Advertisement
Review| Volume 33, P110-114, April 2014

Download started.

Ok

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

  • Alan W.C. Yuen
    Correspondence
    Corresponding author at: Epilepsy Society, Chesham Lane, Chalfont St Peter, Bucks SL9 0RJ, UK. Tel.: +44 1494601348; fax: +44 1494874136.
    Affiliations
    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
    Search for articles by this author
  • Josemir W. Sander
    Affiliations
    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

      Highlights

      • 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.

      Abstract

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Epilepsy & Behavior
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • McCay C.M.
        • Crowell M.F.
        • Maynard L.A.
        The effect of retarded growth upon the length of life span and upon the ultimate body size.
        J Nutr. 1935; 10: 63-79
        • Anderson R.M.
        • Shanmuganayagam D.
        • Weindruch R.
        Calorie restriction and aging: studies in mice and monkeys.
        Toxicol Pathol. 2009; 37: 47-51
        • Colman R.J.
        • Anderson R.M.
        • Johnson S.C.
        • Kastman E.K.
        • Kosmatka K.J.
        • Beasley T.M.
        • et al.
        Calorie restriction delays disease onset and mortality in rhesus monkeys.
        Science. 2009; 325: 201-204
        • Speakman J.R.
        • Mitchell S.E.
        Calorie restriction.
        Mol Aspects Med. 2011; 32: 159-221
        • Chung K.W.
        • Kim D.H.
        • Park M.H.
        • Choi Y.J.
        • Kim N.D.
        • Lee J.
        • et al.
        Recent advances in calorie restriction research on aging.
        Exp Gerontol. 2013; 48: 1049-1053
        • Harvie M.N.
        • Pegington M.
        • Mattson M.P.
        • Frystyk J.
        • Dillon B.
        • Evans G.
        • et al.
        The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.
        Int J Obes (Lond). 2011; 35: 714-727
        • Halagappa V.K.
        • Guo Z.
        • Pearson M.
        • Matsuoka Y.
        • Cutler R.G.
        • Laferla F.M.
        • et al.
        Intermittent fasting and calorie restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease.
        Neurobiol Dis. 2007; 26: 212-220
        • Mager D.E.
        • Wan R.
        • Brown M.
        • Cheng A.
        • Wareski P.
        • Abernethy D.R.
        • et al.
        Calorie restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats.
        FASEB J. 2006; 20: 631-637
        • Martin B.
        • Mattson M.P.
        • Maudsley S.
        Calorie restriction and intermittent fasting: two potential diets for successful brain aging.
        Ageing Res Rev. 2006; 5: 332-353
        • Greene A.E.
        • Todorova M.T.
        • McGowan R.
        • Seyfried T.N.
        Calorie restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose.
        Epilepsia. 2001; 42: 1371-1378
        • Mantis J.G.
        • Centeno N.A.
        • Todorova M.T.
        • McGowan R.
        • Seyfried T.N.
        Management of multifactorial idiopathic epilepsy in EL mice with calorie restriction and the ketogenic diet: role of glucose and ketone bodies.
        Nutr Metab (Lond). 2004; 1: 11
        • Eagles D.A.
        • Boyd S.J.
        • Kotak A.
        • Allan F.
        Calorie restriction of a high-carbohydrate diet elevates the threshold of PTZ-induced seizures to values equal to those seen with a ketogenic diet.
        Epilepsy Res. 2003; 54: 41-52
        • Bough K.J.
        • Schwartzkroin P.A.
        • Rho J.M.
        Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo.
        Epilepsia. 2003; 44: 752-760
        • Hartman A.L.
        • Zheng X.
        • Bergbower E.
        • Kennedy M.
        • Hardwick J.M.
        Seizure tests distinguish intermittent fasting from the ketogenic diet.
        Epilepsia. 2010; 51: 1395-1402
        • Kawamura Jr., M.
        • Ruskin D.N.
        • Masino S.A.
        Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels.
        J Neurosci. 2010; 30: 3886-3895
        • Chung H.Y.
        • Kim H.J.
        • Kim J.W.
        • Yu B.P.
        The inflammation hypothesis of aging: molecular modulation by calorie restriction.
        Ann N Y Acad Sci. 2001; 928: 327-335
        • Vezzani A.
        • French J.
        • Bartfai T.
        • Baram T.Z.
        The role of inflammation in epilepsy.
        Nat Rev Neurol. 2011; 7: 31-40
        • Devinsky O.
        • Vezzani A.
        • Najjar S.
        • De Lanerolle N.C.
        • Rogawski M.A.
        Glia and epilepsy: excitability and inflammation.
        Trends Neurosci. 2013; 36: 174-184
        • Yuen A.W.
        • Sander J.W.
        Impaired mitochondrial energy production: the basis of pharmacoresistance in epilepsy.
        Med Hypotheses. 2011; 77: 536-540
        • Han Y.
        • Xie N.
        • Cao L.
        • Zhao X.
        • Liu X.
        • Jiang H.
        • et al.
        Adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1alpha signaling provides neuroprotection in status epilepticus in rats.
        Neurosci Lett. 2011; 500: 133-138
        • Galanopoulou A.S.
        • Gorter J.A.
        • Cepeda C.
        Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target.
        Epilepsia. 2012; 53: 1119-1130
        • Ryther R.C.
        • Wong M.
        Mammalian target of rapamycin (mTOR) inhibition: potential for antiseizure, antiepileptogenic, and epileptostatic therapy.
        Curr Neurol Neurosci Rep. 2012; 12: 410-418
        • Raffo E.
        • Coppola A.
        • Ono T.
        • Briggs S.W.
        • Galanopoulou A.S.
        A pulse rapamycin therapy for infantile spasms and associated cognitive decline.
        Neurobiol Dis. 2011; 43: 322-329
        • McDaniel S.S.
        • Rensing N.R.
        • Thio L.L.
        • Yamada K.A.
        • Wong M.
        The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway.
        Epilepsia. 2011; 52: e7-e11
        • Hartman A.L.
        • Santos P.
        • Dolce A.
        • Hardwick J.M.
        The mTOR inhibitor rapamycin has limited acute anticonvulsant effects in mice.
        PLoS One. 2012; 7: e45156
        • Potter W.B.
        • O'Riordan K.J.
        • Barnett D.
        • Osting S.M.
        • Wagoner M.
        • Burger C.
        • et al.
        Metabolic regulation of neuronal plasticity by the energy sensor AMPK.
        PLoS One. 2010; 5: e8996
        • Weston M.C.
        • Chen H.
        • Swann J.W.
        Multiple roles for mammalian target of rapamycin signaling in both glutamatergic and GABAergic synaptic transmission.
        J Neurosci. 2012; 32: 11441-11452
        • McMahon J.
        • Huang X.
        • Yang J.
        • Komatsu M.
        • Yue Z.
        • Qian J.
        • et al.
        Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesis.
        J Neurosci. 2012; 32: 15704-15714
        • Polajnar M.
        • Zerovnik E.
        Impaired autophagy: a link between neurodegenerative diseases and progressive myoclonus epilepsies.
        Trends Mol Med. 2011; 17: 293-300
        • Contestabile A.
        • Ciani E.
        • Contestabile A.
        Dietary restriction differentially protects from neurodegeneration in animal models of excitotoxicity.
        Brain Res. 2004; 1002: 162-166
        • Youssef F.F.
        • Ramchandani J.
        • Manswell S.
        • McRae A.
        Adult-onset calorie restriction attenuates kainic acid excitotoxicity in the rat hippocampal slice.
        Neurosci Lett. 2008; 431: 118-122
        • Duan W.
        • Lee J.
        • Guo Z.
        • Mattson M.P.
        Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury.
        J Mol Neurosci. 2001; 16: 1-12
        • Duan W.
        • Guo Z.
        • Mattson M.P.
        Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice.
        J Neurochem. 2001; 76: 619-626
        • Wu Z.
        • Xu Q.
        • Zhang L.
        • Kong D.
        • Ma R.
        • Wang L.
        Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats.
        Neurochem Res. 2009; 34: 1393-1400
        • Alcain F.J.
        • Villalba J.M.
        Sirtuin activators.
        Expert Opin Ther Pat. 2009; 19: 403-414
        • Kossoff E.H.
        • Rowley H.
        • Sinha S.R.
        • Vining E.P.
        A prospective study of the modified Atkins diet for intractable epilepsy in adults.
        Epilepsia. 2008; 49: 316-319
        • Hartman A.L.
        • Rubenstein J.E.
        • Kossoff E.H.
        Intermittent fasting: a “new” historical strategy for controlling seizures?.
        Epilepsy Res. 2013; 104: 275-279