Molecular Mechanisms Underlying the Bioactive Properties of a Ketogenic Diet

Abstract

The consumption of a high-fat, low-carbohydrate diet (ketogenic diet) has diverse effects on health and is expected to have therapeutic value in neurological disorders, metabolic syndrome, and cancer. Recent studies have shown that a ketogenic diet not only pronouncedly shifts the cellular metabolism to pseudo-starvation, but also exerts a variety of physiological functions on various organs through metabolites that act as energy substrates, signaling molecules, and epigenetic modifiers. In this review, we highlight the latest findings on the molecular mechanisms of a ketogenic diet and speculate on the significance of these functions in the context of the epigenome and microbiome. Unraveling the molecular basis of the bioactive effects of a ketogenic diet should provide solid evidence for its clinical application in a variety of diseases including cancer.

The Influence of Ketone Bodies on Circadian Processes Regarding Appetite, Sleep and Hormone Release: A Systematic Review of the Literature

“…Evidence from a clinical study evaluating an LCD suggests it could be the same in human subjects [ 121 ]. The ability of KD to modulate cyclic genes expression is partially attributable to beta-OHB non-canonical direct actions, which are independent of dietary total calorie intake [ 122 ].…”

Role of Short Chain Fatty Acids in Epilepsy and Potential Benefits of Probiotics and Prebiotics: Targeting “Health” of Epileptic Patients

“…Though the exact mechanisms are unknown, ketone bodies are thought to be linked to inhibitory NT release and the activation of ATP-sensitive potassium channels, with a KD tied to fundamental biochemical pathways linked to the cellular substrates and mediators responsible for neuronal hyperexcitability [ 28 ]. According to a recent review, the mechanisms by which a KD counteracts DRE may involve GABAergic activity enhancement, mitochondrial energy metabolism, and reactive oxygen species production, as well as the gut–brain axis as implied by changes in the GM [ 29 ].…”

Core outcome set development for childhood epilepsy treated with ketogenic diet therapy: Results of a scoping review and parent interviews

“…are not yet fully understood [21]. Typically, seizure reduction or seizure freedom are the primary outcomes in clinical trials, with tolerability and adverse effects usually considered secondary outcomes.…”