Copper Peptide

The human copper-binding peptide GHK-Cu (glycyl-l-histidyl-l-lysine) is a small, naturally occurring tri-peptide present in the blood plasma. The peptide is released from tissues in case of an injury and accelerates wound healing and skin repair.1

Copper peptide is a powerful protective and regenerative agent extensively used in dermatological and hair care products. It stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis; it also supports the function of dermal fibroblasts.1

Improves Collagen Production

Copper peptide improves skin appearance, firmness, and increases skin density and thickness. Copper peptide stimulates the synthesis of collagen, selected glycosaminoglycans, and small proteoglycan decorin. Glycosaminoglycans maintain skin structural proteins such as collagen and elastin, while decorin regulates the collagen matrix assembly.2,3,4

In a study by Abdulghani et al., collagen synthesis was studied after topical application of creams containing copper peptide, tretinoin, and vitamin C for 12 weeks. The study found that the copper peptide cream stimulated collagen production in 70% of the study participants, in contrast to 50% treated with vitamin C cream and 40% treated with retinoic acid.5

Copper peptide cream applied twice daily for 12 weeks also strongly stimulated dermal keratinocyte proliferation.6

Copper peptides regulate the activity of metalloproteinases and their inhibitors, thus supporting skin regeneration and improving skin appearance. Metalloproteinases are enzymes responsible for the degradation of collagen and other proteins in the extracellular matrix.7,8

Excessive breakdown of the dermal matrix and inadequate removal of damaged proteins can negatively affect skin’s health and appearance. 7,8  By regulating metalloproteinases and protein breakdown in the skin, copper peptide prevents the accumulation of damaged proteins and excessive proteolysis.1

Copper peptides also show beneficial effects on skin fibroblasts. Skin fibroblasts synthesize collagen and extracellular matrix components and function in building and repairing the skin’s structural components. Apart from synthesizing structural elements of the skin, fibroblasts also produce a wide range of growth factors essential for skin repair. Copper peptides, in combination with LED (light-emitting diode) irradiation, compared with the LED irradiation alone, increased the cell viability 12.5-fold. Copper peptide also increased the production of the basic fibroblast growth factor (bFGF) by 230% and collagen synthesis by 70%.9

The anti-aging properties of copper peptides have been established in numerous studies. A facial cream containing copper peptides was applied for 12 weeks in 71 women with mild to advanced signs of photoaging. The cream increased skin density and thickness, reduced laxity, improved clarity, reduced fine lines, and the depth of wrinkles.2

Studies by Krüger et al. showed that copper peptide increased skin thickness and improved skin hydration. Copper peptide also caused skin smoothing, increased skin elasticity, improved skin contrast, and stimulated collagen production.10,11

The wound healing process comprises hemostasis, inflammation, repair, and remodeling. Supplementing with copper peptides during the healing process can augment the healing process, due to which the tissue can heal faster and better.1

Copper peptides protect from tissue damage and act as an anti-inflammatory agent in injured tissue. They play a vital role in signaling tissue remodeling, removing damaged/scarred tissue, and generating new, healthy tissue.1

Several animal studies have demonstrated the wound healing capability of copper peptide. In a study conducted on rabbit wounds, copper peptide alone or in combination with high dose helium-neon laser improved wound contraction and formation of granular tissue. It also increased the activity of antioxidant enzymes and stimulated blood vessel growth.12,13

In a study by Canapp et al., copper peptide effectively stimulated the healing of ischemic open wounds in rats. Ischemic open wounds are often slow to heal. Compared with vehicle alone (hydroxypropyl-methylcellulose) or with no treatment (control), the use of copper peptide was associated with faster healing.  On day 13, the initial wound area had decreased by 64.5% in the copper peptide group, 45.6% in the vehicle group, and 28.2% in the control group. Copper peptide also decreased the concentration of metalloproteinases as well as of tumor necrosis factor – β (TNF-β), a potent multifunctional cytokine involved in inflammation.14

Apart from the wound healing activity, copper peptide also possesses strong antioxidant and anti-inflammatory actions, reducing inflammation and preventing further damage. Oxidants and free radicals play a crucial role in skin aging, taking an active part in lipidic peroxidation, breakage of proteins and DNA, etc. Copper peptide inactivates damaging free radical by-products of lipid peroxidation and protects cultured skin keratinocytes from ultraviolet (UV)-radiation.1

  1. 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.
  2. Leyden J, Stephens T, Finkey M, et al. Skin Care Benefits of Copper Peptide Containing Facial Cream; Proceedings of the American Academy of Dermatology 60th Annual Meeting; New Orleans, LA, USA. 22–27 February 2002; p. 68.
  3. Siméon A, Wegrowski Y, Bontemps Y, et al. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol. 2000;115(6):962-968.
  4. Wegrowski Y, Maquart FX, Borel JP. Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Life Sci. 1992;51(13):1049-1056.
  5. Abdulghani A, Sherr A, Shirin S, et al. Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin—A pilot clinical, histologic, and ultrastructural study.  Manag. Clin. Outcomes. 1998;1:136–141.
  6. Finkley M, Appa Y, Bhandarkar S. Copper Peptide and Skin. In: Elsner P., Maibach H., editors. Cosmeceuticals and Active Cosmetics: Drugs vs. Cosmetics.Marcel Dekker; New York, NY, USA: 2005. pp. 549–563.
  7. Siméon A, Monier F, Emonard H, et al. Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. J Invest Dermatol. 1999;112(6):957-964. 
  8. Siméon A, Emonard H, Hornebeck W, Maquart FX. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sci. 2000;67(18):2257-2265.
  9. Huang PJ, Huang YC, Su MF, et al. In vitro observations on the influence of copper peptide aids for the LED photoirradiation of fibroblast collagen synthesis. Photomed Laser Surg. 2007;25(3):183-190.
  10. Krüger N., et al. Topische Applikation eines Kupfertripeptidkomplexes: Pilotstudie bei gealterter Haut.  Dtsch. Dermatol. Ges. 2003;1
  11. Krüger N, Fiegert ., Becker D, et al. Zur Behandlung der Hautalterung: Spurenelemente in Form eines Kupfertripeptidkomplexes.  Med. 2003;24:31–33. 
  12. Cangul IT, Gul NY, Topal A, et al. Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits. Vet Dermatol. 2006;17(6):417-423.
  13. Gul NY, Topal A, Cangul IT, et al. The effects of topical tripeptide copper complex and helium-neon laser on wound healing in rabbits. Vet Dermatol. 2008;19(1):7-14.
  14. Canapp SO Jr, Farese JP, Schultz GS, et al. The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Vet Surg. 2003;32(6):515-523.

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