From Refractory Epilepsy to Neurodegeneration: Emerging Mechanistic and Clinical Insights Into the Ketogenic Diet.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and clinical literature without systematic review methodology
PubMed 41846418 · doi:10.1096/fj.202503317R
What was done
This review synthesized experimental and clinical literature evaluating the ketogenic diet (a high-fat, low-carbohydrate intervention) across drug-resistant epilepsy and various neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease.
What was found
The abstract reports no quantitative data or specific numerical outcomes. Preclinical evidence indicates that the ketogenic diet reduces neuronal hyperexcitability via enhanced GABAergic transmission and modulates mitochondrial bioenergetics, oxidative stress, neuroinflammation, neurotransmitter signaling, and gut-brain interactions. Clinical studies in neurodegenerative diseases were noted to be heterogeneous, short-term, and restricted to small cohorts.
Why it matters
It maps how metabolic and cellular mechanisms established in refractory epilepsy may translate to neurodegenerative disorders while emphasizing the substantial gap between animal models and human clinical application.
Limits
This is a narrative review without systematic search or meta-analytic pooling. Clinical data for neurodegenerative diseases are constrained by small sample sizes, short study durations, heterogeneous outcome measures, poor dietary adherence, and uncertain long-term safety.
Cited by
- context Ketogenic diets reduce brain inflammation.