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Changes in tryptophan and kynurenine pathway metabolites in the blood of children treated with ketogenic diet for refractory epilepsy
Journal article   Open access   Peer reviewed

Changes in tryptophan and kynurenine pathway metabolites in the blood of children treated with ketogenic diet for refractory epilepsy

Iwona Żarnowska, Dominika Wróbel-Dudzińska, Maria Tulidowicz-Bielak, Tomasz Kocki, Krystyna Mitosek-Szewczyk, Maciej Gasior and Waldemar Andrzej Turski
Seizure (London, England), v 69, pp 265-272
Jul 2019
DOI: https://doi.org/10.1016/j.seizure.2019.05.006
PMID: 31129366
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.seizure.2019.05.006View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Epilepsy Ketogenic diet Kynurenic acid Kynurenine Neuroprotection Tryptophan
•The kynurenic pathway may be modulated by ketogenic diets (KDs).•KDs affect plasma levels of kynurenines in refractory epileptic patients.•Specifically tryptophan and kynurenine levels decrease, kynurenic acid levels increase, while levels of 3-hydroxykynurenine remain unchanged.•Increases in plasma levels of kynurenic acid correlate with greater seizure reduction. There is growing evidence to support the role of the kynurenine pathway in the anticonvulsant efficacy of ketogenic diets (KDs) in refractory epilepsy. The aim of the present study was to measure blood levels of tryptophan (TRP) and its kynurenine derivatives and correlate them with seizure reduction after starting the KD in children with refractory epilepsy. Sixteen children (9 F/7 M; 7.1 ± 5.1 years) with refractory epilepsy were treated with the KDs. Clinical efficacy and metabolic ketosis were monitored throughout the study; blood levels of TRP, kynurenine (KYN), kynurenic acid (KYNA), and 3-OH-kynurenine (3-OH-KYN) were measured at 3, 6, and 12 months on the diet and compared to the pre-KD levels. Out of 16 children, 14 attained a ≥50% reduction (responders) in seizure frequency 3 months after starting the KD. In the 14 responders, TRP levels decreased numerically (18–25%) but not significantly (P = 0.077) compared to the pre-KD control values. KYN levels decreased significantly (30–57%; P = 0.001) compared to the pre-KD control levels while KYNA levels significantly increased (38–96%; P < 0.001). KYNA/KYN ratios significantly increased (100–323%; P = 0.003) while 3-OH-KYN levels (P = 0.680) and KYN/TRP ratios (P = 0.385) remained unchanged. Higher concentrations of KYNA and lower concentrations of KYN (P < 0.05) were found in patients who attained a higher reduction in seizure frequencies on the KD. We report a pattern of changes in the blood level of kynurenines in patients with refractory epilepsy who started the KD. The results of this study further support the role of specific kynurenines (e.g. KYNA) in the efficacy of the KD in refractory epilepsy.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Clinical Neurology
Neurosciences
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