Intermittent metabolic switching, neuroplasticity and brain health
Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A · 2018 · Nature Reviews Neuroscience
DOI: 10.1038/nrn.2017.156View source ↗
“Intermittent metabolic switching (IMS) occurs when eating and exercise patterns result in periodic depletion of liver glycogen stores and the associated production of ketones from fatty acids.”
Summary
This Nature Reviews Neuroscience paper from Mark Mattson — the most cited researcher on fasting and brain health — synthesizes the case that periodic shifts between fed and fasted metabolic states are essential for optimal brain function. Mattson coined the term "intermittent metabolic switching" (IMS) for the pattern: eating depletes liver glycogen, fasting forces ketone production, and the cycle repeats. The review argues this oscillation is what humans evolved with, and that modern continuous-feeding patterns disrupt it with cognitive and neurological consequences. The mechanistic story focuses on β-hydroxybutyrate (BHB), which is transported into neuronal mitochondria as fuel but also acts as a signaling molecule. BHB induces brain-derived neurotrophic factor (BDNF), which promotes synaptic plasticity, neurogenesis in the hippocampus, and resistance to neuronal injury. Mattson reviews evidence connecting IMS to improved cognition, mood regulation, motor performance, autonomic-nervous-system function, and resistance to neurodegenerative disease. The framework has shaped subsequent fasting-and-brain-health research and is heavily cited in popular literature on fasting's cognitive benefits.
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References cited by this entry
Mattson's 2017 Nat Rev Neuro on intermittent metabolic switching and brain health is the conceptual companion to his 2019 NEJM review on intermittent fasting and disease — same author building the framework progressively.
Alirezaei 2010 demonstrated short-fasting-induced neuronal autophagy in mice; Mattson 2017 extends the framework to clinical implications for cognitive aging and neurodegenerative disease.
Entries that reference this one
Alirezaei demonstrated short-term-fasting brain autophagy in mice; Mattson's 2017 Nat Rev Neuro extends the framework to clinical implications for neuroplasticity and brain aging.
- ExtendsFlipping the Metabolic Switch: Understanding and Applying the Health Benefits of FastingAnton SD et al. · 2018
Mattson is co-author on both pieces; the 2018 Anton-led review formalizes the 'metabolic switch' framing introduced in Mattson 2017 and applies it to dietary protocols.
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