Lactate Reimagined as an Exerkine: Emerging Evidence, Physiological Benefits, Controversies, and Clinical Applications
Keywords:
Lactate, Exerkine, Exercise physiology, Exercise medicineAbstract
Misconceptions surrounding lactate have persisted for centuries; once dismissed as a mere by-product of anaerobic metabolism and a culprit of fatigue, lactate is now recognized as a powerful exerkine with broad physiological influence across multiple systems. This shift in understanding redefines lactate as more than a waste product, recognizing its critical role in inter-organ communication and physiological regulation during and after exercise. This narrative review explores the multifaceted functions of lactate, highlighting its impact on metabolic regulation, neuroplasticity, immune modulation, muscle adaptation, and angiogenesis. Lactate's interaction with the G-protein-coupled receptor 81 (GPR81) mediates numerous beneficial processes, including anti-inflammatory responses, upregulation of brain-derived neurotrophic factor (BDNF), mitochondrial biogenesis through PGC-1α activation, and vascular endothelial growth factor (VEGF) expression, which supports angiogenesis. While the majority of scientists acknowledge lactate’s vital role in energy homeostasis and systemic signaling, controversies persist concerning the extent of its effects and their dependence on exercise context, intensity, and individual variability. Future research directions include the development of lactate-based therapeutic applications, personalized exercise prescriptions, and integrative approaches with other exerkines. The potential of lactate to enhance patient care, from neurorehabilitation to chronic disease management, underscores its promise as a powerful target for health optimization and performance enhancement. This narrative review aims to deepen our understanding of lactate’s complex roles and guide innovative strategies in health sciences, exercise physiology, and clinical care
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