01 Identity
| Common name | GHK-Cu (copper tripeptide) |
|---|---|
| Peptide | GHK — glycyl-L-histidyl-L-lysine (Gly-His-Lys) |
| Complex | Copper(II) complex of GHK |
| Cosmetic name (INCI) | Copper Tripeptide-1 |
| CAS numbers | GHK 49557-75-7 · complex 89030-95-5 · confirmed (PubChem) |
| Origin | Naturally occurring; first isolated from human plasma (1973) |
A small copper-binding tripeptide occurring naturally in human plasma, where reported levels decline with age. It binds copper to form GHK-Cu; most of its activity is attributed to copper delivery and modulation of extracellular-matrix synthesis.
02 Regulatory status
The status splits the same way the evidence does. Topical (Copper Tripeptide-1) is an established cosmetic ingredient, used widely in skincare; it is not approved as a drug for any therapeutic indication. Injectable / systemic GHK-Cu holds no marketing authorisation anywhere and is not an approved medicine.
In the United States, injectable GHK-Cu was placed on the FDA's Category 2 compounding list in 2023; 2026 reporting indicates the relevant nominations were withdrawn, with a Pharmacy Compounding Advisory Committee review anticipated. Confirm against FDA primary documents. No controlled-substance scheduling.
03 Mechanism of action
Copper delivery and ECM stimulation. GHK-Cu stimulates fibroblast synthesis of collagen and glycosaminoglycans and modulates MMPs and their inhibitors (TIMPs). Best-grounded mechanism; in-vitro and some human-tissue work.
Wound-repair signalling and antioxidant effects. Largely preclinical.
Broad gene-expression modulation ("resetting" expression of many genes). Microarray / review-level and frequently overstated, and a change in gene expression in cells is not a demonstrated clinical outcome.
The collagen/ECM mechanism is consistent with the topical skin findings. The sweeping "genome-resetting, whole-body anti-aging" framing rests on mechanistic and review material, not human outcomes.
04 Pharmacokinetics / pharmacodynamics
Active at very low (nanomolar) concentrations in cell culture. For the topical route the relevant question is local delivery into skin, addressed through formulation.
For a systemic route there is no human pharmacokinetic characterisation: absorption, distribution, and the fate of the copper complex after injection in humans are not established. Copper homeostasis is tightly regulated, which is itself a reason systemic dosing cannot be assumed benign by analogy to topical use.
05 Evidence by endpoint
Almost everything tested in people here was applied to the skin. Systemic benefit rests on cell, animal, and review material, not on human trials.
5.1 — Skin appearance / photoaging (topical)
Several small human studies support topical benefit: Leyden et al. (facial and eye-cream RCTs, 2002/2005) reported improved skin density, thickness, elasticity, and reduced fine lines over 12 weeks; Abdulghani et al. (1999) reported topical GHK-Cu increased collagen in ~70% of volunteers, versus ~50% for vitamin C and ~40% for retinoic acid. Balance: a randomised trial after CO₂ laser resurfacing (13 patients) found no significant objective improvement, with higher patient satisfaction the only positive — these are small, often cosmetic-industry studies with soft endpoints.
Human topical/local only5.2 — Wound healing
A long preclinical history (collagen and GAG synthesis, animal wound models) and historical topical use. Rigorous human wound-healing RCTs are limited.
Preclinical (+ topical historical use)5.3 — Hair growth
Copper peptides (including the related AHK-Cu) have been studied for hair; GHK-Cu-specific human evidence is limited.
Preclinical / limited5.4 — Systemic / injected use (anti-aging, "wellness," inflammation)
The popular community use, and the weakest-supported. Systemic effects have been shown in animals (e.g. intraperitoneal GHK-Cu reduced emphysema and inflammation in mice; an older implanted-wound-chamber animal study reported systemic collagen effects). No human trial has evaluated injected or systemic GHK-Cu for any indication.
Preclinical only — no human trials5.5 — Antioxidant / gene-expression modulation
Reported in vitro and in review articles, including effects on large numbers of genes.
Mechanistic06 Safety and adverse events
Safety, like efficacy, splits by route.
Topical: GHK-Cu has a long history of cosmetic use and is generally well tolerated; the most common issues are local — irritation, tingling, or flushing, and possible copper sensitivity. A reasonably characterised topical picture by cosmetic standards.
07 Evidence summary
| Endpoint | Grade |
|---|---|
| Skin appearance / photoaging (topical) | Human topical/local only |
| Wound healing | Preclinical |
| Hair growth | Preclinical / limited |
| Systemic / injected use | Preclinical — no human data |
| Antioxidant / gene modulation | Mechanistic |
| Long-term human safety (systemic) | No data |
08 References
- Leyden JJ, et al. Anti-aging benefits of a GHK-Cu facial and eye cream: a randomised 12-week clinical trial. Dermatologic Surgery. 2005;31(7).Confirm full pagination
- Leyden JJ, et al. Clinical evaluation of a copper tripeptide cream and serum for photodamaged skin. Journal of Cosmetic Dermatology. 2002;1(3):197–204.
- Abdulghani AA, et al. Topical GHK-Cu versus vitamin C and retinoic acid — collagen comparison. 1999.Confirm full citation
- Maquart FX, Pickart L, et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide–copper complex GHK-Cu. FEBS Letters. 1988;238(2):343–346.
- Siméon A, Wegrowski Y, Bontemps Y, Maquart FX. Expression of glycosaminoglycans and small proteoglycans in wounded skin and regulation by GHK-Cu. J Invest Dermatol. 2000;115(6):962–968.
- Effects of a topical copper tripeptide complex on CO₂ laser–resurfaced skin — randomised study. Archives of Facial Plastic Surgery.No significant objective improvement; included for balance — confirm citation
- GHK-Cu attenuates cigarette-smoke-induced pulmonary emphysema and inflammation in mice (intraperitoneal; preclinical systemic).PMC9354777
- Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging. Oxid Med Cell Longev. 2012;2012:324832. Review
- Pickart L, Vasquez-Soltero JM, Margolina A. GHK and DNA: resetting the human genome to health. BioMed Research International. 2014;2014:151479. Review — gene-expression claims originate largely here