Neuroketotherapeutics: A modern review of a century-old therapy.
Level 5 - mechanism / opinion, no new human data
Narrative review of historical clinical use and molecular mechanisms without systematic review methodology.
PubMed 28579059 · doi:10.1016/j.neuint.2017.05.019
What was done
Narrative review evaluating neuroketotherapeutics—interventions inducing ketosis such as classic ketogenic and modified Atkins diets, medium-chain triglyceride supplements, ketone esters, fasting, and strenuous exercise—focusing on their established clinical use in epilepsy and underlying molecular and bioenergetic mechanisms.
What was found
The abstract reports no quantitative data or effect sizes. It notes established clinical benefit of ketogenic diets in epilepsy (particularly pediatric epilepsy) and identifies multiple cellular mechanisms: enhanced mitochondrial respiration, promotion of neuronal long-term potentiation, increased BDNF expression, enhanced G-protein coupled receptor (GPR) signaling, reduced oxidative stress and inflammation, and altered protein post-translational modifications (lysine acetylation and β-hydroxybutyrylation) influencing Akt, PLCγ, CREB, Sirtuin, and mTORC pathways.
Why it matters
This review outlines the broad cellular and epigenetic signaling networks regulated by ketone bodies, supporting research into bioenergetic therapies for neurological conditions beyond epilepsy.
Limits
The abstract describes a non-systematic narrative review without defined search methods, study selection criteria, or quantitative synthesis. Many highlighted signaling pathways rely on preclinical mechanistic models rather than direct human clinical trial outcomes, and efficacy data beyond pediatric epilepsy are not detailed.
Cited by
- supports Beta-hydroxybutyrate functions as a signaling molecule that activates sirtuins, stimulating mitochondrial oxidative burning.