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Research information only. Not medical advice. 18+ only. Not FDA-approved for human therapeutic use.

GHK-Cu

Also known as: GHK, glycyl-L-histidyl-L-lysine, Gly-His-Lys, copper peptide, copper tripeptide complex, glycyl-L-histidyl-L-lysine-Cu(2+), glycyl-L-histidyl-L-lysine copper(II) complex, GHK-Cu2+

Endogenous copper-binding tripeptide / matrikine / cosmeceutical peptide

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What it is

GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring tripeptide found in human plasma, saliva, urine, and tissue that declines with age. It forms a complex with copper(II) ions (GHK-Cu), which shares copper affinity similar to the transport site on albumin. GHK-Cu activates tissue remodeling through multiple mechanisms: (1) chemoattraction of macrophages, mast cells, and capillary endothelial cells to sites of injury; (2) anti-inflammatory actions including suppression of free radicals, thromboxane formation, TNF-α, and TGF-β1, while increasing superoxide dismutase activity; (3) stimulation of collagen, elastin, glycosaminoglycan, VEGF, FGF-2, NGF, and other growth factor synthesis; (4) promotion of angiogenesis, fibroblast and keratinocyte proliferation, and nerve outgrowth. GHK-Cu modulates metalloproteinase and anti-protease activity. At the molecular level, GHK-Cu directly binds and activates SIRT1, which deacetylates FoxO3a (reducing protein degradation), Nrf2 (reducing oxidative stress), and increases PGC-1α expression to promote mitochondrial function. GHK-Cu suppresses the JAK1 and STAT3 pathways, modulates PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK signaling, and has been found to up- and downregulate at least 4,000 human genes. Copper ions facilitated by GHK-Cu activate copper-dependent proteins such as lysyl oxidase (LOX) via ATOX1-mediated transport into the Golgi apparatus, promoting collagen crosslinking and extracellular matrix remodeling. GHK also chelates and reduces copper redox activity, preventing copper- and zinc-induced protein aggregation and cell death in vitro. Copper-free GHK (apo-GHK) retains some biological effects, including increased keratinocyte proliferation and integrin expression, suggesting partial activity independent of copper coordination.

Class: Endogenous copper-binding tripeptide / matrikine / cosmeceutical peptide

What it's studied for

  • Wound healing and skin repair Mixed
    • 13-patient RCT of GHK-Cu skin care products after CO2 laser resurfacing found no statistically significant reduction in erythema or objective improvement in wrinkles, but patient-reported satisfaction was significantly higher in the GHK-Cu group (P=0.04). PMID 16847171 Miller TR et al. Arch Facial Plast Surg. 2006.
    • GHK-Cu-liposomes promoted HUVEC proliferation (33.1% increased rate), upregulated VEGF and FGF-2, and shortened wound healing time to 14 days post-injury in a mouse scald model, outperforming free GHK-Cu for angiogenesis. PMID 28370978 Wang X et al. Wound Repair Regen. 2017.
    • In vitro study: GHK-Cu (1×10⁻⁹ mol/L) accelerated growth of normal and irradiated fibroblasts; irradiated fibroblasts treated with GHK-Cu approximated population-doubling time of normal controls and produced more FGF-2 and VEGF early after exposure. PMID 15655171 Pollard JD et al. Arch Facial Plast Surg. 2005.
    • Review: GHK accelerates wound healing of skin, hair follicles, GI tract, boney tissue, and dog foot pads; induces systemic wound healing in rats, mice, and pigs; and in cosmetic products tightens skin, improves elasticity, reduces fine lines, wrinkles, photodamage, and hyperpigmentation. PMID 26236730 Pickart L et al. BioMed Res Int. 2015.
    • Gly-His-Lys-D-Ala (0.5 µg/kg, intracutaneous daily injection) in Wistar rats promoted wound regeneration, increased fibroblastic cells and macrophages, decreased granulocytes, and promoted wound contraction on day 30. PMID 38345677 Rakhmetova KK et al. Bull Exp Biol Med. 2024.
    • Systematic review (64 studies, 2005–2026): preclinical data consistently support GHK-Cu in matrix remodeling, epithelial repair, anti-inflammatory/redox regulation, and angiogenesis; clinical evidence remains sparse and fragmented; no adequately powered human RCT of microneedle-delivered GHK-Cu published as of review. PMID 42787770 Najafi N et al. Arch Intern Med Res. 2026.
    • Systematic review (20 studies: 18 preclinical, 2 RCTs): GHK-Cu enhanced ECM synthesis, modulated MMP activity, promoted angiogenesis, suppressed TGF-β and IL-6; clinically improved patient-reported satisfaction after laser resurfacing and reduced wrinkle volume vs. controls; advanced delivery systems (microneedles, lip PMID 42619529 Mokhtar J et al. Aesthetic Surg J. 2026.
  • Anti-aging and skin rejuvenation (topical/cosmeceutical) Mixed
    • GHK-Cu combined with low-molecular-weight HA at 1:9 ratio elevated collagen IV synthesis 25.4-fold in fibroblast cell test and 2.03-fold in ex-vivo skin test, demonstrating synergy on collagen IV at the dermal-epidermal junction. PMID 37062921 Jiang F et al. J Cosmet Dermatol. 2023.
    • Review: GHK stimulates collagen, elastin, and glycosaminoglycan synthesis; supports dermal fibroblast function; improves tissue repair in skin, lung, liver, bone, and stomach; possesses anti-cancer and anti-inflammatory activities; modulates thousands of human genes. PMID 29986520 Pickart L & Margolina A. Int J Mol Sci. 2018.
    • Review: based on cellular studies, GHK can be considered an anti-wrinkle ingredient; GHK-Cu and Pal-GHK are widely used in anti-wrinkle products; clinical studies are surprisingly absent despite broad market use; permeation enhancement via microneedles, CPPs, and chemical modification is promising. PMID 39963574 Mortazavi SM et al. BioImpacts. 2025.
    • Review: tripeptide (GHK-Cu) formulation shown to offer improved healing and clinical outcomes in conjunction with resurfacing and cryolipolysis, and benefit for cutaneous rejuvenation. PMID 33938433 Wang JV et al. Skinmed. 2021.
  • Anti-inflammatory and antioxidant effects Animal studies only
    • GHK-Cu reduced neutrophil and macrophage migration, suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased IL-10, reduced NO and ROS, improved SOD activity, and downregulated the JAK1 pathway in zebrafish larvae acute inflammation models (CuSO4 and LPS). PMID 41997403 Hu J et al. Eur J Pharmacol. 2026.
    • GHK-Cu attenuated lung inflammation and fibrosis in a silicosis mouse model by binding PRDX6 and inhibiting oxidative stress in alveolar macrophages, without significant systemic toxicity. PMID 38879894 Bian Y et al. Redox Biol. 2024.
    • TJE-GHK-Cu complex (6:4 ratio) synergistically suppressed Th2 cytokines (IL-4, IL-5, IL-10, IL-13), AD-related chemokines, and IgE production in TNF-α/IFN-γ-stimulated HaCaT cells, and promoted keratinocyte migration. PMID 42510549 Jeon S et al. Antioxidants. 2026.
  • Skeletal muscle dysfunction / COPD-related sarcopenia Mixed
    • Plasma GHK levels were significantly lower in COPD patients than healthy controls (70.27±38.87 vs 133.0±54.54 ng/mL, P=0.009) and correlated with pectoralis muscle area, TNF-α, and SOD2. GHK-Cu (0.2 and 2 mg/kg) in CS-exposed C57BL/6 mice reduced muscle mass loss and improved grip strength via SIRT1 activation. Human p PMID 36905132 Deng M et al. J Cachexia Sarcopenia Muscle. 2023.
  • Airway remodeling in asthma Mixed
    • Plasma GHK levels were significantly lower in asthma patients than controls and correlated with FAO. GHK-Cu administration in OVA-induced mice alleviated peribronchial collagen deposition, mucus secretion, and epithelial-mesenchymal transition via SIRT1 activation and decreased TGF-β1. Human data were observational. PMID 37257226 Zhang Q et al. Biomed Pharmacother. 2023.
  • Pulmonary fibrosis / silicosis Animal studies only
    • GHK-Cu attenuated lung inflammation and fibrosis in a crystalline silica mouse model by binding PRDX6 and reducing oxidative stress in alveolar macrophages, without significant systemic toxicity. PMID 38879894 Bian Y et al. Redox Biol. 2024.
  • Ulcerative colitis / inflammatory bowel disease Animal studies only
    • GHK-Cu alleviated DSS-induced UC in mice: reduced weight loss, improved disease activity index, suppressed TNF-α/IL-6/IL-1β, increased ZO-1 and Occludin, and promoted mucosal healing via the SIRT1/STAT3 pathway. PMID 40672369 Mao S et al. Front Pharmacol. 2025.
    • In vitro study: GHK-Cu-loaded Zn-pectinate microparticles compression-coated with HPC showed delayed release (lag time ~6 h) suitable for colonic delivery to inhibit MMP and promote TIMP secretion for IBD mucosal healing. PMID 21457130 Ugurlu T et al. Drug Dev Ind Pharm. 2011.
  • Neuroprotection / neurodegenerative disease Animal studies only
    • Intranasal GHK-Cu (15 mg/kg, 3×/week for 3 months) in 5xFAD mice delayed cognitive impairment, reduced amyloid plaques, and lowered MCP1-mediated inflammation in frontal cortex and hippocampus. PMID 40766919 Tucker M et al. Aging Pathobiol Ther. 2024.
    • In aged C57BL/6J mice (20–21 months), GHK-Cu 15 mg/kg IP (5 days) or IN (8 weeks) both improved hippocampal-dependent escape learning but via divergent molecular programs; IN treatment increased synaptophysin and decreased GFAP in females, IP reduced TGF-β and MCP-1 in males. PMID 42245779 Mazzola J et al. Res Sq. 2026.
    • GHK (copper-free) prevented copper- and zinc-induced CNS cell death in vitro, reduced copper redox activity, prevented and reversed BSA aggregation, and attenuated copper-enhanced paraquat toxicity. PMID 38599632 Min JH et al. Metallomics. 2024.
    • Review: GHK-Cu proposed as therapeutic agent against age-associated neurodegeneration and cognitive decline based on antioxidant, anti-inflammatory, copper-chelating, and gene-regulatory properties; noted as having a long history of safe use in wound healing and antiaging skin care. PMID 22666519 Pickart L et al. Oxid Med Cell Longev. 2012.
  • Anti-aging (lifespan/longevity models) Animal studies only
    • GHK-Cu significantly extended lifespan of C. elegans, improved stress resistance, motility, and pharyngeal function, reduced lipofuscin accumulation, preserved mitochondrial membrane potential, promoted mitochondrial fusion, and activated DAF-16 and SKN-1 pathways. PMID 42084774 Wen H et al. Biogerontology. 2026.
  • Osteoblast biology / bone tissue In vitro only
    • GHK:Cu coating increased attachment of rat calvaria and human trabecular osteoblastic cells; however, GHK:Cu slightly inhibited basal and 1,25(OH)2D-induced alkaline phosphatase activity and osteocalcin production in rat and human osteoblastic cells in vitro. PMID 8747089 Godet D & Marie PJ. Cell Mol Biol. 1995.
  • Fascia regeneration Animal studies only
    • A Golgi-targeted system using GHK-Cu as copper source combined with LNP-ATOX1 mRNA promoted collagen alignment and neovascularization, elevated LOX activity 1.78-fold over control, and improved fascia regeneration in a rabbit fascia defect model. PMID 41476424 Wang R et al. J Control Release. 2026.
  • Hair growth promotion Animal studies only
    • An ionic liquid microemulsion (IL-M) system improved local delivery of GHK-Cu approximately 3-fold vs. conventional formulation in mice and was effective for hair growth promotion, activating Wnt/β-catenin signaling and VEGF expression; described as a powerful hair growth promoter with minimal side effects compared wit PMID 38026438 Liu T et al. Bioact Mater. 2024.
  • Diabetic wound healing Animal studies only
    • GOX-loaded hydrogel with GHK-Cu enabled cascade catalysis: GOX oxidized glucose (reducing hyperglycemia, generating H2O2), GHK-Cu Cu ions decomposed H2O2 (CAT-like) releasing oxygen, alleviating hypoxia, with additional antibacterial, tissue repair, antioxidant, and angiogenesis effects confirmed in vitro and in vivo. PMID 42404628 Huang ZJ et al. Mater Today Bio. 2026.
  • Musculoskeletal conditions (orthopaedic/sports medicine) Animal studies only
    • Narrative review: GHK-Cu showed promise in wound healing and anti-inflammatory effects, but no clinical data support its use for musculoskeletal conditions. PMID 41476424 Mayfield CK et al. Am J Sports Med. 2026.
    • Scoping review: 67% of identified publications on emerging peptides (including GHK-Cu) used preclinical animal models; human clinical studies were limited, lacked robust controls, and revealed modest improvements at best; peptide supplements should not currently be recommended as replacement or adjunct for orthopaedic PMID 42578445 Tewari K et al. Am J Sports Med. 2026.

Community-reported dosing

RouteDoseFrequency / DurationPopulation / contextSource tier
Not specified (in vivo, C57BL/6 mice)0.2 mg/kg and 2 mg/kgNot explicitly stated for the full treatment course; assessed across multiple timepointsanimalResearch PMID 36905132
Intranasal15 mg/kg3 months (3 times per week)animalResearch PMID 40766919
Intraperitoneal (IP) or intranasal (IN)15 mg/kgIP: 5 days; IN: 8 weeksanimalResearch PMID 42245779
In vitro (serum-free media)1 × 10⁻⁹ mol/LNot specifiedin_vitroResearch PMID 15655171
In vitro (fibroblast culture)10⁻⁹ to 10⁻⁸ M (maximal stimulation); biphasic dose-responseNot specifiedin_vitroResearch PMID 1522753
Intracutaneous0.5 µg/kg30 days (daily)animalResearch PMID 38345677
Not specifiedVarious methods and dosages discussed (no single explicit dose stated)Not specifiedhumanResearch PMID 25302294
Transdermal (microneedle-assisted)134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated through microneedle-treated human skin in 9 h (delivery study, not therapeutic dose)9 hours (in vitro permeation study)in_vitroResearch PMID 25690343
Oral (colonic delivery, in vitro model)50 mg and 250 mg (microparticle formulation, colonic delivery in vitro)4 h release in simulated intestinal fluid; 6 h lag time for colonic tabletsin_vitroResearch PMID 21457130
subcutaneous injection1-2 mgdailybiohackers and anti-aging enthusiasts seeking systemic regenerative or nootropic effects[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection500 mcgdailybeginners or cautious biohackers starting injectable GHK-Cu[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection2 mgdailyexperienced biohackers and longevity-focused users stacking GHK-Cu with other peptides[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal1 mgonce dailybiohackers and nootropic users seeking cognitive or neuroprotective effects[S] Claude Sonnet 4.6 — synthesized from aggregate training data
intranasal500 mcgonce dailybeginners using intranasal GHK-Cu for cognitive or neuroprotective purposes[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection1 mgevery other day (EOD)biohackers preferring less frequent injection schedules or managing injection site sensitivity[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection1-2 mgdailyusers post-injury or post-surgery seeking soft-tissue and wound healing acceleration[S] Claude Sonnet 4.6 — synthesized from aggregate training data

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

References

  1. [1] PMID 16847171 — 13-patient RCT of GHK-Cu skin care products after CO2 laser resurfacing found no statistically significant reduction in erythema or objective improvement in wri
  2. [2] PMID 28370978 — GHK-Cu-liposomes promoted HUVEC proliferation (33.1% increased rate), upregulated VEGF and FGF-2, and shortened wound healing time to 14 days post-injury in a m
  3. [3] PMID 15655171 — In vitro study: GHK-Cu (1×10⁻⁹ mol/L) accelerated growth of normal and irradiated fibroblasts; irradiated fibroblasts treated with GHK-Cu approximated populatio
  4. [4] PMID 26236730 — Review: GHK accelerates wound healing of skin, hair follicles, GI tract, boney tissue, and dog foot pads; induces systemic wound healing in rats, mice, and pigs
  5. [5] PMID 38345677 — Gly-His-Lys-D-Ala (0.5 µg/kg, intracutaneous daily injection) in Wistar rats promoted wound regeneration, increased fibroblastic cells and macrophages, decrease
  6. [6] PMID 42787770 — Systematic review (64 studies, 2005–2026): preclinical data consistently support GHK-Cu in matrix remodeling, epithelial repair, anti-inflammatory/redox regulat
  7. [7] PMID 42619529 — Systematic review (20 studies: 18 preclinical, 2 RCTs): GHK-Cu enhanced ECM synthesis, modulated MMP activity, promoted angiogenesis, suppressed TGF-β and IL-6;
  8. [8] PMID 37062921 — GHK-Cu combined with low-molecular-weight HA at 1:9 ratio elevated collagen IV synthesis 25.4-fold in fibroblast cell test and 2.03-fold in ex-vivo skin test, d
  9. [9] PMID 29986520 — Review: GHK stimulates collagen, elastin, and glycosaminoglycan synthesis; supports dermal fibroblast function; improves tissue repair in skin, lung, liver, bon
  10. [10] PMID 39963574 — Review: based on cellular studies, GHK can be considered an anti-wrinkle ingredient; GHK-Cu and Pal-GHK are widely used in anti-wrinkle products; clinical studi
  11. [11] PMID 33938433 — Review: tripeptide (GHK-Cu) formulation shown to offer improved healing and clinical outcomes in conjunction with resurfacing and cryolipolysis, and benefit for
  12. [12] PMID 41997403 — GHK-Cu reduced neutrophil and macrophage migration, suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased IL-10, reduced NO and ROS, improved SO
  13. [13] PMID 38879894 — GHK-Cu attenuated lung inflammation and fibrosis in a silicosis mouse model by binding PRDX6 and inhibiting oxidative stress in alveolar macrophages, without si
  14. [14] PMID 42510549 — TJE-GHK-Cu complex (6:4 ratio) synergistically suppressed Th2 cytokines (IL-4, IL-5, IL-10, IL-13), AD-related chemokines, and IgE production in TNF-α/IFN-γ-sti
  15. [15] PMID 36905132 — Plasma GHK levels were significantly lower in COPD patients than healthy controls (70.27±38.87 vs 133.0±54.54 ng/mL, P=0.009) and correlated with pectoralis mus
  16. [16] PMID 37257226 — Plasma GHK levels were significantly lower in asthma patients than controls and correlated with FAO. GHK-Cu administration in OVA-induced mice alleviated peribr
  17. [17] PMID 40672369 — GHK-Cu alleviated DSS-induced UC in mice: reduced weight loss, improved disease activity index, suppressed TNF-α/IL-6/IL-1β, increased ZO-1 and Occludin, and pr
  18. [18] PMID 21457130 — In vitro study: GHK-Cu-loaded Zn-pectinate microparticles compression-coated with HPC showed delayed release (lag time ~6 h) suitable for colonic delivery to in
  19. [19] PMID 40766919 — Intranasal GHK-Cu (15 mg/kg, 3×/week for 3 months) in 5xFAD mice delayed cognitive impairment, reduced amyloid plaques, and lowered MCP1-mediated inflammation i
  20. [20] PMID 42245779 — In aged C57BL/6J mice (20–21 months), GHK-Cu 15 mg/kg IP (5 days) or IN (8 weeks) both improved hippocampal-dependent escape learning but via divergent molecula
  21. [21] PMID 38599632 — GHK (copper-free) prevented copper- and zinc-induced CNS cell death in vitro, reduced copper redox activity, prevented and reversed BSA aggregation, and attenua
  22. [22] PMID 22666519 — Review: GHK-Cu proposed as therapeutic agent against age-associated neurodegeneration and cognitive decline based on antioxidant, anti-inflammatory, copper-chel
  23. [23] PMID 42084774 — GHK-Cu significantly extended lifespan of C. elegans, improved stress resistance, motility, and pharyngeal function, reduced lipofuscin accumulation, preserved
  24. [24] PMID 8747089 — GHK:Cu coating increased attachment of rat calvaria and human trabecular osteoblastic cells; however, GHK:Cu slightly inhibited basal and 1,25(OH)2D-induced alk
  25. [25] PMID 41476424 — A Golgi-targeted system using GHK-Cu as copper source combined with LNP-ATOX1 mRNA promoted collagen alignment and neovascularization, elevated LOX activity 1.7
  26. [26] PMID 38026438 — An ionic liquid microemulsion (IL-M) system improved local delivery of GHK-Cu approximately 3-fold vs. conventional formulation in mice and was effective for ha
  27. [27] PMID 42404628 — GOX-loaded hydrogel with GHK-Cu enabled cascade catalysis: GOX oxidized glucose (reducing hyperglycemia, generating H2O2), GHK-Cu Cu ions decomposed H2O2 (CAT-l
  28. [28] PMID 42578445 — Scoping review: 67% of identified publications on emerging peptides (including GHK-Cu) used preclinical animal models; human clinical studies were limited, lack
  29. [29] PMID 1522753 — 10⁻⁹ to 10⁻⁸ M (maximal stimulation); biphasic dose-response In vitro (fibroblast culture) (in_vitro)
  30. [30] PMID 25302294 — Various methods and dosages discussed (no single explicit dose stated) Not specified (human)
  31. [31] PMID 25690343 — 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated through microneedle-treated human skin in 9 h (delivery study, not therapeutic dose) Tr
  32. [32] PMID 24350846 — in-prose reference
  33. [33] PMID 18644225 — in-prose reference
  34. [34] PMID 41490200 — in-prose reference
  35. [35] PMID 23019153 — in-prose reference
  36. [36] PMID 40716276 — in-prose reference
  37. [37] PMID 41966639 — in-prose reference
  38. [38] PMID 42797253 — in-prose reference
  39. [39] PMID 23019152 — in-prose reference
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