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What is GHK-Cu used for?

FAQ

GHK-Cu is a three-amino-acid peptide that binds copper, first isolated from human blood plasma. It is sold as a cosmetic skin-care ingredient, and its human research on GHK-Cu alone is two small topical skin trials. No FDA-approved GHK-Cu drug exists; injectable GHK-Cu is no longer in FDA’s compounding Category 2, while non-injectable GHK-Cu is back in 503A Category 1.

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What it is being studied for

  • Facial wrinkles (topical serum): wrinkle volume 55.8% lower than a plain vehicle serum and 31.6% lower than a commercial Matrixyl 3000 product after 8 weeks in 40 women; a human randomized trial, double-blind and split-face, published in a journal not indexed in PubMed [1]
  • Skin after CO2 laser resurfacing (topical): no difference between groups in redness resolution or wrinkle improvement; patients rated overall skin quality higher with GHK-Cu (P=.04); a small human randomized trial, 13 completers [2]
  • Hair loss (scalp injection): hair-pull test improved in 83% of 1,000 patients, but the injected formulation also held five growth factors, so GHK-Cu’s part cannot be separated; a human study with no control group [3]
  • Wound healing: in rabbits, topical copper tripeptide wounds filled with new tissue in 14 vs 25 days (mean healing 29.8 vs 34.6 days); in rats, more glycosaminoglycans, a skin-matrix building block, in wound chambers; animal studies [4][5]
  • Ligament graft healing: rats injected in the knee after ACL reconstruction had less knee laxity at 6 weeks (p=0.009) but no difference at 12 weeks; an animal study [6]
  • Lung injury and lung scarring: lower inflammatory signals (TNF-alpha, IL-6) in mice with induced lung injury, and less scarring in mice with induced fibrosis; animal studies [7][8]
  • Alzheimer’s-type changes: 5xFAD mice given GHK-Cu in the nose 3 times a week for 3 months showed delayed memory decline and fewer amyloid plaques; an animal study [9]
  • No human study of injected, intranasal or oral GHK-Cu on its own was found.

How it works

  1. Copper carrier: GHK (glycine-histidine-lysine) was isolated from blood and found bound to roughly equal amounts of copper; its discoverer proposed that it helps cells take up copper [10][11].
  2. Skin-matrix building: in cultured human skin cells (fibroblasts) GHK-Cu raised collagen and elastin output and stimulated sulfated glycosaminoglycan production [1][12][13].
  3. Tissue remodelling: it shifted the balance of matrix-cutting enzymes (MMPs) and their blockers (TIMPs) in skin cells, and in rat wounds it raised MMP-2 and kept MMP-9 present longer [1][14].
  4. Inflammation: in mice and mouse immune cells it lowered reactive oxygen species, TNF-alpha and IL-6 through the NF-kB and p38 pathways, and in lung scarring it acted on the TGF-beta1/Smad pathway [7][8].
  5. What sets it apart: it is a copper complex that crosses skin; in a laboratory test a 0.68% copper tripeptide solution moved copper through human skin samples [15], and in a head-to-head trial it reduced wrinkle volume more than a commercial cosmetic peptide product [1].

Adverse events reported

  • Topical wrinkle trial: 39 of 40 women tolerated the serums over 8 weeks; one had minor skin reactions on both sides of the face (GHK-Cu and comparator), stopped, and recovered without medical treatment [1].
  • Post-laser trial: the published abstract reports no adverse-event data [2].
  • Scalp-injection combination study: the authors reported that treatment was well tolerated [3].
  • No safety data for injected or systemic GHK-Cu on its own in people were found.

Forms

Topical GHK-Cu is the only form tested on its own in people, in two small trials [1][2]. Injected into the scalp it appears only inside a multi-ingredient formulation [3]; injections into the knee, the abdomen or wound chambers were studied in rats and mice [5][6][8]. Intranasal GHK-Cu has one mouse study [9], and no oral study was found.

For how topical and injected GHK-Cu compare, see GHK-Cu topical vs injection.

Sources

  1. Badenhorst T et al. Effects of GHK-Cu on MMP and TIMP expression, collagen and elastin production, and facial wrinkle parameters. J Aging Sci 2016;4:166. DOI 10.4172/2329-8847.1000166 (not indexed in PubMed). doi.org/10.4172/2329-8847.1000166 →
  2. Miller TR et al. Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg 2006;8(4):252-259. PMID 16847171. pubmed.ncbi.nlm.nih.gov/16847171/ →
  3. Kapoor R et al. Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth. J Cosmet Laser Ther 2018;20(6):369-379. PMID 29482481. pubmed.ncbi.nlm.nih.gov/29482481/ →
  4. Gul NY et al. The effects of topical tripeptide copper complex and helium-neon laser on wound healing in rabbits. Vet Dermatol 2008;19(1):7-14. PMID 18177285. pubmed.ncbi.nlm.nih.gov/18177285/ →
  5. Siméon A et al. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol 2000;115(6):962-968. PMID 11121126. pubmed.ncbi.nlm.nih.gov/11121126/ →
  6. Fu SC et al. Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction. J Orthop Res 2015;33(7):1024-1033. PMID 25731775. pubmed.ncbi.nlm.nih.gov/25731775/ →
  7. Park JR et al. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget 2016;7(36):58405-58417. PMID 27517151. pubmed.ncbi.nlm.nih.gov/27517151/ →
  8. Zhou XM et al. GHK peptide inhibits bleomycin-induced pulmonary fibrosis in mice by suppressing TGFβ1/Smad-mediated epithelial-to-mesenchymal transition. Front Pharmacol 2017;8:904. PMID 29311918. pubmed.ncbi.nlm.nih.gov/29311918/ →
  9. Tucker M et al. Behavioral and neuropathological features of Alzheimer’s disease are attenuated in 5xFAD mice treated with intranasal GHK peptide. Aging Pathobiol Ther 2024;6(3):102-108. PMID 40766919. pubmed.ncbi.nlm.nih.gov/40766919/ →
  10. Schlesinger DH et al. Growth-modulating serum tripeptide is glycyl-histidyl-lysine. Experientia 1977;33(3):324-325. PMID 858356. pubmed.ncbi.nlm.nih.gov/858356/ →
  11. Pickart L et al. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature 1980;288(5792):715-717. PMID 7453802. pubmed.ncbi.nlm.nih.gov/7453802/ →
  12. Maquart FX et al. 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. PMID 3169264. pubmed.ncbi.nlm.nih.gov/3169264/ →
  13. Wegrowski Y et al. Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Life Sci 1992;51(13):1049-1056. PMID 1522753. pubmed.ncbi.nlm.nih.gov/1522753/ →
  14. Siméon A et al. Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. J Invest Dermatol 1999;112(6):957-964. PMID 10383745. pubmed.ncbi.nlm.nih.gov/10383745/ →
  15. Hostynek JJ et al. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res 2011;60(1):79-86. PMID 20721598. pubmed.ncbi.nlm.nih.gov/20721598/ →

For other common questions regarding GHK-Cu, see the full GHK-Cu profile.

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