GHK-Cu (Copper Tripeptide-1)
GHK-Cu (Copper Tripeptide-1) — evidence, uses & status

Class: peptide
Synonyms: copper peptide
copper tripeptide
GHK-copper
glycyl-L-histidyl-L-lysine copper(II) complex
INCI: Copper Tripeptide-1
Function tags: skin appearance (cosmetic)
antioxidant
(research context:) tissue repair
angiogenesis
hair
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-20

In brief: GHK-Cu is a naturally occurring copper-binding tripeptide. As a topical cosmetic ingredient it has several small human studies showing improved appearance of photoaged skin (fine lines, firmness, density). As an injectable / systemic "research" compound it is studied mainly in vitro and in animals, with little human data and no approval. A well-documented limitation: GHK-Cu barely penetrates intact skin, so topical results depend heavily on formulation and delivery.

## Identity

a **tripeptide** (3 amino acids: glycine, L-histidine, L-lysine, < 40 aa → peptide) coordinated with a **copper(II)** ion. Occurs naturally in human plasma, saliva and urine; plasma levels decline ~60% between ages ~20 and ~60. First described by Loren Pickart (1973).

## Development & history

- Discovered by **Loren Pickart in 1973**: he identified a factor in human plasma that made aged liver tissue synthesise proteins like younger tissue — that factor was GHK, which binds copper as GHK-Cu (reported in *Nature*).
- Over the following decades it was studied primarily for **wound healing and tissue remodeling** (including some clinical wound-care use), then migrated into **cosmetics** as **Copper Tripeptide-1**, commercialised first by Pickart's own company (Skin Biology) and later by many brands.
- Today the **topical** form is a mainstream cosmetic ingredient; the **injectable / systemic** form remains a research compound with no approval anywhere in the world.

## Mechanism (as proposed)

a copper-binding tripeptide that, in vitro, stimulates fibroblast **collagen/elastin** synthesis (Maquart 1988), modulates **MMP/TIMP** balance (orderly remodeling), acts as an **antioxidant** and **anti-inflammatory** (lowers IL-6/TNF-α), and is **pro-angiogenic** (VEGF); bioinformatic analyses report broad gene-expression modulation. Most of this is in vitro; in-vivo topical relevance is constrained by poor skin penetration.

## Related reading

- The [copper uglies](/learn/copper-uglies) — why GHK-Cu can make skin look worse before better when introduced too aggressively, and how to tell adjustment from a genuine reaction.
- Its anti-inflammatory profile in context, alongside the other soothing peptides, in our [anti-inflammatory peptides reference list](/learn/anti-inflammatory-peptides).
- Where copper peptides fit in a topical routine — layering, timing, and what to keep them apart from — in [how to use peptides](/learn/how-to-use-peptides).
- Where GHK-Cu sits among the cosmetic peptides, ranked by evidence, in [cosmetic peptides ranked by evidence](/learn/best-peptides-for-skin).
- What copper peptides are, and how GHK-Cu differs from the hair-focused AHK-Cu, in [what are copper peptides](/learn/what-are-copper-peptides).

Evidence grades by outcome:
outcome: Topical: appearance of photoaged skin (fine lines, firmness, density)
grade: B
base: Small human RCTs — Leyden 2002 (n=71), eye-cream (n=41), Badenhorst 2016 (nano-carrier vs Matrixyl 3000)
effect: Measurable improvement
caveat: Small samples; effect generally smaller than prescription retinoids; highly formulation-dependent
outcome: Collagen/elastin synthesis & balanced MMP/TIMP remodeling
grade: B
base: In-vitro fibroblast studies (Maquart 1988; Pickart)
effect: Stimulates synthesis; orderly turnover
caveat: In vitro; in-vivo relevance limited by skin penetration
outcome: Skin penetration of intact-skin serums
base: Permeation study (Li 2015)
effect: Near-zero through intact stratum corneum
caveat: Key limitation; most benefit shown with enhanced delivery or penetration-optimised formulas
outcome: Post-procedure wound healing (e.g., after laser resurfacing)
grade: C
base: Small controlled trials + animal models
effect: Faster healing / less irritation
caveat: Medicinal context — not a cosmetic-product claim
outcome: Hair growth / density
grade: D
base: Mechanistic + small studies
effect: Suggestive
caveat: Weak human evidence
outcome: Systemic / injectable "anti-aging / resets gene expression"
grade: F
base: In-vitro / bioinformatic (Connectivity Map, ~4,000 genes toward a "younger" profile)
effect: Broad gene modulation in vitro
caveat: Bioinformatic/in vitro only; no human systemic-efficacy trials; "reverses aging" is not demonstrated
outcome: "Rebuilds collagen" dermal synthesis
grade: D
base: Marketing claim
caveat: The human trials scored appearance endpoints — fine lines, firmness, the look of density — not dermal collagen; no biopsy or histology has measured collagen in skin after topical application. Synthesis of collagen and elastin was shown in fibroblast culture, and permeation through intact skin is near-zero.
outcome: Safety (topical)
base: Widely used cosmetic; small trials
effect: Well tolerated
caveat: Topical generally well tolerated (occasional mild redness); systemic/injectable human safety not established

Legal status:
region: INT
status: See note
note: Topical (INCI Copper Tripeptide-1) — a lawful cosmetic ingredient in the EU (Regulation (EC) 1223/2009) and widely used globally; this is the form sold. Claims are constrained by cosmetic regulation — see the cosmetic_claims block.

Injectable / systemic — Not approved anywhere as a medicine. EU: not eligible for magistral / officinal compounding (no Ph. Eur. monograph exists). US: on 15 April 2026 the FDA removed injectable GHK-Cu from the Category 2 bulks list (previously restricting 503A compounding since 2023–2024) but did NOT add it to Category 1 — creating an interim regulatory posture. A PCAC (Pharmacy Compounding Advisory Committee) review of both injectable and non-injectable GHK-Cu is scheduled before end-February 2027; some 503A compounding pharmacies have resumed preparation on the basis of the Category 2 removal, others await affirmative Category 1 authorization. The topical / non- injectable route sits on Category 1 pending the same PCAC review. Recheck the early-2027 PCAC outcome before any US injectable references are updated.

Cosmetic claims:
allowed: for the appearance of firmer, smoother-looking skin
helps improve the look of fine lines
for a more even, radiant-looking complexion
antioxidant
forbidden: stimulates collagen synthesis
wound healing
heals
repairs skin
increases skin density/thickness
appearance of denser-looking skin
reverses aging
resets gene expression
treats…
hair growth
increases hair density

Note: Dual-form compound. The topical form (INCI Copper Tripeptide-1) is a lawful cosmetic ingredient — this is the sellable serum. The injectable / systemic form is a research compound, not approved. Reference science below is neutral; the sellable product uses cosmetic (appearance/feel) claims only — see the cosmetic_claims block above.
Status note: US injectable status: interim — Category 2 removed 15 April 2026, PCAC review scheduled before end-February 2027; recheck after outcome

Sources:
Maquart FX, Pickart L, et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide–copper complex GHK-Cu. FEBS Lett. 1988.
Leyden JJ, et al. Clinical evaluation of a copper tripeptide cream and serum for photodamaged skin. J Cosmet Dermatol. 2002.
Li (et al.). Skin permeation of GHK-Cu. Pharm Res. 2015. (near-zero permeation through intact skin.)
Badenhorst T, et al. GHK-Cu nano-lipid carrier vs Matrixyl 3000, 8-week RCT. 2016.
Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide (gene-expression review). Int J Mol Sci. 2018 (PMID 29986520).
Mortazavi SM, et al. Topically applied GHK as an anti-wrinkle peptide: advantages, problems, prospects. BioImpacts. 2024.
FDA. Update to 503A Bulk Drug Substances Category 2 List — Removal of GHK-Cu and 10 other peptides. 15 April 2026 (Docket No. FDA-2025-N-6895).
FDA. Pharmacy Compounding Advisory Committee — announced review of GHK-Cu (injectable and non-injectable routes) scheduled before end-February 2027.