Review| Volume 33, P110-114, April 2014

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Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy

  • Alan W.C. Yuen
    Corresponding author at: Epilepsy Society, Chesham Lane, Chalfont St Peter, Bucks SL9 0RJ, UK. Tel.: +44 1494601348; fax: +44 1494874136.
    NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, WC1N 3BG London, UK

    Epilepsy Society, Chalfont St Peter, UK
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  • Josemir W. Sander
    NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, WC1N 3BG London, UK

    Epilepsy Society, Chalfont St Peter, UK

    SEIN-Epilepsy Institute in The Netherlands Foundation, Achterweg 5, 2103 SW Heemstede, The Netherlands
    Search for articles by this author


      • Current dietary therapies require significant medical and dietetic support.
      • Intermittent calorie restriction (CR) is a less restrictive dietary treatment.
      • CR reduces blood glucose, inflammatory markers, AMPK, and mTOR and increases autophagy.
      • These changes are expected to decrease ictogenesis and epileptogenesis.


      There has been resurgence in the use of dietary treatment, principally the classical ketogenic diet and its variants, for people with epilepsy. These diets generally require significant medical and dietician support. An effective but less restrictive dietary regimen is likely to be more acceptable and more widely used. Calorie-restricted diets appear to produce a range of biochemical and metabolic changes including reduced glucose levels, reduced inflammatory markers, increased sirtuins, increased AMPK signaling, inhibition of mTOR signaling, and increase in autophagy. There are studies in animal seizure models that suggest that these biochemical and metabolic changes may decrease ictogenesis and epileptogenesis. A calorie-restricted diet might be effective in reducing seizures in people with epilepsy. Hence, there is a sufficient rationale to undertake clinical trials to assess the efficacy and safety of calorie-restricted diets in people with epilepsy.


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