Abstract
We propose that cerebral ketone body utilization underlies the anticonvulsant mechanism of a ketogenic diet. Blood and forebrain analyses (freeze-blowing technique) performed on adult rats fed an 80% fat diet for 20 days (FF group) were compared to a control group. Blood [glucose] was ↓ and blood [BOMB] and [acetoacetate] were + (p < .005) in the FF group. Brain concentrations of Na, K, Cl, glucose, malate, AMP, phosphocreatine, oxaloacetate and water content were similar in the two groups. Brain glycogen, glucose 6-P, pyruvate, lactate, BOHB, citrate, α-ketoglutarate, and ATP concentrations were ↓ (p < .005) and brain fructose 1, 6-P2, ADP, cyclic AMP, and cyclic GMP concentrations were ↓ (p < .05) in the FF group. We conclude from these observations that chronic ketosis effects cerebral metabolism: (1) like certain anticonvulsant drugs by slowing brain phosphofructokinase, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase; (2) by ↑ the brain/blood glucose ratio by 21% and the cerebral energy reserves by 12%; (3) unlike certain anticonvulsant and sedative drugs, by maintaining the concentrations of citric acid cycle intermediates reflecting the precursor role of ketone bodies for acetyl-CoA synthesis; and (4) by decreasing cyclic nucleotide concentrations 12-21% presumably reflecting a depression in neuronal activity. It is suggested that each of these metabolic effects contributes to the anticonvulsant action of the ketogenic diet.
(Supported by USPHS Grants #NS 09808 and #NS 13104.
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Devivo, D., Leckie, M. & Ferrendelli, J. CHRONIC KETOSIS AND CEREBRAL METABOLISM. Pediatr Res 11, 561 (1977). https://doi.org/10.1203/00006450-197704000-01146
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DOI: https://doi.org/10.1203/00006450-197704000-01146
