Muscle fiber hypertrophy and myonuclei addition: a systematic review and meta-analysis

Introduction The myonuclear domain theory postulates that myonuclei are added to muscle fibers when increases in fiber cross-sectional area (i.e., hypertrophy) are ≥26%. However, recent studies have reported increased myonuclear content with lower levels (e.g., 12%) of muscle fiber hypertrophy. Purpose This study aimed to determine whether a muscle fiber hypertrophy "threshold" is required to drive the addition of new myonuclei to existing muscle fibers. Methods Studies of resistance training endurance training with or without nutrient (i.e., protein) supplementation and steroid administration with measures of muscle fiber hypertrophy and myonuclei number as primary or secondary outcomes were considered. Twenty-seven studies incorporating 62 treatment groups and 903 subjects fulfilled the inclusion criteria and were included in the analyses. Results Muscle fiber hypertrophy of ≤10% induces increases in myonuclear content, although asignificantly higher number of myonuclei are observed when muscle hypertrophy is 22%. Additional analyses showed that age, sex, and muscle fiber type do not influence muscle fiber hypertrophy or myonuclei addition. Conclusions Although a more consistent myonuclei addition occurs when muscle fiber hypertrophy is > 22%, our results challenge the concept of a muscle hypertrophy threshold as significant myonuclei addition occurs with lower muscle hypertrophy (i.e., < 10%