GHK-Cu

What it is

GHK-Cu (glycyl-histidyl-lysine copper) is a naturally occurring tripeptide complex that exists in human plasma at concentrations of approximately 200 ng/mL in young adults, declining to about 80 ng/mL by age 60. The molecule consists of the GHK tripeptide bound to a copper(II) ion in a 1:1 ratio. In laboratory studies, copper binding appears important to GHK’s biological activity.

GHK was first isolated from human plasma in 1973 by Loren Pickart, who observed that it stimulated growth and survival of liver cells in culture. Subsequent research has examined its role in skin, hair follicle biology, and wound healing, mainly in laboratory and animal studies and in studies of topical cosmetic products.

GHK-Cu is used in topical cosmetic products but is not FDA-approved as a drug.

Mechanism of action

Proposed mechanisms come from laboratory and animal research:

• Collagen and extracellular matrix synthesis: in laboratory (cell) studies, GHK-Cu has been reported to increase fibroblast production of collagen (types I and III), elastin, glycosaminoglycans, and proteoglycans.
• Wound healing: in animal and laboratory studies, GHK-Cu has been reported to increase expression of growth factors at wound sites, increase fibroblast and keratinocyte migration, and be associated with new blood vessel formation.
• Antioxidant effects: laboratory studies have reported increased superoxide dismutase activity and other antioxidant activity.
• Anti-inflammatory effects: in laboratory and animal studies, GHK-Cu has been reported to reduce pro-inflammatory cytokine production and neutrophil infiltration.
• Hair follicle biology: laboratory studies have reported effects on the anagen (growth) phase of the hair cycle and on dermal papilla cell proliferation.
• Gene expression modulation: a 2010 analysis of gene expression data by Pickart and colleagues reported that GHK was associated with changes in expression of over 4,000 human genes in cell-based data; the clinical significance of this is unknown.

Research findings

Skin and photoaging: small studies of topical cosmetic formulations containing GHK-Cu have been published; benefit in people has not been established.

Wound healing: animal studies have reported faster wound closure. Small studies of topical or local application in people have been published; benefit in people has not been established.

Hair density: small studies of formulations combining GHK-Cu with other ingredients in androgenetic alopecia have been published; benefit in people has not been established.

Injectable use: human research on injected GHK-Cu is very limited. Well-controlled human trials establishing the effectiveness and safety of GHK-Cu as a drug are lacking.

Side effects and contraindications

The safety of injected GHK-Cu has not been established in well-controlled human trials, and long-term effects are unknown. Skin irritation and allergic-type reactions have been reported with topical products. Products sold outside regulated channels (for example, as “research peptides”) may vary in purity, dose, and sterility.

Concerns have been raised for:

• Wilson disease and other disorders of copper metabolism
• Documented copper allergy
• Active malignancy (theoretical concern given reported growth-related effects)
• Pregnancy and breastfeeding (absence of safety data)

What we don’t yet know

Effects of injected GHK-Cu in humans have not been characterized, and long-term effects of repeated use are unknown. Whether GHK-Cu has effects on tissues distant from the site of application is not established. Comparative effectiveness against established treatments for skin aging, hair loss, and wound healing has not been evaluated in head-to-head studies.