Dienel · Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2012 · narrative review · n=?

Brain lactate metabolism: the discoveries and the controversies.

Cited 483 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of cellular and physiological literature without systematic review methodology.

PubMed 22186669 · doi:10.1038/jcbfm.2011.175 · record verified 2026-08-29

What was done

This narrative review synthesized experimental findings and tabular data from multiple laboratories examining brain lactate transport, cellular glycolysis, and metabolic responses to excitatory neurotransmission across astrocyte cultures, neuronal preparations, synaptosomes, and human physiological studies.

What was found

The abstract reports no numeric values or statistical effect sizes. It reports that glutamate-stimulated glycolysis is not universal across astrocyte cultures; synaptosomes and cultured neurons increase glucose transport, glycolysis, and respiration upon glutamate stimulation; lactate accumulation during brain activation reflects a minor fraction of total glucose metabolism; brain activation with low plasma lactate produces outward brain-to-blood gradients with rapid lactate release; and brain lactate uptake increases during strenuous exercise or exogenous lactate infusions.

Why it matters

It provides critical context to the astrocyte-neuron lactate shuttle debate, concluding that glucose remains the predominant fuel for brain activation under normal conditions, with lactate serving as an opportunistic, glucose-sparing substrate when blood levels rise.

Limits

The review lacks systematic search methods and quantitative meta-analytic pooling. The underlying evidence relies heavily on discordant in vitro preparations (cell cultures and synaptosomes) whose metabolic behaviors may not fully replicate intact human brain physiology.

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