Abstract
GHK-Cu (glycyl-L-histidyl-L-lysine complexed with Cu²⁺), often listed in cosmetics as Copper tripeptide-1, is a naturally occurring tripeptide-metal complex with documented roles in tissue remodeling, wound healing, anti-inflammatory activity, and skin regeneration. Preclinical and clinical reports indicate GHK-Cu stimulates collagen and glycosaminoglycan synthesis, modulates gene expression related to tissue repair, and shows activity in hair growth models. Applications include topical anti-aging formulations, wound healing research, and experimental hair regrowth studies. Key chemical identifiers and representative literature are provided below. PMC+2PMC+2
Chemical identity
- Name (common): GHK-Cu; Copper tripeptide-1
- Tripeptide sequence (free peptide): Gly-His-Lys (GHK)
- Common forms / salts: GHK-Cu (monocopper complex), palmitoyl-GHK (Pal-GHK) derivatives for cosmetic formulation.
- Primary CAS numbers: GHK (free peptide) / GHK-Cu complex: 49557-75-7 (GHK); some commercial/complex salts and TFA/salts reported as 89030-95-5 for certain copper-tripeptide preparations. AAPPTEC+1
Introduction & historical notes
GHK was first isolated from human plasma as a small, naturally occurring peptide with growth-modulating activity. When complexed with Cu²⁺ (GHK-Cu) it was found to accelerate tissue repair and influence multiple cellular pathways. Interest in GHK-Cu has grown in both academic research and the cosmetic industry because it combines relatively low molecular size (improving tissue access) with pleiotropic regenerative effects. PubMed+1
Mechanisms of action (research overview)
- Copper delivery / metal biology: GHK-Cu binds copper in a coordination geometry that facilitates cellular copper uptake/transfer; copper is a cofactor for enzymes (e.g., lysyl oxidase) important to connective tissue crosslinking and matrix remodeling. Wikipedia+1
- Stimulation of extracellular matrix synthesis: GHK-Cu upregulates genes and cellular programs that increase collagen, elastin, and glycosaminoglycan synthesis in dermal fibroblasts—supporting skin firmness and repair. PMC
- Anti-inflammatory and antioxidant effects: Reports show reductions in markers of inflammation and oxidative stress in tissues treated with GHK-Cu; this contributes to improved healing and reduced photo-damage signatures. PMC+1
- Gene modulation / regenerative gene signature: Transcriptomic analyses indicate GHK-Cu can modulate expression of multiple gene clusters involved in tissue regeneration, metalloproteinase balance, and cellular senescence pathways. PMC
Preclinical and clinical evidence (selected studies)
- Tissue remodeling and wound healing: Pickart and colleagues reviewed regenerative effects of GHK-Cu across multiple tissues and summarized gene-level data supporting repair and protective actions. The review compiles in-vitro, animal, and human topical studies. PMC
- Pickart L. Regenerative and Protective Actions of the GHK-Cu Peptide. Int J Mol Sci. 2018. (PMC review). PMC
- Anti-aging / skin improvement: Controlled facial studies and human topical trials reported improvements in skin elasticity, reduction in fine lines/wrinkles, and improved appearance after formulations containing copper peptides or Pal-GHK. Systematic mechanistic data support increased dermal matrix synthesis. PubMed+1
- Hair growth / follicle stimulation: Several in-vitro and ex-vivo studies and animal models show copper peptides can stimulate hair follicle cells and promote anagen-phase markers; some small human studies indicate improved hair transplant outcomes and potential to support hair regrowth. Delivery and formulation remain active research areas. PubMed+1
- Oxidative stress & protective effects: Evidence suggests GHK-Cu exerts antioxidant effects in damaged tissues and may protect against experimentally induced injury in models of liver and lung damage. PMC+1
(Selected representative publications and reviews are listed in the References section below.)
Applications in research & formulation
- Topical cosmetics: Anti-wrinkle serums, creams, and post-procedural products that aim to accelerate recovery and stimulate collagen; palmitoylated GHK derivatives (e.g., Pal-GHK) are used to improve skin penetration. PubMed+1
- Wound healing models: Used in in-vitro wound assays and animal studies to study matrix remodeling, angiogenesis, and re-epithelialization. PMC
- Hair growth research: Investigational topical formulations for promoting follicle health, hair transplants, and counteracting miniaturization. Formulation challenges (stability and skin penetration) are active areas of study (liposomes, microemulsions, pro-drugs). PMC+1
Formulation & stability considerations
- Molecular size & penetration: GHK is small (tri-peptide), which helps tissue diffusion, but Cu²⁺ coordination and salt form (e.g., TFA, acetate) can affect solubility and stability. Liposomal or microemulsion carriers can improve topical delivery. PMC+1
- pH and oxidation: Copper coordination chemistry and peptide stability are pH-sensitive; antioxidants and chelator-compatible excipients are often required in formulations. PMC
Safety, regulatory, and handling
- Cosmetic use: GHK-Cu is widely used in cosmetic products and is generally regarded as safe at typical topical concentrations; patch testing is recommended since copper ions and peptides may rarely cause irritation. PMC+1
- Research chemical handling: As with any research peptide, handle per institutional safety guidelines: use PPE, avoid ingestion/inhalation, store as recommended by supplier (usually cool, dry, protected from light). Not intended for unregulated human use. AAPPTEC
Limitations & open questions
- Many clinical studies are small or proprietary (industry). Larger randomized controlled trials are limited, so while mechanistic and preclinical evidence is strong, broader clinical confirmation for some indications (e.g., robust hair regrowth comparable to FDA-approved therapies) is incomplete. Delivery and long-term safety data at higher systemic exposures remain areas for future research. PubMed+1
References / Key PubMed / PMC links
(Representative articles & reviews; click to open on PubMed/PMC)
- Pickart L. The human tri-peptide GHK and tissue remodeling. Ageing Res Rev. 2008. PubMed. PubMed
- Pickart L; Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018; PMC review. PMC
- Pickart L; The Human Tripeptide GHK in Prevention of Oxidative Damage. (2012) PMC article. PMC
- Pyo HK et al. The effect of tripeptide-copper complex on human hair follicles in vitro. 2007. PubMed. PubMed
- Dou Y. The potential of GHK as an anti-aging peptide. (Review) PubMed. PubMed
- Dymek M et al. Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Applications. 2023. PMC. PMC
- Liu T et al. Delivery challenges and prospects of GHK-Cu for hair growth. 2023. PubMed. PMC
Chemical / catalog references: product listings and CAS numbers from peptide suppliers. AAPPTEC+1
10 Frequently Asked Questions (FAQ)
1. What is GHK-Cu?
GHK-Cu is a complex of the tripeptide glycyl-histidyl-lysine (GHK) with copper (Cu²⁺). It is commonly called copper tripeptide-1 in cosmetics and is reported to support tissue repair, collagen synthesis, and skin remodeling. PMC
2. What are the CAS numbers for GHK and its copper complex?
Commonly cited CAS numbers include 49557-75-7 (GHK / some GHK-Cu listings) and 89030-95-5 for certain salt/complex forms used commercially. Check supplier documentation for the exact CAS on a product lot. AAPPTEC+1
3. How does GHK-Cu work in skin?
GHK-Cu appears to deliver copper for enzymatic processes (e.g., crosslinking of collagen), stimulate fibroblast activity to produce collagen/elastin/GAGs, and modulate inflammation and antioxidant responses—together improving skin repair and appearance. PMC+1
4. Is GHK-Cu effective for wound healing?
Preclinical and some human topical studies indicate GHK-Cu accelerates wound healing and improves tissue remodeling; it is used experimentally in wound-care research. PMC
5. Can GHK-Cu help with hair growth?
In vitro and some clinical/ex-vivo data suggest GHK-Cu promotes follicle health and may support hair growth or improve transplant outcomes, but larger clinical trials are limited. Delivery to the follicle (formulation) is an important variable. PubMed+1
6. How is GHK-Cu formulated for topical use?
GHK-Cu is formulated as aqueous serums, creams, or incorporated into carriers (liposomes, microemulsions) or as palmitoylated pro-peptides (Pal-GHK) to enhance skin penetration and stability. PMC+1
7. Is GHK-Cu safe? Any side effects?
At cosmetic topical concentrations it is generally well tolerated. Rare irritation or sensitivity is possible (as with any active). Systemic or injectable use outside approved contexts should be avoided; only qualified researchers should handle research preparations. PMC+1
8. What concentrations are used in studies / products?
Cosmetic product concentrations vary widely (parts per million to low percentage ranges) depending on formulation. Published controlled topical studies usually use concentrations optimized by the investigators or manufacturers—always consult supplier specs and published protocols. PMC
9. Are there stability or compatibility concerns?
Yes—copper coordination, pH, oxidizing agents, and some preservatives may affect GHK-Cu stability. Formulators often use stabilized salts or encapsulation to improve shelf-life. PMC+1
10. Where can I find authoritative studies on GHK-Cu?
Start with the Pickart reviews and PMC articles cited above, which summarize much of the mechanistic and translational literature. The PubMed links in the References section are a good curated starting point. PMC+1
Final notes & disclaimer
This document is for research and informational purposes only. GHK-Cu and related compounds should be handled by qualified researchers; topical cosmetic uses should follow regulatory and safety guidelines in the intended market. Nothing in this document is medical advice or an endorsement of off-label human use for research chemicals.
