GHK-Cu: research reference

What the copper tripeptide is, what the published research has examined, and how to handle and verify it in a laboratory.

1. What GHK-Cu is

GHK is the tripeptide glycyl-L-histidyl-L-lysine. GHK-Cu is its complex with a copper(II) ion. Loren Pickart first isolated GHK from human plasma in 1973 while studying why plasma from young donors behaved differently from plasma from older donors in liver cell culture [1]. The sequence occurs naturally: it circulates in plasma and is also found within larger proteins such as collagen and the matrix protein SPARC, from which it can be released when those proteins are broken down [2]. Pickart's group has reported plasma GHK of about 200 ng/mL in young adults, falling to about 80 ng/mL by age 60 [2].

GHK-Cu has been a cosmetic ingredient for decades, listed as copper tripeptide-1 (INCI) in topical skincare. The material sold as a research chemical is the same peptide-copper complex, supplied as a lyophilised powder in a sealed vial.

2. Chemistry and properties

3. What has been studied

The research record is broad in cell culture and animal models and narrow in humans, where nearly all of it concerns topical formulations. By model:

• Fibroblast culture. Maquart and colleagues reported in 1988 that GHK-Cu increased collagen synthesis in cultured fibroblasts [3]. Later work reported increases in glycosaminoglycans and decorin and changes in matrix metalloproteinases and their inhibitors [2,4].
• Copper delivery. Copper is a cofactor for lysyl oxidase (which cross-links collagen and elastin), superoxide dismutase 1 and cytochrome c oxidase. A small peptide that carries copper into cells is a tool for studying copper-dependent enzymes [2].
• Hair follicle organ culture. Pyo and colleagues reported in 2007 that GHK-Cu increased dermal papilla cell proliferation and hair follicle elongation ex vivo [5].
• Wound models. Animal studies in rats, rabbits and pigs reported faster closure and more granulation tissue with topical GHK-Cu. A 1994 clinical study tested a topical GHK-Cu gel on foot ulcers in people with diabetes [6]. All of this is topical.
• Topical cosmetic studies. Twelve-week studies of copper-peptide creams measuring skin density and appearance were mostly presented at industry conferences rather than published in peer-reviewed journals. That is what "the evidence is cosmetic" means in practice.
• Systemic route. There are no published controlled clinical trials of GHK-Cu given by a systemic route in humans. Any statement about systemic effects extrapolates from cell and animal work.

4. Gene expression work

Hong and colleagues used the Broad Institute Connectivity Map in 2010 to search for compounds that reversed a "metastasis-prone" gene signature in colon cancer samples, and GHK was among the hits [7]. Campbell and colleagues applied the same approach in 2012 to a gene signature of emphysema-related lung destruction and reported that GHK reversed the signature in lung fibroblasts in vitro, restoring contraction and collagen remodelling in that model [8]. Pickart's group later reported, from the same database, that GHK altered the expression of a large fraction of human genes in the profiled cell lines [2,4].

These are in vitro transcriptomic screens. They generate hypotheses about pathways. They do not establish effects in an organism, and the "thousands of genes" figure that circulates online comes from this work.

5. Regulatory status in Australia

• Topical GHK-Cu (copper tripeptide-1) is a cosmetic ingredient in skincare sold in Australia, regulated as a cosmetic, not as a medicine.
• No GHK-Cu product is registered on the Australian Register of Therapeutic Goods (ARTG) as a medicine.
• Research-grade vials, including those in this catalogue, are research chemicals. They are not medicines, they are not for human use, and they are not approved by the TGA.

6. Storage and handling

7. Reconstitution for lab work

1. Bring the vial to room temperature.
2. Swab the stopper.
3. Add bacteriostatic water (0.9% benzyl alcohol) down the side of the glass, not onto the powder.
4. Swirl gently until dissolved. Do not shake.
5. Label the vial with the compound, the concentration in mg/mL and the date.
6. Refrigerate.

The reconstitution calculator does the arithmetic. For example, 50 mg in 2 mL of bacteriostatic water is 25 mg/mL; 100 mg in 4 mL is also 25 mg/mL. Bacteriostatic water is a laboratory diluent with a preservative. Sterile water and saline have none, so solutions made with them should be used the same day.

8. Reading a GHK-Cu certificate

• Purity by HPLC. The main peak area as a percentage. Catalogue batches are listed with the lab, the batch number and the figure on the lab results page.
• Identity by mass spectrometry. Expect the tripeptide at about 340 Da and/or the copper complex at about 402 Da, depending on the ionisation. A spectrum showing neither is not GHK-Cu.
• Copper content. Some labs report copper by ICP or a colorimetric assay. A "GHK-Cu" with no copper is just GHK.
• Water content and counterion. Both reduce how much of a labelled 50 mg is peptide. The certificate guide shows how to work out net peptide content.

9. Quick answers

Why is the solution blue?

Copper(II) complexes absorb red and orange light, so they look blue to violet. The colour is the copper in the complex. Green tints can appear with pH shifts or copper loss. A colourless solution means no copper complex is present.

Is GHK the same as GHK-Cu?

No. GHK is the free peptide; GHK-Cu is its complex with copper. Free GHK picks up copper from any medium that contains it, which is why some studies use GHK and others use GHK-Cu.

Can it be stored at room temperature?

Lyophilised powder tolerates short periods at room temperature, such as transit. For storage, refrigerate or freeze.

Why do some certificates say "GHK-Cu acetate"?

Acetate is the counterion left from synthesis. It adds to the weight on the label. Net peptide content tells you how much of the 50 mg is peptide.

Where does the "thousands of genes" figure come from?

From in vitro Connectivity Map analyses [2,4,7,8]. It describes gene expression changes in profiled cell lines, not outcomes in an organism.

10. In the catalogue

GHK-Cu is listed in 50 mg and 100 mg vials. Blends that contain GHK-Cu (GLOW and KLOW) are on the catalogue page.

11. References

1. Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nature New Biology. 1973;243:85-87.
2. Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International Journal of Molecular Sciences. 2018;19(7):1987.
3. 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 Letters. 1988;238(2):343-346.
4. Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed Research International. 2015;2015:648108.
5. Pyo HK, Yoo HG, Won CH, et al. The effect of tripeptide-copper complex on human hair growth in vitro. Archives of Pharmacal Research. 2007;30(7):834-839.
6. 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 and Regeneration. 1994;2(4):259-269.
7. Hong Y, Downey T, Eu KW, Koh PK, Cheah PY. A "metastasis-prone" signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clinical and Experimental Metastasis. 2010;27(2):83-90.
8. Campbell JD, McDonough JE, Zeskind JE, et al. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Medicine. 2012;4(8):67.

Citations are given so you can read the primary sources. Nothing on this page is a claim about what the compound does in a person.