Antioxidants in Therapeutics

Antioxidants in Therapeutics

1. Definition, scope & why antioxidants matter therapeutically

• Antioxidants are endogenous or dietary substances believed to quench free radicals — reactive species that damage biomolecules — and thereby limit oxidative tissue injury (KDT 8e Ch.69, pp.971–2).
• A free radical is an atom or molecule carrying a 'singlet' (unpaired) electron, which makes it highly reactive; oxidative free radicals are generated by normal metabolic reactions and propagate as a chain reaction (KDT 8e Ch.69, p.971).
  • The chain reaction leads to membrane lipid peroxidation, DNA damage and protein oxidation, generating further toxic peroxidation products (KDT 8e Ch.69, p.971).
• Free-radical oxidation has been implicated in atherosclerosis (oxidised LDL is more atherogenic), cancers, neurodegenerative diseases and inflammatory bowel disease — the disease-association rationale that underpins therapeutic antioxidant use (KDT 8e Ch.69, p.971).
• Oxidative stress is a recognised driver of disease severity in the airways: it is important in severe asthma and COPD and may contribute to corticosteroid resistance (G&G 14e Ch.44, p.892).
• The central therapeutic tension of the whole topic: a strong mechanistic/epidemiological rationale exists, but the evidence of clinical benefit from antioxidant supplementation is "highly equivocal" and in places suggests harm (KDT 8e Ch.69, p.972). This paradox is the examinable heart of the topic (see §7).