The Effect of Resistance Training Volume on Individual-Level Skeletal Muscle Adaptations: A Novel Replicated Within-Participant Unilateral Trial

PurposeThere is growing emphasis on investigating heterogeneity in resistance training (RT) outcomes, likely motivated by observations of substantial gross variability in training effects. However, gross variability does not necessarily represent true inter-individual response variation (IRV) and can be obscured by measurement error, sampling variance, and biological variability. Appropriate study design and statistical analysis are required to distinguish IRV from these confounding sources of within-participant variation. Methods16 recreationally trained participants completed a novel replicated within-participant unilateral design across two 11-week training phases separated by a 6-8 week washout. Lower limbs were randomized to a low volume ([~]8 sets/week) or high volume ([~]16 sets/week) training protocol in each phase. We assessed both general (GEN; average response across conditions) and condition-specific (CON; difference between volumes) IRV for vastus lateralis cross-sectional area and leg press one-repetition maximum using a multi-stage statistical approach. ResultsHigher weekly set volumes demonstrated a detectable advantage for muscle hypertrophy (1.8 cm{superscript 2} [95% HDI: 0.29, 3.41]; 98.77% posterior probability) but not maximal strength (3.48 kg [95% HDI: -5.1, 12.15]; 80.01% posterior probability). Despite substantial gross variability, we failed to detect irrefutable evidence of meaningful IRV. Integrated methods revealed stronger evidence for GEN versus CON IRV, with correlation coefficients ranging from 0.67 to 0.7 for GEN versus 0.04 to 0.06 for CON. ConclusionsOur findings clearly illustrate that gross variability in training outcomes does not necessarily indicate true inter-individual differences, a distinction critical for both research and practice. KEY POINTSO_LIGross variability in resistance training outcomes is commonly interpreted as evidence of meaningful inter-individual response variation (IRV), but this variability often reflects confounding sources of within-participant variation rather than true inter-individual differences. C_LIO_LIUsing a novel replicated within-participant unilateral design, we investigated the effects of different weekly set volumes on changes in muscle size and maximal strength, as well as the inter-individual variation thereof. C_LIO_LIAt the group level, higher weekly set volumes produced modest but detectable benefits for muscle hypertrophy but not maximal strength. At the individual level, we failed to reveal irrefutable evidence of true IRV for either primary outcome, though there was stronger support for variability in training responses independent of weekly set volume (i.e., general IRV) compared to differential responses between volume conditions (i.e., condition-specific IRV). C_LIO_LIWhile this study has limitations, it highlights that appropriate study design and statistical analysis are essential for investigating IRV in resistance training. Our findings, along with the broader research in multiple disciplines (i.e., medicine, nutrition science, and exercise physiology), demonstrate that gross variability can purely reflect confounding sources of within-participant variation (e.g., sampling variance, measurement error, biological variability) rather than true inter-individual differences--a distinction critical for both research and practice. C_LI