{"format":"citation-manifest/v1","page":"https://copperpeptidedirect.com/monograph","claim_count":55,"claims":[{"id":"clm-001","text":"GHK is the tripeptide glycyl-L-histidyl-L-lysine, molecular formula C14H24N6O4, molecular weight 340.38 (PubChem CID 73587). Its 1:1 copper(II) complex, GHK-Cu, is represented in PubChem with formula C14H22CuN6O4 and molecular weight 401.91 (CID 165429100); several charged and 2:1 complex records also exist under the same common name.","source_url":"https://pubchem.ncbi.nlm.nih.gov/compound/73587","grade":"chemical-reference","grade_label":"Chemical reference"},{"id":"clm-002","text":"On cosmetic ingredient labels GHK-Cu appears under the INCI name copper tripeptide-1; the CIR safety assessment covers it under that name and describes preparation by combining glycyl-L-histidyl-L-lysine with equimolar cupric acetate.","source_url":"https://www.cir-safety.org/sites/default/files/tripep062014final.pdf","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-003","text":"No FDA-approved drug contains GHK-Cu in any form or by any route. A Drugs@FDA query for ghk-cu as an active ingredient returns no matches, and the same is true for glycyl-histidyl-lysine.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-004","text":"Cosmetic products and their ingredients, other than color additives, do not require FDA approval before going on the market; copper peptide serums and creams are regulated only as cosmetics so long as they make no drug claims.","source_url":"https://www.fda.gov/cosmetics/cosmetics-laws-regulations/fda-authority-over-cosmetics-how-cosmetics-are-not-fda-approved-are-fda-regulated","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-005","text":"Non-injectable GHK-Cu sits in Category 1 (bulk drug substances under evaluation) of FDA's interim 503A compounding policy. The entry reads GHK-Cu (except for injectable routes of administration).","source_url":"https://www.fda.gov/media/94155/download","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-006","text":"The 2026 sequence: GHK-Cu was removed from Category 1 on April 22, 2026 because its nominations were withdrawn; on May 5, 2026 a nominator clarified it withdrew only the injectable route and retained its nomination for non-injectable routes, and FDA restored GHK-Cu (except for injectable routes of administration) to Category 1.","source_url":"https://www.fda.gov/media/94155/download","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-007","text":"FDA has announced it intends to consult the Pharmacy Compounding Advisory Committee before the end of February 2027 regarding the potential inclusion of GHK-Cu on the 503A bulks list.","source_url":"https://www.fda.gov/media/94155/download","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-008","text":"Injectable GHK-Cu appears on FDA's compounding safety-risks page, which states that compounded injectable drugs containing GHK-Cu may pose risk for immunogenicity due to the potential for aggregation and peptide-related impurities, and that there are limited data in humans to inform safety-related considerations.","source_url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-009","text":"Category 1 placement is an interim compounding policy, not an approval and not a safety or efficacy finding: it describes bulk substances under FDA evaluation for the 503A list, for which FDA has stated interim enforcement expectations while rulemaking proceeds.","source_url":"https://www.fda.gov/media/94155/download","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-010","text":"The CIR Expert Panel reviewed tripeptide-1 and copper tripeptide-1 as cosmetic ingredients and concluded they are safe in the present practices of use and concentration, noting that typical use concentrations reported in its survey were under 10 ppm.","source_url":"https://www.cir-safety.org/sites/default/files/tripep062014final.pdf","grade":"expert-panel","grade_label":"Expert panel"},{"id":"clm-011","text":"ClinicalTrials.gov lists three registered studies mentioning GHK-Cu as of 2026-08-14: a completed cosmetic facial-device study, a recruiting phase 2 trial of a topical GHK-Cu gel for acute skin wounds (NCT07437586), and a not-yet-recruiting wellness-patch study measuring circulating GHK. None studies injectable GHK-Cu.","source_url":"https://clinicaltrials.gov/search?term=GHK-Cu","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-012","text":"An April 2026 preprint analyzing 6,441 consumer research peptide samples across fourteen compounds including GHK-Cu found that 41.6% to 71.1% of samples failed basic quality criteria depending on the standard applied, and measurable endotoxin contamination was present in 15% of samples. Preprint, not yet peer reviewed.","source_url":"https://europepmc.org/article/PPR/PPR1182497","grade":"preprint","grade_label":"Preprint, not peer-reviewed"},{"id":"clm-013","text":"GHK was described in 1973 by Pickart and Thaler as a tripeptide in human serum that prolonged survival of normal liver cells and stimulated growth in neoplastic liver cell cultures; the 2012 review summarizes the discovery as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue.","source_url":"https://europepmc.org/article/MED/4349963","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-014","text":"The age-decline figures quoted across the copper peptide market, plasma GHK averaging about 200 ng/mL at age 20 falling to about 80 ng/mL by age 60, come from the originating research lineage and are stated in a 2020 review; they are not a modern population study.","source_url":"https://europepmc.org/article/MED/35083444","grade":"review","grade_label":"Review or guideline"},{"id":"clm-015","text":"The only recent measured human plasma GHK values in this pack come from a 2023 COPD study: 70.27 +/- 38.87 ng/mL in 9 COPD patients vs 133.0 +/- 54.54 ng/mL in 11 age-paired healthy adults (P = 0.009). The healthy-control mean does not match the 80 ng/mL age-decline narrative, and we display both numbers rather than choose one.","source_url":"https://europepmc.org/article/MED/36905132","grade":"human-obs","grade_label":"Human observational"},{"id":"clm-020","text":"In the 1988 founding in vitro study, GHK-Cu stimulated collagen synthesis in fibroblast cultures beginning between 10^-12 and 10^-11 M, maximal at 10^-9 M, independent of cell-number changes.","source_url":"https://europepmc.org/article/MED/3169264","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-021","text":"In rat wound chambers injected with GHK-Cu, dry weight, DNA, total protein, collagen and glycosaminoglycan content rose concentration-dependently; collagen stimulation was twice that of noncollagen proteins; type I and III collagen mRNAs increased while TGF-beta mRNA did not; a control tripeptide had no effect.","source_url":"https://europepmc.org/article/MED/8227353","grade":"animal","grade_label":"Animal"},{"id":"clm-022","text":"GHK-Cu increased MMP-2 (and TIMP-1/TIMP-2) in fibroblast cultures; the effect was reproduced by copper ions alone but not by copper-free GHK, evidence that copper delivery is the active principle in at least some assays.","source_url":"https://europepmc.org/article/MED/11045606","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-023","text":"GHK-Cu at 10^-9 mol/L shortened population-doubling times of normal and irradiated human dermal fibroblasts; irradiated fibroblasts approached untreated-control growth rates and produced significantly more bFGF and VEGF early after exposure.","source_url":"https://europepmc.org/article/MED/15655171","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-024","text":"Copper-GHK increased keratinocyte proliferation and raised PCNA, p63 and integrin alpha6/beta1 expression in skin-equivalent models, interpreted by the authors as supporting basal keratinocyte and stem-cell survival.","source_url":"https://europepmc.org/article/MED/19319546","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-025","text":"In a 2012 Genome Medicine study, GHK emerged from a Connectivity Map screen as a compound opposing a 127-gene emphysema-destruction signature derived from 64 human lung samples; treating human lung fibroblasts with GHK recapitulated TGF-beta-induced expression patterns and restored actin organization. In vitro and computational, with no clinical endpoint.","source_url":"https://europepmc.org/article/MED/22937864","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-026","text":"A 2023 cosmetic-ingredient study reported that GHK-Cu combined 1:9 with low-molecular-weight hyaluronic acid raised collagen IV expression 25.4-fold in fibroblast culture and 2.03-fold in ex vivo skin; this is a combination result in models, not a human trial of GHK-Cu.","source_url":"https://europepmc.org/article/MED/37062921","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-033","text":"In the 1993 hair-growth report, a copper binding peptide coded PC1031 enlarged follicles on fuzzy rat back skin with an effect described as similar to topical minoxidil; the study is rodent data on a ProCyte compound, not a human GHK-Cu trial.","source_url":"https://europepmc.org/article/MED/8326148","grade":"animal","grade_label":"Animal"},{"id":"clm-034","text":"In 18 rabbits with full-thickness open wounds, topical tripeptide-copper complex produced significantly smaller unhealed wound area than no treatment at days 7, 14 and 21, beat zinc oxide at day 7, and showed the fastest granulation-bed coverage and best neovascularization.","source_url":"https://europepmc.org/article/MED/17083573","grade":"animal","grade_label":"Animal"},{"id":"clm-035","text":"In irradiated rat flaps, twice-daily topical GHK-Cu gel for 10 days produced no difference vs control ointment in flap ischemia, blood vessel number or area, or VEGF expression: a published negative animal study.","source_url":"https://europepmc.org/article/MED/23744835","grade":"animal","grade_label":"Animal"},{"id":"clm-036","text":"In mouse scald wounds, liposome-encapsulated GHK-Cu improved angiogenesis markers and shortened healing time to 14 days, outperforming free GHK-Cu; HUVEC proliferation rose 33.1%. The advantage belonged to the liposomal delivery system over the plain compound.","source_url":"https://europepmc.org/article/MED/28370978","grade":"animal","grade_label":"Animal"},{"id":"clm-043","text":"In the 1994 multicenter randomized evaluator-blinded placebo-controlled trial in diabetic neuropathic plantar ulcers, topical GHK-Cu gel (Iamin) on top of standardized wound care produced 98.5% median area closure vs 60.8% for vehicle (p < 0.05), about 3x faster closure, 89.2% vs -10.3% median closure in ulcers over 100 mm2 (p < 0.01), and 7% vs 34% ulcer infections (p < 0.05). A ProCyte scientist is a co-author; no FDA approval followed.","source_url":"https://europepmc.org/article/MED/17147644","grade":"human-rct","grade_label":"Human RCT"},{"id":"clm-044","text":"In the 2006 randomized CO2-laser resurfacing study (13 patients completed), GHK-Cu skin care produced no significant differences on any objective endpoint (erythema resolution, wrinkles, overall skin quality by blinded evaluation and computer analysis); patient-reported skin quality favored GHK-Cu (P = .04).","source_url":"https://europepmc.org/article/MED/16847171","grade":"human-rct","grade_label":"Human RCT"},{"id":"clm-045","text":"The 2016 randomized 6-month trial in 45 men with pattern hair loss tested ALAVAX, a complex of 5-aminolevulinic acid and copper-free GHK: hair count rose 52.6 and 71.5 in the two active arms vs 9.6 with placebo (p < 0.05), with no differences in hair length or thickness. It is combination evidence, not GHK-Cu evidence.","source_url":"https://europepmc.org/article/MED/27489425","grade":"human-rct","grade_label":"Human RCT"},{"id":"clm-046","text":"The most-quoted copper peptide hair paper (2007) studied AHK-Cu, alanyl-histidyl-lysine copper, not GHK-Cu: AHK-Cu stimulated human hair follicle elongation ex vivo and dermal papilla cell proliferation at 10^-12 to 10^-9 M, and the apoptosis reduction was not statistically significant.","source_url":"https://europepmc.org/article/MED/17703734","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-047","text":"A 2025 report describes enhanced hair regrowth using five monthly sessions of tattooing with a minoxidil-dutasteride-copper peptides mixture in androgenetic alopecia; copper peptides are one component of a three-drug cocktail delivered by microneedling, so no GHK-Cu-specific effect can be isolated. The record carries no indexed abstract.","source_url":"https://europepmc.org/article/MED/40225275","grade":"review","grade_label":"Review or guideline"},{"id":"clm-048","text":"The widely-cited cosmetic-effect claims for GHK-Cu facial products (firmness, elasticity, wrinkle reduction, photodamage) are summarized in reviews co-authored by the originating researcher, who founded a company selling copper peptide products; the underlying facial studies are conference-era reports that were never indexed as peer-reviewed papers.","source_url":"https://europepmc.org/article/MED/26236730","grade":"review","grade_label":"Review or guideline"},{"id":"clm-053","text":"In LPS-induced acute lung injury in mice, GHK-Cu reduced ROS, TNF-alpha and IL-6, increased SOD activity, suppressed NF-kB p65 and p38 MAPK signaling, and attenuated lung histological damage and inflammatory infiltration.","source_url":"https://europepmc.org/article/MED/27517151","grade":"animal","grade_label":"Animal"},{"id":"clm-054","text":"In bleomycin-induced pulmonary fibrosis in mice, intraperitoneal GHK-Cu (0.2 to 20 ug/g on alternate days) reduced inflammatory cytokines, MPO activity and collagen deposition, partially reversed the MMP-9/TIMP-1 imbalance and partially prevented epithelial-mesenchymal transition.","source_url":"https://europepmc.org/article/MED/31809714","grade":"animal","grade_label":"Animal"},{"id":"clm-055","text":"In 12-week cigarette smoke exposure in mice, intraperitoneal GHK-Cu attenuated emphysematous changes and partially reversed the MMP-9/TIMP-1 imbalance while reducing inflammation and oxidative stress.","source_url":"https://europepmc.org/article/MED/35936787","grade":"animal","grade_label":"Animal"},{"id":"clm-056","text":"In an experimental silicosis mouse model, GHK-Cu bound peroxiredoxin 6 and attenuated lung inflammation and fibrosis without significant systemic toxicity reported in the model, tied to reduced alveolar macrophage oxidative stress.","source_url":"https://europepmc.org/article/MED/38879894","grade":"animal","grade_label":"Animal"},{"id":"clm-057","text":"In a rat ACL-reconstruction model with weekly intra-articular GHK-Cu injections, benefits at 6 weeks (smaller knee-laxity difference, higher graft stiffness) disappeared by 12 weeks after treatment stopped; no differences in ultimate load, gait or histology; the authors describe the improvement as transient.","source_url":"https://europepmc.org/article/MED/25731775","grade":"animal","grade_label":"Animal"},{"id":"clm-058","text":"Plasma GHK was lower in 9 COPD patients than in 11 age-paired healthy adults (70.27 vs 133.0 ng/mL, P = 0.009) and correlated with pectoralis muscle area; GHK-Cu rescued cigarette smoke-induced dysfunction in myotubes and mice via a sirtuin-1 pathway. Observational human data plus preclinical rescue, not a human treatment trial.","source_url":"https://europepmc.org/article/MED/36905132","grade":"human-obs","grade_label":"Human observational"},{"id":"clm-059","text":"In aging mice, 15 mg/kg/day injected GHK for five days prevented the acute learning impairment caused by two days of sleep deprivation and blocked hippocampal MCP-1 and nitrotyrosine increases.","source_url":"https://europepmc.org/article/MED/37035833","grade":"animal","grade_label":"Animal"},{"id":"clm-060","text":"In C. elegans, GHK-Cu significantly extended lifespan and improved aging phenotypes (stress resistance, motility, pharyngeal pumping, lipofuscin) through DAF-16/SKN-1 activation and mitochondrial regulation. This 2026 worm study is the entire published whole-organism longevity evidence for GHK-Cu.","source_url":"https://europepmc.org/article/MED/42084774","grade":"animal","grade_label":"Animal"},{"id":"clm-063","text":"In flow-through diffusion cells on isolated human skin under 48-hour infinite-dose conditions, 0.68% aqueous copper tripeptide gave a permeability coefficient of 2.43 +/- 0.51 x 10^-4 cm/h through dermatomed skin, with 136.2 +/- 17.5 ug/cm2 of copper permeating over 48 hours and 82 to 97 ug/cm2 retained as a skin depot.","source_url":"https://europepmc.org/article/MED/20721598","grade":"human-pk","grade_label":"Human PK"},{"id":"clm-064","text":"In a 9-hour intact-human-skin experiment, almost no GHK-Cu peptide or copper permeated untreated skin; microneedle pretreatment raised permeation to 134 +/- 12 nanomoles of peptide and 705 +/- 84 nanomoles of copper. Passive short-term penetration of intact skin is close to nil in this model.","source_url":"https://europepmc.org/article/MED/25690343","grade":"human-pk","grade_label":"Human PK"},{"id":"clm-065","text":"A 2008 cosmetic-science study showed copper complexes with GHK permeate liposome-membrane models of the stratum corneum lipid barrier and influence copper-ion transport dynamics; it is a membrane model, not skin.","source_url":"https://europepmc.org/article/MED/18350235","grade":"in-vitro","grade_label":"In vitro"},{"id":"clm-066","text":"The 2025 methods review of GHK-Cu skin-permeation measurement concludes the published information on skin permeability, effectiveness and physicochemical properties of GHK-Cu and Pal-GHK is insufficient, despite their wide use in anti-wrinkle products.","source_url":"https://europepmc.org/article/MED/39963574","grade":"review","grade_label":"Review or guideline"},{"id":"clm-071","text":"A publication-type census finds exactly one randomized controlled trial tagged to GHK-Cu or copper tripeptide in the indexed literature: the 2006 CO2-laser study, whose objective endpoints were null. The only other RCT-tagged record under the copper peptide search is a collagen-tripeptide formulation, a different substance.","source_url":"https://europepmc.org/search?query=%28%22GHK-Cu%22%20OR%20%22copper%20tripeptide%22%20OR%20%22copper%20tripeptide-1%22%29%20AND%20PUB_TYPE%3A%22Randomized%20Controlled%20Trial%22","grade":"absence-of-evidence","grade_label":"Absence of evidence"},{"id":"clm-072","text":"No registered clinical trial studies injectable GHK-Cu: the ClinicalTrials.gov census returns three records (cosmetic device, topical wound gel, wellness patch), none injectable.","source_url":"https://clinicaltrials.gov/search?term=GHK-Cu","grade":"absence-of-evidence","grade_label":"Absence of evidence"},{"id":"clm-073","text":"No published human trial of injected GHK-Cu exists in the indexed literature; the injectable evidence base is intraperitoneal or intra-articular rodent work plus cell studies.","source_url":"https://europepmc.org/search?query=%22GHK-Cu%22%20AND%20%28injectable%20OR%20subcutaneous%20OR%20intravenous%29%20AND%20%28patients%20OR%20%22healthy%20volunteers%22%29","grade":"absence-of-evidence","grade_label":"Absence of evidence"},{"id":"clm-074","text":"No human pharmacokinetic study exists for any marketed GHK-Cu form: no serum-level measurements after cosmetic application, compounded non-injectable use, or vial injection.","source_url":"https://europepmc.org/search?query=%22GHK-Cu%22%20AND%20%28injectable%20OR%20subcutaneous%20OR%20intravenous%29%20AND%20%28patients%20OR%20%22healthy%20volunteers%22%29","grade":"absence-of-evidence","grade_label":"Absence of evidence"},{"id":"clm-075","text":"No randomized monotherapy trial of a GHK-Cu cosmetic serum on wrinkles, firmness or photoaging exists in the indexed literature; the facial-benefit studies quoted by marketing are conference-era industry reports described in reviews but never indexed as papers.","source_url":"https://europepmc.org/search?query=%28%22GHK-Cu%22%20OR%20%22copper%20tripeptide-1%22%20OR%20%22copper%20peptide%22%29%20AND%20%28wrinkle%20OR%20photoaging%29%20AND%20PUB_TYPE%3A%22Randomized%20Controlled%20Trial%22","grade":"absence-of-evidence","grade_label":"Absence of evidence"},{"id":"clm-080","text":"Independent 2025 reviews treat GHK/GHK-Cu as a promising wound-repair and skin-regeneration ingredient while noting the evidence base consists mainly of preclinical work and formulation studies.","source_url":"https://europepmc.org/article/MED/41209547","grade":"review","grade_label":"Review or guideline"},{"id":"clm-081","text":"The tissue-remodeling framework for GHK-Cu (chemoattraction of repair cells, collagen and glycosaminoglycan synthesis, MMP/TIMP modulation, angiogenesis and nerve outgrowth) is articulated in reviews authored by the originating researcher, whose commercial interest in copper peptide skincare we disclose wherever those reviews are cited.","source_url":"https://europepmc.org/article/MED/18644225","grade":"review","grade_label":"Review or guideline"},{"id":"clm-085","text":"A fingertip unit (FTU) is the amount of product expressed from a tube with a 5 mm nozzle applied from the distal skin-crease to the tip of the index finger; treating the face and neck took 2.5 FTU (sd 0.8) and one hand 1.2 FTU in the defining study, and one FTU covers a mean of 286 cm2.","source_url":"https://europepmc.org/article/MED/1806320","grade":"human-trial","grade_label":"Human trial"},{"id":"clm-086","text":"The companion rule of hand states that 4 hand areas = 2 FTU = 1 g, making one adult fingertip unit approximately 0.5 g of product.","source_url":"https://europepmc.org/article/MED/1497374","grade":"human-trial","grade_label":"Human trial"},{"id":"clm-087","text":"Cosmetic copper peptide products carry no drug label, no established dose and no dosing studies; quantity arithmetic on this site is an education device about how much product typical applications consume, never an efficacy claim.","source_url":"https://www.fda.gov/cosmetics/cosmetics-laws-regulations/fda-authority-over-cosmetics-how-cosmetics-are-not-fda-approved-are-fda-regulated","grade":"regulatory","grade_label":"Regulatory record"},{"id":"clm-100","text":"Counts displayed in the hero and authority band (study rows, human rows, citation count, source-mix percentage) are computed from this pack's own rendered content and recomputable by script.","source_url":"https://europepmc.org/search?query=%28%22GHK-Cu%22%20OR%20%22copper%20tripeptide%22%20OR%20%22copper%20tripeptide-1%22%29%20AND%20PUB_TYPE%3A%22Randomized%20Controlled%20Trial%22","grade":"internal-measurement","grade_label":"Internal measurement"}]}