4.5 Article

The ketogenic diet in a pill: Is this possible ?

Journal

EPILEPSIA
Volume 49, Issue -, Pages 127-133

Publisher

WILEY
DOI: 10.1111/j.1528-1167.2008.01857.x

Keywords

Ketogenic diet; Mechanism; GABA; Ketone; Mitochondria; Reactive oxygen species; Calorie restriction; Glycolysis; Fatty acids

Funding

  1. Barrow Neurological Foundation
  2. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R13NS062642] Funding Source: NIH RePORTER

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Over the past decade, much progress has been made in understanding the mechanisms of ketogenic diet (KD) action. From the complex systemic and metabolic changes induced by the KD have emerged innovative hypotheses attempting to link biochemical adaptations to its clinical effects. Despite such developments, the fundamental question of how the KD works remains as elusive as ever. At present, it is unclear which of the many potential mechanisms proposed thus far are directly relevant to the clinical effects of the KD. It is unlikely that these numerous hypotheses can be unified into a single mechanism (or a final common pathway). Nevertheless, it may be instructive to consider each of these putative mechanisms in turn and ask the following question: if the mechanism or target in question is a critical determinant of the anticonvulsant efficacy of the KD, then would a similar intervention known to be based on that mechanism yield a comparable effect ? Perhaps answering this question for each mechanistic speculation might help substantiate (or invalidate) that particular hypothesis. Can the KD be packaged into a pill ? At present, the answer is likely no. We have yet to discover a magic bullet that completely mirrors the anticonvulsant (and potential neuroprotective) effects of the KD. However, without a clearer understanding of the mechanistic elements comprising the complex metabolic puzzle posed by the KD, we would be left only with empiric observations, and to wonder curiously how a high-fat diet can exert such profound clinical effects.

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