Abstracts

RATIONALE: Clinically, the ketogenic diet (KD) has been felt to be more efficacious at younger ages, presumably because of the enhanced ability of the immature brain to extract and utilize ketone bodies. The present study was designed to investigate age-related effects of the KD on ketosis and flurothyl-induced seizure susceptibility.
METHODS: A KD ([fat]:[protein + carbohydrate] ratio of 4.3:1) was administered to male Sprague-Dawley rats for 3 weeks, while control animals were fed a standard rodent chow. Dietary treatment was initiated at postnatal 3, 6, 9, or 12 weeks. Blood [beta]-hydroxybutyrate (BHB) levels were assayed and seizures were chemically induced by flurothyl infusion (40 [mu]l/min) on treatment day 21. Seizure susceptibility was defined as the latency from the start of flurothyl infusion to the onset of a generalized seizure (loss of posture with bilateral hindlimb tonic extension). Shorter latencies reflect greater seizure susceptibility.
RESULTS: The mean ([plusminus] SEM) blood BHB level in the KD-treated group was significantly higher than that of the control group in 3 (6.77 [plusminus] 0.79 [n=15] vs. 0.28 [plusminus] 0.04 [n=15] mM, respectively; p[lt]0.001), 6 (4.88 [plusminus] 0.23 [n=20] vs. 0.25 [plusminus] 0.02 [n=20] mM, respectively; p[lt]0.001), 9 (2.28 [plusminus] 0.40 [n=17] vs. 0.17 [plusminus] 0.02 [n=16] mM, respectively; p[lt]0.001), or 12 (0.95 [plusminus] 0.06 [n=18] vs. 0.27 [plusminus] 0.02 [n=17] mM, respectively; p[lt]0.001) weeks old animals. The mean ([plusminus] SEM) latencies to the onset of a generalized seizure were 554 [plusminus] 29 [KD-treated group, n=15] and 457 [plusminus] 28 [control group, n=15] seconds in 3 weeks old rats (p[lt]0.05), 571 [plusminus] 30 [KD-treated group, n=20] and 458 [plusminus] 24 [control group, n=20] seconds in 6 weeks old rats (p[lt]0.01), 508 [plusminus] 18 [KD-treated group, n=17] and 453 [plusminus] 19 [control group, n=16] seconds in 9 weeks old rats (p[lt]0.05), or 494 [plusminus] 23 [KD-treated group, n=18] and 430 [plusminus] 16 [control group, n=17] seconds in 12 weeks old rats (p[lt]0.05).
CONCLUSIONS: This study demonstrates that the KD causes significant ketosis and also significant reduction of flurothyl-induced seizure susceptibility in 3 - 12 weeks old rats. However, the levels of KD-induced ketosis were prominently lower and the seizure latencies tended to be shorter at older ages. These results parallel clinical experience, where the KD has been felt to be more efficacious at younger ages.
[Supported by: This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea. (HMP-99-N-02-0003)]