Write a PREreview

The energy balance model (EBM) has dominated human body weight regulation research for nearly a century, yet its reliance on indirect mass-to-energy conversions introduces propagated uncertainties that obscure the stoichiometric mechanisms governing tissue accretion and loss. A mass balance model (MBM), which tracks macronutrient mass flows directly in grams without intermediary energy-unit transformations, has recently been proposed as a conceptually simpler, mathematically consistent, and mechanistically faithful alternative. However, widespread adoption of the MBM has been hindered by the absence of standardized protocols, validated analytical frameworks, and practical implementation guidance. This paper fills that gap. I provide a comprehensive, step-by-step guide to MBM implementation, organized into five interdependent modules: (1) quantification of mass intake via precise food and beverage weighing with macronutrient composition analysis, (2) respiratory gas exchange measurement by indirect calorimetry for stoichiometric determination of substrate oxidation, (3) 24-hour urine and fecal collection protocols for nitrogen and carbon outflow quantification, (4) body composition assessment methods for independent validation of MBM predictions, and (5) data integration and computational workflows that produce complete daily mass balances for carbon, nitrogen, and water. The mathematical and computational framework is fully specified, including the core dynamic equation, derivation of the mass clearance coefficient, and prediction of body composition trajectories via Forbes's relationship. Translational applications are discussed, including early detection of lean tissue loss, real-time dietary monitoring, personalized protein prescription, and pharmacotherapy evaluation. By equipping researchers and clinicians with the tools necessary to adopt direct mass accounting, this paper aims to accelerate the transition from an energy-centric to a mass-centric paradigm in human metabolism research.