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GHK

Also known as glycyl-L-histidyl-L-lysine, Gly-His-Lys, copper-free GHK, Tripeptide-1 (INCI), Kollaren

The copper-free tripeptide itself; in the body it binds copper and largely becomes GHK-Cu.

preclinical Recovery & tissue endogenous peptide

At a glance

Category
Recovery & tissue
Status
endogenous peptide
Route
topical; subcutaneous injection outside any approval framework
Half-life
No reliable published human pharmacokinetics. As an unmodified tripeptide it is expected to be cleared rapidly by plasma aminopeptidases; circulating half-life figures found on supplier pages have no traceable primary source.
Onset
8-12 weeks in the topical cosmetic studies of the copper complex
Molecular weight
340.4 g/mol (CAS 49557-75-7)
Sequence
GHK (glycyl-L-histidyl-L-lysine)

A naturally occurring fragment of human albumin, present in plasma. As Tripeptide-1 it is a catalogued cosmetic ingredient, reviewed by the US Cosmetic Ingredient Review panel and concluded to be "safe in the present practices of use and concentration in cosmetics, as described in this safety assessment", with reported use in 36 products at 0.00002-0.001% 46. There is no approved medicinal product containing GHK in any form, and no injectable product outside the grey market.

Doping status: Not listed by name by WADA. A non-approved injectable form could fall under S0; athletes should check with their anti-doping authority.

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

This is a short entry. There is little or no published research on this compound, so there is correspondingly little to report. Empty dosing or reconstitution sections mean no credible figures exist — not that they were left out.

Mechanism of action

GHK is a fragment of human serum albumin, isolated from plasma by Pickart and Thaler in 1973. Its defining chemical property is a very high affinity for copper(II): the histidine imidazole, the N-terminal amine and the peptide backbone form a strong chelate. This is the reason the free peptide and the copper complex are difficult to separate biologically. Introduced into plasma or tissue, free GHK will readily acquire copper from albumin and other copper pools and form GHK-Cu in situ. For practical purposes, administering copper-free GHK is not a way of avoiding copper delivery; it is a way of recruiting the body's own copper to the peptide.

That said, the two are not fully interchangeable in the laboratory. Work that identified GHK through gene-expression screening used the free tripeptide: in the 2012 Genome Medicine study on emphysema, GHK was pulled out of the Connectivity Map as a compound whose transcriptional signature reversed that of emphysematous lung destruction, and free GHK restored collagen gel contraction and remodelling in fibroblasts from COPD lungs. Conversely, effects that depend on delivering copper as a cofactor - lysyl oxidase-driven collagen and elastin cross-linking is the clearest example - require the copper complex and would be expected to depend on local copper availability if free peptide is used. Where a claimed effect sits on this spectrum is usually not stated in the marketing, and often has not been tested.

What the research shows

Nearly all of the applied research, and all of the human cosmetic studies, were done with GHK-Cu rather than free GHK. The free peptide has a genuine but narrow research literature, mostly transcriptomic and cell-culture work. There is no human clinical study of copper-free GHK by any route, and none at all of injected GHK.

Research in humans

No published human study has administered copper-free GHK, topically or by injection, for any indication. The human data cited in GHK marketing - the facial cream study in 71 women, the eye cream study in 41 women, the thigh skin study - all used the copper complex. See the GHK-Cu entry for those.

Animal and lab research

The free tripeptide appears mainly in cell-culture work: fibroblast collagen remodelling in the COPD study, gene-expression profiling, and assorted wound-healing and antioxidant assays. Animal work on wound healing and lung injury generally uses GHK-Cu. Concentrations in cell culture are typically nanomolar to low micromolar.

Caveats. Three caveats dominate. First, the in-vivo distinction between GHK and GHK-Cu is largely notional, because free GHK chelates available copper; studies rarely control for the copper status of the medium or the animal, so it is often unclear which species was actually active. Second, much of the review literature promoting GHK was written by its discoverer, who founded and ran companies selling GHK-Cu skincare - a conflict that is sometimes not declared. Third, the frequently repeated statement that plasma GHK falls from around 200 ng/ml at age 20 to around 80 ng/ml at age 60 is cited to those same reviews rather than to a primary analytical measurement; the figure circulates far more widely than its evidential basis warrants.

What it is used for

  • Cosmetic formulation as Tripeptide-1, usually alongside or instead of the copper complex 6
  • Research reagent in gene-expression and fibroblast studies - it was identified in a Connectivity Map screen as reversing the transcriptional signature of emphysematous lung destruction, and restored collagen gel contraction in fibroblasts from COPD lungs 1
  • Sold for subcutaneous injection for tissue repair and anti-ageing, with no published human basis for that route

Dosing

Route
topical in cosmetic use; injection use is unstudied
  • No dosing range is given because no human study has established one for the copper-free peptide by any route.
  • Vendor protocols simply reuse GHK-Cu injection figures (commonly 1-2 mg per day). Those figures were not validated for the copper complex either, and there is no reason to assume they transfer to the free peptide, whose molar mass differs and whose copper loading is uncontrolled.
  • In cosmetic products the catalogued concentrations are specific and low. The Cosmetic Ingredient Review survey recorded Tripeptide-1 in 36 uses at 0.00002-0.001%, that is 0.2 to 10 ppm, with the single rinse-off use at 0.00003% 6. These are formulation concentrations in a finished cosmetic, not a dose, and they cannot be read across to the milligram injection figures quoted for the copper complex.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Safety

Side effects

  • Topical: skin irritation and redness, generally reported as milder than with the copper complex
  • Injection: injection site irritation; no controlled safety data
  • Copper handling remains a consideration even for the copper-free peptide, because it mobilises endogenous copper rather than adding none

Do not use if

  • Wilson's disease and other disorders of copper handling - in Wilson disease copper is not excreted normally and accumulates in the liver and brain, and dietary copper restriction is part of management 5. A high-affinity copper chelator that then delivers copper to tissue is not a safe choice in such patients
  • Concurrent copper-lowering therapy - penicillamine and trientine chelate copper and increase urinary excretion, and zinc blocks enteric copper absorption 5; GHK would be expected to counteract all three
  • Pregnancy and breastfeeding: no data for injection use
  • Known hypersensitivity

Interactions

Not systematically studied. The mechanistically plausible interactions are with copper-modifying agents: chelators and copper-lowering drugs on one side, copper supplementation on the other. No study has quantified either.

Sources