Seizure tests distinguish intermittent fasting from the ketogenic diet

Authors

  • Adam L. Hartman,

    1. Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland, U.S.A.
    2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, U.S.A.
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  • Xiangrong Zheng,

    1. Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland, U.S.A.
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  • Emily Bergbower,

    1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, U.S.A.
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  • Michiko Kennedy,

    1. Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland, U.S.A.
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  • J. Marie Hardwick

    1. Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland, U.S.A.
    2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, U.S.A.
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Address correspondence to Adam L. Hartman, M.D., 600 N. Wolfe St., Meyer 2-147, Baltimore, MD 21287, U.S.A. E-mail: ahartma2@jhmi.edu and J. Marie Hardwick, Ph.D., 615 N. Wolfe St. MMI/JHSPH, Baltimore, MD 21205, U.S.A. E-mail: hardwick@jhu.edu

Summary

Purpose:  Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests.

Methods:  Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol.

Results:  The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol.

Discussion:  In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption.

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