Exogenous Substrate Interventions: Mechanisms and Applications in Health and Exercise

Skeletal muscle and whole-body metabolism depend on the coordinated use of endogenous carbohydrates, lipids, proteins, and ketone bodies to support energy production during rest, exercise, and recovery. Exogenous substrate interventions—including ketone esters, exogenous lactate, and diverse carbohydrate formulations—offer a means of modifying substrate availability, oxidation, and metabolic signaling. Evidence increasingly indicates that these compounds may influence gene expression, mitochondrial biogenesis, inflammation, and other adaptive pathways in addition to serving as energy sources. These effects have generated interest in their potential to improve endurance performance, accelerate recovery, and support metabolic health in clinical and aging populations. However, important questions remain regarding how exogenous substrates are absorbed, transported, oxidized, and integrated with endogenous fuel metabolism. The extent to which mechanistic findings translate into meaningful benefits also remains uncertain, particularly given substantial variation according to exercise status, nutritional state, health, age, sex, dose, timing, and intervention type. Although recent studies have expanded understanding of substrate-specific responses, evidence is often heterogeneous and practical recommendations remain difficult to establish. Further research is therefore needed to clarify mechanisms, identify determinants of individual responsiveness, and evaluate the effectiveness and safety of exogenous substrate interventions across diverse contexts.This Research Topic aims to advance understanding of exogenous substrate interventions from fundamental mechanisms to practical applications in health and exercise. It will examine how different substrates affect absorption, transport, oxidation, energy metabolism, cellular signaling, exercise performance, training adaptation, recovery, and health-related outcomes. The Research Topic also seeks to identify the factors that explain interindividual variability and to assess how intervention characteristics—including substrate type, dose, timing, formulation, and combination with nutrition or exercise—shape physiological responses. By connecting basic, translational, and applied research, it will support the development of evidence-informed and individualized strategies while highlighting unresolved questions, methodological challenges, and priorities for future investigation.To gather further insights into the mechanisms, effectiveness, safety, and application of exogenous substrate interventions in healthy, athletic, clinical, and aging populations, we welcome articles addressing, but not limited to, the following themes:Mechanisms of exogenous substrate digestion, absorption, transport, oxidation, and tissue utilizationInteractions between exogenous substrates and endogenous fuel selectionMetabolic and cellular signaling effects, including mitochondrial, inflammatory, and transcriptional pathwaysEffects on exercise performance, fatigue, recovery, and training adaptationApplications in metabolic disease, cardiometabolic health, rehabilitation, and healthy agingIndividual variability in response and the roles of sex, age, training status, diet, genotype, and metabolic phenotypeDose, timing, formulation, delivery methods, and combinations with exercise or other nutritional interventionsNovel and emerging exogenous substrate compounds and intervention strategiesSafety, tolerability, feasibility, and long-term adherenceTranslational, field-based, and real-world applications of exogenous substrate interventionsAppendix: We welcome original research, reviews, systematic reviews, opinion articles, and perspectives. Topic editors: Ruben Robberechts, Jeremy J Walsh, Myrthe Stalmans Source: https://www.frontiersin.org/research-topics/84783/exogenous-substrate-interventions-mechanisms-and-applications-in-health-and-exercise