Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

Qian Zhao, Carl Stafstrom, Dong Dong Fu, Yingchu Hu, Gregory L. Holmes

Research output: Contribution to journalArticle

Abstract

The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/ pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.

Original languageEnglish (US)
Pages (from-to)498-506
Number of pages9
JournalPediatric Research
Volume55
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Fingerprint

Ketogenic Diet
Cognition
Status Epilepticus
Seizures
Flurothyl
Brain
Diet
Epilepsy
Protein-Restricted Diet
Pilocarpine
Vision Disorders
Growth
Lithium

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats. / Zhao, Qian; Stafstrom, Carl; Fu, Dong Dong; Hu, Yingchu; Holmes, Gregory L.

In: Pediatric Research, Vol. 55, No. 3, 03.2004, p. 498-506.

Research output: Contribution to journalArticle

Zhao, Qian ; Stafstrom, Carl ; Fu, Dong Dong ; Hu, Yingchu ; Holmes, Gregory L. / Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats. In: Pediatric Research. 2004 ; Vol. 55, No. 3. pp. 498-506.
@article{40a2152aacd64e7c882af8b96f26c54c,
title = "Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats",
abstract = "The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/ pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.",
author = "Qian Zhao and Carl Stafstrom and Fu, {Dong Dong} and Yingchu Hu and Holmes, {Gregory L.}",
year = "2004",
month = "3",
doi = "10.1203/01.PDR.0000112032.47575.D1",
language = "English (US)",
volume = "55",
pages = "498--506",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

AU - Zhao, Qian

AU - Stafstrom, Carl

AU - Fu, Dong Dong

AU - Hu, Yingchu

AU - Holmes, Gregory L.

PY - 2004/3

Y1 - 2004/3

N2 - The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/ pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.

AB - The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/ pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.

UR - http://www.scopus.com/inward/record.url?scp=1242342179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1242342179&partnerID=8YFLogxK

U2 - 10.1203/01.PDR.0000112032.47575.D1

DO - 10.1203/01.PDR.0000112032.47575.D1

M3 - Article

C2 - 14711901

AN - SCOPUS:1242342179

VL - 55

SP - 498

EP - 506

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 3

ER -