Does redox regulation of cell function explain why antioxidants perform so poorly as therapeutic agents?

Abstract

In normal health, there is a balance between the formation of oxidising chemical species and their effective removal by protective antioxidants. Antioxidants are a diverse group of molecules with diverse functions. For example, they range from large highly specific proteinaceous molecules with catalytic properties to small lipid- and water-soluble molecules with non-specific scavenging or metal chelating properties. Antioxidants control the prevailing relationship between reducing or oxidising (redox) conditions in biological systems. Such control offers two major advantages: (i) the ability to remove toxic levels of oxidants before they damage critical biological molecules; and (ii) the ability to manipulate changes, at the subtoxic level, of molecules that can function as signal, trigger or messenger carriers. If cellular functions are signalled through redox control mechanisms, it would explain why we see such a poor response to antioxidants as therapeutic agents in human medicine.