GHK (glycyl-l-histidyl-l-lysine) is a tiny protein found naturally in the blood of many mammals, including humans, where it is often attached to copper (Cu) to form GHK-Cu. Early research has revealed that GHK-Cu could restore function to liver cells, making old cells act like much younger cells. Subsequent animal studies have found that the protein has an ability to reduce the effects of aging in a number of tissues.

Animal studies have revealed that GHK’s effects are particularly pronounced in skin where it acts to promote the production of supporting structures (extracellular matrix) in the skin, increase collagen synthesis, regulate copper levels, and activate reparative cells (fibroblasts and mast cells). The protein is now being investigated as an anti-inflammatory to replace cortico-steroids, for use in nerve regeneration, as a stem cell growth factor, as a DNA protectant, and as a general anti-cancer agent. GHK-Cu is widely used in cosmetics and has been investigated for use in wound healing and hair growth. For reasons that aren’t clear, GHK production declines with age. The utility of GHK supplementation is currently being researched. This peptide will be lyophilized as light blue in vials.

Several copper-peptide complexes occur naturally. GHK-Cu is proposed to promote wound healing, attraction of immune cells, antioxidant and anti-inflammatory effects, stimulation of collagen and glycosaminoglycan synthesis in skin fibroblasts and promotion of blood vessels growth. Recent studies revealed its ability to modulate expression of a large number of human genes, generally reversing gene expression to a healthier state. Synthetic GHK-Cu is used in cosmetics as a reparative and anti-aging ingredient.

In the late 1980s, copper peptide GHK-Cu started attracting attention as a promising wound healing agent. GHK-Cu stimulated the synthesis of collagen in skin fibroblasts, increased accumulation of total proteins, glycosaminoglycans. They also found out that the GHK sequence is present in collagen and suggested that the GHK peptide is released after tissue injury. They proposed a class of emergency response molecules which are released from the extracellular matrix at the site of an injury. GHK-Cu also increased synthesis of decorin – a small proteoglycan involved in the regulation of collagen synthesis, wound healing regulation and anti-tumor defense.

It was also established that GHK-Cu stimulates both the synthesis of metalloproteinase, the enzymes which break down dermal proteins, and their inhibitors (anti-proteases).

GHK-Cu has been found to induce a systemic enhancement of healing in animal research. GHK-Cu peptide injected in one area of the body (such as the thigh muscles) improved healing at distant body areas (such as the ears). These treatments strongly increased healing parameters such as collagen production, angiogenesis, and wound closure in both wound chambers and full thickness wounds.

GHK-Cu treatment resulted in faster wound contraction and epithelization, higher level of glutathione and ascorbic acid, increased synthesis of collagen, and activation of fibroblasts and mast cells. Ischemic open wounds in rats treated with GHK-copper healed faster.

Human trials

A 2% GHK gel showed promising results in treatment of 120 diabetic patients, increasing the percentage of ulcer closure from 60.8% to 98.5%, and decreasing the percentage of infection from 34% to 7%. The rate of healing was three times greater with GHK. However, a 0.4% GHK-Cu cream failed to reach therapeutic goal in treatment of venous ulcers.

DNA repair

Radioactive anti-cancer treatment slows cell replication by breaking DNA strands. A recent study showed GHK-Cu’s ability to restore function of irradiated fibroblasts to that of intact cells. The researchers used cultured human fibroblasts obtained from cervical skin that was either intact or exposed to radioactive treatment (5000 rad).

Nerve regeneration‍

Axon regeneration was studied using collagen tubes with incorporated peptides. GHK increased migration of haematogenous cells into collagen tube, production of nerve growth factors, expression of integrin’s and the rate of regeneration of myelinated nerve fibers.

GHK-Cu stimulates proliferation of keratinocytes and increased expression of integrins and p63 protein in the epidermal stem cells. Since p63 is considered to be an important marker of stem cell and anti-senescence protein, the authors concluded that GHK-copper is able to recover epidermal stem cells and increase their ability to repair tissue [25]. Similar activity was observed for copper-free GHK.

Anti-cancer effect

GHK-Cu reverses the expression of certain genes involved in metastatic spreading of colon cancer. GHK-Cu was effective at a very low concentration with anti-cancer effects.

Copper peptide GHK-Cu is widely used in anti-aging cosmetics Several controlled facial studies confirmed anti-aging, firming and anti-wrinkle activity of copper peptide GHK-Cu.

Facial cream containing GHK-Cu and melatonin increased collagen in photo aged skin of 20 female volunteers, performing better than vitamin C and retinoic acid. The study was not controlled for cream vehicle application alone without active ingredients.

A 12-week facial study on 67 women indicated that GHK-Cu cream applied twice daily improved aged skin appearance, increased thickness, reduced wrinkles and strongly stimulated dermal keratinocyte proliferation as determined by histological analysis of biopsies. The same study found copper peptide GHK-Cu to be non-toxic and non-irritating.

Hair Growth

Copper peptide GHK-Cu and its analogues were found to stimulate hair growth. In some circumstances, the efficiency of synthetic analog of GHK-Cu was similar to that of 5% minoxidil. A commercial product Graft Cyte was clinically proven to improve hair transplantation outcome. Shown to promote collagen production, using copper peptides topically on the scalp will help strengthen already existing hair, while stimulating growth in areas that are lacking thickness.

Biological chemistry
Copper binding
Replacement of histidine with other amino acids showed that the glycine residue plays major role in copper binding, whereas lysine can interact with copper only at alkaline pH. At physiological pH, lysine is able to interact with a cellular receptor. The ability of GHK to interact both with copper and with a cellular receptor may allows it to transfer copper into and from cells. The small size of GHK permits speedy traveling in extracellular space and its easy access to cellular receptors.

The molecular structure of the GHK copper complex (GHK-Cu) has been determined X-ray crystallography, EPR spectroscopy, X-ray absorption spectroscopy, NMR spectroscopy, as well as other methods such as titration. In the GHK-Cu complex, the Cu (II) ion is coordinated by the nitrogen from the imidazole side chain of the histidine, another nitrogen from the alpha-amino group of glycine and the deprotonated amide nitrogen of the glycine–histidine peptide bond. Since such a structure could not explain a high stability constant of the GHK-Cu complex (log 10 =16.44 vs. 8.68 of the GH copper complex, which is similar to the GHK-Cu structure), it was proposed that another amino group participates in the complex formation. Cu(II) is also coordinated by the oxygen from the carboxyl group of the lysine from the neighboring complex. Another carboxyl group of lysine from a neighboringcomplex provides the apical oxygen, resulting in the square-planar pyramid configuration. Many researchers proposed that at the physiological pH, GHK-Cu complexes can form binary and ternary structures which may involve amino acid histidine and/or the copper binding region of the albumin molecule.

Lau and Sarkar found also that GHK can easily obtain copper 2+ bound to other molecules such as the high affinity copper transport site on plasma albumin (albumin binding constant log 10 =16.2 vs. GHK binding constant 16 log 10 =16.44). It has been established that copper (II) redox activity is silenced when copper ions are complexed with the GHK tripeptide, which allows the delivery of non-toxic copper into the cell.

Biological significance
Copper is vital for all eukaryotic organisms from microbes to humans. A dozen enzymes (cuproenzymes) use changes in copper oxidation state to catalyze important biochemical reactions including cellular respiration (cytochrome c oxidase), antioxidant defense (ceruloplasmin, superoxide dismutase (SOD), detoxification (metallothioneins), blood clotting (blood clotting factors V and VIII), melanin production (tyrosinase) and the connective tissue formation (lysyl peroxidase). Copper is required for iron metabolism, oxygenation, neurotransmission, embryonic development and many other essential biological processes.

Another function of copper is signaling – for example, stem cells require a certain level of copper in the media to start their differentiation into cells needed for repair. Thus, GHK-Cu’s ability to bind copper and to modulate its tissue level is a key factor determining its biological activity.

Dosage

The recommended program is 100mg taken at 5mg daily dosages over 20 days and can be repeated every 4 months. GHK-Cu can be inject SubQ under the skin or directly into the muscle. Take before bed.