Abstracts

RATIONALE: Beta-hydroxybutyrate, a ketone body produced in the Ketogenic Diet may correlate with seizure control. This trial is to assess whether oral supplementation with beta-hydroxybutyrate in rats is feasible by studying the optimal pharmacokinetic dosage of the drug. We will determine the efficacy by administering different BHB dosing by gastric lavage, and then measuring blood levels immediately afterward.
METHODS: There are four phases to this study. For each phase, blood samples were taken prior to BHB dose. Blood levels were measured by the Keto-Site monitoring system. In the first phase, rats in the experimental group were food deprived for twelve hours prior to blood draw; rats in control group received food ad libitum. Rats were given unlimited access to food following blood draw. In the second phase, both groups were given doses of BHB every eight hours and blood levels were taken. In the third phase, doses of BHB were stopped and all rats were deprived of food for twelve hours, and blood samples taken at short intervals to determine the time BHB is removed from the blood. In the fourth phase, BHB doses and blood levels were taken at 15-minute intervals. Rats in this final phase were not deprived of food.
RESULTS: The average BHB blood level was 0.06mM/L in rats fed ad libitum; whereas in the food deprived rats, the average was 0.69mM/L, with seven of 12 levels above 0.7mM/L, which is the minimum seizure protection level (Likhodli, et al. Epilepsia 2000, 41:1400-10). There were no differences in BHB blood levels after rats were given unlimited access to food. Administration of BHB every eight hours was insufficient in maintaining the food deprivation levels of BHB. Subsequent doses of BHB were ineffective in raising blood levels. Blood levels taken after two hours were equivalent to those at eight hours, suggesting that BHB is removed before this time. Upon stopping BHB doses, it was determined that majority of BHB was removed from blood after thirty minutes, with baseline levels reached in less than 45 minutes. It was shown by administering BHB at 15-minute intervals, the BHB levels in blood showed a continual increase, without exception.
CONCLUSIONS: There is a noticeable difference in the blood BHB levels between rats given food ad libitum versus restricted food access. When rats with restricted access to food were then given ad libitum access to food, BHB levels returned to a baseline level within 45 minutes. BHB levels can be increased above baseline levels with repeated doses of BHB administered at short intervals, even if food access is unrestricted.
Support: The Charlie Foundation.