GHK

GHK (Glycyl-L-histidyl-L-lysine) is a naturally occurring human tripeptide found in plasma, saliva, and urine. It is the copper-free precursor to GHK-Cu and retains significant biological activity on its own. Plasma levels decline from approximately 200 ng/mL at age 20 to around 80 ng/mL by age 60, a decline associated with reduced tissue repair capacity and skin aging.

GHK chelates copper ions to form the active GHK-Cu complex, delivering bioavailable copper to sites of tissue injury and remodeling. It upregulates collagen and glycosaminoglycan synthesis in dermal fibroblasts, promotes angiogenesis, and activates the FAK-paxillin signaling pathway critical for cell migration. Gene expression analyses by Pickart et al. identified modulation of over 4,000 human genes by GHK treatment.

GHK is the copper-free tripeptide that retains meaningful biological activity on its own through receptor-mediated signaling, while GHK-Cu is the copper-bound form that also delivers bioavailable copper directly to tissue repair sites. GHK-Cu is generally considered the more potent form for wound healing applications, but the two are closely related and the copper-free peptide has independent activity distinct from simple copper delivery.

GHK is widely sold over the counter as a cosmetic ingredient and peptide precursor without prescription in most countries. It is not subject to FDA drug scheduling. Injectable GHK falls into a similar unregulated research chemical category as GHK-Cu. No regulatory agency has approved GHK as a drug for any indication.

Topical cosmetic formulations typically use 1 to 5 percent GHK applied once or twice daily to the face or target skin area. Research subcutaneous protocols typically use 100 to 200 mg per day, though human clinical evidence is primarily limited to topical cosmetic formulations rather than injectable use. All injectable protocols are user-derived and not from clinical trials.

GHK has a favorable safety profile in the available evidence. Subcutaneous injection may cause mild injection site redness, and topical use rarely causes skin irritation, particularly on sensitive skin or at higher concentrations. No serious adverse events or systemic toxicity have been documented in the published literature, though the evidence base is limited primarily to in vitro studies and small cosmetic trials.

GHK has a plasma half-life of approximately 30 minutes following injection or systemic exposure, making it shorter-lived than GHK-Cu's ~1-hour half-life. Its short half-life is consistent with its small tripeptide structure and reflects rapid tissue uptake and copper chelation at sites of repair. Topical delivery bypasses systemic pharmacokinetics and provides direct local delivery to dermal tissue.