Aerobic exercise, whey protein, and creatine in adolescents: implications for performance, recovery, immunometabolic adaptation, and muscle-bone-brain crosstalk

Adolescence constitutes a pivotal developmental phase for the enhancement of musculoskeletal and metabolic wellbeing, as well as neurodevelopment, during which specific exercise regimens and nutritional interventions can precipitate enduring physiological transformations. Although aerobic exercise has conventionally been linked to enhancements in cardiovascular fitness and metabolic control, the confluence of this form of exercise with anabolic and ergogenic supplements, including whey protein and creatine, in adolescent populations has not been extensively investigated. This narrative review examines current evidence on aerobic exercise, whey protein, and creatine in adolescents, with particular emphasis on exercise performance, recovery, immunometabolic adaptation, and muscle-bone-brain crosstalk. A narrative literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar using combinations of terms related to aerobic exercise, whey protein, creatine, adolescents, exercise performance, recovery, immunometabolism, and muscle-bone-brain signaling. Relevant peer-reviewed studies published from database inception to May 2026 were considered, with emphasis on adolescent human studies and selected mechanistic evidence from experimental and adult populations when directly relevant to biological interpretation. Aerobic exercise promotes oxidative metabolic processes, mitochondrial functionality, and endurance performance, thereby enhancing mitochondrial biogenesis and metabolic flexibility. Whey protein supplies critical amino acids that incite muscle protein turnover and modulate pivotal signaling cascades, thereby supporting muscle remodeling and recovery. Creatine, in addition to its function in the swift regeneration of adenosine triphosphate, plays a significant role in cellular hydration, the preservation of mitochondrial integrity, and the maintenance of antioxidant defense mechanisms, while also potentially influencing brain energy metabolism and brain-derived neurotrophic factor-mediated neuroplasticity. Emerging evidence further suggests that exercise and nutritional interventions may influence inflammatory mediators, myokines, osteokines, and neurotrophic pathways involved in muscle-bone-brain communication. However, mechanistic evidence is frequently derived from animal or non-adolescent human studies, and direct evidence for combined interventions in adolescents remains limited. Overall, aerobic exercise, whey protein, and creatine may have complementary roles in supporting exercise performance, recovery, and metabolic adaptation during adolescence, although further well-controlled adolescent studies are needed to establish their long-term efficacy, safety, and optimal use.