GHK-Cu

Also known as: Copper Peptide, GHK-Copper, Glycyl-L-histidyl-L-lysine:copper(II), Prezatide copper, Copper tripeptide-1

Evidence: Preclinical

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Overview

Copper complex of the tripeptide Gly-His-Lys, isolated from human plasma in 1973; raises collagen synthesis in cell and rat studies, with mixed results in small topical human trials.

GHK was isolated from human plasma in 1973 and binds copper(II) tightly. Cell and rat studies show raised collagen and glycosaminoglycan synthesis and faster wound closure. Human data are topical only: a gel helped diabetic foot ulcers close in one RCT, a 0.4% cream did no better than placebo in venous ulcers, and a 13-person post-laser study found no objective skin benefit. No injected or oral human study has been published, and a 2026 independent review calls the clinical evidence sparse. Much of the review literature comes from the discoverer's group. Same molecule as the GHK-Cu Capsule entry (id 28). Listed on FDA's 503A category 2 (safety concerns) page as GHK-Cu for injectable routes, withdrawn-nomination table, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks

Benefits

Wound healing (topical; 1 positive RCT in diabetic foot ulcers, 1 negative in venous ulcers), collagen synthesis (cell culture, rat wounds), hair follicle growth (mouse), skin appearance (topical, no objective benefit in 1 small RCT)

Dosing reference

Research dose: 1 to 2 mg daily SC: vendor/community range, no published human injected dose. Topical trial products included a 0.4% cream
Range: 1000 to 2000 mcg, 1x daily
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 50 mg, 100 mg

Subcutaneous injection is community practice; no injected human study has been published. Human data are topical: daily gel after debridement in diabetic foot ulcers, 0.4% cream in venous ulcers. GHK-Cu is about 16% copper by mass, so 2 mg carries about 0.3 mg copper, against a US adult upper intake level of 10 mg/day for oral copper. No parenteral limit is set for this compound.

Mechanism

Proposed. GHK binds Cu2+ with high affinity. In fibroblast culture GHK-Cu raised collagen synthesis starting at 10^-12 to 10^-11 M, maximal at 10^-9 M, independent of cell number (Maquart et al., 1988). Injected into rat wound chambers it increased collagen, glycosaminoglycans, DNA and type I and III collagen mRNA in a concentration-dependent way, without raising TGF-beta mRNA (Maquart et al., 1993). Topical gel lowered TNF-alpha, MMP-2 and MMP-9 in ischemic rat wounds (Canapp et al., 2003). Claims that GHK resets thousands of human genes come from cell-line expression database analyses in reviews by the discovering group and have not been tested in tissue.

Evidence

Preclinical: animal or in vitro data only

Collagen synthesis in fibroblast culture rose from 10^-12 M GHK-Cu and peaked at 10^-9 M, independent of cell number (Maquart et al., 1988)
In rat wound chambers GHK-Cu raised collagen, glycosaminoglycan and DNA content in a concentration-dependent way (Maquart et al., 1993)
Topical gel on ischemic rat wounds: 64.5% area reduction by day 13 vs 45.6% with vehicle and 28.2% untreated (Canapp et al., 2003)
Multicenter evaluator-blinded RCT of a GHK-Cu gel in diabetic neuropathic plantar ulcers: median closure 98.5% vs 60.8% with vehicle, infections 7% vs 34% (Mulder et al., 1994)
Evaluator-blinded RCT in venous stasis ulcers (n=86): 0.4% GHK-Cu cream was no better than placebo, while silver sulfadiazine was (Bishop et al., 1992)
Human-trial status: topical only, with mixed results; a 13-person post-laser trial found no objective benefit (Mateescu et al., 2026). No injected or oral human study. Hair claims rest on mouse data (Trachy et al., 1991). Most reviews come from the discovering group

References

Side effects

No controlled safety data exist for injected GHK-Cu. Topical RCTs in diabetic and venous ulcers and post-laser skin reported no specific safety signal in their abstracts, and the diabetic ulcer trial found fewer infections (7% vs 34%) (Mulder et al., 1994). FDA's category 2 entry for injectable GHK-Cu cites possible immunogenicity from aggregation and peptide-related impurities and limited human data; the nomination was later withdrawn. Copper load is a theoretical concern in disorders of copper excretion such as Wilson's disease. Commonly reported (anecdotal): injection-site stinging, redness and lumps; topical irritation.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: Not measured: no published pharmacokinetic study by any route or species
Bioavailability: Topical: in human skin in vitro, copper from GHK-Cu permeated dermatomed skin at 2.43 x 10^-4 cm/h, 136 mcg/cm2 over 48 h (Hostynek et al., 2011). Injected: not measured
Molecular weight: 402.92 Da
Sequence: GHK [Cu2+ complex]