What is GHK-Cu (Copper tripeptide) used in cosmetics?

The copper tripeptide complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) is a naturally occurring tripeptide. It was first isolated from human plasma but can be found in saliva and urine. It may be freed from existing extracellular proteins via proteolysis during wound healing. In the wound environment, it is a chemoattractant for inflammatory and endothelial cells. It naturally occurs at a concentration of 200 ng/mL (10−7 mol/L) by 20 years of age. By 60 years of age, the concentration declines to 80 ng/mL. Cell culture studies have shown that GHK-Cu has a maximal biological effect at 10−9 mol/L. GHK-Cu has been shown to increase messenger RNA production for collagen, elastin, proteoglycans, and glycosaminoglycans in fibroblasts at this concentration[1].

Several clinical studies confirmed GHK-Cu’s ability to improve the appearance of aging skin. A facial cream containing GHK-Cu was applied for 12 weeks to the facial skin of 71 women with mild to advanced signs of photoaging. The cream increased skin density and thickness, reduced laxity, improved clarity, reduced fine lines, and reduced the depth of wrinkles.

A GHK-Cu eye cream applied for 12 weeks to the around-the-eye area of 41 women with mild to advanced photodamage performed better than placebo and vitamin K cream. It reduced lines and wrinkles, improved overall appearance, and increased skin density and thickness.

GHK-Cu applied to thigh skin for 12 weeks improved collagen production in 70% of the women treated, in contrast to 50% treated with the vitamin C cream and 40% treated with retinoic acid. In addition to improving skin laxity, clarity, firmness, and appearance, reducing fine lines, coarse wrinkles, and mottled pigmentation, and increasing skin density and thickness, GHK-Cu cream applied twice daily for 12 weeks also strongly stimulated dermal keratinocyte proliferation[2].

With their pilot study of the topical application of copper tripeptide complexes in aged skin, Krüger et al. confirmed an increase in skin thickness in the range of the epidermis and dermis, improved skin hydration, a significant smoothing of the skin by stimulating collagen synthesis, increased skin elasticity, a significant improvement in skin contrast, and an increased production of collagen I.

GHK-Cu at 0.01, 1, and 100 nM incubated with human adult dermal fibroblasts increased the production of elastin and collagen. GHK also increased gene expression of MMP1 and MMP2 at the 0.01 nM. All concentrations increased TIMP1. The effects of GHK-Cu were also investigated in a randomized, double-blind clinical trial. Female volunteers applied GHK-Cu, encapsulated in a nano-lipid carrier twice a day over the course of 8 weeks using either carrier alone or the commercially available peptide Matrixyl® 3000 as controls. Compared to Matrixyl® 3000, GHK-Cu produced a 31.6% reduction in wrinkle volume. Compared to the control serum, GHK-Cu reduced wrinkle volume by 55.8% and wrinkle depth by 32.8%.

[1] Jeffrey D Pollard. “Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts.” Archives of Facial Plastic Surgery 7 1 (2005): 27–31.

[2] Loren Pickart, Anna Margolina. “Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.” International Journal of Molecular Sciences 19 7 (2018).