Na Ji-Hoon, Lee Hyunjoo, Lee Young-Mock
Departments of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06229, Republic of Korea.
Nutrients. 2025 Mar 11;17(6):979. doi: 10.3390/nu17060979.
Drug-resistant epilepsy (DRE) affects 20-30% of patients with epilepsy who fail to achieve seizure control with antiseizure medications, posing a significant therapeutic challenge. In this narrative review, we examine the clinical efficacy and safety of the classic ketogenic diet (cKD) and its variants, including the modified Atkins diet (MAD), medium-chain triglyceride diet (MCTD), and low glycemic index treatment (LGIT), in patients with genetically confirmed drug-resistant epilepsy. These diets induce a metabolic shift from glucose to ketones, enhance mitochondrial function, modulate neurotransmitter balance, and exert anti-inflammatory effects. However, genetic factors strongly influence the efficacy and safety of the cKD, with absolute indications including glucose transporter type 1 deficiency syndrome (GLUT1DS) and pyruvate dehydrogenase complex deficiency (PDCD). Preferred adjunctive applications of the KD include genetic epilepsies, such as -related Dravet syndrome, -related tuberous sclerosis complex, and -related Angelman syndrome. However, because of the risk of metabolic decompensation, the cKD is contraindicated in patients with pathogenic variants of pyruvate carboxylase and . Recent advancements in precision medicine suggest that genetic and microbiome profiling may refine patient selection and optimize KD-based dietary interventions. Genome-wide association studies and multiomics approaches have identified key metabolic pathways influencing the response to the cKD, and these pave the way for individualized treatment strategies. Future research should integrate genomic, metabolomic, and microbiome data to develop biomarker-driven dietary protocols with improved efficacy and safety. As dietary therapies continue to evolve, a personalized medical approach is essential to maximize their clinical utility for genetic epilepsy and refractory epilepsy syndromes.
耐药性癫痫（DRE）影响着20%-30%使用抗癫痫药物仍无法控制癫痫发作的癫痫患者，这构成了重大的治疗挑战。在这篇叙述性综述中，我们研究了经典生酮饮食（cKD）及其变体，包括改良阿特金斯饮食（MAD）、中链甘油三酯饮食（MCTD）和低血糖指数疗法（LGIT），对基因确诊的耐药性癫痫患者的临床疗效和安全性。这些饮食可诱导代谢从葡萄糖向酮类转变，增强线粒体功能，调节神经递质平衡，并发挥抗炎作用。然而，遗传因素强烈影响cKD的疗效和安全性，其绝对适应症包括1型葡萄糖转运体缺乏综合征（GLUT1DS）和丙酮酸脱氢酶复合物缺乏症（PDCD）。KD的首选辅助应用包括遗传性癫痫，如与相关的德雷维特综合征、与相关的结节性硬化症复合体以及与相关的天使综合征。然而，由于存在代谢失代偿的风险，丙酮酸羧化酶和 基因有致病性变异的患者禁用cKD。精准医学的最新进展表明，基因和微生物组分析可能会优化患者选择，并优化基于KD的饮食干预措施。全基因组关联研究和多组学方法已经确定了影响对cKD反应的关键代谢途径，这些为个性化治疗策略铺平了道路。未来的研究应整合基因组、代谢组和微生物组数据，以开发具有更高疗效和安全性的生物标志物驱动的饮食方案。随着饮食疗法不断发展，个性化医疗方法对于最大限度地提高其对遗传性癫痫和难治性癫痫综合征的临床效用至关重要。
