GHK-Cu – Copper Tripeptide

GHK-Cu is a naturally occurring peptide complex first isolated from human blood plasma and later identified in urine and saliva. Scientific investigation has shown that this short peptide has notable benefits in wound healing and immune system function. It demonstrates anti-aging properties and has been reported to inhibit free radical damage, enhance protein synthesis, combat bacteria, and improve the health of skin and skin fibroblasts.

GHK-Cu Research

1. GHK-Cu and Skin Healing

GHK-Cu is a natural component of human blood and plays an integral role in skin regeneration pathways. Studies in skin cell cultures have demonstrated that GHK:

• Stimulates the synthesis and breakdown of collagen
• Modulates glycosaminoglycans
• Influences other extracellular matrix components such as proteoglycans and chondroitin sulfate

At least part of this effect is mediated through the positive recruitment of:

• Fibroblasts
• Immune cells
• Endothelial cells

GHK-Cu appears to recruit these cells to the site of injury and coordinate their activity in repairing tissue damage.

Research indicates that GHK-Cu administration can improve overall skin characteristics, including:

• Increased skin elasticity
• Skin tightening and firming
• Reduced sun-induced damage
• Reduced hyperpigmentation
• Diminished appearance of fine lines and wrinkles

Its ability to modulate collagen synthesis is important for:

• Reducing the appearance of scars
• Preventing hypertrophic healing
• Smoothing rough skin
• Repairing the structure of aged skin

These roles of GHK-Cu are mediated in part by its ability to boost levels of transforming growth factor-β (TGF-β). It is likely that GHK-Cu acts through several biochemical pathways, including effects at the level of gene transcription.

In mouse models, GHK-Cu has been shown to increase the rate of healing following burns by as much as 33%. In addition to recruiting immune cells and fibroblasts, GHK-Cu appears to promote angiogenesis (growth of blood vessels). Because burned skin often regrows blood vessels slowly due to cauterization effects, these findings suggest a potential role for GHK-Cu in improving wound care for burns and burn-related injuries.

2. GHK-Cu and Bacteria

Infectious pathogens are a major reason wounds heal slowly or fail to heal. Bacterial and fungal infections are especially problematic in burn patients and individuals with compromised immune systems (e.g., diabetes, HIV).

GHK-Cu, when combined with certain fatty acids, forms a potent antimicrobial compound that is active against a variety of bacteria and fungi known to complicate wound healing.

Research in diabetic patients has shown that GHK-Cu can be superior to standard care regimens for treating diabetic ulcers. In these studies, GHK-Cu treatment:

• Produced an approximate 40% increase in wound closure
• Resulted in a 27% decrease in infection rates

Overall, healthier new tissue was observed in patients with ischemic open wounds.

3. GHK-Cu, Cognition, and Nervous System Function

The death of neurons in degenerative diseases such as Alzheimer’s is poorly understood, which complicates the development of effective treatments. Research suggests that GHK-Cu may help counteract age-associated declines in neuronal function and may help outpace neuron loss.

Reported effects of GHK-Cu include:

• Improved angiogenesis within nervous system tissues
• Increased nerve growth factor (NGF) levels
• Reduced anxiety-like behavior in rodent models
• Partial normalization (“reprogramming”) of pathological gene expression toward a healthier state

GHK-Cu is found in relatively high concentrations in the brain, but levels decline with age. Accumulating evidence suggests that physiological levels of GHK-Cu help protect tissues against natural insults such as gene dysregulation and that age-related declines in GHK-Cu may contribute to the onset of new disease processes and neurodegeneration.

Research in rats indicates that one mechanism by which GHK-Cu protects brain function is by preventing apoptosis (programmed cell death). This action appears to be mediated via the miR-339-5p/VEGFA pathway, which is activated following intracerebral hemorrhage and stroke. In rat models, administration of GHK-Cu after stroke substantially reduced—and in some cases inhibited—the neuronal death typically caused by overexpression of miR-339-5p.

4. GHK-Cu and Side Effects of Chemotherapy

Mouse studies show that GHK-Cu can protect the lungs against fibrosis that occurs following chemotherapy with bleomycin. These findings raise the possibility that GHK-Cu might be used as a chemotherapy adjuvant to help reduce pulmonary side effects and potentially allow higher or more effective dosing of certain chemotherapeutic agents.

The study further showed that the pulmonary protective activity of GHK-Cu appears to arise from several mechanisms. In particular, GHK-Cu seems to reprogram levels of:

• TNF-α
• IL-6

Both molecules are key inflammatory mediators that act within the extracellular matrix and epithelial cells of the lung. By dampening inflammation, GHK-Cu helps prevent fibrotic remodeling and protects against respiratory insufficiency.

Similar lung-protective benefits of GHK-Cu were observed in mouse models of acute respiratory distress syndrome (ARDS), a rapidly developing, life-threatening inflammatory lung condition with high mortality. GHK-Cu was found to be beneficial in these models as well, again appearing to mediate its effects primarily through inhibition of inflammation.

5. GHK-Cu and Pain Reduction

In rat models, administration of GHK-Cu produced a dose-dependent reduction in pain-induced behaviors, indicating that the peptide has peripheral analgesic properties. It is thought that GHK-Cu may also increase levels of L-arginine, an amino acid with known analgesic effects. These findings suggest that GHK-Cu could open new avenues for pain control beyond the use of addictive medications or NSAIDs, which are associated with cardiovascular risks.

GHK-Cu has been reported to exhibit minimal side effects, low oral bioavailability, and excellent subcutaneous bioavailability in mice. Per-kilogram dosing in mice does not directly translate to humans. GHK-Cu, as supplied by Peptide Sciences, is limited to educational and scientific research use only and is not for human consumption. Only purchase GHK-Cu if you are a licensed medical or research professional.

Article Author

The above literature was researched, edited, and organized by Dr. Logan, M.D. Dr. Logan holds a Doctor of Medicine degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Scientific Journal Author

Loren Pickart, Ph.D. has published 109 scientific papers and has been instrumental in developing patents and analyzing GHK’s effects on human gene expression across 4,150 genes. In his published work on GHK’s potential uses in skin inflammation, metastatic cancer, and COPD, the peptide also appears to exert beneficial effects on other tissue systems, including:

• Nervous system
• Gastrointestinal system
• Mitochondrial system

His brief but detailed autobiography describes the motivations, background experiences, and lifelong training that shaped his research career.

Loren Pickart, Ph.D., is referenced here as one of the leading scientists involved in GHK-Cu research and development. This reference does not imply endorsement or support of this product, nor is there any known or suggested financial, professional, or other relationship between Peptide Sciences and Dr. Pickart. The purpose of citing Dr. Pickart is solely to acknowledge and credit the extensive research and development efforts of scientists studying this peptide. Loren Pickart has published extensively in , , and and in various journals throughout his career.

Referenced Citations

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2. Gruchlik A, Chodurek E, Dzierzewicz Z. Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts. Acta Pol Pharm. 2014;71(6):954–958.
3. Pickart L, Margulies 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).
4. Wang X, et al. GHK-Cu liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis. Wound Repair Regen. 2017;25(2):270–278.
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6. Mulder GD, et al. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-L-histidyl-L-lysine copper. Wound Repair Regen. 1994;2(4):259–269.
7. Canapp SO, et al. The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Vet Surg. 2003;32(6):515–523.
8. Pickart L, Vasquez-Soltero JM, Margulies A. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline. Brain Sci. 2017;7(2).
9. Zhang H, Wang Y, He Z. Glycine-Histidine-Lysine (GHK) Alleviates Neuronal Apoptosis Due to Intracerebral Hemorrhage via the miR-339-5p/VEGFA Pathway. Neuropsychiatr Dis Treat. 2018;14:643–655.
10. Zhou XM, et al. GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition. Front Pharmacol. 2017;8:904.
11. Park J-R, Lee H, Kim S-I, Yang S-R. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget. 2016;7(35):58405–58417.
12. Senel-Yanova LA, Deligheyan ME. Effects of Tripeptide Gly-His-Lys in Pain-Induced Aggressive-Defensive Behavior in Rats. Bull Exp Biol Med. 2017;164(2):140–143.
13. Senel-Yanova LA, Proshlyakov DV. Binding of Oligopeptides to L-Arginine Inverts Its Analgesic and Antiepileptogenic Effects. Bull Exp Biol Med. 2018;165(5):621–624.