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Wednesday, May 3, 2017

Ketogenic Diet And Lowered Seizure Incidence Due to Tryptophan

The recently released study by P. Maciejak et al. (2016) examined whether the interaction between fatty acids from the ketogenic diet and the amino acid tryptophan was responsible for the decreased seizure risk in epileptics, with an emphasis of the interaction pathway in children.  The study allegedly found that the efficacy of the ketogenic diet in reducing seizures seems to be due primarily to an increased presence of the ketones known as "acetoacetic acid", "acetone" and "β-hydroxybutyric acid" in hepatic (liver) cells. The authors previously published work which found that an anti-epileptic drug mimicking the structure of a medium-chain triglyceride (MCT) led to an increase in the metabolism of tryptophan 3. The previous study also noted that the increased levels of trytophan passed into the central nervous system (CNS), which were then converted into kynurenic acid, potentially explaining the role of tryptophan in the CNS to control seizures. Other studies have also confirmed that tryptophan leads to an increase in levels of kynurenic acid in the CNS 4.  Kynurenic acid itself is believed to play a role in seizure incidence.

So, through an elaborate pathway, it seems that tryptophan may indirectly regulate and lower the incidence of seizures when its metabolism is increased in the presence of fatty acids. The new study found that increased levels of fatty acids led to a significant increase in the amount of current required to induce typical seizure symptoms such as "after discharges" (ADs), or rather an increase in the seizure threshold level. The mechanism was examined extensively within rat hippocampal cells and it was concluded to most likely be due to increased tryptophan metabolism, confirming the hypothesis from the prior study.

To conclude, these findings show that the primary benefits of a ketogenic diet in the treatment of epileptic seizures are most likely due to higher levels of tryptophan crossing into the CNS. Despite these findings, there are numerous older studies which have failed to show that tryptophan supplemented directly reduces seizure incidence or intensity 5.  This could mean that the pathway with which tryptophan enters the CNS to increase seizure threshold cannot be activated by consuming the amino acid directly, but rather requires indirect activation through MCTs. This study does seem to confirm that a ketogenic diet, under appropriate medical advise and supervision, may be used in the management of epilepsy, and furthermore demonstrates why this is so.


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