K4 Elite
K4 Elite
GHK-Cu is the copper(II) complex of the endogenous tripeptide Gly-His-Lys, first isolated from human plasma. Human data are limited to topical use: a multicentre randomised, evaluator-blinded trial of a GHK-Cu gel (Iamin) on diabetic neuropathic ulcers (Mulder 1994) and a small randomised study of GHK-Cu skin-care products after CO2 laser resurfacing (Miller 2006, n=13), plus in-vitro human skin penetration work. The remaining literature is in-vitro (fibroblast and gene-expression studies) and animal wound models, summarised in Pickart & Margolina's 2018 review. No human trial of injectable GHK-Cu has been published; FDA's Category 2 entry for injectable GHK-Cu cites immunogenicity risk and 'limited data in humans'.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Mulder et al., Wound Repair Regen 1994 (multicentre randomised, evaluator-blinded, placebo-controlled; topical; human) | Patients with diabetic neuropathic plantar ulcers enrolled in a standardised wound-care protocol (sharp debridement, pressure-relieving footwear) | Patients received a daily metered dose of glycyl-L-histidyl-L-lysine:copper gel (Iamin Gel) or vehicle applied to the ulcer after initial debridement. | Median percentage ulcer-area closure was 98.5% with the GHK-Cu gel versus 60.8% with vehicle (p < 0.05); ulcer infection incidence was 7% versus 34% (p < 0.05) in ulcers treated immediately after debridement. |
| Miller et al., Arch Facial Plast Surg 2006 (randomised, blinded-evaluator; topical; human) | 13 patients completing the study after circumoral CO2 laser skin resurfacing | Patients were randomised to post-treatment skin-care regimens with or without GHK-Cu-containing products and evaluated for erythema, wrinkles and overall skin appearance over 12 weeks. | Blinded evaluators and computer analysis found no significant between-group difference in erythema resolution, wrinkles or skin quality; patient-questionnaire satisfaction was higher in the GHK-Cu group (P = .04). |
| Hostynek, Dreher & Maibach, Inflamm Res 2011 (in-vitro human skin penetration) | Isolated human stratum corneum, heat-separated epidermis and dermatomed skin in flow-through diffusion cells | A 0.68% aqueous solution of copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was applied under infinite-dose conditions and copper in tissue and receptor fluid was measured by ICP-MS over 48 h. | Copper from the tripeptide complex penetrated and was retained in human skin layers in vitro, characterising its potential for transdermal copper delivery. |
| Parker et al., Otolaryngol Head Neck Surg 2013 (irradiated rat wound model; preclinical) | Sprague-Dawley rats with dorsal irradiation, a 28-day recovery period and 2 x 8 cm cranially based dorsal flaps | Rats received twice-daily topical GHK-Cu gel or aquaphilic ointment control applied to the flap for 10 days before harvest. | The study compared flap outcomes and immunohistochemical vascular markers (caveolin-1, VEGF) between GHK-Cu and control-treated irradiated wounds in rats. |
| Pollard et al., Arch Facial Plast Surg 2005 (in-vitro human fibroblasts) | Primary human dermal fibroblast lines from normal and previously irradiated tissue obtained intraoperatively from head and neck cancer patients | Fibroblasts were cultured serum-free with copper tripeptide (GHK-Cu) and growth and autocrine production of bFGF, TGF-β1 and VEGF were measured. | The study characterised growth-factor expression responses of normal and irradiated fibroblasts to GHK-Cu in vitro. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| No treatment-related adverse events specified in the topical human trials located | The Mulder 1994 abstract reports safety and effectiveness were evaluated but gives no adverse-event frequencies; the Miller 2006 abstract does not report adverse-event data. These are small topical studies and do not address other routes. | Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper (Wound Repair Regen 1994) ↗ |
| Injectable GHK-Cu: immunogenicity / impurity risk and limited human data (regulatory assessment) | FDA's Category 2 entry for 'GHK-Cu (for injectable routes of administration)' states compounded injectable GHK-Cu 'may pose risk for immunogenicity due to the potential for aggregation and peptide-related impurities' and that 'there are limited data in humans to inform safety-related considerations'. The nomination was later withdrawn. | FDA — Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks ↗ |
| Copper delivery through skin (mechanistic caution, in vitro) | In-vitro human skin studies show copper applied as the GHK complex penetrates stratum corneum, epidermis and dermis; the studies were designed to assess transdermal copper delivery and do not report toxicity. GHK's biological role is described by Pickart as a copper-binding/transport peptide, so systemic copper exposure from non-topical routes has not been characterised. | Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy (Inflamm Res 2010) ↗ |
No interactions with a verifiable citation have been indexed for this compound.
Exclusions and label contraindications recorded in the cited sources.