Title: Calorie Restriction of a High-Carbohydrate Diet Increased the Threshold of Pentylenetetrazole-Induced Seizures with Minimal Elevation of Ketonemia
Abstract number :
1.155
Submission category :
Year :
2000
Submission ID :
2861
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Douglas A Eagles, Suzanne V Jabbour, Maryann C Deak, Mary Anne Horta, Anandi Kotak, Georgetown Univ, Washington, DC.
RATIONALE: Calorie restriction increases both the level of ketonemia and the level of seizure protection afforded by ketogenic diets. The purpose of this study was to discriminate between the role of calorie restriction and that of ketonemia by feeding rats a calorie-restricted anti-ketogenic (high carbohydrate) diet. METHODS: Eighty-eight male Sprague-Dawley rats were divided into five diet groups fed: (1) a normal (Purina Rodent chow 5001) diet ad lib. (NAL), (2) a ketogenic (Bioserve F3666) diet at 90% recommended daily allowance (RDA), (3) a high-carbohydrate (BioServe 3701) diet at 90% RDA (C90), 65% RDA (C65) or 50% RDA (C50). Levels of ?-hydroxybutyric acid (?-OHB) in tail-vein blood were assayed spectrophotometrically and and seizure threshold was determined by timed infusion of pentylenetetrazole (PTZ) into the tail vein for all animals. The metabolic rates of a subset of 20 animals (five each of NAL, K90, C90 and C65) were determined by indirect calorimetry. RESULTS: Compared to rats in the NAL diet group, seizure threshold was raised in the K90 and C65 diet groups and the K90 threshold was greater than that of the C65 group (unpaired, two-tailed Student's t-test). Ketonemia (as ?-OHB) was elevated in the K90 group relative to that in the C65 group, which was not different from that in the NAL group. Weight-specific metabolic rate was greatest in rats fed the K90 diet, lowest in the NAL and intermediate in the C90 and C65 groups. CONCLUSIONS: These results confirm the effectiveness of a calorie-restricted ketogenic diet in elevating both seizure threshold and seizure resistance but, surprisingly, show that elevated ketonemia is not necessary for seizure threshold elevation. Equally surprising is the observation that calorie-restricted high-fat and high-carbohydrate diets elevate weight-specific metabolic rates, as each was assumed to mimic starvation, a condition associated with lowered metabolic activity. Together, these findings question the premise that the ketogenic diets mimics fully the metabolism of starvation and that ketonemia is central to the protection it confers.