Control of seizures by ketogenic diet-induced modulation of metabolic pathways
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- 作者：Ryan M. Clanton ; Guoyao Wu ; Gamal Akabani ; Rodolfo Aramayo
- 关键词：Epilepsy ; Ketogenic diet ; Hypomyelination ; Malate ; aspartate shuttle ; Ketone bodies ; Mitochondrial disorders ; Short chain fatty acids ; Medium chain fatty acids ; Monocarboxylic acid transporters
- 刊名：Amino Acids
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：49
- 期：1
- 页码：1-20
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
- 出版者：Springer Vienna
- ISSN：1438-2199
- 卷排序：49
文摘
Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug’s mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD’s modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, d-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD’s ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.