Abstracts

Rationale: Epilepsy is a syndrome characterized by seizures, which can be caused by diverse etiologies. Pharmacotherapy can only help specific individuals in which the drug’s therapeutic mechanism is relevant to their diseases. Ketogenic diet(KD) had been introduced in the treatment of epilepsy in 1921, by Dr Wilder. The anti-seizure effect of KD is gradually discovered, however, the metabolomics analysis after long-term consuming KD is scanty investigated. Our study aims are addressed to compare metabolic changes in KD responders and non-responders. Methods: In this prospective study, total 29 patients, aged ranging from 2 months to 17 years old, fitting the diagnostic definition of drug-resistant epilepsy (DRE) were enrolled under supervision of the Ethics Committee of Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan), and informed consent was obtained from the parents or guardians of the study subjects. All study subjects were admitted for receiving Modified Atkin Diet (MAD) under the surveillance of same dietitian based on the “ Five -Day Ketogenic Diet Program” created by Kaohsiung Chang Gung Memorial Hospital Ketogenic Diet Research Team. Seven patients quitted from study because of parental or children’s factors. Only 22 patients completed blood spots for Tandem Mass Spectrometry at baseline, 3months-, 6 months- and 9 months- of ketogenic diet therapy. Amino acids and fatty acids profiles were compared between responders (seizure reduction rate ≥50%) and non-responders (seizure reduction rate < 50%). Results: Twenty-nine patients, aged from 8 months to 20 years old, were enrolled in this study. All of them received MAD under the same dietitian. The etiologies of refractory epilepsy were variable, however, genetic epilepsy accounts for most of the etiologies (45%). The six-month KD compliance was 87%. 55% of the patients showed greater than 50 % of seizure reduction rate after 6 month of KD therapy (responders). Our study demonstrated that total free-carnitine significantly decreased for all patients at 9-month of KD therapy (P<0.001). The serum total carnitine level was maerkedly lower in responders after 6 months of KD (P<0.05). In addition, serum short –chain and medium-chain fatty acid in responders were significantly lower than non-responders at 6-month of KD therapy (P<0.005). Very-long chain fatty acids in responders were significantly lower than non-responders at 6-month or 9-month of KD therapy (P<0.05, P<0.005). Urea synthesis amino acid, ornithine was significantly lower and L-citrulline was significantly higher in non-responders (P<0.05; P<0.01). Conclusions: Our pilot study revealed that ketogenic diet therapy alters the metabolic status of fatty acid and amino acids in human body, and this biological alteration is closely correlated with anti-seizure effect. Further investigation of the mechanism is worthy to be investigated. Funding: No funding