How to define low muscle mass: A critical exploration of current definitions supports a reference equation-based approach

BACKGROUND AND AIMS: Current definitions of low muscle mass rely on ratios in combination with gender-specific cut-offs. While these approaches aim to adjust for differences in body metrics, their mathematical validity has not been systematically examined and may introduce bias-not only in relation to muscle mass itself, but also in relation to adiposity. METHODS: ), of the Foundation for the National Institutes of Health sarcopenia project (ALST/BMI) and of the ESPEN and EASO consensus for sarcopenic obesity (ALST/weight) were analyzed for proportional (isometric) scaling by regression analysis, calculation of scaling exponents of the denominators and graphical illustrations. The complex relationship between muscle mass, fat mass and BMI was analyzed and the adiposity related bias, cut-offs entail, explored. To illustrate the clinical relevance, we examined the relationship between low muscle mass and fatty liver disease in a second NHANES cohort (2017-2018, n = 673). RESULTS: ). CONCLUSION: , ALST/BMI and ALST/weight were not mathematically valid. Normalization of muscle mass by these ratios cannot correctly account for the complex association of muscle mass with fat mass, BMI and age and therefore potentially confounds results when cut-offs are applied. Reference equations that adjust for age and BMI and yield standard deviation scores may offer a more valid and clinically meaningful alternative.