GHK-Cu
Summary
GHK-Cu (glycyl-L-histidyl-L-lysine-copper) is a naturally occurring copper-binding tripeptide first isolated from human plasma in 1973. It functions as a signaling molecule that modulates multiple cellular pathways involved in tissue repair and regeneration. The peptide's concentration in human plasma declines from approximately 200 ng/mL at age 20 to 80 ng/mL by age 60, correlating with decreased regenerative capacity. GHK-Cu works through several mechanisms including copper ion transport, gene expression modulation (affecting over 4,000 human genes), collagen and elastin synthesis stimulation, antioxidant activity via superoxide dismutase enhancement, and growth factor pathway activation. Research demonstrates efficacy in wound healing, skin regeneration, hair follicle stimulation, and anti-inflammatory responses across multiple tissue types. The peptide is not FDA-approved for therapeutic use but is widely used in cosmetic products. It was recently added to FDA's Category 1 bulk substances list for 503A compounding, though not for injectable routes. GHK-Cu is available primarily through compounding pharmacies for research purposes and in topical cosmetic formulations marketed for anti-aging and skin rejuvenation applications.
Potential Benefits
Wound Healing and Tissue Regeneration
- Accelerated wound closure: Studies show 30-50% reduction in healing time across various wound models, with GHK-Cu promoting cell proliferation and angiogenesis [1][7]
- Enhanced collagen synthesis: Stimulates collagen production in fibroblasts at nanomolar concentrations (10⁻⁹ M), with studies showing increased procollagen synthesis in 70% of subjects compared to 50% with vitamin C [2][8]
- Matrix remodeling: Modulates matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs), balancing collagen synthesis and breakdown for optimal tissue repair [9][12]
Skin Anti-Aging Effects
- Wrinkle reduction: Randomized clinical trial demonstrated 31.6% reduction in wrinkle volume after 8 weeks of twice-daily application with nano-lipid carrier formulation [2]
- Skin firmness improvement: Clinical studies measured 20-30% improvements in skin firmness and elasticity after 12 weeks of topical treatment [2]
- Collagen IV enhancement: When combined with hyaluronic acid at 1:9 ratio, increased collagen IV production by 25.4-fold in cellular tests and 2.03-fold in ex-vivo skin models [6]
- Multi-collagen stimulation: Promotes synthesis of collagen types I, IV, and VII, along with elastin, proteoglycans, and glycosaminoglycans [1][2][6]
Gene Expression Modulation
- Genome-wide effects: Influences expression of 31.2% of human genes with changes ≥50%, upregulating 59% and downregulating 41% [1]
- DNA repair activation: Primarily stimulatory for DNA repair genes (47 upregulated, 5 downregulated), suggesting enhanced cellular repair mechanisms [10][11]
- Stem cell enhancement: Increases stem cell markers including integrins and p63, while promoting secretion of trophic factors by mesenchymal stem cells [10]
Antioxidant and Anti-Inflammatory Properties
- ROS reduction: Decreased reactive oxygen species production and increased superoxide dismutase (SOD) activity in multiple studies [4][13]
- Anti-inflammatory response: Reduced TNF-α and IL-6 production in lipopolysaccharide-induced acute lung injury models, with suppression of inflammatory cell infiltration [13]
- Neuroprotective effects: Demonstrated potential for preventing oxidative stress and age-related cognitive decline through copper regulation without oxidative toxicity [3][14]
Hair Growth Stimulation
Safety Information
Clinical Safety Profile
- Favorable tolerability: Extensive published research demonstrates minimal side effects with GHK-Cu exhibiting a generally safe profile when used appropriately [1][2]
- Wide therapeutic window: Estimated lethal dose of approximately 330 mg/kg body weight, over 300 times the known effective dose, indicating low acute toxicity risk with prudent administration [2]
- Cosmetic safety record: Authors note "no issues have ever arisen during its use as a skin cosmetic" despite decades of widespread use [2]
- Effective concentrations: Research demonstrates efficacy at picomolar to nanomolar concentrations (10⁻¹² to 10⁻⁹ M), with maximal collagen stimulation at 10⁻⁹ M [8]
Regulatory Status
- Not FDA-approved: GHK-Cu has not been approved for any therapeutic use in humans by the FDA or international regulatory counterparts [1][2]
- Compounding restrictions: Added to FDA's Category 1 bulk substances list for 503A compounding but specifically excluded for injectable routes of administration
- Cosmetic use permitted: Legal for cosmetic applications and commonly found in skin care products as copper peptide-1
- Research-only status: Injectable forms available through compounding pharmacies are intended for research purposes only, not for human therapeutic use
Side Effects and Contraindications
- Minimal reported adverse effects: Early studies and anecdotal reports suggest GHK-Cu is well-tolerated with few documented side effects
- Copper sensitivity considerations: Individuals with copper metabolism disorders or sensitivities should exercise caution
- Skin application: Topical use generally well-tolerated; transdermal penetration study showed permeability coefficient of 2.43 × 10⁻⁴ cm/h with potentially therapeutic copper delivery [5]
- Unknown long-term effects: While short-term studies (8-12 weeks) show safety, comprehensive long-term human safety data remains limited
Research Gaps
- Limited large-scale RCTs: Most human evidence is from small studies or observational data; large randomized controlled trials specifically for wound healing are notably absent
- Dosing standardization: Optimal dosing protocols, treatment duration, and delivery methods require further clinical investigation
- Drug interactions: Potential interactions with other medications or supplements have not been comprehensively studied
- Special populations: Safety data in pregnant/nursing women, children, and individuals with chronic diseases is lacking