Mass Balance over Energy Balance: Why Direct Mass Accounting Offers a More Precise and Mechanistically Faithful Framework for Human Body Weight Regulation

The energy balance model (EBM) and its operational form, calories-in-calories-out (CICO), have dominated obesity research and clinical practice for nearly a century. While these frameworks have delivered valuable public-health insights, they rest on indirect mass-to-energy conversions and persistent misconceptions about thermodynamic principles. Here I demonstrate that a first-principles mass balance model (MBM) provides a conceptually simpler, mathematically consistent, and mechanistically superior alternative. By tracking macronutrient mass directly in grams – without intermediate energy conversions or misapplications of the laws of thermodynamics – the MBM aligns analysis with physiological reality and delivers 40–65 % lower propagated uncertainty than conventional energy-balance approaches. Clarifying that calories cannot be eaten or oxidized, that E=mc² is irrelevant to human metabolism, and that the First Law of Thermodynamics concerns only energy (not mass), paves the way for more precise and actionable interventions in metabolic medicine.