The ketogenic diet: from molecular mechanisms to clinical effects

Recent years have witnessed an increased interest from pediatric neurologists, neuropediatricians, epileptologists and general neurologists in the use of the ketogenic diet (KD) for the management of refractory epilepsies, particularly in children and
adolescents. This article summarizes current knowledge on various issues related to its use, as discussed at a recent international
workshop. Aspects discussed in some detail include (i) the putative mechanisms responsible for the diet’s anticonvulsant effects,
based on results of biochemical and neurophysiological studies in experimental models; (ii) consensus and controversies on the
modalities of initiation of the diet, and different protocols of implementation; (iii) indications and contraindications; (iv) efficacy
data, also in relation to seizure type, syndromic form and patients age; (v) adverse effects; (vi) methodological aspects related to
assessment of the diet’s clinical effects, and perspectives for future research. Overall, the data reviewed indicate that considerable
advances have been made in understanding the modes of action of the diet, its efficacy and tolerability profiles and its potential role
in different types of epilepsy. Although clinical studies performed to date have important methodological limitations, including
suboptimally characterized patients’ populations and an uncontrolled design, a number of innovative, prospective randomized
study protocols have been recently proposed and are being implemented. The results of these will hopefully provide much needed
high-quality information to better define the role of the diet in the treatment algorithms in different epilepsy syndromes.