Copper Peptides: The New Skin and Hair Product

What are Copper Peptides?

Copper peptides (GHK-Cu), also known as Cu peptides, are a natural tripeptide present in human plasma, saliva, and urine, extensively studied by medical researchers for almost four decades. These peptides have demonstrated the ability to facilitate wound healing and skin regeneration by attracting capillary cells, promoting new blood vessel formation aiding in hair growth, eliminating damaged cellular debris, and initiating the synthesis of crucial proteins for tissue healing.

GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide found in human serum and was shown to stimulate growth in hepatoma cells. It also has a high affinity for copper and forms the compound GHK-Cu. GHK-Cu is a small, naturally occurring tri-peptide present in human plasma.GHK and GHK-Cu both have been studied and shown to have anti-inflammatory properties as well as tissue remodeling properties which have positive effects on skin remodeling/regeneration and hair growth.

Despite being naturally occurring in the body, the levels of Cu peptides decrease with age. Research indicates that the average level in blood plasma is around 200 ng/ml at age 20, decreasing to an average of 80 ng/ml by age 60. Copper is considered an essential nutrient for humans, playing a vital role in various physiological processes across all tissues, including the skin. Researchers propose that replenishing these depleted copper peptides could potentially reverse certain signs of aging.

In recent years, the application of Cu peptides has expanded from the medical field to cosmetics. Small-scale studies suggest their effectiveness in improving the appearance and texture of sun-damaged or aging skin, as well as stimulating hair growth. These peptides may reduce fine lines, wrinkles, and increase skin density and thickness. Copper peptides are now commonly found in various skincare products like face creams, moisturizers, and anti-aging serums, available over the counter without a prescription. They might also be listed as GHK-Cu or copper tripeptides on product packaging.

How does it work?

Mechanism of action for hair

It works by stimulating the fibroblasts to produce vascular endothelial growth factor (VEGF) which promotes the formation of new blood vessels. When specifically used for hair growth, the new blood vessels form around hair follicles which then provide nutrients required for hair growth preventing premature conversion of hair follicles.

When specifically used for skin regeneration or remodeling, as the new blood vessels form, blood flow is increased into damaged tissues which promotes angiogenesis and that aids in wound/skin healing.GHK-Cu creams applied to facial, eye, and thigh skin show increased skin density, thickness, collagen production, and reduced wrinkles. GHK and related peptides, produced during protein breakdown after injury, stimulate new blood vessel growth initially and later inhibit it. GHK's antioxidant and anti-inflammatory actions protect skin cells from UV radiation and prevent lipid peroxidation damage. GHK-Cu reduces iron release from ferritin, offering additional anti-oxidative properties. Gene activation effects on neurons reveal GHK's significant impact, with specific genes upregulated and downregulated, influencing skin repair and regeneration.

Potential benefits of copper peptides for skin and hair include:

• Increase hair growth and thickness, enlarge hair follicle size
• Improve hair transplant results
• Tighten loose skin and reverse thinning of aged skin
• Repair protective skin barrier proteins
• Improve skin firmness, elasticity, and clarity
• Reduce fine lines, depth of wrinkles, and improve structure of aged skin
• Smooth rough skin
• Reduce photodamage, mottled hyperpigmentation, skin spots and lesions
• Improve overall skin appearance
• Stimulate wound healing
• Protect skin cells from UV radiation
• Reduce inflammation and free radical damage

Increased Collagen Production:

Copper tripeptides may stimulate fibroblasts to produce more collagen and elastin, enhancing skin elasticity, enriching the scalp with nutrients, and reducing fine lines and wrinkles.

Skin Regeneration Stimulation:

Scientific studies show that the Cu-GHK complex, a well-studied copper peptide, stimulates skin regeneration, improving the appearance of aging skin.

Reduction of Sun Damage:

Copper peptide face creams may help minimize the signs of sun damage and hyperpigmentation caused by prolonged sun exposure.

Protection Against Free Radicals:

Copper, acting as a cofactor, supports the antioxidant superoxide dismutase, aiding in the removal of free radicals and preventing cell damage.

FDA Approval

It is on the FDA 503A Category 1 - Bulk Drug Substances Under Evaluation List for oral and topical use, but can not be used as an injection. The FDA will add GHK-Cu for injectable routes of administration to Category 2 due to significant safety risks associated with its use in compounding.

Preparations

Oral Formulation

GHK-Cu is widely used as a topical agent, whether it's creams, serums, or ointments, but there has been research studying whether an oral formulation is just as effective as the topical formulation. GHK-Cu's permeability through the skin's stratum corneum suggests its potential for internal use, however, susceptibility to proteolytic enzymes necessitates sustained delivery for bioactive concentrations. Formulation studies explore different delivery systems such as biotinylated peptide-incorporated collagen matrix, Zn-pectinate microparticles for colon delivery, as well as liposomal formulations. Studies suggest that GHK-Cu tablets encapsulated in liposomes could be efficacious with a daily dosage of 10 mg or higher, however there is no concrete evidence of its use.These different methods are being studied to improve oral routes of administration and to see the potential benefits within the human body and not just limited to skin. Breakdown-resistant mixed copper peptide complexes show promise in infected wounds, resisting rapid breakdown by proteases.

Different Types of Topical Formulations Available

GHK-Cu is commonly administered in the form of skin creams, hair serums, shampoos, or topical ointments, applied once or twice daily to specific areas like the face for skin tightening, the scalp for hair growth, or other regions for scar or wound healing.

Formulations for hair growth involve applying a solution with concentrations ranging from 50mg/ml to 100mg/ml, containing GHK and 5-aminolevulinic acid. GHK-Cu skin creams and patches demonstrate the ability to deliver therapeutic amounts of the copper peptide within the skin layers. For instance, cream or foam can be directly applied to clean skin as needed. Facial creams often have a concentration of 0.05%, and the topical foam comes with a 50 mL foaming applicator.

It's crucial to note that GHK-Cu has a wide safety range, and its toxic dose is very high.

Dosing

Over-the-Counter (OTC):

GHK-Cu is available OTC with a dosing range typically from 1 to 3% depending on the manufacturer.

Prescription:

Prescription dosing can go as high as 30% with compounded dosing

Possible dosing for different formulations in regards to different diagnoses

• GHK-Cu/ Argireline/Leuphasyl 0.2%/10%/5% Gel or cream (wrinkles)
• GHK-Cu/Hyaluronic Acid 2/ 10 mg/ml cream (wrinkles)
• GHK-Cu 5 mg/mL dropper or foam (hair restoration)
• GHK-Cu/Hyaluronic Acid 2 mg/mL cream (wounds)

How Do I Get GHK-Cu?

Copper peptides are commonly included in various skincare items like face creams, moisturizers, and anti-aging serums. These products are accessible without a prescription, making them available over the counter. Look for GHK-Cu or copper tripeptides on product packaging to identify the presence of copper peptides in these skincare formulations. Alternatively, a prescription-grade GHK-Cu is available, allowing it to be combined with other prescription-only ingredients that enhance hair growth or address skin conditions more effectively. This would require a valid prescription from a medical physician, where they would dictate the dose and formulation. OTC serums, creams, and ointments typically contain lower percentages of copper peptides and vary in formulations compared to custom-made compounded prescription formulas tailored specifically to the patient's needs and/or condition.

Overall, GHK and its copper-bound form, GHK-Cu, emerge as peptides with significant potential in skin regeneration and hair growth.Though the risk of copper toxicity through topical use is minimal, copper has a lower risk of causing sensitivity reactions compared to other metals, making it a generally safe option for skincare and haircare.

References:

• 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 Jul 7;19(7):1987. doi: 10.3390/ijms19071987. PMID: 29986520; PMCID: PMC6073405.
• Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi: 10.1155/2015/648108. Epub 2015 Jul 7. PMID: 26236730; PMCID: PMC4508379.TK328726
• Liu T, Liu Y, Zhao X, Zhang L, Wang W, Bai D, Liao Y, Wang Z, Wang M, Zhang J. Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application. Bioact Mater. 2023 Nov 1;32:502-513. doi: 10.1016/j.bioactmat.2023.10.002. PMID: 38026438; PMCID: PMC10643103.
• Dou Y, Lee A, Zhu L, Morton J, Ladiges W. The potential of GHK as an anti-aging peptide. Aging Pathobiol Ther. 2020 Mar 27;2(1):58-61. doi: 10.31491/apt.2020.03.014. PMID: 35083444; PMCID: PMC8789089.
• Borkow G. (2014). Using Copper to Improve the Well-Being of the Skin. Current chemical biology, 8(2), 89-102. https://doi.org/10.2174/2212796809666150227223857
• Pickart L, Vasquez-Soltero J. M., & Margolina A. (2015). GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. BioMed research international, 2015, 648108. https://doi.org/10.1155/2015/648108
• Pickart, L., & Margolina, A. (2018). Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. International journal of molecular sciences, 19(7), 1987. https://doi.org/10.3390/ijms19071987
• Pickart L, Vasquez-Soltero JM, Margolina A. GHK-Cu may Prevent Oxidative Stress in Skin by Regulating Copper and Modifying Expression of Numerous Antioxidant Genes. Cosmetics. 2015; 2(3):236-247. https://doi.org/10.3390/cosmetics2030236
• Badenhorst T, Svirskis D, Merrilees M, Bolke L, Wu Z (2016) Effects of GHK-Cu on MMP and TIMP expression, collagen and elastin production, and facial wrinkle parameters. J Aging Sci 4: 166. doi:10.4172/2329-8847.1000166
• Leyden J., Stephens T., Finkey M., Appa Y., Barkovic S. Skin care benefits of copper peptide containing facial cream. Proceedings of the American Academy of Dermatology Meeting; February 2002; New York, NY, USA
• Jiang F, Wu Y, Liu Z, Hong M, Huang Y. Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests. J Cosmet Dermatol. 2023 Sep;22(9):2598-2604. doi: 10.1111/jocd.15763. Epub 2023 Apr 16. PMID: 37062921.
• https://www.peptides.org/ghk-cu/