Nitrate pharmacokinetics: Taking note of the difference

It is now recognised that administration of oral nitrate (NO₃ ^-), in its various forms, increases the level of nitric oxide (NO) metabolites in the circulation of humans. Its application to modulate physiology and alleviate cardiovascular dysfunction in some patients is now recorded and shows particular promise in hypertension, in modifying platelet activation/aggregation, and in conditions where tissue ischaemia prevails. The potential of oral NO₃ ^- to modify exercise/performance via elevation of plasma nitrite concentration ([NO₂ ^-]) has been applied across a range of human test systems. Herein we discuss how the choice of NO₃ ^- source, route of administration and resulting pharmacokinetics might influence the outcome of physiological measures and potentially contribute to discrepancies in performance trials. There are but a few examples of detailed pharmacokinetic data on which the majority of researchers base their test protocols in different cohorts/settings. We compare and contrast the results of key publications with the aim of highlighting a consensus of our current understanding and critical considerations for those entering the field.