This study determined the effects of heavy resistance training and peri-exercise ergogenic multi-ingredient nutritional supplement ingestion on blood and skeletal markers of muscle protein synthesis (MPS), body composition, and muscle performance. Twenty-four college-age males were randomly assigned to either a multi-ingredient SizeOn Maximum Performance (SIZE) or protein/carbohydrate/creatine (PCC) comparator supplement group in a double-blind fashion. Body composition and muscle performance were assessed, and venous blood samples and muscle biopsies were obtained before and after 6 weeks of resistance training and supplementation. Data were analyzed by 2-way ANOVA (p ≤ 0.05). Total body mass, body water, and fat mass were not differentially affected (p > 0.05). However, fat-free mass was significantly increased in both groups in response to resistance training (p = 0.037). Lower-body muscle strength (p = 0.029) and endurance (p = 0.027) were significantly increased with resistance training, but not supplementation (p > 0.05). Serum insulin, IGF-1, GH, and cortisol were not differentially affected (p > 0.05). Muscle creatine content was significantly increased in both groups from supplementation (p = 0.044). Total muscle protein (p = 0.038), MHC 1 (p = 0.041), MHC 2A, (p = 0.029), total IRS- (p = 0.041), and total Akt (p = 0.011) were increased from resistance training, but not supplementation. In response to heavy resistance training when compared to PCC, the peri-exercise ingestion of SIZE did not preferentially improve body composition, muscle performance, and markers indicative of MPS.

• In response to 42 days of heavy resistance training and either SizeOn Maximum Performance or protein/carbohydrate/creatine supplementation, similar increases in muscle mass and strength in both groups occurred; however, the increases were not different between supplement groups.

• The supplementation of SizeOn Maximum Performance had no preferential effect on augmenting serum insulin, IGF-1, and GH, or in decreasing cortisol.

• While resistance training was effective in increasing total creatine content in skeletal muscle, myofibrillar protein, and the content of total IRS-1 and Akt, it was not preferentially due to SizeOn Maximum Performance supplementation.

• At the daily dose of 50 g, SizeOn Maximum Performance supplementation for 42 days combined with resistance training does not increases muscle mass and strength due to its ability to elevate serum hormones and growth factors or in its ability to augment skeletal muscle signaling pathway markers indicative of muscle protein synthesis when compared to an equivalent daily dose of protein/carbohydrate/creatine.