GHK-Cu, the copper complex of the tripeptide glycyl-L-histidyl-L-lysine, was first isolated from human plasma in 1973 by biochemist Loren Pickart. He observed that plasma from younger donors stimulated regenerative activity in liver tissue from older donors, and the active component responsible for this effect was identified as the GHK tripeptide [1].

GHK is naturally present in human plasma, saliva, and urine. Its concentration declines significantly with age: approximately 200 ng/mL at age 20 drops to around 80 ng/mL by age 60, a reduction that correlates with diminished regenerative capacity across multiple organ systems [2].

The Copper Connection

GHK has a high natural affinity for copper (II) ions, forming the biologically active complex GHK-Cu. Copper is an essential trace mineral involved in more than a dozen enzymatic reactions, including those governing connective tissue formation, antioxidant defense, and cellular respiration.

By binding copper, GHK silences the ion’s oxidative activity and delivers it in a stable, bioavailable form to tissues that require it [3].

Documented Biological Actions

Gene profiling studies have revealed that GHK modulates approximately 31.2% of human genes, with 59% upregulated and 41% downregulated when changes of 50% or greater are considered [4]. Documented activities include:

• Stimulation of collagen, elastin, and glycosaminoglycan synthesis in dermal fibroblasts
• Modulation of matrix metalloproteinases (MMPs) and their inhibitors
• Activation of epidermal basal cells and upregulation of integrin and p63 expression
• Anti-inflammatory effects, including reduction of TNF-α induced IL-6 secretion
• Restoration of fibroblast viability following radiation exposure
• Accelerated wound contraction and angiogenesis in preclinical wound models

GHK-Cu appears to pass the skin’s horny layer in quantities sufficient to activate regenerative events. Clinical studies confirm its ability to improve the appearance of aging skin, increase skin density and thickness, and reduce wrinkles.

— Pickart L., Margolina A., Int J Mol Sci (2018)

Clinical Evidence

A controlled study of 71 women with mild to advanced photoaging applied a facial cream containing GHK-Cu for 12 weeks. Results showed measurable increases in skin density and thickness and reductions in visible signs of aging [5].

Earlier clinical work by Leyden et al. evaluated a copper tripeptide cream and serum for photodamaged skin, and subsequent investigations have reinforced GHK-Cu’s status as one of the most extensively studied bioactive peptides in dermatological research [6].

References

[1] Pickart L., Freedman J.H., Loker W.J., et al. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980;288:715-717. doi:10.1038/288715a0

[2] Pickart L., Vasquez-Soltero J.M., Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. PMC4508379.

[3] Pickart L., Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018;19(7):1987. PMC6073405.

[4] Maquart F.X., Pickart L., Laurent M., et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex GHK-Cu. FEBS Lett. 1988;238(2):343-346.

[5] Leyden J.J., et al. Clinical evaluation of a copper tripeptide cream and serum for photodamaged skin. J Cosmet Dermatol. 2002;1(3):197-204.

[6] Pickart L., Margolina A. Skin Regenerative and Anti-Cancer Actions of Copper Peptides. Cosmetics. 2018;5(2):29. doi:10.3390/cosmetics5020029