Pitfalls in the measurement of some intermediary metabolites

Lactate, pyruvate, 3-hydroxybutyrate, acetoacetate and non-esterified fatty acids are intermediary metabolites that normally occur in blood and all have a vital role in energy metabolism. Their relative concentrations are an expression of nutritional balance, providing a snapshot of the metabolic disturbances arising in a patient. They are therefore invaluable tools to investigate intermediary metabolism in health and disease, particularly in the fields of diabetes and inherited metabolic disease. Although the analysis of these key metabolites would appear to be straightforward, with apparently simple assays widely available, there are many pitfalls in their measurement. To compound this difficulty there is limited advice available for the optimum pre-analytical and analytical aspects of their measurement and also for the interpretation of results. In this personal view, we aim to highlight a number of these problems, such as sample stability, assay interference and availability of reference ranges, with the aim of producing guidelines for the measurement and interpretation of these metabolites.