GHK-Cu

Overall Health Benefits of GHK-Cu

• Tightens loose skin [1-3]
• Enhances skin elasticity [4-7]
• Reduces fine lines and wrinkles [8-12]
• Reverses thinning of aging skin [13-17]
• Evens out skin texture [1, 3, 4, 8]
• Prevents aging through its antioxidant effects [1, 13-16]
• Accelerates wound healing [1, 6, 17-50]
• Improves lung health [51-54]
• Fights hair loss [55-59]
• Fights different cancer types [60-63]
• Accelerates nerve regeneration [64-67]
• Fights anxiety [68-71]
• Combats cognitive dysfunction [72-83]
• Protects the liver [84-87]
• Promotes bone repair [1, 88-89]
• Fights Inflammation [90-91]

What is GHK-Cu?

The human copper-binding peptide GHK-Cu (glycyl-l-histidyl-l-lysine) is a natural peptide that is currently used as a protective a regenerative ingredient in skin and hair products because of its numerous benefits on the skin and hair. For instance, GHK-Cu improves wound healing, stimulates collagen and glycosaminoglycan synthesis in the skin, boosts the immune system, and promotes growth of blood vessels. GHK-Cu also has significant anti-aging effects as it has antioxidant and anti-inflammatory properties.

How GHK-Cu Works?

GHK-Cu works by boosting collagen and elastin production in the skin. Collagen makes the skin strong and resilient while elastin makes the skin flexible enough to regain its shape when stretched. It also has the ability to regulate both metalloproteinases (a group of enzymes that can break down proteins such as collagen) and their inhibitors, which in turn improves skin regeneration and appearance. In addition, GHK-Cu also promotes hair growth by blocking the hormone dihydrotestosterone (DHT). Finally, it promotes nerve regeneration by increasing the production of nerve growth factors.

Chemical Structure of GHK-Cu

GHK-Cu (glycyl-l-histidyl-l-lysine) is a tripeptide found in human plasma, saliva, and urine. It was first discovered by Loren Pickart in 1973 by isolating the tripeptide from the human plasma. The GHK molecule has a very high affinity for Cu²⁺, hence forming the GHK-Cu complex. The chemical structure of GHK-Cu below shows the Cu²⁺ being directly linked to three nitrogen atoms – one from the imidazole group, one from glycine, and another one from the glycine-histidine bond. [1]

Research on GHK-Cu

Tightens loose skin

Research studies have shown that GHK-Cu has significant regenerative and antioxidant properties that improve skin health and prevent skin aging. For instance, animal studies and clinical trials have demonstrated that GHK-Cu tightens loose skin, which is one of the most apparent sign of skin aging:

1. In women with mild to advanced signs of photoaging, application of a facial cream containing GHK-Cu for 12 weeks reduced the laxity of skin. [1]
2. In healthy subjects, application of GHK-Cu cream to thigh skin for 12 weeks improved skin laxity, firmness, and appearance compared to vitamin C cream and retinoic acid. [2]
3. When applied to the skin twice daily for 12 weeks, GHK-Cu cream strongly stimulated the production of keratinocytes which maintain skin tightness. [3]

Enhances skin elasticity

Another benefit of GHK-Cu on the skin is that it stimulates the production of collagen and elastin, which are primary structural components of the dermis. Collagen and elastin maintain the elasticity and integrity of the skin. Reduced collagen and elastin production has been linked to aging-related loss of elasticity and weakening of the skin. The following studies provide evidence that GHK-Cu promotes collagen and elastin production, hence enhancing skin elasticity:

1. GHK-Cu directly induces skin-derived human fibroblasts to increase collagen synthesis and secretion in vitro. [4]
2. Addition of GHK-Cu in cell cultures of primary human dermal fibroblasts resulted in increased production of both collagen and elastin. [5]
3. When applied to aged skin, GHK-Cu improved skin elasticity, hydration, and contrast by increasing the production of collagen I. [6]
4. A study reported that GHK-Cu can help improve overall skin structure by boosting type I collagen. [7]

Reduces fine lines and wrinkles

Fine lines and deep wrinkles are the most apparent signs of skin aging. The development of fine lines and wrinkles is linked to the loss of collagen and elastin in the dermis that occurs with age. Chronic exposure to UV light from the sun also contributes to the development of wrinkles. Research studies show that GHK-Cu helps reduce the appearance of fine lines and wrinkles on the skin:

1. In female volunteers, GHK-Cu treatment resulted in a 55.8% reduction in wrinkle volume and a 32.8% reduction in wrinkle depth. [8]
2. Application of a facial cream that contains GHK-Cu in women with photodamaged skin resulted in reduction of fine lines and depth of wrinkles. [9]
3. Female study participants noted significant reduction of fine lines and coarse wrinkles around the eye area after application of eye cream that contains GHK-Cu. [10]
4. The use of a serum that contains GHK-Cu resulted in 31.6% greater reduction in wrinkle volume compared to the use of a serum that does not contain GHK-Cu, as shown by a controlled trial that involved 40 female volunteers who used the product for 8 weeks. [11]
5. GHK-Cu has been shown to induce collagen synthesis and elastin production in the skin, which then improve skin appearance and prevent the appearance of fine lines and wrinkles. [12]

Reverses thinning of aged skin

Thinning of the skin with age is the result of the loss of keratinocytes in the skin and the reduced volume of the dermis, which is due to the loss of collagen and elastin in this skin layer. Thinning makes the skin appear translucent, causing veins and tendons to become apparent. Research studies and controlled trials provide scientific evidence that GHK-Cu effectively reverses thinning of aged skin:

1. Use of a facial cream containing GHK-Cu for 12 weeks resulted in improved skin density and thickness in women with visible signs of skin aging. [13]
2. Application of GHK-Cu eye cream for 12 weeks caused visible improvement in skin thickness and overall appearance, in comparison to the use of vitamin K. [14]
3. Improved skin thickness, density, and appearance of thigh skin was noted in healthy subjects who used GHK-Cu cream. [15]
4. Application of cream containing GHK-Cu for 12 weeks effectively resulted in increased keratinocyte proliferation in the dermis, thereby improving skin density and thickness. [16]
5. GHK-Cu stimulated collagen I synthesis when applied to aged skin, resulting in enhanced skin thickness and color. [17]

Evens out skin texture

Research studies have shown that GHK-Cu also smoothens and evens out skin texture:

1. Topical application of a cream formulated with GHK-Cu resulted in significant smoothing of aged skin, secondary to increased collagen synthesis. [1,3]
2. A series of facial studies provide direct evidence that application of GHK-Cu to uninjured skin induces remodeling of the skin, resulting in improved skin appearance, including evened out skin texture. [4]
3. After 12 weeks of using a facial cream containing GHK-Cu, female participants noted reduction of coarse wrinkles and mottled hyperpigmentation and improved overall appearance. [8]

Prevents aging through its antioxidant effects

In vitro and chemical studies provide definitive evidence that GHK-Cu prevents skin aging through its antioxidant properties:

1. GHK-Cu blocks the formation and accumulation of reactive carbonyl species and neutralizes toxic products of lipid peroxidation. GHK-Cu has also been found to protect keratinocytes from UVB damage. [1]
2. An in vitro study showed that GHK blocks oxidation of lipoproteins, hence preventing oxidative stress which is a major cause of skin aging. [13]
3. GHK also effectively inhibits the generation of acrolein, a well-known toxin that contributes to aging. [14]
4. Another in vitro study reported that GHK prevents ultraviolet radiation damage to skin keratinocytes by inactivating reactive carbonyl species and toxins, including acrolein, malondialdehyde, 4-hydroxynoneal, and glyoxal. [15]
5. GHK-Cu was also shown to significantly reduce iron release from ferritin by 87%. This is an important finding because free iron is a potent agent of lipid peroxidation and an inducer of the conversion of superoxide anion to hydroxyl radical, which is a key component of oxidative stress and aging. [16]

Accelerates Wound Healing

GHK-Cu plays an integral role in tissue remodeling and other phases of the wound healing process. An overwhelming body of scientific evidence supports the regenerative properties of this tripeptide:

1. A 2008 study published in the Journal of Biomaterials Sciencefound that GHK-Cu attracts repair cells such as macrophages, mast cells, capillary cells at the site of injury. [1]
2. In mice, GHK-Cu improved wound healing by promoting cell proliferation and angiogenesis. [17]
3. A 2015 study published in the Biomed Research International found that GHK-Cu tripeptide acts as a natural modulator of multiple cellular pathways in skin regeneration. [18]
4. A study found that GHK-Cu improves wound healing by increasing extracellular matrix (ECM) proteins, collagen, glycosaminoglycans, and DNA synthesis. [19]
5. Studies found that GHK-Cu modulates various aspects of the wound healing process, including attraction of the cells of the immune system, formation of new blood vessels (angiogenesis), and collagen synthesis. [20-21]
6. In patients with wounds induced by CO₂ laser skin resurfacing, GHK-Cu treatment is associated with higher patient satisfaction. [22]
7. A study also found that GHK-Cu stimulates the breakdown of existing collagens in wounds. [23]
8. In rats, GHK-Cu improved skin remodeling process by modulating activity of different metalloproteinases, which are enzymes that remodel wounds. [24-25]
9. A study reported that GHK-Cu improves wound healing by increasing the levels of decorin, a substance that influences tissue tensile strength and prevents scarring. [26-28]
10. A cell study found that GHK-Cu increases fibroblasts, which are the key cells in skin reparative and renewal processes. [29]
11. In rabbits, GHK-Cu treatment resulted in better wound contraction, faster development of granular tissue, and improved blood vessel growth. [30]
12. When given in combination with laser treatment, GHK-Cu increased the formation of new blood vessels and increased the levels of antioxidant enzymes in the dermal wounds. [31-32]
13. In rats with difficult to heal wounds, such as diabetic wounds, GHK-Cu treatment resulted in faster wound contraction and closure. [33-34]
14. In pigs with mild thermal burns, GHK-Cu triggered an accelerated healing of the injury. [35]
15. In animal models, GHK-Cu treatment accelerated closure in both wound chambers and full thickness wounds. [36]
16. In patients with diabetic ulcers, application of GHK-Cu gel is associated with faster wound closure and lower rate of infection. [37]
17. In normal human dermal fibroblasts (skin cells), treatment with GHK-Cu accelerated skin cell renewal by decreasing the secretion of transforming growth factor β (TGF-β), a cytokine involved in programmed cell death. [38-39]
18. A 2015 study published in Bioorganic and Medicinal Chemistry Letters found that GHK-Cucan help accelerate the wound healing process through its antimicrobial properties. [40]
19. In animals, GHL-Cu was shown to be an effective wound-healing and anti-inflammatory agent. [41]
20. A study showed that GHK-Cu promotes wound healing by stimulating glycosaminoglycans (GAGs) synthesis. [42]
21. A study showed that GHK-Cu modulates MMP expression by acting directly on wound fibroblasts. [43]
22. In warm-blooded animals, GHK-Cu accelerated wound healing following injury or surgery. [44]
23. In pad wounds of dogs, locally injected tripeptide-copper complex (TCC) significantly improved wound healing. [45]
24. A study showed that GHK and GGH play a role in the process of wound healing, tissue repair and skin inflammation. [46]
25. In skin wound healing, GHK-Cu administration resulted in increased collagen expression. [47]
26. A study showed that GHK-Cu effectively improves wound healing. [48]
27. Studies reported that GHK-Cu speeds up wound healing through its anti-oxidant and anti-inflammatory actions. [49-50]

Improves Lung Health

Because of its regenerative properties, GHK-Cu has also been used for the treatment of several lung conditions, as evidenced by the following studies:

1. A 2012 study published in Genome Medicine found that GHK-Cu improves lung tissue regeneration by restoring the activity of genes involved in the TGF-beta pathway (involved in cell growth and other cellular functions). [51]
2. In patients with chronic obstructive pulmonary disease (COPD), GHK-Cu administration accelerated lung tissue repair by restoring the contraction and remodeling of collagen. [52]
3. GHK-Cu administration in mice protected their lung tissue from lipopolysaccharide-induced acute lung injury by suppressing the infiltration of inflammatory cells. [53]
4. In mice, GHK-Cu administration reversed bleomycin-induced inflammation and scarring of the lungs. [54]

Fights Hair Loss

There is also strong scientific evidence that supports the effects of GHK-Cu in stimulating hair growth and preventing age-related hair loss:

1. Injection of GHK-Cu in shaved mice for 12 days resulted in strong hair growth stimulation at the injection site. [55]
2. GHK-Cu administration in rats for 3-4 months doubled follicle size and caused 80% increase in the number of hair follicles that are in the anagen or growth phase. [56]
3. A cell study found that GHK-Cu accelerates hair growth by stimulating dermal papilla cells, which play an integral role in the growth and development of hair follicles. [57]
4. A cell study assessing the effect of GHK-Cu on human hair growth reported that the treatment stimulated the proliferation of dermal papilla cells. [58]
5. A study also found that GHK-Cu exhibits more superior hair growth promoting effects than other peptides. [59]

Fights Different Cancer Types

Evidence suggests that GHK-Cu also has potent anti-cancer properties that can help suppress the growth and reproduction of aggressive cancer cells:

1. A cell study found that GHK-Cu suppressed 70% of genes involved in the development of aggressive colon cancer. [60]
2. Another cell study found that treatment of three lines of human cancer cells with GHK-Cu resulted in activation of programmed cell death (apoptosis). [61]
3. In a mouse model of bone cancer, GHK-Cu strongly inhibited the growth of cancer cells. [62]
4. A gene study reported that GHK-Cu has the ability to suppress DNA repair of cancer cells. [63]

Accelerates Nerve Regeneration

Studies show that GHK-Cu has the capacity to heal the most debilitating nerve injuries:

1. A study found that GHK-Cu stimulates new blood vessel growth at the site of nerve injury. [64]
2. Cell studies found that GHK-Cu stimulates nerve outgrowth and restores skin’s innervation by increasing the production of neurotrophic factors. [65]
3. A cell study also found that GHK-Cu sped up the regeneration of nerve fibers by increasing the production of nerve growth factor and the neurotrophins NT-3 and NT-4. [66]
4. In rats, GHK-Cu injection alleviated programmed cell death of nerve cells in the brain. [67]

Fights Anxiety

A number of studies also found that GHK-Cu exerts anti-anxiety effect that can help improve overall mood:

1. In rats, injection with GHK-Cu at 0.5 micrograms per kilogram resulted in a significant reduction of fear and anxiety as evidenced by increased amount of time spent exploring in more open and lighted areas of the maze. [68]
2. In another rat study, GHK-Cu injection produced anti-anxiety effect as evidenced by less time hiding and more time exploring the area in the open field test. [69]
3. When injected to aggressive rats, GHK-Cu significantly reduced anxiety-like behaviors. [70]
4. Studies suggest that GHK-Cu can help relieve anxiety via its pain-relieving properties. [71]

Combats Cognitive Dysfunction

Studies show that GHK-Cu can potentially combat cognitive dysfunction related to aging and brain disorders through various important mechanisms:

1. GHK-Cu can prevent cognitive dysfunction induced by Alzheimer’s disease by reducing the brain levels of an abnormal sticky compound known as amyloid beta. [72]
2. GHK-Cu can potentially prevent Alzheimer’s disease by increasing the levels of antioxidant enzymes. [73-74]
3. GHK-Cu can improve cognitive health by effectively neutralizing damaging oxygen-derived free radicals. [75-76]
4. By decreasing the pro-inflammatory cytokine TGF-beta, GHK-Cu can prevent the development of Alzheimer’s disease. [77-81]
5. GHK-Cu can prevent age-related cognitive decline by improving nervous system function. [82]
6. In chicks, it was found that GHK-Cu induced formation of brain neurons. [83]

GHK-Cu – Protects the Liver

A number of studies reported that GHK-Cu has the ability to protect liver cells against various types of injury:

1. In rats who suffered liver toxicity due to dichloromethane poisoning, the injection of 1.5 mg/kg of GHK-Cu provided protection of the functional activity of hepatocytes (liver cells). [84]
2. A study reported that GHK-Cu can help promote repair of liver cells. [85]
3. A study showed that Tripeptide in human blood helps in prolonging the survival of normal liver cells and stimulates growth in tumor of the liver. [86]
4. A study showed that GHL enhances the uptake of metal into cultured liver tumor cells. [87]

GHK-Cu – Promotes Bone Repair

The regenerative properties of GHK-Cu have also been shown to be beneficial in bone disorders:

1. In rats with experimental bone fractures, GHK-Cu injections resulted in a marked increase in bone reparative activity. [88]
2. A study found that GHK-Cu stimulated the repair of bone tissues. [1]
3. In normal rat and human bone cells, GHK-Cu inhibited the production of cells responsible for bone breakdown. [89]

Fights Inflammation

GHK-Cu has also been shown to exert anti-inflammatory properties:

1. A study showed that copper tripeptide is a potentially effective treatment for various inflammatory diseases. [90]
2. A cell study found that copper tripeptide can reduce the levels of inflammatory substances. [91]

Associated Side Effects of GHK-Cu

GHK-Cu side effects are very uncommon. There have been some side effects associated with the use of this peptide wherein the patient had one of the issues listed below at some point while being on GHK-Cu. However, the issue wasn’t’ confirmed to be caused by the treatment and could have been a coincidence and not related to the use of GHK-Cu. Despite this, it was listed as a side effect associated with GHK-Cu even these associated side effects are very uncommon.
Side effects associated with GHK-Cu may include the following:

• Dizziness
• Fatigue
• Headache
• Increased appetite
• Increased blood pressure
• Nausea
• Redness or pain at the injection site

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