The Ketogenic Diet (KD), which combines initial food deprivation with a diet high in fat, was first used to treat childhood epilepsy in the 1920s. The KD induces ketosis, producing β-hydroxybutyrate (BHB), which appears to be a factor that reduces the frequency of seizures. The purpose of this study was to develop an animal model in which the direct administration of BHB produced the same effect as the KD. Techniques were developed for administering BHB by gastric gavage and measuring its levels in blood; levels were measured after periods of food given ad libitum and food deprivation. Rats fed ad libitum had average blood BHB levels of 0.06 mmol/L, while rats deprived of food for 12 hr had average levels of 0.69 mmol/L. The seizure protection range in rats begins at 0.7 mmol/L (Likhodii et al., 2000). The time necessary for the body to remove BHB from the blood was determined to be less than 1 hr. Repeated doses were given at short intervals to increase BHB levels from baseline. Repeated doses of BHB at 15 min intervals caused a continual increase in blood BHB levels, with seizure protection levels being reached. Blood BHB levels elevated by initial food deprivation were maintained above baseline with repeated administration of BHB. Current research is focusing on comparing blood BHB levels achieved by orally administered BHB, the KD, and a combination of orally administered BHB and the KD. Additionally, blood BHB levels resulting from more concentrated doses of BHB are being measured.
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