Ghk Cu: Safety Profile & Research Summary
Preclinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Canapp et al. (2003) | Rats — ischemic open wounds, topical daily × 13d | Wound size ↓ 64.5% vs 28.2% control; ↓ TNF-α, MMP-2, MMP-9 | [11] |
| Maquart et al. (1993) | Sprague-Dawley rats — wound chambers | Dose-dependent ↑ Collagen I/III, GAGs, DNA content (days 3–14) | [10] |
| Zhang et al. (2022) | C57BL/6J mice — CS-induced emphysema, 0.2–20 µg/g/day IP × 12 wk | Significantly ↓ airspace enlargement; reversed MMP-9/TIMP-1 imbalance; Nrf2/Keap1 activation | [5] |
| Mao et al. (2025) | BALB/c mice — DSS-induced colitis, 20 mg/kg oral × 14d | ↓ DAI score; mitigated colon shortening; SIRT1/STAT3 mechanism; ↑ ZO-1/Occludin | [6] |
| Dou et al. (2020) | 28-month-old C57BL/6 mice — 10 mg/kg 5x/wk × 3 wk | Significantly faster maze completion; ↓ inflammation; ↑ histone deacetylase 2 | [15] |
| Bobyntsev et al. (2015) | Rats — 0.5 µg/kg IP | Analgesic, anxiolytic effects; aggression reduced 5-fold | [15] |
| Gul et al. (2008) | Rabbits — full-thickness wounds × 21–28d | Faster granulation, improved contraction, increased neovascularization | [17] |
| Cherdakov et al. (2010) | Rats — bone fractures, 0.5 µg/kg IP × 10d | Marked ↑ reparative osteogenesis; ↑ antioxidant activity | [16] |
Clinical / Human Studies
| Study | Population | Key Results | Ref |
|---|---|---|---|
| Photoaged Skin (12-wk) | n=71 women | Significantly improved laxity, clarity, firmness; ↓ fine lines and wrinkles; ↑ skin density/thickness | [12] |
| vs. Vitamin C & Retinoic Acid | n=20 women | GHK-Cu ↑ collagen in 70% vs 50% (Vit C) and 40% (retinoic acid) | [12] |
| Periorbital Wrinkles (12-wk) | n=41 women | Wrinkles reduced 55%; outperformed placebo and Vitamin K cream | [12] |
| Nano-Lipid Carrier (RCT, 8-wk) | Female volunteers | Wrinkle volume ↓ 55.8%, depth ↓ 32.8% vs control; 31.6% ↓ vs Matrixyl® 3000 | [18] |
| Skin Hydration (8-wk) | n=30 | 20% increase in hydration; improved epidermal/dermal thickness | [18] |
| Hair Loss — MDCT | n=7 men | SALT score 40%→7.5%; 71.4% achieved TSAR >10%; median TSAR 26.5% | [13] |
| IBD (12-wk) | n=16 | Rectal GHK-Cu; 60% reduction in disease severity | [2] |
Safety Summary
| Parameter | Finding |
|---|---|
| General Safety | Excellent safety record; non-toxic and non-irritating; decades of cosmetic use without adverse issues |
| LD50 | Estimated equivalent to ~23,000 mg in 70 kg human (blood pressure effects); exceptionally safe |
| Common Side Effects | Temporary redness, itching, burning, or stinging at application site (mild) |
| Contraindications | Wilson's disease (copper metabolism disorder); pregnancy/breastfeeding (no safety data); active cancer (theoretical angiogenic concern) |
| Drug Interactions | Do not use with Vitamin C simultaneously (copper dissociation); avoid EDTA/carnosine (chelation strips copper); space retinoids/AHAs |
| Half-Life | ~0.5–1 hour in plasma; susceptible to carboxypeptidase degradation |
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References
- Pickart L, Vasquez-Soltero JM, Margolina A. GHK-Cu may Prevent Oxidative Stress in Skin by Regulating Copper and Modifying Expression of Numerous Antioxidant Genes. Cosmetics. 2015;2(3):236-247.
- Pickart L. The human tri-peptide GHK and tissue remodeling. Journal of Biomaterials Science, Polymer Edition. 2008;19(8):969-988.
- 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.
- Park JR, Lee H, Kim SI, Yang SR. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget. 2016;7(36):58405-58417.
- Zhang Q, Yan L, Lu J, Zhou X. Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway. Frontiers in Molecular Biosciences. 2022;9:925700.
- Mao S, Huang J, Li J, et al. Exploring the beneficial effects of GHK-Cu on an experimental model of colitis and the underlying mechanisms. Frontiers in Pharmacology. 2025;16:1551843.
- 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.
- Miller DM, DeSilva D, Pickart L, Aust SD. Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. Advances in Experimental Medicine and Biology. 1990;264:79-84.
- Pickart L, Vasquez-Soltero JM, Margolina A. GHK and DNA: Resetting the human genome to health. BioMed Research International. 2014;2014:151479.
- Maquart FX, Pickart L, Laurent M, et al. 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.
- Canapp SO Jr, Farese JP, Schultz GS, et al. The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Veterinary Surgery. 2003;32(6):515-523.
- Abdulghani AA, Sherr A, Shirin S, et al. Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin. Disease Management and Clinical Outcomes. 1998;1(4):136-141.
- Kuceki G, Coppinger AJ, Ragi SD, et al. Enhanced hair regrowth with five monthly sessions of minoxidil-dutasteride-copper peptides tattooing for androgenetic alopecia. JAAD International. 2025;20:38-40.
- Pollard JD, Quan S, Kang T, Koch RJ. Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Archives of Facial Plastic Surgery. 2005;7(1):27-31.
- Dou Y, Lee A, Zhu L, et al. The potential of GHK as an anti-aging peptide. Aging Pathobiology and Therapeutics. 2020;2(1):58-61.
- Cherdakov VYu, et al. Peptide combination (GHK, Dalargin, Thymogen) promotes reparative osteogenesis in rats with bone fractures. Bulletin of Experimental Biology and Medicine. 2010.
- Gul NY, Topal A, Cangul IT, Yanik K. The effects of topical tripeptide copper complex and helium-neon laser on wound healing in rabbits. Veterinary Dermatology. 2008;19(1):7-14.
- Badenhorst T, Svirskis D, Merrilees M, et al. Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters. Journal of Aging Science. 2016;4(3):166.
- 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.
- Hong Y, Downey T, Eu KW, et al. A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clinical & Experimental Metastasis. 2010;27(2):83-90.
- Pickart L, Freedman JH, Loker WJ, et al. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980;288(5792):715-717.
- Simeon A, Emonard H, Hornebeck W, Maquart FX. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sciences. 2000;67(18):2257-2265.
- Kang YA, Choi HR, Na JI, et al. Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Archives of Dermatological Research. 2009;301(4):301-306.
- Pickart L, Vasquez-Soltero JM, et al. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline. Brain Sciences. 2017;7(2):20.
Related Research Questions
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This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.
