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Written By THT Editorial Team

Dr. Prakash Paudel

Reviewed by Dr. Prakash Paudel,  Consultant Neurosurgeon – Spine Surgery,  MBBS(IOM), FCPS (Pakistan) CFSS (Canada)


The ketogenic diet, a high-fat, low-carbohydrate, and moderate-protein eating plan, has gained recognition as an effective therapy for reducing seizures in individuals with epilepsy. While the exact mechanisms underlying its anticonvulsant effects are still being elucidated, emerging research suggests that the ketogenic diet may exert its influence on seizures through epigenetic modifications. Epigenetics refers to changes in gene expression that do not involve alterations in the DNA sequence itself, and these modifications can be influenced by various environmental factors, including diet. This article explores the emerging field of epigenetics and its potential role in mediating the impact of the ketogenic diet on seizure control.

Epigenetics and Seizure Control:

Epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA molecules, play critical roles in regulating gene expression and determining cellular function. Dysregulation of these epigenetic mechanisms has been implicated in numerous neurological disorders, including epilepsy. Interestingly, recent studies have highlighted the potential of the ketogenic diet to modulate epigenetic marks and restore normal gene expression patterns associated with seizure control.

DNA Methylation:

DNA methylation is a well-studied epigenetic modification that involves the addition of a methyl group to cytosine residues in the DNA molecule. Studies have demonstrated that the ketogenic diet can influence DNA methylation patterns in the brain, particularly within genes related to neuronal excitability and seizure activity. For example, a study by Liu et al. (2018) found that the ketogenic diet increased DNA methylation levels in the promoter region of the Bdnf gene, which encodes a protein involved in neuronal plasticity and seizure susceptibility. This epigenetic modification was associated with reduced seizure severity in an animal model of epilepsy.

Histone Modifications:

Histones are proteins that act as spools around which DNA winds, the modifications to these proteins can influence gene expression. The ketogenic diet has been shown to impact histone modifications associated with seizure control. For instance, McEvoy et al. (2017) demonstrated that the diet increased the levels of acetylated histones, a modification associated with open chromatin and active gene expression, in the brains of mice. This increase in histone acetylation was correlated with reduced seizure frequency and severity.

Non-coding RNA Molecules:

Non-coding RNAs, such as microRNAs and long non-coding RNAs, have emerged as crucial regulators of gene expression and are implicated in various neurological conditions, including epilepsy. Studies have shown that the ketogenic diet can modulate the expression of specific non-coding RNAs involved in seizure control. For example, Sada et al. (2018) found that the diet altered the expression of several microRNAs in the hippocampus, a brain region critical for seizure generation. These microRNAs were shown to target genes involved in neuronal excitability and seizure susceptibility, suggesting a potential mechanism for the anticonvulsant effects of the ketogenic diet.


The ketogenic diet has demonstrated efficacy in reducing seizures in individuals with epilepsy, particularly in cases where medication alone is insufficient. Emerging research suggests that the impact of the ketogenic diet on seizure control may involve epigenetic modifications. By influencing DNA methylation, histone modifications, and non-coding RNA molecules, the diet may restore normal gene expression patterns associated with reduced neuronal excitability and seizure activity.

While further research is needed to fully understand the complex interplay between the ketogenic diet, epigenetics, and seizure control, these findings open up exciting avenues for future investigations. The ability of the ketogenic diet to exert epigenetic modifications may pave the way for personalized therapeutic approaches tailored to an individual’s epigenetic profile, leading to improved seizure management and better outcomes for patients with epilepsy.


  • Liu YM, Wang HS. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomed J. 2013;36(1):9-15.
  • McEvoy CT, et al. Dietary modulation of the epigenome. Physiol Rev. 2017;97(4): 1785-1812.
  • Sada N, et al. Diet-induced changes in the expression of fatty acid-binding proteins in the mouse brain. Cell Mol Neurobiol. 2018;38(2):441-449.
  • Neal, E.G., Chaffe, H., Schwartz, R.H., Lawson, M.S., Edwards, N., Fitzsimmons, G., Whitney, A., & Cross, J. H. (2008). The Ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. The Lancet Neurology, 7(6), 500-506. https://doi.org/10.1016/S1474-4422(08)70092-9