol
Collagen and extracellular matrix
Animalwound chamber
Rat wound-chamber model and rat dermal fibroblasts
GHK-Cu (copper complex)
The study measured increased wound-tissue dry weight, protein, type I collagen and glycosaminoglycans with repeated GHK-Cu injections, with greater chondroitin and dermatan sulfate accumulation.Rats; chamber delivery.Evidence grade C
Siméon 1999
J Invest Dermatol
Collagen and extracellular matrix
Animalwound chamber
Rat wound-chamber model
GHK-Cu (copper complex)
The study measured matrix metalloproteinase expression and activation in wound fluid; GHK-Cu did not alter interstitial collagenase activity and changed MMP-2 and MMP-9 profiles.Rats; chamber delivery; abstract truncated in PubMed.Evidence grade C
Endo 1997
J Chromatogr B Biomed Sci Appl
Laboratory analytical methods · Non-topical routes
Chemistryintravenous
Rat plasma
GHK without copper
The method reached detection limits of 50 ng/mL (GHK) and 15 ng/mL (His-Lys) in rat plasma; in the applied rat study, intravenously given GHK was rapidly degraded to His-Lys, which was rapidly eliminated.Rats only; copper-free peptide; the abstract gives no half-life values.Evidence grade D
Pesáková 1995
Biomaterials
Collagen and extracellular matrix
In vitroCell culture
Chick embryo chondrocytes on three supports
GHK-Cu (copper complex)
The study measured chondrocyte proliferation and synthesis of collagen types I, II and III with the copper-tripeptide supplement on plastic and collagen supports.Avian cells; biomaterials context; abstract truncated in PubMed.Evidence grade D
Godet 1995
Cell Mol Biol (Noisy-le-grand)
Collagen and extracellular matrix
In vitroCell culture
Rat calvaria cells, human trabecular osteoblasts, human marrow stromal cells
GHK-Cu (copper complex)
The study found that GHK-Cu and GHK coatings (10⁻¹⁰–10⁻⁸ M) did not change cell spreading but increased the attachment of rat and human osteoblastic cells.Cultured cells on coated surfaces.Evidence grade D
Buffoni 1995
Arch Int Pharmacodyn Ther
Collagen and extracellular matrix · Skin research
Animaltopical
Guinea-pig dorsal skin wounds; cultured fibroblasts
GHK-Cu (copper complex)
The study measured hydroxyproline, protein, DNA and amine-oxidase activity and observed slower skin reorganisation and delayed fibroblast activation with the copper-peptide complexes.Guinea pigs; findings run opposite to several other animal reports.Evidence grade C
Mulder 1994
Wound Repair Regen
Skin research · Collagen and extracellular matrix
Humantopical
Adults with neuropathic plantar ulcers
GHK-Cu (copper complex) · n = Not reported in the abstract
The trial reported median plantar-ulcer area closure of 98.5% with the gel vs 60.8% with vehicle (p < 0.05), a larger difference in ulcers over 100 mm², and fewer ulcer infections (7% vs 34%).Sample size not given in the abstract; one 1994 topical gel; the authors note the effect depended on starting immediately after debridement. No independent replication is indexed.Evidence grade A
Maquart 1993
J Clin Invest
Collagen and extracellular matrix
Animalwound chamber
Rat wound-chamber model (mesh chamber implanted under the skin)
GHK-Cu (copper complex)
The study measured concentration-dependent increases in dry weight and connective-tissue components (collagen, DNA, glycosaminoglycans) in GHK-Cu-injected wound chambers compared with saline.Rats; material delivered directly into an implanted chamber, which is not a route of administration to a person.Evidence grade C
Bishop 1992
J Vasc Surg
Skin research · Collagen and extracellular matrix
Humantopical
Adults with venous leg ulcers
GHK-Cu (copper complex) · n = 86 evaluable
The trial measured ulcer size: silver sulfadiazine reduced it more than the copper tripeptide cream or placebo, and there was no difference between the copper tripeptide cream and placebo.Single trial of one 1992 topical formulation; the comparison with placebo was null.Evidence grade A
Wegrowski 1992
Life Sci
Collagen and extracellular matrix
In vitroCell culture
Normal human fibroblast cultures
GHK-Cu (copper complex)
The study measured a biphasic increase in glycosaminoglycan synthesis, maximal at 10⁻⁹–10⁻⁸ M and returning to control at higher concentrations, mainly dermatan sulfate and heparan sulfate.Cultured cells.Evidence grade D
Maquart 1988
FEBS Lett
Collagen and extracellular matrix
In vitroCell culture
Fibroblast cultures
GHK-Cu (copper complex)
The study measured collagen synthesis in fibroblast cultures that rose from 10⁻¹²–10⁻¹¹ M GHK-Cu and peaked at 10⁻⁹ M, independent of cell number.Cultured cells; the wound-site liberation hypothesis is the authors’ suggestion.Evidence grade D
Laussac 1983
Biochem J
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution
GHK-Cu (copper complex)
The EPR spectra between pH 6.0 and 9.6 showed seven-line nitrogen superhyperfine splitting, read by the authors as three nitrogen atoms coordinated to Cu(II); the study cautioned that NMR line broadening mainly reflected minor species.Spectroscopic inference; no crystal structure in this paper.Evidence grade D
Freedman 1982
Biochemistry
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution
GHK-Cu (copper complex)
The study found a mononuclear 1:1 complex at neutral pH with Cu(II) equatorially bound by two or three nitrogen atoms, one of them in the histidine imidazole ring, and transitions with apparent pK values of 3.6, 9.2 and 11.4.Solution structure inferred from spectroscopy; differs from the oxygen-bridged solid-state structure.Evidence grade D
Lau 1981
Biochem J
Copper binding · Chemical characterisation
ChemistryNo organism
Aqueous solution, 25 °C, 0.15 M NaCl
GHK-Cu (copper complex)
The study measured multiple Cu(II)–GHK species across pH 3.5–10.6, derived their stability constants, and found by equilibrium dialysis that GHK competed with albumin for Cu(II) at pH 7.5.Solution equilibria at fixed temperature and ionic strength; species assignments are proposed from the data.Evidence grade D
Pickart 1980
J Cell Physiol
Copper binding
In vitroCell culture
Human plasma fractions; rat hepatoma cell line (HTC4)
GHK-Cu (copper complex)
The study reported that GHK in plasma was associated with copper and iron, and that at physiological pH in vitro it associated with several transition-metal ions but not with calcium, potassium or sodium.1980 methods; the cell-growth findings are in a single transformed cell line.Evidence grade D
Rabenstein 1977
Biochemistry
Chemical characterisation
ChemistryNo organism
Aqueous solution, proton NMR
GHK without copper
The study measured the acid dissociation constants of the glycyl amine, histidyl imidazole and lysyl amine groups; the lysyl amine titrated over a much higher pH range than the other two groups.Copper-free peptide; solution chemistry only.Evidence grade D
Schlesinger 1977
Experientia
Chemical characterisation
ChemistryNo organism
Human serum fraction
GHK without copper
This 1977 report identified the growth-modulating tripeptide isolated from human serum as glycyl-histidyl-lysine.No abstract is indexed; the identification is reported from the title and later citing work.Evidence grade D

Frequently asked questions

How many GHK-Cu studies are there?

A PubMed title and abstract search returned 259 records in November 2026. This database holds 81 of them, screened and verified, across skin, collagen, hair, chemistry, copper binding and analytical methods.

Are there GHK-Cu clinical trials?

This database includes 3 randomised human trials, all of topical products, and 7 other human studies, most of multi-ingredient products. Four studies were registered on ClinicalTrials.gov at our last check, none with posted results.

References

  1. Bishop JB, Phillips LG, Mustoe TA et al. (1992). A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. J Vasc Surg. PubMed 1495150 · doi:10.1067/mva.1992.37086[Human, grade A]
  2. Mulder GD, Patt LM, Sanders L et al. (1994). Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair Regen. PubMed 17147644 · doi:10.1046/j.1524-475X.1994.20406.x[Human, grade A]
  3. Miller TR, Wagner JD, Baack BR et al. (2006). Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg. PubMed 16847171 · doi:10.1001/archfaci.8.4.252[Human, grade A]