Inside the body with GHK-Cu (copper peptide)

GHK binds Cu(II) with high affinity and competes with albumin for the metal: at equimolar concentrations about 42% of copper was on the peptide in vitro at pH 7.5 (Lau 1981), which led to the proposal that it helps move copper from blood to tissues. Review articles by the discoverer's group report a plasma level of about 200 ng/mL at age 20 falling to about 80 ng/mL at age 60; this comes from author reviews rather than a large independent cohort. In electrochemical experiments Cu(II)GHK could be reduced to Cu(I) with release of the copper ion (Hureau 2011).[src][src][src]

In fibroblast cultures, GHK-Cu stimulation of collagen synthesis began between 10^-12 and 10^-11 M and was maximal at 10^-9 M, independent of any change in cell number (Maquart 1988). In rat wound chambers the same group found a concentration-dependent rise in dry weight, DNA, total protein, collagen and glycosaminoglycan content, with increased type I and III collagen mRNAs but not TGF-beta mRNAs (Maquart 1993). These are in vitro and rodent findings.[src][src]

In a rat wound-chamber model, GHK-Cu injections did not change interstitial collagenase activity but prolonged MMP-9 expression in wound tissue and increased pro-MMP-2 and activated MMP-2 at later stages (days 18 to 22), suggesting altered remodelling (Simeon 1999). In rat ischemic wounds, topical tripeptide-copper reduced wound area (day 13: 64.5% smaller vs 45.6% vehicle and 28.2% untreated) with lower TNF-alpha, MMP-2 and MMP-9 concentrations than untreated control wounds (Canapp 2003). Animal-only.[src][src]

In bleomycin-induced pulmonary fibrosis in mice, intraperitoneal GHK reduced inflammatory infiltration, TNF-alpha and IL-6 in lavage fluid, collagen deposition and MMP-9/TIMP-1 imbalance, and reversed increases in TGF-beta1, phospho-Smad2/3 and IGF-1 (Zhou 2017). These are mouse data only, and the study used the peptide named GHK; copper contribution was not the focus.[src]

Connectivity Map analysis identified GHK as a compound reversing a gene-expression signature of emphysematous lung destruction and inducing TGF-beta pathway-like patterns; in human fibroblasts GHK increased integrin beta-1 expression, organised the actin cytoskeleton and restored collagen I contraction in COPD-derived fibroblasts (Campbell 2012). A review from the discoverer's group extends this to claims that GHK alters expression of roughly a third of human genes at a 50% threshold (Pickart 2018); these are cell-line and in-silico observations without clinical confirmation.[src][src]

A multicentre randomised, evaluator-blinded, vehicle-controlled trial of topical GHK-copper gel in diabetic neuropathic plantar ulcers reported greater median area closure (98.5% vs 60.8%, P < 0.05) and, in ulcers treated immediately after debridement, lower infection incidence (7% vs 34%) (Mulder 1994). A 13-patient randomised trial after CO2 laser resurfacing found no significant objective difference in erythema resolution, wrinkles or skin quality; subjective overall skin quality favoured GHK-Cu (P = .04) (Miller 2006). Cosmetic cream trials of 41 to 71 women over 12 weeks are described in reviews by the discoverer's group (Pickart 2015).[src][src][src]

In 5xFAD transgenic Alzheimer's model mice, intranasal GHK-Cu given for three months delayed cognitive impairment, reduced amyloid plaque burden and lowered MCP1-mediated inflammation in frontal cortex and hippocampus (Tucker 2024). It is a single mouse study; the authors describe it as a rationale for further studies. No human data were verified.[src]