Inorganic phosphate: a link between processed food and exercise intolerance in the modern world

Abstract

Physical inactivity and reduced cardiorespiratory fitness are major public health concerns worldwide. In recent decades, the modern western diet has undergone a dramatic shift toward ultra-processed foods (UPFs) that are rich in inorganic phosphate (Pi) additives used as preservatives, emulsifiers, leavening agents, and flavor enhancers. Unlike organic phosphorus found in natural foods, inorganic Pi additives are nearly completely absorbed in the gastrointestinal tract, contributing to habitual Pi intake that exceeds the recommended daily allowance by two- to three-fold in many western populations. Accumulating evidence suggests that this chronic Pi excess may impair skeletal muscle energetics and exercise capacity. In population-based cohort studies, higher serum Pi has been independently associated with reduced physical activity and increased sedentary time. Using 7-Tesla 31P magnetic resonance spectroscopy, higher dietary Pi intake has been correlated with lower resting muscle ATP synthesis and greater phosphocreatine depletion during exercise. Experimental studies have shown that a high-Pi diet reduces maximal oxygen uptake, treadmill endurance, and fat oxidation, and downregulates skeletal muscle fatty acid metabolism genes. At the cellular level, elevated Pi promotes muscle atrophy via autophagy and oxidative stress and reduces mitochondrial membrane potential. Endocrine mediators, including elevated fibroblast growth factor 23 and suppressed Klotho, may further contribute to muscle dysfunction. The present review synthesizes current evidence linking UPF consumption, dietary Pi excess, and exercise intolerance, with focus on skeletal muscle dysfunction, including impaired contractile mechanics, disrupted energy metabolism, and mitochondrial injury, as potential mechanisms, and highlights future directions for research and public health intervention.