Comprehensive Epilepsy Center, New York University Grossman School of Medicine, New York, New York, USA.
Center for Cognitive Neurology, Department of Neurology, New York University Grossman School of Medicine, New York, New York, USA.
Epilepsia. 2023 Apr;64(4):1046-1060. doi: 10.1111/epi.17540. Epub 2023 Feb 24.
High-fat and low-carbohydrate diets can reduce seizure frequency in some treatment-resistant epilepsy patients, including the more flexible modified Atkins diet (MAD), which is more palatable, mimicking fasting and inducing high ketone body levels. Low-carbohydrate diets may shift brain energy production, particularly impacting neuron- and astrocyte-linked metabolism.
We evaluated the effect of short-term MAD on molecular mechanisms in adult epilepsy patients from surgical brain tissue and plasma compared to control participants consuming a nonmodified higher carbohydrate diet (n = 6 MAD, mean age = 43.7 years, range = 21-53, diet for average 10 days; n = 10 control, mean age = 41.9 years, range = 28-64).
By metabolomics, there were 13 increased metabolites in plasma (n = 15 participants with available specimens), which included 4.10-fold increased ketone body 3-hydroxybutyric acid, decreased palmitic acid in cortex (n = 16), and 11 decreased metabolites in hippocampus (n = 6), which had top associations with mitochondrial functions. Cortex and plasma 3-hydroxybutyric acid levels had a positive correlation (p = .0088, R = .48). Brain proteomics and RNAseq identified few differences, including 2.75-fold increased hippocampal MT-ND3 and trends (p < .01, false discovery rate > 5%) in hippocampal nicotinamide adenine dinucleotide (NADH)-related signaling pathways (activated oxidative phosphorylation and inhibited sirtuin signaling).
Short-term MAD was associated with metabolic differences in plasma and resected epilepsy brain tissue when compared to control participants, in combination with trending expression changes observed in hippocampal NADH-related signaling pathways. Future studies should evaluate how brain molecular mechanisms are altered with long-term MAD in a larger cohort of epilepsy patients, with correlations to seizure frequency, epilepsy syndrome, and other clinical variables. [Clinicaltrials.gov NCT02565966.].
高脂肪、低碳水化合物饮食可以降低一些耐药性癫痫患者的癫痫发作频率，包括更灵活的改良阿特金斯饮食（MAD），这种饮食更可口，模拟禁食并诱导酮体水平升高。低碳水化合物饮食可能会改变大脑的能量产生，特别是影响神经元和星形胶质细胞相关的代谢。
我们评估了短期 MAD 对来自手术脑组织和血浆的成年癫痫患者的分子机制的影响，并将其与食用非改良高碳水化合物饮食的对照参与者（n = 6 MAD，平均年龄 43.7 岁，范围 21-53 岁，饮食平均 10 天；n = 10 名对照，平均年龄 41.9 岁，范围 28-64 岁）进行比较。
通过代谢组学分析，在血浆中有 13 种代谢物增加（n = 15 名有可用标本的参与者），其中包括酮体 3-羟丁酸增加 4.10 倍，皮质中的棕榈酸减少（n = 16），以及海马中有 11 种代谢物减少（n = 6），这些代谢物与线粒体功能有最强的关联。皮质和血浆 3-羟丁酸水平呈正相关（p =.0088，R =.48）。脑蛋白质组学和 RNAseq 鉴定出的差异很少，包括海马中 MT-ND3 增加 2.75 倍和海马中烟酰胺腺嘌呤二核苷酸（NADH）相关信号通路的趋势（p <.01，错误发现率 >.5%）（激活氧化磷酸化并抑制沉默信息调节因子信号）。
与对照组相比，短期 MAD 与血浆和切除的癫痫脑组织中的代谢差异有关，同时在海马中 NADH 相关信号通路中观察到趋势表达变化。未来的研究应该评估在更大的癫痫患者队列中，长期 MAD 如何改变大脑的分子机制，并与癫痫发作频率、癫痫综合征和其他临床变量相关联。[Clinicaltrials.gov NCT02565966]。
