Chelation Therapy

Introduction & the chelate principle

• Definition — chelating agents are drugs that sequester toxic metallic ions by forming a ring structure within their molecule (Greek chele = crab's claw); they are used principally in heavy-metal poisonings.
• What a chelate is — a chelate is a stable, non-toxic, water-soluble, readily-excreted complex between the agent and the metal; only agents forming such a complex are clinically useful.
• Ligand — a ligand is a group forming a coordinate (dative) covalent bond; biologically relevant donor atoms are O, N or S (in –OH, –COOH, keto, –SH, disulfide, amino and phosphate groups). A useful agent carries ≥2 ligand groups that grip the metal from two sides — the ring is most stable when 5- to 7-membered.
• How chelation reverses toxicity — heavy metals are toxic because they combine with and inactivate functional ligand groups of enzymes/critical biomolecules; the chelator competes with these body ligands, mobilises the metal and promotes its excretion.
• Earlier is better — efficacy declines rapidly as the interval between metal entry and chelator administration lengthens — chelation works best given soon after exposure (it prevents, rather than reverses, enzyme inhibition).
• Acute vs chronic — chelation reduces toxicity in acute high-dose exposure, but after chronic exposure gives no benefit beyond stopping exposure and may do more harm than good (metal redistribution); it is recommended only for acute poisonings. Source removal is the most important step.