Oxygen - the forgotten nutrient

O₂ is essential for the maintenance and growth of aerobic animals, similar to the essentiality of what are classically considered nutrients. Nevertheless, O₂ is not customarily regarded as a nutrient, this reflecting the route by which it enters the body - through the lungs or gills in vertebrates, rather than via the mouth and gastrointestinal tract. A relative deficiency of O₂ occurs at high altitudes and during deep-sea diving, to which distinct adaptations occur. Deficiency is also evident in lung diseases such as emphysema. Without O₂, mitochondrial respiration and oxidative phosphorylation cannot take place. At a molecular level, cells adapt to O₂ deficiency by switching from oxidative metabolism to anaerobic glycolysis and there are changes in the expression of a multiplicity of genes, driven by hypoxia-sensitive transcription factors, particularly hypoxia-inducible factor-1. It is argued that O₂ should be fully included within the remit of nutritional science alongside the other essential macronutrients.