2.1.2 Additional metabolic changes that may mediate seizure control

Emerging evidence suggests that a number of additional metabolic changes induced by ketogenic diets may also contribute to enhanced neuron energetics, reduced neuron excitability, and direct antiseizure effects, improving seizure control [7, 8].

Ketogenic diets can improve seizure control in patients with mitochondrial disorders [19]. This observation may be partly explained by the action of the medium-chain fatty acid, decanoic acid, on peroxisomal proliferator-activated receptor γ, which stimulates neuronal mitochondrial biogenesis [19]. The increased mitochondrial biomass enhances neuron ATP production capacity and cell energy reserves.

Ketogenic diets may also alter brain levels of the neurotransmitter adenosine. The disruption of adenosine signaling induces seizures; this effect is reversible by a ketogenic diet [20]. This observation suggests that the diet increases extracellular adenosine levels, activating inhibitory adenosine A1 receptors and reducing neuron hyperexcitability [7].

Lastly, ketogenic diets may exert direct antiseizure effects by raising mediumchain fatty acid levels and decreasing glucose metabolism [7, 8]. The medium-chain fatty acid, decanoic acid, blocks seizure-like activity in animals [21]. Moreover, since the antiseizure effects of ketogenic diets can be rapidly reversed by glucose infusions, decreased glucose metabolism is thought to contribute to seizure control. The mechanism for this effect could be partially explained by the observation that ketogenic diets induce a reduction in glycolysis, subsequently repressing the expression of brain-derived neurotrophic factor, a known pro-convulsant [7].
