New insights into the mechanisms of the ketogenic diet.
New insights into the mechanisms of the ketogenic diet.
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DOI：
10.1097/wco.0000000000000432
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发表时间：
2017-04
影响因子：
4.8
通讯作者：
Boison D
中科院分区：
文献类型：
--
作者：
Boison D
高脂肪、低碳水化合物生酮饮食（KD）已被用于治疗癫痫近世纪。传统上用于治疗难治性儿科癫痫，近年来，KD的使用经历了复兴，包括治疗成年癫痫以及从自闭症到慢性疼痛和癌症的疾病。尽管KD治疗能够抑制抗癫痫药物难治性癫痫发作，并报告了持久的癫痫发作自由，但其潜在机制仍知之甚少。这篇综述探讨了KD疗法动员机制的新见解。KD通过多种机制的组合起作用，这些机制与酮和葡萄糖限制的作用以及与受体、通道和代谢酶的相互作用有关。癸酸是中链甘油三酯的一种成分，通过直接抑制AMPA受体有助于癫痫发作控制，而靶向乳酸脱氢酶的药物通过抑制代谢途径减少癫痫发作。KD治疗还影响DNA甲基化，这是饮食的一种新的表观遗传机制。KD疗法结合了几种有益的机制，为癫痫的治疗提供了广泛的益处，不仅有可能抑制癫痫发作，而且还可能改变癫痫的病程。
High-fat, low-carbohydrate ketogenic diets (KDs) have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of KDs has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of KD therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by KD therapies. KDs act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium chain triclycerides, contributes to seizure control through direct AMPA receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. KD therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. KD therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.