Date of Award:

1990

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Nutrition, Dietetics, and Food Sciences

Department name when degree awarded

Nutrition and Food Sciences

Advisor/Chair:

Arthur W. Mahoney

Abstract

Fasting and ketogenic diet prevent seizures in epileptic children, magnesium-deficient rats and other animal models of seizure disorders. This effect has been attributed to increased levels of circulating ketone bodies. The purpose of this study was to determine the role of serum ketone bodies, measured as beta-hydroxybutyrate (BHB), in preventing audiogenically-induced seizures in weanling rats fed a magnesium-deficient diet for 17 days.

The effect on seizure susceptibility was investigated by feeding a magnesium-deficient diet to weanling rats for 17 days. Fasting and ketogenic diet (dietary medium chain triglycerides, MCT) markedly decreased seizure incidence that was associated with increased serum BHB level. Also, rats fasted for 24h or fed 28 percent dietary MCT had decreased seizure incidence as compared with rats fed 3 percent dietary MCT or rats fasted for 6h. These effects were not caused by differences in caloric density or percentage of calories from fat in the diets.

Gavaging 2 mmoles of BHB resulted in lower seizure incidence; as compared with rats gavaged with 0.5 mmoles BHB when measured 30 min after dosing. In contrast, gavaging 5.6 mmoles of glucose resulted in increased seizure incidence in 24-h-fasted rats.

Gavaging 5.6 mmoles of glucose with 0.5 mmole of BHB simultaneously resulted in higher seizure incidence than gavaging with 2.0 mmole BHB and 1.4 mmole glucose simultaneuosly. In addition, gavaging 5.6 mmoles of glucose with 2 mmoles of BHB resulted in higher seizure incidence than gavaging 2 mmoles of BHB alone, which markedly reduced seizure incidence in fasted animals.

Fasting, ketogenic diet (MCT) and gavaging BHB increase serum BHB and decrease serum glucose concentrations . Gavaging glucose reduced serum BHB and increased serum glucose concentration. There was an inverse relationship between serum BHB and glucose in all treatments of this study. Although some treatments affected serum minerals, these effects were not consistent among experiments. Therefore, fasting, ketogenic diet (MCT) and gavaging BHB or glucose does not affect serum minerals markedly or consistently; and modifications in serum minerals caused by these treatments do not account for this effect on seizure incidence and severity. Finally, increases in serum BHB and decreases in serum glucose were consistently associated with dose-dependent reductions in seizure susceptibility of rats fed a magnesium-deficient diet for 17 days.

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