Masino Susan A, Ruskin David N, Freedgood Natalie R, Lindefeldt Marie, Dahlin Maria
Department of Psychology and Neuroscience Program, Trinity College, Hartford, CT, 06106, USA.
Neuropediatric Department, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden.
Nutr Metab (Lond). 2021 Mar 1;18(1):23. doi: 10.1186/s12986-020-00524-1.
The low carbohydrate, high fat ketogenic diet can be an effective anticonvulsant treatment in some pediatric patients with pharmacoresistant epilepsy. Its mechanism(s) of action, however, remain uncertain. Direct sampling of cerebrospinal fluid before and during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites.
We performed metabolomic analysis of cerebrospinal fluid samples taken before and during ketogenic diet treatment in patients with optimal response (100% seizure remission) and patients with no response (no seizure improvement) to search for differential diet effects in hallmark metabolic compounds in these two groups. Optimal responders and non-responders were similar in age range and included males and females. Seizure types and the etiologies or syndromes of epilepsy varied but did not appear to differ systematically between responders and non-responders.
Analysis showed a strong effect of ketogenic diet treatment on the cerebrospinal fluid metabolome. Longitudinal and between-subjects analyses revealed that many lipids and carbohydrates were changed significantly by ketogenic diet, with changes typically being of larger magnitude in responders. Notably, responders had more robust changes in glucose and the ketone bodies β-hydroxybutyrate and acetoacetate than non-responders; conversely, non-responders had significant increases in fructose and sorbose, which did not occur in responders.
The data suggest that a differential and stronger metabolic response to the ketogenic diet may predict a better anticonvulsant response, and such variability is likely due to inherent biological factors of individual patients. Strategies to boost the metabolic response may be beneficial.
低碳水化合物、高脂肪的生酮饮食对一些药物难治性癫痫患儿可能是一种有效的抗惊厥治疗方法。然而，其作用机制仍不确定。在代谢治疗前后直接采集脑脊液样本，可能会揭示与不同临床结果相关的关键变化。我们对癫痫发作反应性与脂质和碳水化合物代谢物变化之间的关系进行了特征描述。
我们对生酮饮食治疗前和治疗期间采集的脑脊液样本进行了代谢组学分析，这些样本来自反应最佳（癫痫发作100%缓解）和无反应（癫痫发作无改善）的患者，以寻找这两组患者在标志性代谢化合物方面的饮食差异效应。反应最佳者和无反应者在年龄范围上相似，包括男性和女性。癫痫发作类型以及癫痫的病因或综合征各不相同，但在反应者和无反应者之间似乎没有系统性差异。
分析表明生酮饮食治疗对脑脊液代谢组有显著影响。纵向分析和受试者间分析显示，生酮饮食使许多脂质和碳水化合物发生了显著变化，反应者的变化幅度通常更大。值得注意的是，反应者的葡萄糖、酮体β-羟基丁酸酯和乙酰乙酸的变化比无反应者更明显；相反，无反应者的果糖和山梨糖显著增加，而反应者没有这种情况。
数据表明，对生酮饮食的不同且更强的代谢反应可能预示着更好的抗惊厥反应，这种变异性可能是由于个体患者的内在生物学因素。增强代谢反应的策略可能是有益的。
