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Control of seizures by ketogenic diet-induced modulation of metabolic pathways

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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.

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Ryan Clanton was supported by the National Space Biomedical Research Institute funded Mentored Research Fellowship in Space Life Sciences (NASA NCC 9-58). This work was supported by U. S. Public Health Service Grant GM58770 to R.A.

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Correspondence to Ryan M. Clanton or Rodolfo Aramayo.

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We state that: The manuscript has not been submitted to more than one journal for simultaneous consideration, has not been published previously (partly or in full), has not been split up into several parts to increase the quantity of submissions and submitted to various journals or to one journal over time (e.g., “salami-publishing”). No data have been fabricated or manipulated (including images) to support our conclusions. No data, text, or theories by others are presented as if they were our own “plagiarism”. Consent to submit has been received explicitly from all co-authors, as well as from the responsible authorities—tacitly or explicitly—at the institute/organization where the work has been carried out, before this work was submitted. Authors whose names appear on the submission have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results.

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None of the authors have a conflict of interest.

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This review is based on previously published studies and does not require IRB approval.

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Clanton, R.M., Wu, G., Akabani, G. et al. Control of seizures by ketogenic diet-induced modulation of metabolic pathways. Amino Acids 49, 1–20 (2017).

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