Tripeptide-29vsCopper Tripeptide-1 (GHK-Cu)

Molecular Formula

C₁₂H₁₉N₃O₅

Molecular Weight

285.3 Da

Half-Life

Oral: rapidly metabolized to Pro-Hyp; accumulates in skin tissue over hours; topical: sustained local activity

Bioavailability

4.4% absolute oral bioavailability; transporter-mediated intestinal absorption; preferential skin tissue accumulation

CAS Number

2239-67-0

Molecular Formula

C₁₄H₂₂N₆O₄Cu

Molecular Weight

401.9 Da

Half-Life

Susceptible to enzymatic degradation; liposomal formulation extends stability. Highly water-soluble (325 mg/mL).

Bioavailability

Limited percutaneous absorption at topical concentrations (local dermal effects primary); systemic bioavailability via injection

CAS Number

49557-75-7

Common

• Mild Gastrointestinal Adjustment
• Aftertaste (oral)
• Mild Skin Warmth (topical)
• Initial Skin Purging

Uncommon

• Allergic Sensitivity

Serious

• Anaphylaxis (theoretical)
• Limited Bioavailability and Potential Immunogenicity

Common

• Mild Tingling or Warmth
• Transient Redness
• Skin Dryness or Peeling

Uncommon

• Injection Site Reactions
• Allergic Contact Dermatitis

Serious

• Copper Accumulation (Theoretical with Injection)
• Copper Toxicity from Excessive Accumulation

Evidence Level

Limited human trials

FDA Status

Research compound

Safety Overview

Tripeptide-29 (Gly-Pro-Hyp, glycyl-prolyl-hydroxyproline) is a naturally occurring collagen-derived tripeptide with an excellent cosmetic safety profile. This is the fundamental repeat unit of collagen protein, making it highly biocompatible. Both oral and topical forms demonstrate minimal adverse effects in clinical trials. No serious adverse events have been reported in published clinical studies spanning over 15 years. The tripeptide is generally recognized as safe (GRAS) for both topical and oral use by regulatory authorities. Individual responses are generally benign and limited to mild gastrointestinal adjustment with oral supplementation or transient dermal warmth with topical application. The primary safety consideration is allergenicity in individuals with gelatin or collagen allergies, which is rare but requires awareness. Molecular weight (285.3 Da) ensures limited systemic absorption when applied topically.

Contraindications

• xKnown allergy to collagen, gelatin, or animal-derived protein products
• xActive skin infections or dermatitis at the topical application site
• xHypersensitivity to hydroxyproline-containing peptides
• xConcurrent use with products at extreme pH that may hydrolyze the peptide

Evidence Level

Limited human trials

FDA Status

Research compound

Safety Overview

Copper Tripeptide-1 (GHK-Cu) is not FDA-approved and lacks human clinical safety data, though cosmetic use in topical formulations is generally recognized as safe based on its composition. The tripeptide-copper complex has been shown to be non-toxic in in vitro cell studies and animal models at cosmetic concentrations (< 200 ppm). However, systemic absorption and safety at higher concentrations or with chronic use remain untested in humans. Copper accumulation in tissues is theoretically possible with repeated systemic use, and effects on copper metabolism have never been characterized. No human Phase 1 studies or formal toxicology assessments have been conducted.

Contraindications

• xWilson's disease (genetic copper metabolism disorder)
• xKnown hypersensitivity to copper compounds or GHK-Cu
• xActive skin infections at the application site
• xSevere hepatic impairment (reduced copper clearance capacity)