GHK-Cu

GHK-Cu (Glycyl-L-Histidyl-L-Lysine copper(II) complex) is a naturally occurring tripeptide bound to a copper(II) ion. It was first isolated from human plasma in 1973 by Loren Pickart and has been the subject of over 200 peer-reviewed studies on skin remodeling, wound healing, and gene-expression modulation.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / GHK-Cu](https://peppudex.com/peptides/ghk-cu).

Overview

The free GHK tripeptide (without copper) has been measured in human plasma, saliva, and urine. Published assays have reported a decline in plasma concentration with age (Pickart 1973 and subsequent reviews); the often-quoted "200 µg/L at 20 → 80 µg/L at 60" range comes from Pickart's review summaries and is not from a single prospective cohort. The copper-bound form is the biologically active species in most in-vitro readouts.

Mechanism

In a 2015 transcriptomic study, GHK-Cu was reported to modulate expression of several thousand genes in cultured human fibroblasts at the dose studied (Pickart, Vasquez-Soltero, Margolina 2015). The often-cited "4,000 genes" figure comes from that specific in-vitro readout; the magnitude varies by cell type, dose, and exposure window and should not be assumed to translate directly to whole-organism effects. Specific cellular actions observed across the literature:

• Stimulates collagen, elastin, and proteoglycan synthesis in dermal fibroblasts
• Enhances angiogenesis via FGF-2 upregulation
• Anti-inflammatory via TGF-β1 modulation
• Antioxidant via copper-dependent SOD-1 activity
• Reverses transcriptional signatures of emphysema, COPD, and metastatic colon cancer in tissue-culture readouts

See: Collagen_synthesis, Angiogenesis, Gene_expression.

Evidence

Cosmetic-dermatology evidence is extensive · GHK-Cu is the active ingredient in multiple FDA-approved topical formulations. Skin-clinical readouts:

• Facial application (n=71 women, 12 weeks) · improved skin density, thickness and clarity, reduced fine lines (Leyden et al., 2002, AAD 60th Annual Meeting conference abstract · not a peer-reviewed full publication)
• Photo-damage protocol · reduced fine lines and increased thickness in damaged skin (Finkley et al., 2005, book chapter in Cosmeceuticals and Active Cosmetics, 2nd ed., Marcel Dekker)
• Ischemic open-wound model · accelerated healing in dogs (Canapp et al., 2003, Vet Surg, PMID 14648531)

Systemic injectable use has weaker evidence · most published work centers on topical delivery.

Dosing literature

Topical: 0.01% to 0.1% in cream or serum (1–10 mg per gram of base).

Injectable (community-reported research use): 1–2 mg per administration, 2–3 times per week, subcutaneous. Frequency stacks vary widely; no standardized injectable protocol in the academic literature.

Storage

Lyophilized: 4 °C, stable 24 months. Reconstituted: 2–8 °C, use within 14 days (copper-peptide complexes degrade faster than uncomplexed peptides in solution). Protect from light · the complex is photosensitive.

Regulatory status

• United States. Topical formulations are marketed as cosmetic ingredients under FDA cosmetic regulation (cosmetics generally do not require FDA premarket approval). Injectable forms are research-use only.
• WADA. Not on the prohibited list ([2026 list](https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf)).

See also

• Copper_peptides · broader class
• Reconstitution
• Storage · 14-day reconstituted shelf is shorter than other peptides
• [Peppudex card · GHK-Cu](https://peppudex.com/peptides/ghk-cu) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Pickart L, Vasquez-Soltero JM, Margolina A. "GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration." Biomed Res Int. 2015;2015:648108. PMID 26236730. ([PMC4508379](https://pmc.ncbi.nlm.nih.gov/articles/PMC4508379/))
• Pickart L, Margolina A. "Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data." Int J Mol Sci. 2018;19(7):1987. PMID 29986520.
• Leyden J, et al. "Skin care benefits of copper peptide containing facial cream." 60th Annual Meeting of the American Academy of Dermatology, New Orleans, February 22-27 2002 · conference abstract.
• Finkley MB, Appa Y, Bhandarkar S. "Copper Peptide and Skin." In: Cosmeceuticals and Active Cosmetics, 2nd ed. Marcel Dekker; 2005:549-563.
• Canapp SO Jr, et al. "The effect of topical tripeptide-copper complex on healing of ischemic open wounds." Vet Surg. 2003;32(6):515-23. PMID 14648531.