Mattson · Nature reviews. Neuroscience 2018 · narrative review · n=?

Intermittent metabolic switching, neuroplasticity and brain health.

Cited 620 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing evolutionary and mechanistic models with no new human data.

PubMed 29321682 · doi:10.1038/nrn.2017.156 · record verified 2026-08-26

What was done

This narrative review synthesizes evolutionary, cellular, and molecular concepts regarding intermittent metabolic switching. The authors evaluate how repeated cycles of energy challenge (fasting and extended exercise that deplete liver glycogen and stimulate ketone production) followed by recovery periods (eating, resting, sleeping) affect neural circuits involved in cognition and mood.

What was found

The abstract reports no numerical data or specific statistical endpoints. It qualitatively describes that metabolic switching from liver glycogen depletion to ketone utilization initiates cellular and molecular adaptations in neural networks, promoting neuroplasticity, brain resilience to stress and injury, and maintenance of cognitive and mood circuits across the lifespan.

Why it matters

The paper outlines a mechanistic framework connecting evolutionary fasting adaptations and exercise-induced ketone metabolism directly to brain plasticity and neuroprotection.

Limits

The abstract contains no primary empirical human data, quantitative outcome measures, or systematic search methodology. The conclusions rely on theoretical and mechanistic reasoning rather than direct clinical trial evidence.

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