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The copper content of GHK-Cu formulations has been a theoretical safety consideration, given that excessive copper can be toxic - however, the amounts used in cosmetic and research applications are extremely small, the copper is tightly chelated by the peptide (reducing free copper availability), and topical absorption of copper from these products appears minimal and well below levels that would cause systemic copper accumulation or toxicity

lvarez-Rivera would like to acknowledge Ministerio Ciencia e Innovacin (MICINN/AEI, Spain) for his RYC2022-037949-I contract

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Indeed, it necessitates the activation of thiolate form of glutathione for direct glutathionylation reaction toward non-conjugated substrates (Dirr et al., 1994