Lactate and cognition: a dual modulator

TL;DR

Lactate, once seen as a waste product, is now understood to play a complex role in brain metabolism and cognitive function.

Contribution

This paper reviews lactate's dual role as both a metabolic substrate and a signaling molecule with bidirectional effects on cognition.

Findings

Lactate supports neuronal function through the astrocyte–neuron lactate shuttle.

Lactate influences synaptic plasticity, neuroinflammation, and mitochondrial dynamics.

Lactate can enhance cognition but may also contribute to dysfunction when imbalanced.

Abstract

Lactate, traditionally regarded as a byproduct of glycolysis, has emerged as a key metabolic substrate and signaling molecule in the brain. Through the astrocyte–neuron lactate shuttle, lactate provides an essential link between energy metabolism and neuronal function. Beyond its metabolic role, lactate influences synaptic plasticity, neuroinflammation, mitochondrial dynamics, and epigenetic regulation, thereby exerting multifaceted effects on cognitive processes. Accumulating evidence demonstrates that lactate acts as a double-edged regulator: under certain conditions, it promotes neuronal resilience and cognitive enhancement, whereas excessive accumulation or impaired transport may contribute to dysfunction. This review synthesizes current knowledge of lactate metabolism in the central nervous system, highlighting its physiological functions, bidirectional impact on cognition, and emerging role as both a biomarker and therapeutic target. A deeper understanding of lactate-mediated mechanisms may pave the way for novel strategies in the prevention and intervention of cognitive impairment. Clinically, lactate is best interpreted as a context-sensitive metabolic readout rather than a standalone disease-specific biomarker.

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