GLYCYL-L-HISTIDYL-L-LYSINE-COPPER (GHK-CU)

Mechanism of Action
GHK-Cu is a natural tripeptide (Glycyl-L-Histidyl-L-Lysine) with high affinity for copper (II), to which it binds to form a stable complex. Discovered in 1973 as a factor present in young human plasma, GHK-Cu acts as a biochemical signal that triggers regenerative and reparative processes in damaged tissues. Its mechanism of action is multimodal: on one hand, it delivers bioavailable copper to cells, an essential cofactor for repair enzymes; on the other, it modulates gene expression on a large scale. Transcriptomic studies reveal that GHK-Cu significantly up- or down-regulates approximately 30% of the human genome, activating genes related to extracellular matrix synthesis and cell proliferation while repressing pro-inflammatory and pro-degenerative genes. As a result, it stimulates the synthesis of collagen, elastin, proteoglycans, and other skin components, while coordinately increasing the activity of matrix metalloproteinases (MMPs) and their inhibitors, promoting a balance between degradation of damaged tissue and deposition of new, healthy tissue.
GHK-Cu also exhibits antioxidant and anti-inflammatory properties: it scavenges free radicals and reduces inflammatory cytokines (for example, suppressing TNF-α and IL-6). In addition, it promotes migration of fibroblasts and keratinocytes toward wound sites and increases the production of growth factors (FGF, VEGF) by these cells. It has even been observed to enhance the “stemness” of epidermal stem cells (increasing integrins and p63), stimulating regeneration from the basal layer of the skin. In summary, GHK-Cu acts as a master modulator of healing, sending molecular signals that reduce inflammation and oxidative stress while reactivating embryonic development and tissue repair pathways in the skin and other organs.
 
Known or Proposed Clinical/Therapeutic Uses
GHK-Cu is widely recognized for its applications in dermatology and aesthetic medicine. It has been used for decades in topical formulations (creams, serums) for skin rejuvenation and wound healing. Clinical studies have confirmed that cosmetic treatments containing GHK-Cu improve the appearance of aged skin: they increase thickness and firmness, reduce fine wrinkles and hyperpigmentation, and enhance type I collagen production. For example, in a trial involving 71 women, a facial cream containing GHK-Cu used for 12 weeks significantly increased skin density and elasticity and reduced wrinkle depth compared with placebo.
GHK-Cu has also shown efficacy in difficult-to-heal ulcers and wounds. When applied to diabetic and pressure ulcers, it accelerated granulation and epithelialization, leading to faster wound closure. Its ability to stimulate angiogenesis and attract reparative cells is particularly valuable in poorly perfused or chronic wounds. Another area of interest is trichology: GHK-Cu appears to promote hair growth by increasing hair follicle size and prolonging the anagen phase, resulting in thicker and more abundant hair. For this reason, it is included in anti-hair-loss and hair-thickening lotions.
More recently, preclinical research suggests potential systemic applications. For instance, in a murine model of ulcerative colitis, intraperitoneally administered GHK-Cu showed notable therapeutic effects, reducing intestinal inflammation, restoring the mucosal barrier, and decreasing the release of pro-inflammatory cytokines in the colon. This indicates potential utility in inflammatory diseases of the gastrointestinal tract. Additionally, due to its broad anti-inflammatory properties, GHK-Cu has been proposed for the treatment of age-related chronic diseases (such as COPD, macular degeneration, and cognitive decline), with the hypothesis that it could mitigate oxidative stress and cellular senescence. However, systemic use of GHK-Cu is not yet clinical and remains at the level of basic research and animal models. By contrast, its established uses are topical: improving wound healing in skin and superficial tissues and reversing signs of cutaneous aging—fields in which it has demonstrated both efficacy and safety.
 
Side Effects or Associated Risks
GHK-Cu has an outstanding safety record. It is a peptide naturally present in the human body (plasma levels are approximately 200 ng/mL at around 20 years of age and decline with aging), and decades of topical use have not revealed serious adverse effects. Studies in cell cultures, tissues, and animals over more than 40 years confirm that it is neither cytotoxic nor mutagenic, and that its biological effects are beneficial without evidence of harm. In dermatological products, the incidence of irritation is very low: individuals with highly sensitive skin may experience mild redness or transient stinging, but overall GHK-Cu is better tolerated than many other active ingredients (such as retinoids or acids).
Because it does not drastically alter immune function but rather modulates it gently, its use is not associated with immunosuppression or increased susceptibility to infections. Significant allergic reactions to the peptide have not been reported in the literature. Regarding systemic exposure, the limited available studies suggest low toxicity: in animal models, high doses of GHK-Cu did not produce signs of hepatic, renal, or hematological toxicity. Moreover, as a small tripeptide, it is efficiently metabolized without generating harmful byproducts. A theoretical risk is copper imbalance if administered excessively, since GHK facilitates cellular copper uptake; however, in cosmetic practice this has not posed a clinical problem. On the contrary, GHK-Cu tends to restore tissue copper homeostasis, which may be disrupted in aging and degenerative diseases. To date, there is no evidence that GHK-Cu causes undesirable systemic effects, cancer, or cumulative toxicity. That said, as a precaution, long-term systemic use has not been evaluated in humans, so unknown effects cannot be completely ruled out. Nevertheless, the scientific community considers GHK-Cu to be a safe agent, supported by its extensive history of complication-free use and by the fact that it activates the body’s own repair pathways without forcing physiological imbalances.