GHK is a tripeptide present in human plasma that binds copper(II) with high affinity. Plasma levels decline with age, which is the observation that anchors most of the interest in it.

The literature is unusual in shape: a large body of in vitro and gene-expression work reporting effects on hundreds of genes, and a much smaller body of small topical cosmetic trials. It is a clean example of what a mechanistic-only evidence base looks like, and of how easily "modulates 4,000 genes in cell culture" turns into a claim about skin.

GHK-Cu delivers copper into cells, and copper is a required cofactor for lysyl oxidase, superoxide dismutase, and other enzymes central to connective tissue and redox biology.

In vitro it stimulates collagen, elastin, and glycosaminoglycan synthesis in fibroblasts, and gene-expression profiling reports broad transcriptional effects. Whether concentrations achievable in human skin after topical application reproduce any of this is the question the in vitro literature structurally cannot answer, and it is the question that matters.

Mechanistic, with limited topical clinical work.

The in vitro and gene-expression literature is extensive. Human evidence is limited to small cosmetic trials of topical formulations reporting modest improvements in skin appearance measures, generally without independent replication, frequently sponsored by formulators, and often without an active comparator.

There is essentially no human evidence for systemic administration for any indication, and injectable use has no clinical evidence base at all.

Topical use has a long cosmetic history with a good tolerability record; contact irritation and sensitisation are the reported effects.

Systemic administration is a different question and is not supported by data. Copper homeostasis is tightly regulated, and copper overload is a real toxic syndrome affecting liver and neurological function. Introducing a copper-delivering agent systemically without monitoring is a genuinely bad idea, and it is one of the few places in this compendium where the mechanism itself flags the hazard.

Used in cosmetic products in many jurisdictions under cosmetic rather than pharmaceutical regulation, which means efficacy claims are not assessed the way drug claims are. Not approved as a drug for any indication. Injectable preparations are unapproved research chemicals.