Abstracts

Rationale: Several complications have been reported with the administration of Ketogenic diet (KD) and the exact mechanism underlying its clinical efficacy has been largely debated. Additionally, cognitive decline in children with epilepsy on KD has been a concern, but it is unclear if cognition improves after cessation of KD. Methods: 36 Sprague-Dawley rats at postnatal day 20 were randomly assigned into 4 groups to receive Rodent chow(Ad lib), 8%KD, 14%KD and 18%KD respectively. All rats had ad libitum access to water and were housed in individual cages. Spatial Acquisition Trial (T1) was done after 22 weeks of assigned diet administration. Spatial Reversal Trial (T2) was done 1 week after T1. Trial 3 (T3) was done 6 weeks after KD cessation during which time all rats were fed on rat chow. Results: All rat groups had 9 animals at the start of the experiment. 1 rat in the 8% KD died during the diet, the cause of death was unknown. Bonferroni Post-Hoc Test for combined T1, T2 showed a mean difference of -115.44 (SE 5.5 ), -31.0 (SE 5.5) and -30.11 (SE 5.7) for Ad lib compared to 8%KD, 14%KD and 18%KD respectively, which were statistically significant (p<0.001). The mean difference for same groups for T3 were -2.14 (SE 7.84), -7.25 (SE 7.8) and -11.23 (SE 8.08), which were not statistically significant (P = 1). Sphericity tests were performed to measure the change in cognitive function of all KD rat groups from T1 to T3. They showed a significant difference in the performance of rats between these two periods when the diets were changed. [F=256.884 (1), p< 0.001]. All Rats fed on calorie restricted ketogenic diet had ketones, average Ad lib=0, 8%KD=1.035, 14%KD=0.881 and 18%KD=0.791. Conclusions: The highest ketone concentration was seen in 8% KD Rats as they received a greater fat concentration and lower protein and carbohydrate concentration in their diet. Cognitive decline was seen with all 3 KD diet groups. The degree of cognitive decline was greater when a severe carbohydrate and protein restricted high fat diet is used. This cognitive decline improves after cessation of KD and no significant cognitive differences existed in them compared to Ad lib diet.