A Nigerian‐Made Modified Atkins Diet: Hope for Patients with Intractable Epilepsy

Abstract

Introduction : Modified Atkins diet (MAD), a variant of ketogenic diet (KD) has been reported in many studies to have equal potency to the classical KD. The unpalatable taste of the classical KD has led to its unpopular use, making it necessary to use it variants. This work involved investigating the anti-epileptic and nootropic effect of a Nigerian-made Modified Atkins Diet that failed in some acute seizure tests in mice. Research Hypothesis : It was hypothesized that the formulated MAD will produce significant anti-convulsant activity in mice. Methods Ethical Approval: Ethical approval for the study was obtained from the ABU Committee on Animal Use and Care. Dietary Pre-treatment: The mice, at P28 were given appropriate diet (Normal Laboratory diet or MAD) for thirty (30) days. Twenty-one (21) litters were weaned at P28 onto modified Atkins diet for 4 weeks. Other litters were fed normal laboratory diet and started on MAD at P56 (8 weeks) for 30 days. PTZ-Induced Kindling: Protocol described by Shimada and Yamagata (2018) was adopted. Each mouse was observed for 30 minutes after every PTZ administration and the seizure behavior was scored as follows; 0: normal behavior, no abnormality; 1: immobilization, lying on belly; 2: head nodding, facial, forelimb, or hindlimb myoclonus; 3: continuous whole-body myoclonus, myoclonic jerks, tail held up stiffly; 4: rearing, tonic seizure, falling down on its side; 5: tonic-clonic seizure, falling down on its back, wild rushing and jumping; 6: death. Morris Water Maze: The effect of the diet on learning and reference memory was investigated using the Protocol described by Zhao et al. (2004) with adopted with slight modifications: 4 daily trials instead of 6 daily trials were done, non-toxic blue dye was used in place of non-fatty milk to make the pool opaque. Statistical analysis: Data were analyzed aligned-rank test followed by Mann-U Whitney correction, Kruskal-Wallis test and Kaplan Meier survival analysis where appropriate. Results As shown in the fig.1a, MAD statistically significantly increased seizure threshold in the first half of epilepsy induction before the mice in the two diet eventually became refractory to the effect of PTZ at sub-convulsive doses. Kaplan Meier survival analysis revealed the ability of Modified Atkins Diet to decrease seizure susceptibility as shown in fig.1b; Mice treated with MAD had a tonic-clonic seizure survival probability of approximately 60% while mice on LD has a probability of just 20% at the end of the injection period. Modified Atkins diet did not negatively impair learning and memory. As shown in fig. 2a, it significantly increased escape latency of the mice over time when compared to the laboratory diet group in which the escape time was not different in all test days. There however, was no significant difference (p<0.05) in the time spent in all quadrants in both diet groups, an indication of a lack of influence on reference memory. Fig. 2b. Conclusion The formulated modified Atkins diet has potential for use in the management of intractable epilepsy in humans. The diet has also shown superiority over the classical ketogenic diet in its ability to not impair visual-spatial learning and memory.