GHK-Cu

Overview

One of the few peptides on this list with credible controlled human data — for skin, applied topically. It occurs naturally in plasma, and its discoverer reports levels falling by more than half between young adulthood and old age, which is the origin of its anti-aging framing.

GHK-Cu sequence & structure

GHK-Cu is a 3-residue linear peptide with a free C-terminal acid, carrying a bound metal ion; molecular weight 401.91 Da.

Sequence Gly-His-Lys and the identifiers are confirmed independently by FDA GSRS and PubChem (and match Pickart & Thaler, Nature 1973). Quoted MWs differ by how the copper is counted: 401.91 for the neutral chelate C14H22CuN6O4 (two N–H protons lost on binding; the FDA GSRS/USAN structure), 402.92 for the monocation C14H23CuN6O4+ (PubChem CID 71587328) and ~403.9 (free peptide 340.38 + Cu 63.55) as printed by most vendors; NovoPro prints 400.9. GHK-Cu is often supplied as the acetate (prezatide copper acetate) or with excess free GHK, so peptide content per vial differs from the labelled mass. DrugBank (DB14683) returns HTTP 403 to automated requests; its id is confirmed from the FDA GSRS and PubChem cross-references rather than from DrugBank itself.

Record confidence: high — two independent authoritative sources agree on the sequence and modifications. Every sequence on the site is listed with its sources on the peptide sequences index.

How it works

Chelates copper(II) and delivers it to cells, modulating expression of a broad set of genes involved in extracellular matrix remodelling. Stimulates collagen I, elastin, glycosaminoglycan and proteoglycan synthesis while modulating metalloproteinase activity, and has antioxidant and anti-inflammatory effects.

Evidence base

Rated 3 of 5 — Moderate. Small or early-phase human trials, or good controlled topical human data.

• Among the better-supported peptides for topical use.
• Systemic evidence is essentially absent — do not conflate the two.
• What the controlled human topical data actually consists of. The best-designed study is a multicentre, randomised, evaluator-blinded, vehicle-controlled trial of a topical copper tripeptide gel in diabetic neuropathic foot ulcers, reported by Mulder and colleagues in 1994, which found faster closure of plantar ulcers and a lower rate of ulcer infection than vehicle on top of standardised wound care — a wound-healing indication, not a cosmetic one. The same maker's larger 511-patient phase III trial of the gel failed against control in 1994, ending the drug programme; the gel was later cleared only as a wound dressing. The cosmetic results everyone quotes are two twelve-week vehicle- and comparator-controlled studies, a facial cream in women with photoaged facial skin and an eye cream in women with periorbital photodamage, both presented as abstracts in the 2002 American Academy of Dermatology meeting proceedings by investigators working with the manufacturer, and never published as full peer-reviewed papers. The thigh-skin comparison against vitamin C, melatonin and tretinoin was a 1998 pilot histologic and ultrastructural study in a minor journal. For context, a 2025 Bayesian network meta-analysis of topical treatments for facial photoaging pooled 23 randomised trials in 3,905 participants and contained no copper-peptide arm at all.
• The mechanistic literature is overwhelmingly cultured cells. The collagen, elastin, glycosaminoglycan, proteoglycan and metalloproteinase findings come from fibroblast monolayers, with keratinocyte and osteoblast work alongside and rat wound models behind them. In a dish the experimenter chooses the concentration, no stratum corneum stands between the molecule and the cell, and no plasma albumin or liver competes for the copper — the three things that decide whether any of it happens in a person. A large share of the foundational work and of the most-cited reviews comes from the investigator who discovered GHK and holds a commercial copper-peptide interest, so the direction of effect is better supported than its size.
• For the injected route there is nothing controlled, in any indication. A search of ClinicalTrials.gov returns only topical or patch interventions — a vehicle-controlled phase 2 gel study in acute skin wounds recruiting through 2026, a patch study measuring circulating GHK, and a completed facial-treatment device trial — and no registered trial of injected GHK-Cu at all. The only human reports involving injection are uncontrolled studies of multi-ingredient intradermal hair formulations in which copper tripeptide-1 is one of five actives sitting beside several growth factors, which cannot attribute anything to GHK-Cu. Systemic administration has been tested only in rodents.

Who should avoid it

• Wilson disease or copper metabolism disorders (systemic use)
• Known copper allergy
• Broken or actively infected skin without medical advice

If used under medical supervision, monitor

• Topical use: none required
• Systemic use: not advised outside research

Interactions

Not exhaustive. Always have a pharmacist or physician review your full medication list — including supplements.

• Zinc supplements and other heavy zinc sources — inferred from copper physiology, not from any GHK-Cu study. Zinc and copper compete for intestinal uptake, and zinc induces metallothionein in the enterocyte, which binds copper more tightly than zinc and traps it in the gut lining. Sustained high zinc intake is a well documented cause of copper deficiency, with anaemia, neutropenia and a myelopathy that mimics B12 deficiency; published cases trace back to zinc supplements and even zinc-containing denture adhesive. The practical problem is that zinc pushes copper status one way while a copper complex pushes it the other, and serum copper and ceruloplasmin become hard to read in someone doing both.
• Penicillamine and trientine are the prescribed chelators, and both increase urinary copper excretion, with trientine additionally blocking intestinal uptake - shown directly in a copper isotope imaging study in healthy volunteers. Zinc is used as maintenance therapy but does not strip copper: it induces intestinal metallothionein and blocks absorption. Tetrathiomolybdate is not a prescribed drug at all. It is investigational, approved in no market, with a rolling application to the FDA begun in 2026, and it works by locking copper into a stable complex with albumin rather than by increasing urinary copper.
• Wilson disease and anything that impairs biliary copper excretion — bile is the body's main exit route for copper and it is run by the ATP7B transporter, which is defective in Wilson disease; in cholestasis or advanced hepatobiliary disease the route is physically obstructed. Parenteral nutrition practice reduces or withholds intravenous copper in cholestasis for exactly this reason. Wilson disease is already listed as a contraindication here; the wider point is that anyone with cholestatic liver disease has no reliable way to clear copper that was never metered at the gut wall.
• Ascorbic acid — two separate issues that get merged. In a formulation, ascorbate reduces Cu(II) to Cu(I), which the tripeptide holds far less tightly, and the pair generates hydrogen peroxide as it cycles. That chemistry is what the layering rule is reaching for, though one study found the copper-GHK complex itself redox-inert to ascorbate under moderate conditions, and no published stability or clinical study of a copper peptide layered with ascorbic acid appears to exist. Systemically, controlled feeding studies in young men found that high supplemental ascorbate lowered serum ceruloplasmin oxidase activity — by roughly a fifth in one of them — without changing measured copper absorption. So heavy vitamin C use can shift the very laboratory values a clinician would use to judge copper status, in the opposite direction to copper loading.
• Other copper sources — copper-containing multivitamins and mineral supplements, and stacking a topical copper peptide with an injected one — are additive, and the tolerable upper intake level for copper is defined for oral intake, where the intestine still regulates how much gets in. There is no equivalent ceiling for an injected route and no study of combined exposure. Inferred from copper physiology.
• Estrogens, including combined oral contraceptives and hormone therapy — increase ceruloplasmin synthesis and therefore total serum copper, an elevation a meta-analysis found consistent across preparations. This adds no copper to the body, but it can make serum copper look high in someone who is not loaded, or unremarkable in someone who is. It matters for interpreting labs, not for the compound's action.
• Iron supplements and iron status - copper deficiency produces an anaemia that does not respond to iron, because the copper-dependent ferroxidases ceruloplasmin and hephaestin are what move iron out of cells onto transferrin. Iron given for that anaemia will not correct it, and only copper does. Very high dietary iron may also blunt copper absorption, described mainly in infants.
• Molybdenum supplements - the copper-stripping reputation comes from grazing animals, where sulphide in the rumen converts molybdenum into thiomolybdates that bind copper. People have no rumen, and controlled feeding of very high molybdenum intakes to healthy young men did not disturb copper status. The drug form, tetrathiomolybdate, is a separate matter and is given deliberately to remove copper.
• Vitamin B12 - relevant not because it interacts with the compound but because it is what copper deficiency gets mistaken for. The copper myelopathy presents with spastic gait and sensory ataxia and is indistinguishable, clinically and on imaging, from the subacute combined degeneration of B12 deficiency, and the two can coexist. The wrong deficiency gets treated.
• Vitamin C and copper taken together systemically - in mice given both by mouth, protein oxidation rose in serum, intestine, bladder and kidney and renal function and structure deteriorated. Neither agent alone did this, and a thiol antioxidant prevented it entirely. The pair redox-cycles to hydrogen peroxide. Animal work, with no human counterpart.
• Antacids and acid-suppressing drugs - stomach acid is what frees copper from food into an absorbable form, and antacids at very high intakes are described as interfering with copper absorption; in rats, omeprazole reduced intestinal copper uptake and left copper accumulating in the stomach. The human evidence is thin, and the direction is lower copper status rather than higher.

Commonly confused with

These mix-ups cause real harm — two products sold under one name, or two molecules whose effects run in opposite directions.

Regulatory & legal status

Lawful as a cosmetic ingredient. Injectable preparations are unapproved.

Infographic

GHK-Cu — benefits & risks at a glance Share Download SVG

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

• PubMed — all published literature on GHK-Cu
• PubMed — randomized controlled trials only
• ClinicalTrials.gov — registered human trials

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