Is maximal oxygen consumption an appropriate metric for metabolic health?

Cardiorespiratory fitness (CRF), assessed by maximal oxygen consumption ( $\dot{\text{V}}$ O₂ max) testing, is a strong predictor of chronic disease and all-cause mortality. However, recent evidence suggests that $\dot{\text{V}}$ O₂ max may lack specificity and sensitivity in assessing metabolic health, particularly mitochondrial function, which is associated with metabolic diseases such as type 2 diabetes, insulin resistance, and metabolic syndrome. While aerobic training leads to improvements in mitochondrial function, studies have found a disparity between $\dot{\text{V}}$ O₂ max and mitochondrial content, with some individuals showing increases in mitochondrial oxidative capacity without changes in $\dot{\text{V}}$ O₂ max. Furthermore, the criteria used to determine $\dot{\text{V}}$ O₂ max, such as the plateau in oxygen consumption, may not be achieved by all individuals, leading to inaccurate assessments. Technological advances in metabolomics and lipidomics may provide insights into metabolic health, but their cost and practicality for routine use in clinical settings remain a challenge. Alternatively, indirect calorimetry during submaximal exercise has shown promise as a non-invasive marker of mitochondrial function and metabolic flexibility. However, further research is needed to establish appropriate protocols and analyses for various populations.