Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet

Bough, Kristopher J.; Valiyil, Ritu; Han, Frederick T.; Eagles, Douglas A.

doi:10.1016/s0920-1211(98)00125-9

Cited by 140 publications

(133 citation statements)

References 33 publications

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“…Fasting is known to result in an increased production of ketone bodies, which can be used as an energy source (23,24) and are known to provide some protective effects including neuroprotection and resistance to epileptic seizures (25)(26)(27). We therefore measured serum levels of ␤-hydroxybutyrate after an overnight fast in mice that had been maintained on AL, LDF, and IF diets.…”

Section: Resultsmentioning

confidence: 99%

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Anson

Guo

Cabo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

612

537

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Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL͞6 mice are maintained on an intermittent fasting (alternateday fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.caloric restriction ͉ hippocampus ͉ insulin ͉ ␤-hydroxybutyrate ͉ ketosis

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Section: Resultsmentioning

confidence: 99%

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Anson

Guo

Cabo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

612

537

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“…Despite severely restricted carbohydrate, HP rats did not have elevated levels of β-hydroxybutyrate. Ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) are products of lipid metabolism and while HP rats were consuming a diet with greater fat content than CH, others have demonstrated that in order to achieve ketosis in rats, the diet must contain at least 80% of the kcals from fat, and 5% or less from carbohydrates [22][23][24]. While the carbohydrate content of the diet used in the current studies is sufficiently low, the fat content is likely not high enough.…”

Section: Discussionmentioning

confidence: 99%

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet

Kinzig¹,

Hargrave²,

Hyun

et al. 2007

Physiology & Behavior

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Diets high in fat or protein and extremely low in carbohydrate are frequently reported to result in weight loss in humans. We previously reported that rats maintained on a low carbohydrate-high fat diet (LC-HF) consumed similar kcals/day as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC-HF rats had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and increased plasma leptin and ghrelin. In the present study we assessed the effects of a low carbohydrate-high protein diet (HP: 30% fat, 65% protein, and 5% CHO) on body weight, caloric intake, plasma hormone levels and hypothalamic gene expression. Male rats (n=16) were maintained on CH or HP for 4 weeks. HP rats gained significantly less weight than CH rats (73.4 +/− 9.4 and 125.0 +/− 8.2 g) and consumed significantly less kcals/day (94.8 +/− 1.5 and 123.6 +/− 1.1). Insulin was significantly reduced in HP rats (HP: 1.8 +/− 0.6 vs. CH: 4.12 +/− 0.8 ng/ml), there were no differences between groups in plasma leptin and plasma ghrelin was significantly elevated in HP rats (HP: 127.5 +/− 45 vs. CH: 76.9 +/− 8 pg/ml). Maintenance on HP resulted in significantly increased ARC POMC (HP: 121 +/− 10.0 vs. 100 +/− 5.9) and DMH NPY (HP: 297 +/− 82.1 vs. CH: 100+/− 37.7) expression compared to CH controls. These data suggest that the macronutrient content of diets differentially influences hypothalamic gene expression in ways that can affect overall intake.

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“…Anticonvulsant agents that target the GABA system are usually only weakly effective in the maximal electroshock test and some are ineffective. In contrast, the ketogenic diet was found to be protective in the pentylenetetrazol test in rats [25][26][27][28]. The diet also was effective against seizures induced by the GABA A receptor antagonists bicuculline and picrotoxin in rats [31], but did not confer sustained protection against fully kindled seizures in the rat amygdala kindling model [21,22].…”

Section: Gaba Systemsmentioning

confidence: 99%

The Neuropharmacology of the Ketogenic Diet

Hartman

Gąsior

Vining

et al. 2007

Pediatric Neurology

270

169

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The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone bodies partly replacing glucose as fuel. Whether these metabolic changes contribute to acute seizure protection is unclear; however, the ketone body acetone has anticonvulsant activity and could play a role in the seizure protection afforded by the diet. In addition to acute seizure protection, the ketogenic diet provides protection against the development of spontaneous recurrent seizures in models of chronic epilepsy, and it has neuroprotective properties in diverse models of neurodegenerative disease.

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Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet

Cited by 140 publications

References 33 publications

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet

The Neuropharmacology of the Ketogenic Diet

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