GHK-Cu

What is GHK-Cu?

GHK-Cu is a naturally occurring tripeptide (Gly-His-Lys) that has a strong affinity for copper ions (Cu²⁺). It was first identified in human plasma and has been found to decline significantly with age. The copper complex is essential for its biological activity.

Structure: Glycyl-L-Histidyl-L-Lysine with bound copper ion

Natural Occurrence: Found in human plasma, saliva, and urine

Age-Related Decline: Levels drop from ~200 ng/mL at age 20 to ~80 ng/mL by age 60

Discovery: First isolated from human plasma albumin by Dr. Loren Pickart in 1973

Mechanism of Action

Copper Delivery and Enzyme Activation

Copper-Dependent Enzymes:

• Activates lysyl oxidase (collagen cross-linking)
• Stimulates superoxide dismutase (antioxidant)
• Enhances cytochrome c oxidase (cellular energy)
• Supports copper-zinc SOD activity

Gene Expression Modulation

Documented Effects on Gene Expression:

• Upregulates collagen synthesis genes (COL1A1, COL3A1)
• Increases elastin production
• Enhances proteoglycan synthesis
• Modulates TGF-β signaling
• Over 4,000 genes affected based on gene array studies

Wound Healing Enhancement

Multi-Phase Support:

• Attracts immune cells and fibroblasts to wound sites
• Stimulates angiogenesis
• Enhances collagen remodeling
• Reduces scar tissue formation
• Anti-inflammatory effects

Anti-Aging Mechanisms

Skin Rejuvenation:

• Increases collagen and elastin synthesis
• Enhances skin thickness and density
• Improves skin firmness and elasticity
• Reduces fine lines and wrinkles
• Promotes glycosaminoglycan production

Clinical Applications

Dermatological/Aesthetic

• Skin aging and wrinkle reduction
• Post-procedure healing (lasers, peels, microneedling)
• Acne scarring improvement
• Stretch mark reduction
• Skin tightening and firming
• Hair growth support (topical)

Wound Healing

• Chronic wounds and ulcers
• Surgical wound optimization
• Burn healing support
• Diabetic wound healing
• Post-surgical scar prevention

Hair and Scalp

• Hair follicle support
• Scalp health optimization
• Hair thinning/loss (topical application)
• Post-transplant healing

Potential Systemic Applications

• Tissue repair and regeneration
• Anti-inflammatory effects
• COPD (investigational)
• Neuroprotection (preclinical)

Dosing Protocols

Topical Application (Most Common)

Serums/Creams:

• 0.5-2% GHK-Cu concentration
• Apply 1-2 times daily to cleansed skin
• Can be combined with other actives (vitamin C, retinoids - use separately)
• Use SPF during daytime as part of regimen

Subcutaneous Injection

Systemic/Local Effects:

• 1-2 mg daily subcutaneously
• Can be injected near areas of concern
• Duration: 4-12 weeks
• May be combined with other regenerative peptides

Mesotherapy/Microneedling

Enhanced Delivery:

• GHK-Cu applied during or after microneedling
• Typically 0.1% solution for professional application
• Enhances absorption and effect
• Excellent for facial rejuvenation

Post-Procedure Use

After Lasers/Peels:

• Begin 24-48 hours post-procedure (per practitioner guidance)
• Apply 2-3 times daily during healing phase
• Continue for 2-4 weeks post-procedure

Patient Selection Criteria

Good Candidates

Aesthetic Applications:

• Signs of skin aging (fine lines, loss of firmness)
• Post-procedure optimization (laser, chemical peels)
• Acne scarring
• Those seeking non-invasive anti-aging support
• Hair thinning (topical application)

Wound Healing:

• Chronic wounds responsive to enhanced healing
• Post-surgical patients
• Slow-healing individuals
• Diabetic wound care (adjunctive)

Contraindications

Absolute:

• Wilson's disease (copper metabolism disorder)
• Known copper sensitivity or allergy
• Active skin infection at application site

Relative:

• Pregnancy and nursing (limited safety data)
• History of copper toxicity
• Other copper metabolism disorders

Safety Profile

Generally Well-Tolerated

Topical Use:

• Very low incidence of adverse effects
• Mild tingling or warmth (transient)
• Rare: contact sensitivity
• Compatible with most skincare ingredients

Injectable Use:

• Injection site reactions (mild)
• Transient redness or bruising
• Systemic effects rare at therapeutic doses

Copper Considerations

• Therapeutic doses do not cause copper toxicity
• GHK-Cu provides controlled copper delivery
• No significant systemic copper accumulation at standard doses
• Contraindicated only in copper metabolism disorders

Long-Term Safety

• Extensively studied for cosmetic use
• Good safety record over decades of use
• No significant long-term concerns identified
• Naturally occurring compound

Monitoring Parameters

Baseline Assessment

Aesthetic Use:

• Skin assessment (photos, scoring)
• Review of current skincare regimen
• History of sensitivities or reactions

Injectable Use:

• Medical history review
• Copper metabolism disorder screen
• Document treatment goals

Ongoing Monitoring

Topical:

• Visual assessment of results (photos at 4, 8, 12 weeks)
• Tolerance and compliance assessment
• Adjustment of regimen as needed

Injectable:

• Local reaction monitoring
• Efficacy assessment
• Systemic tolerance evaluation

Drug Interactions

Topical Considerations

Compatible With:

• Most skincare actives
• Hyaluronic acid
• Vitamin C (use at separate times)
• Retinoids (use at separate times)
• Growth factors

Use Separately From:

• Strong acids (may affect stability)
• Vitamin C at same time (copper may oxidize vitamin C)
• Allow time between applications

Injectable Considerations

• No significant drug interactions documented
• Can be combined with other injectable peptides
• Separate from vitamin C injections

Compounding Considerations

Quality Requirements

Peptide Quality:

• Certificate of Analysis with identity verification
• Purity ≥98%
• Copper content verification
• Sterility testing (injectables)
• Endotoxin testing

Formulation Stability

Topical:

• pH 5.5-6.5 for optimal stability
• Protect from oxidation (airless packaging)
• Avoid direct sunlight
• Shelf life typically 6-12 months

Injectable:

• Reconstitute with bacteriostatic water or sterile saline
• Use within 14-21 days of reconstitution
• Refrigerate after reconstitution

Storage

• Lyophilized peptide: Room temperature or refrigerated
• Reconstituted: Refrigerate at 2-8°C
• Topical products: Per manufacturer instructions
• Protect from light and heat

Regulatory Status

• NOT FDA-approved as a drug
• Widely available as cosmetic ingredient
• Available through compounding pharmacies (injectable)
• Generally Recognized as Safe for topical cosmetic use
• Long history of cosmetic industry use

Clinical Pearls

1. Patience required: Collagen remodeling takes 4-12 weeks; set appropriate expectations
2. Post-procedure powerhouse: Excellent for enhancing recovery from aesthetic procedures
3. Copper is key: The Cu²⁺ is essential for activity; pure GHK without copper is less effective
4. Separate from vitamin C: Apply at different times to prevent oxidation interactions
5. Consistency matters: Daily use over months yields best results
6. Natural decline: Explain that GHK-Cu replacement makes physiological sense given age-related decline

References

1. 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.
2. Pickart L. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging. Oxidative Medicine and Cellular Longevity. 2012;2012:324832.
3. Kang YA, et al. Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Arch Dermatol Res. 2009;301(4):301-306.
4. Leyden J, et al. Cosmetics and Dermatology: Copper Peptide and Skin. Springer. 2010.