Mitochondrial function means more than burning calories

Three quantities that should stay separate

Food energy entering the body, energy expended and ATP available for cellular work are different quantities. A whole-body kcal/kg value cannot by itself reveal mitochondrial coupling, respiratory capacity or tissue repair. For EPK, distinguishing these quantities makes the proposed link between intake and function testable.

Mitochondria can use a proton gradient to support ATP synthesis, while proton leak dissipates some energy as heat. Consequently, increased fuel consumption need not mean increased ATP production or improved health. This distinction is a physiological reason to measure function alongside energy expenditure, rather than making the highest expenditure the goal.

Training provides a human example

Robinson and colleagues compared exercise-training modes in young and older adults over 12 weeks. The interventions improved insulin sensitivity, while high-intensity interval and combined training improved mitochondrial respiration. Adaptations differed by training mode. [1]

This supports an interest in the capacity to use energy and maintain function across age. It also cautions against classifying all demanding exercise as metabolically damaging merely because it produces acute physiological stress. Training response and recovery need to be measured; this study did not test an EPK intake threshold.

Lactate is also a usable fuel

In a tracer study of six healthy people, van Hall and colleagues demonstrated uptake and oxidation of circulating lactate by the brain, with its contribution increasing when lactate availability increased during the experimental conditions. Lactate therefore cannot be described simply as unusable waste or proof that oxidative metabolism has failed. [2]

The infusion and exercise conditions do not establish that raising lactate is a general treatment. A concentration measured in blood needs its clinical or exercise context, and cannot alone identify the cause of fatigue.

A stronger test of the EPK proposition

Measure intake and mass alongside a functional endpoint such as strength, exercise capacity or recovery. In a mechanistic subset, add an appropriate respiratory or substrate-use assay. Distinguish measured resting expenditure from reported intake and total expenditure.

The prediction worth testing is whether a prespecified EPK exposure relates to maintained function, and whether measured utilisation explains any association. If cellular function improves without a corresponding EPK relationship, that remains a useful physiological result while limiting the proposed role of the ratio.

Related working papers

Read the relevant PDFs: EPK–001 to 007 are the revised version 1.2 papers; EPK–008 to 010 are version 1.0 supplements. Earlier PDFs and DOI records remain on the paper archive.