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The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism

  • Richard L Veech
    Correspondence
    Tel.: +1-301-443-4620; fax: 1-301-443-0930
    Affiliations
    Laboratory of Membrane Biochemistry and Biophysics, National Institutes of Alcoholism and Alcohol Abuse, 12501 Washington Ave., Rockville, MD 20850, USA
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      Abstract

      The effects of ketone body metabolism suggests that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. These inferences follow directly from the metabolic effects of ketosis and the higher inherent energy present in d-β-hydroxybutyrate relative to pyruvate, the normal mitochondrial fuel produced by glycolysis leading to an increase in the ΔG′ of ATP hydrolysis. The large categories of disease for which ketones may have therapeutic effects are:
      • (1)
        diseases of substrate insufficiency or insulin resistance,
      • (2)
        diseases resulting from free radical damage,
      • (3)
        disease resulting from hypoxia.
      Current ketogenic diets are all characterized by elevations of free fatty acids, which may lead to metabolic inefficiency by activation of the PPAR system and its associated uncoupling mitochondrial uncoupling proteins. New diets comprised of ketone bodies themselves or their esters may obviate this present difficulty.
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