Evidence Grade C — Moderate human evidence. 253 published studies, 85 human. 0 registered clinical trials.
Medically reviewed by a licensed medical professional
GHK is a naturally occurring tripeptide that binds copper, found in human blood. In the cosmetic industry it is known as 'copper tripeptide-1' and is a common ingredient in anti-ageing skincare products. This entry covers the free peptide form without copper; the copper-complexed version (GHK-Cu) is described separately. It has no pharmaceutical approval.
GHK is also known by these brand and alternate names:
253 published studies: 85 human, 49 animal, 46 in-vitro, 23 reviews
GHK has no pharmaceutical authorisation. Small cosmetic studies of the copper-complexed form (GHK-Cu) have reported improvements in skin appearance measures. No pharmaceutical clinical trials for injectable use have been completed.
As with GHK-Cu (#85), the cosmetic evidence base for topical use should be distinguished from claims about injectable use. Gene expression profiling studies have reported broad effects, but observational genomic changes do not constitute evidence of therapeutic efficacy. This entry overlaps substantially with GHK-Cu (#85).
Research suggests GHK's biological activity is primarily mediated through its copper-binding capacity. Gene expression analyses have reported broad effects on gene regulation, but these are observational genomic studies and do not establish specific therapeutic mechanisms. The distinction between the free peptide and the copper-complexed form (GHK-Cu) is pharmacologically relevant.
Research suggests GHK has been studied primarily in the context of topical skincare, where small studies (21-71 participants) of the copper-complexed form have shown improvements in skin appearance. Gene expression profiling has reported broad effects, though these analyses were performed on cancer cell lines rather than normal tissue. The safety record in topical cosmetic use is excellent over approximately 30 years. However, no large randomised controlled trials exist, no systemic pharmacokinetic data are available for injectable use, and most research originates from a single investigator group. Blood levels naturally decline with age, providing biological plausibility for supplementation, but plausibility is not proof of benefit.
PeptideTrace tracks 0 registered clinical trials for GHK sourced from ClinicalTrials.gov.
No trials registered on ClinicalTrials.gov for this compound.
GHK (Glycyl-L-Histidyl-L-Lysine) is a naturally occurring copper-binding tripeptide first isolated from human plasma albumin by Loren Pickart in 1973. It is one of the most commercially successful peptides in the cosmetic industry, marketed as Copper Tripeptide-1 or GHK-Cu. Its sequence is Gly-His-Lys, with molecular formula C14H24N6O4 (free peptide) and molecular weight 340.38 g/mol (CAS free: 49557-75-7; CAS GHK-Cu: 89030-95-5; PubChem CID GHK-Cu: 378611). The GHK-Cu complex has a molecular weight of approximately 401.93 g/mol. In the complex, Cu(II) is coordinated by the histidine imidazole nitrogen, the glycine alpha-amino nitrogen, and the deprotonated glycine-histidine peptide bond amide nitrogen, with a stability constant of log10 = 16.44. Natural plasma levels decline with age: approximately 200 ng/mL at age 20 declining to approximately 80 ng/mL at age 60. Solubility is approximately 325 mg/mL in water. Research administration routes include topical, subcutaneous injection, and intradermal injection.
Research suggests GHK-Cu operates as a pleiotropic signaling molecule affecting a remarkable fraction of the human genome. Broad Institute Connectivity Map analysis revealed GHK stimulates or suppresses approximately 4,192 genes (approximately 31.2% of human genes) at 50% or greater change threshold, with 59% upregulated and 41% suppressed. At picomolar to nanomolar concentrations, research suggests GHK-Cu stimulates synthesis of collagen types I and III, dermatan sulfate, chondroitin sulfate, glycosaminoglycans, and decorin. It stimulates both metalloproteinases (MMP1, MMP2) and their inhibitors (TIMP1, TIMP2), suggesting balanced remodeling rather than simple deposition. Research suggests wound healing effects through macrophage/mast cell attraction, angiogenesis stimulation, TGF-beta1 suppression (reducing scarring), and growth factor release (BDNF, VEGF, BMP-2). Campbell et al. (2012, Genome Med) demonstrated GHK reversed the gene expression signature of emphysema. Research suggests GHK suppressed RNA production in 70% of 54 genes overexpressed in aggressive metastatic colon cancer.
Multiple small clinical trials demonstrate cosmetic efficacy. Leyden et al. (N=71 women, 12 weeks) showed GHK-Cu cream increased skin density/thickness, reduced laxity, improved clarity, and reduced wrinkle depth. Abdulghani et al. (1998; N=41 women, 12 weeks) showed GHK-Cu eye cream reduced periorbital wrinkles by approximately 55%, outperforming placebo and vitamin K, with 70% reporting improved firmness. Badenhorst et al. (2016; randomized double-blind, 8 weeks) showed GHK-Cu in nano-lipid carrier produced 31.6% reduction in wrinkle volume versus Matrixyl 3000 and 55.8% versus control (p < 0.01), with 32.8% decrease in wrinkle depth. Canapp et al. (2003; rat ischemic wounds) showed GHK reduced wound size by 64.5% versus 45.6% vehicle and 28.2% controls. Commercial products include Neutrogena, Osmotics Blue Copper 5, Neova, ProCyte (Tricomin, GraftCyte), and NEEL gel. GHK-Cu has been used in cosmetics for approximately 30+ years.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Argireline has no pharmaceutical authorisation. It is widely available as a cosmetic ingredient in over-the-counter skincare products. Small industry-sponsored studies have reported wrinkle depth reductions of 17–30% with topical application. The key scientific question is whether sufficient peptide penetrates intact skin to reach neuromuscular junctions and produce a meaningful effect. The molecule's size exceeds the conventional limit for transdermal absorption. Argireline's cosmetic use in formulated skincare products represents a fundamentally different risk profile from injectable use.
GHK-Cu has no pharmaceutical authorisation from any regulatory agency. It is widely available as a cosmetic ingredient in over-the-counter skincare products, where it is marketed for skin conditioning. A small study comparing GHK-Cu cream to vitamin C and retinoic acid creams reported improvements in skin appearance measures. No pharmaceutical clinical trials for injectable GHK-Cu have been completed. The compound's cosmetic use (topical, in formulated skincare products) should be clearly distinguished from its unregulated availability as an injectable research compound. These represent fundamentally different risk profiles.
Matrixyl 3000 has no pharmaceutical authorisation. It is widely used as a cosmetic ingredient. Small studies report wrinkle reduction, with a head-to-head comparison against the original Matrixyl suggesting greater statistical significance on wrinkle endpoints. As a two-component combination, Matrixyl 3000's evidence should be interpreted alongside the individual component entries: Palmitoyl Tripeptide-1 (#139) and Palmitoyl Tetrapeptide-7 (#140). It is a topical cosmetic ingredient.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
