Skeletal muscle mass is not compositionally uniform: the role of fluid compartments in health and performance monitoring

Abstract Skeletal muscle mass (SMM) is a central determinant of metabolic health, physical function, and resilience across the lifespan, yet its assessment is often confounded by the assumption that fat-free mass is compositionally uniform and stably hydrated. This narrative review synthesizes discussions from the 12th International Symposium on In Vivo Body Composition Studies and integrates evidence from aging, chronic energy deficit, disuse/microgravity, resistance training, and anabolic interventions to examine how intracellular and extracellular fluid compartments influence the interpretation of muscle mass and quality. We highlight that declines in muscle quality, reflected by loss of intracellular water and reduced cellular integrity, frequently precede measurable losses in muscle quantity and are more closely linked to functional impairment than bulk skeletal mass. Dual-energy X-ray absorptiometry, while valuable for population studies, cannot distinguish water from protein or intracellular from extracellular compartments and therefore may overestimate anabolic gains in fluid-retentive states or underestimate clinically meaningful muscle loss when extracellular water is preserved or expanded. Multi-frequency bioelectrical impedance techniques, including MF-BIA and BIS, complement structural methods by resolving total, extracellular, and intracellular water and by providing indices of cellular integrity, such as phase angle, that reflect muscle quality. We conclude that hydration-sensitive interpretation is essential for accurate assessment of skeletal muscle under physiological stress.