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A large number of studies have investigated peripheral metabolomic changes in the aforementioned conditions, with considerable overlap between PAIS, CFS, and immunometabolic depression: As reviewed by Komaroff et al., the systemic metabolomic changes in ME/CFS patients are characterized by (1) an impairment in the production of ATP from all energy substrates, (2) a general hypometabolic state and (3) an imbalance between pro- and antioxidant metabolites favouring pro-oxidant processes [43, 62]