Effect of Intra-Workout Protein–Carbohydrate Co-Ingestion Versus Isocaloric Carbohydrate During Resistance Training on Muscle Fibre Hypertrophy and Oxidative Capacities in Young Men: A Randomized Controlled Trial

Background: Protein intake in relation to resistance training (RT) is often studied under fasted conditions, although most real-world training is performed in a non-fasted state. This study examined whether intra-workout carbohydrate plus protein (CHO:P) co-ingestion enhances muscle hypertrophy compared with isoenergetic carbohydrate (CHO) alone when RT is performed in a non-fasted state. Additionally, baseline testosterone, insulin-like growth factor 1 (IGF-1), capillary density, and maximal oxygen uptake (VO2max) were evaluated in relation to gains in muscle fibre cross-sectional area (fCSA). Methods: Seventeen physically active young men completed the study (CHO:P, n = 8; CHO, n = 9) as part of an 8-week supervised RT program. Assessments included body composition, physical performance, blood variables, and muscle biopsies obtained before and after the intervention. Fibre-type-specific and distributional (percentile-based) analyses of fCSA were performed. Given the limited sample size, analyses should be considered exploratory. Results: No significant between-group differences were observed for any outcome (all p > 0.05). In contrast, RT induced significant increases in lean mass, muscle strength, VO2max, fat oxidation capacity, and fCSA (all p < 0.05). For example, type IIA fCSA median increased from 5232 μm2 (P10–P90: 2917–7286) to 5925 μm2 (3794–8422 μm2). Distributional analysis revealed that type IIA fibre fCSA increased across the full percentile range, indicating a broad hypertrophic response, whereas type I fibres showed more modest and less uniform changes. A marked fibre-type transition was observed, with type IIX fibres decreasing from ~1.2% (0.5–3.2%) to ~0.0% (0.0–1.3%) and IIA/IIX hybrid fibres from ~8.9% (7.3–12.2%) to ~4.4% (1.1–5.6%). Baseline IGF-1 showed an exploratory association with increases in fCSA (p = 0.04), whereas testosterone, capillary density, and VO2max did not (all p > 0.05). Conclusions: Resistance training performed in a non-fasted state resulted in robust improvements in muscle hypertrophy, metabolic capacity, and physical performance. No additional benefit of intra-workout protein co-ingestion was detected compared with isoenergetic carbohydrate intake under the present experimental conditions. However, given the small sample size and variability in responses, modest effects cannot be excluded. The observed association between baseline IGF-1 and hypertrophy should be interpreted cautiously and requires confirmation in larger studies.