The ketogenic diet in a pill: "as elusive as ever"

Jong M. Rho and Raman Sankar. Barrow. The ketogenic diet in a pill: Is this possible? Epilepsia Volume 49 Issue s8, Pages 127 - 133 2008

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.

Neurological Institute and St. Joseph’s Hospital and
Medical Center, Phoenix, Arizona, U.S.A. ; and David Geffen School of
Medicine and Mattel Children’s Hospital UCLA, University of California
Los Angeles, California, U.S.A.