GHK-Cu is a simple tri-peptide copper complex that was originally isolated from human blood plasma. It has the following sequence: Gly-His-Lys
First isolated in the early 1970’s, human peptide GHK was determined to cause old human tissue to synthesize proteins like younger, healthier tissue. In human blood plasma, GHK peaks at age 20–25 but then gradually declines. Since GHK-Cu promotes cell growth, it was proposed that the GHK acts by delivering elemental copper that is essential for cellular functions across cell membranes . In fact, GHK has a long history of safe use in wound healing and skin care, and it is naturally occurring and active at very low concentrations .
It readily forms complexes with copper, which regulates its metabolism and improves its bioavailability . Recent studies have revealed its ability to regulate a large number of human genes, including those that are involved in nervous system physiology, development, and maintenance . Currently GHK-Cu is being investigated for the potential to improve a variety of age-associated problems in the following ways:
Performing crucial antioxidant and anti-inflammatory roles –
Supporting tissue regeneration , , 
Improving circulation via angiogenesis (new blood-vessel formation), anticoagulation, and vasodilation –
Promoting stem cell recovery, function, and trophic factor secretion –
Encouraging nerve outgrowth and protection from intracerebral hemorrhage , 
In preclinical and clinical studies, GHK-Cu has been administered topically in skin creams, or sublingual (under the tongue). It can also be administered subcutaneously.
In topical creams, GHK-Cu is diluted to 0.5-2.0% w/v. However, current research suggests optimal dosages as being 5 mg per day sublingual, or 1-2 mg per day subcutaneous.
Selected preclinical research findings
Adapted from: L. Pickart and A. Margolina, “The Effect of the Human Plasma Molecule GHK-Cu on Stem Cell Actions and Expression of Relevant Genes,” OBM Geriatr., vol. 2, no. 3, pp. 1–1, Aug. 2018.
GHK-Cu prevents neuronal death and neurological deficits due to brain hemorrhage :
Ischemic and hemorrhagic stroke are among the leading causes of death and disability worldwide. Although it accounts for approximately 15% of all stroke cases, hemorrhagic stroke is associated with the highest mortality rates among the stroke subtypes, thus representing a major public health concern (Donnan et al., 2008; van Asch et al., 2010a). Primary damage is caused by the rupture of blood vessels in the brain, while secondary injuries include hematoma compression, perihematomal edema, neuronal death, and inflammation due to the effects of hemoglobin (Keep et al., 2012; Wang et al., 2014). Current treatment options for patients with intracerebral hemorrhage (ICH) are limited; therefore, timely and targeted treatment is critical...Previous studies have suggested that GHK enhances wound healing and improves inflammation, emphysema-related lung destruction, and tissue regeneration (Campbell et al., 2012; Pickart et al., 2015). Additional studies have indicated that GHK may exert neuroprotective effects against neurodegenerative diseases (Pickart et al., 2012). However, the role of GHK and the mechanisms underlying its effects in patients with ICH remain to be elucidated. In the present study, we investigated the biological function of GHK in a rat model of ICH.
FIGURE 1. Glycine-histidine-lysine (GHK) alleviated neuronal death and neurological deficits following intracerebral hemorrhage (ICH). Analyses of neurological deficits revealed that treatment with both 1 mg/kg and 10 mg/kg GHK facilitates neurological recovery at 7 days after ICH. TOP PANELS: Immunohistochemistry analysis of caspase-3 expression. Paraffin slices (5 μm) from the control and GHK groups were stained with caspase-3. (scale bar = 100 μm). BOTTOM PANELS: Paraffin slices (5 μm) from the control and GHK groups were stained with Cresyl Violet acetate. (scale bar = 100 μm). Data are represented as the mean ± SD, n = 8. #, p < 0.05 vs. control, ##, p < 0.01 vs. control, ∗, p < 0.05 vs. GHK 1 mg/kg, and ∗∗, p < 0.01 vs. GHK 1 mg/kg.
Adapted from: H. Zhang, Y. Wang, and Z. He, “Glycine-Histidine-Lysine (GHK) Alleviates Neuronal Apoptosis Due to Intracerebral Hemorrhage via the miR-339-5p/VEGFA Pathway,” Front. Neurosci., vol. 12, p. 644, Sep. 2018
Conclusion: These findings indicate that GHK-Cu significantly decreases the neuronal damage caused by brain hemorrhage. In addition, GHK-Cu significantly increases neuronal cell viability.
Selected clinical research findings
Gly‐His‐Lys is a tripeptide with affinity for copper(II) ions, and copper‐GHK stimulates collagen synthesis by fibroblasts. Therefore, copper‐GHK is frequently used to make skin and hair care formulations. The epidermis is the outermost layer of the skin, and it is essential for the epidermis to be able to continually self‐renew and regenerate following injury. These characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. In this study, the effect of GHK was tested using cultured normal human keratinocytes and human skin constructs.
We investigated the effects of GHK on keratinocytes and found that it increased the proliferation and the number of keratinocytes. These results suggest that GHK can act as a growth factor for keratinocytes. Then, three‐dimensional skin models were constructed to study the effects of GHK. When GHK was added to the human skin constructs, the basal cells became cuboidal. In normal skin, basal cells are cuboidal in shape, with their long axes aligned perpendicular to the dermoepidermal junction. These cuboidal keratinocytes become flattened as differentiation progresses. Thus, it can be said that cuboid basal cells have greater potential of proliferation than flattened cells. Accordingly, our findings showed that treatment with GHK increased the proliferative potential of basal cells.
Adapted from: H.-R. Choi et al., “Stem cell recovering effect of copper-free GHK in skin,” J. Pept. Sci., vol. 18, no. 11, pp. 685–690, Nov. 2012.
Conclusion: This study demonstrates that the GHK peptide promotes the survival of basal stem cells, essential to the maintenance of youthful skin tissue.
*The information herein is for educational and informational purposes only. THIS PRODUCT IS FOR RESEARCH USE ONLY. For use in animal studies, all research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).
Storage: Lyophilized peptide should be stored at -20°C (freezer), and the reconstituted peptide solution at 4°C (refrigerated). Use within 24 months. Once reconstituted use within 30 days. Do not freeze once reconstituted.
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