Overview
GHK is a tripeptide made of glycine, histidine and lysine. It has a strong affinity for copper(II) ions and readily forms a complex called GHK-Cu, which is the form most research uses (Maquart 1988). It occurs naturally in human plasma, and reviews by its discoverer report that it is also found in saliva and urine and that plasma levels decline with age (Pickart 2015).
GHK-Cu has been studied mainly for skin: collagen production in cultured fibroblasts, animal wound models and a small number of human trials. It is also a common ingredient in cosmetic serums and hair products. The evidence has a consistent laboratory signal, reasonably strong animal wound data and a thin human trial record. Much of the review literature is written by researchers affiliated with companies that sell copper peptide products.
A related peptide, AHK-Cu, swaps glycine for alanine and appears mainly in hair follicle research. It is a different molecule. Our article on copper peptides in skin and hair studies covers each layer of the evidence in more detail.
Research history
Loren Pickart reported in 1973 that a small peptide factor in human serum prolonged the survival of normal liver cells in culture and stimulated growth in liver tumor cells (Pickart 1973). The factor was later identified as GHK.
In 1988 a French group in Reims, working with Pickart, showed that GHK-Cu stimulated collagen synthesis in fibroblast cultures at very low concentrations (Maquart 1988). They noted that the GHK sequence occurs within type I collagen and proposed that it might be released when collagen breaks down at a wound. That idea shaped the field but remains a hypothesis.
Animal wound studies and a diabetic ulcer trial followed in the 1990s. From about 2010, reanalysis of public gene expression data renewed interest, with Pickart and colleagues reporting that GHK shifts the expression of thousands of genes (Pickart 2018).
What published studies have examined
Cell studies
In cultured fibroblasts, GHK-Cu increased collagen synthesis in a way not explained by changes in cell number (Maquart 1988). The gene expression work draws on the Connectivity Map, a database built largely from cancer cell lines, and reports that GHK can up or downregulate at least 4,000 human genes (Pickart 2015; Pickart 2018). Those papers come from authors affiliated with Skin Biology, a company that sells copper peptide products.
In human hair follicles kept alive outside the body, the related peptide AHK-Cu lengthened follicles and increased proliferation of dermal papilla cells (Pyo 2007).
Animal studies
In rats, wire mesh chambers implanted under the skin and injected with GHK-Cu accumulated more collagen, glycosaminoglycans, DNA and total protein than saline chambers, in a concentration-dependent way, while a control tripeptide had no significant effect (Maquart 1993).
Human trials
- Diabetic foot ulcers. A multicenter, randomized, evaluator-blinded, vehicle-controlled trial of a GHK-Cu gel reported a median plantar ulcer closure of 98.5 percent versus 60.8 percent with vehicle, alongside standardized wound care (Mulder 1994). It is one trial of a commercial formulation from the 1990s.
- Laser resurfacing. In a randomized study with 13 patients who completed it, blinded evaluators and computer analysis found no significant difference in redness, wrinkles or overall skin quality after carbon dioxide laser resurfacing. Only patient satisfaction scores differed (Miller 2006).
Open questions
- Human evidence. The peer-reviewed human trial record is short, and several cosmetic facial studies cited in reviews were not published as full peer-reviewed papers.
- Independence. Much of the synthesis comes from researchers with commercial ties to copper peptide products. Independent replication would strengthen the record.
- Hair. We found no published, controlled human trial of GHK-Cu or AHK-Cu for hair growth.
- Gene data. Changing the expression of many genes in cell lines does not show a benefit in intact human skin.
- Material quality. Copper content and peptide purity can vary between sources, which affects how results are interpreted.
The same gap between lab findings and controlled human data appears in oral collagen research, covered in what collagen skin studies actually measure.
Sources
- Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nat New Biol. 1973;243(124):85-87. pubmed.ncbi.nlm.nih.gov/4349963/
- Maquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. 1988;238(2):343-346. doi.org/10.1016/0014-5793(88)80509-x
- Maquart FX, Bellon G, Chaqour B, et al. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest. 1993;92(5):2368-2376. doi.org/10.1172/JCI116842
- Mulder GD, Patt LM, Sanders L, 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. doi.org/10.1046/j.1524-475X.1994.20406.x
- Miller TR, Wagner JD, Baack BR, Eisbach KJ. Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg. 2006;8(4):252-259. doi.org/10.1001/archfaci.8.4.252
- Pyo HK, Yoo HG, Won CH, et al. The effect of tripeptide-copper complex on human hair growth in vitro. Arch Pharm Res. 2007;30(7):834-839. doi.org/10.1007/BF02978833
- Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. Biomed Res Int. 2015;2015:648108. doi.org/10.1155/2015/648108
- Pickart L, Margolina 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):1987. doi.org/10.3390/ijms19071987
Frequently asked questions
What is the difference between GHK and GHK-Cu?
GHK is the tripeptide glycine, histidine and lysine. GHK-Cu is that peptide bound to a copper(II) ion, the form used in most research because copper is thought to be central to many of its reported effects.
Is GHK-Cu FDA approved?
No. GHK-Cu is not an FDA-approved drug. It appears as an ingredient in cosmetic products, which are not approved to treat or prevent any condition.
Is there clinical evidence for GHK-Cu on skin?
Limited. One randomized trial in diabetic foot ulcers reported faster closure with a GHK-Cu gel, while a small laser resurfacing trial found no objective difference and only higher patient satisfaction.
Do copper peptides affect hair growth?
The published evidence is laboratory work, mainly with the related peptide AHK-Cu on isolated human hair follicles and cultured cells. No controlled human hair growth trial has been published in the indexed literature.
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