Antioxidants in Therapeutics

Introduction & definitions

• Antioxidant — an endogenous or dietary substance that quenches free radicals — reactive species that damage biomolecules — thereby limiting oxidative tissue injury.
• Free radical — an atom or molecule carrying an unpaired ('singlet') electron, making it highly reactive; oxidative radicals arise from normal metabolism and propagate as a self-sustaining chain reaction → membrane lipid peroxidation, DNA damage and protein oxidation.
• Disease rationale — free-radical oxidation is implicated in atherosclerosis (oxidised LDL is more atherogenic), cancers, neurodegenerative disease and inflammatory bowel disease; oxidative stress also drives severity in severe asthma and COPD and may contribute to corticosteroid resistance — the mechanistic case for therapeutic antioxidants.
• The central tension — a strong mechanistic and epidemiological rationale exists, but the clinical evidence of benefit from antioxidant supplementation is "highly equivocal" and in places suggests harm — this paradox is the examinable heart of the topic (see §vi).