An Examination of Serum Acylcarnitine and Amino Acid Profiles at Different Time Point of Ketogenic Diet Therapy and Their Association of Ketogenic Diet Effectiveness.

Pi-Lien Hung,Ju-Li Lin,Tzu-Yun Hsieh,Kai-Yin Hung,Chien Chen,Ying-Jui Lin,Mei-Hsin Hsu,Hsuan-Chang Kuo

doi:10.3390/nu13010021

Abstract

Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet with non-fasting, gradual KD initiation protocol (GRAD-KD) for 1 year were enrolled. A total of 22 patients remaining in study received blood examinations at baseline, 3rd, 6th, 9th, and 12th months of KDT. β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and non-responders (seizure reduction rate < 50%) to identify the effectiveness of KDT. Results: The 12-month retention rate was 76%. The responders after 12 months of KDT were 59% (13/22). The free carnitine level decreased significantly at 9th months (p < 0.001) but increased toward baseline without symptoms. Propionyl carnitine (C3), Isovaleryl carnitine (C5), 3-Hydroxyisovalerylcarnitine (C5:OH) and methylmalonyl carnitine (C4-DC) decreased but 3-hydroxybutyrylcarnitine (C4:OH) increased significantly at 12th months of KDT. The glycine level was persistently higher than baseline after KDT. KDT responders had lower baseline C3 and long-chain acylcarnitines, C14 and C18, as well as lower C5, C18, and leucine/isoleucine. Conclusions: KDT should be avoided in patients with non-ketotic hyperglycemia. Routine carnitine supplementation is not recommended because hypocarnitinemia was transient and asymptomatic during KDT. Better mitochondrial βoxidation function associates with greater KDT response.

Highlights

Drug-resistant epilepsy (DRE) refers to epilepsy that does not respond to two or more antiepileptic drugs and accounts for 20–30% of childhood epilepsy
Carnitine is a crucial factor in the transfer of fatty acids for mitochondrial β-oxidation, and βHB is the major product of ketosis, we examined the βHB and free carnitine levels at 6 months to assess the association with efficacy of diet (≥50% seizure reduction)
Our results provide evidence that C2 carnitine level significantly increased throughout the diet therapy; otherwise, the long-chain acylcarnitines, C16 and C16:1 levels were significantly decreased after 12 months of ketogenic diet therapy (KDT)

Summary

Introduction

Drug-resistant epilepsy (DRE) refers to epilepsy that does not respond to two or more antiepileptic drugs and accounts for 20–30% of childhood epilepsy. Thirty-three percent of patients with DRE who receive classic ketogenic diet therapy (KDT) have a more than 50% reduction in seizures and 15–20% become seizure-free [1,2,3,4,5]. Specific electroencephalography parameters had been reported to predict a favorable response to KDT in patients with DRE [7]. Schoeler et al reported a positive association between a higher baseline acetyl-carnitine level and greater efficacy of KDT [9]. This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and nonresponders (seizure reduction rate < 50%) to identify the effectiveness of KDT.

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