Dietary fat, ketosis, and seizure resistance in rats on the ketogenic diet.
OBJECTIVE
Fat is the major component of the ketogenic diet (KD), yet no studies have examined whether the type of fat used in the diet can be optimized to provide additional benefits. The purpose of the present experiments was to compare the efficiency of different fats in inducing ketosis and affording seizure resistance.


METHODS
The effects of KDs that incorporate lard, butter, medium-chain triglycerides (MCT), or flaxseed oil or a mixture of the latter three fats were examined in rats fed KD for up to 98 days. The maximal electroshock (MES) or pentylenetetrazole (PTZ) threshold tests were used to assess seizure susceptibility in two separate experiments.


RESULTS
The rank order of induced ketosis was MCT > mixture > or = flaxseed oil > or = lard = butter > or = control. MES failed to reveal anticonvulsant effects, but the PTZ test indicated that up to 50% of rats fed the KD were seizure protected (p < 0.05). The measures of seizure protection, seizure incidence and score, did not correlate, however, with the level of ketosis in the range of 0. 7-5.2 mmol/L for beta-hydroxybutyrate. In the long-term study, flaxseed oil KD maintained stable ketosis throughout 98 days, whereas ketones declined with lard and butter KD to the control level.


CONCLUSIONS
Seizure protection with the versions of the KD did not improve with the higher level of ketosis. The focus of the KD improvement, therefore, is not the achievement of higher ketosis per se but rather designing a diet that provides steady ketosis, exploits advantages of certain fats for neurological development or seizure protection via a nonketogenic mechanism, and is nutritionally balanced.
Likhodii
S S
SS
Departments of Nutritional Sciences and Pharmacology and Bloorview Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, Canada. sergei.likhodi@utoronto.ca
Musa
K
K
Mendonca
A
A
Dell
C
C
Burnham
W M
WM
Cunnane
S C
SC
D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage / Q000032:analysis / Q000145:classification*; D004044:Dietary Proteins / Q000008:administration & dosage; D004195:Disease Models, Animal; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D005526:Food, Formulated / Q000145:classification; D006801:Humans; D007659:Ketones / Q000097:blood / Q000652:urine; D007662:Ketosis / Q000209:etiology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D012640:Seizures / Q000178:diet therapy / Q000517:prevention & control*
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D007659:Ketones