CEREBRAL METABOLISM IN KETOSIS AND EPILEPSY

$0M01FY2000RRNIH

Yeshiva University, New York NY

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Abstract

This project seeks to understand the basis of brain ketone utilization under states of increased ketone availability such as during prolonged fasting and under the influence of a ketogenic diet. Preliminary work has concluded that the physiologically specific D beta hydroxybutyrate (BHB), gives a greater detectable increase than the unspecific DL anomeric mix in plasma BHB levels when infused, since biochemical assays for BHB are stereospecific for the D isomer. We have demonstrated that after 72 hours fasting, an infusion of sodium D-betahydroxybutyrate can increase plasma BHB levels from about 4mM to 6mM. Acetoacetate (AcAc) levels are about 1mM as expected. Work has been completed on obtaining a pyrogen free supply of sodium acetoacetate. Future infusions will include a physiological mix (4:1) of BHB and AcAc. Initial magnetic resonance studies of brain ketosis at 4.0T indicate that BHB and lactate levels can be quantified in brain tissue when plasma ketone levels are about 4-7mM.

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