Epilepsy is commonly associated with several neurodegenerative and pathological alterations in areas of the brain that are involved in repeated electrographic seizures [1]. While the exact cause of epilepsy is sometimes unknown, it can arise from several factors like central nervous system (CNS) injury, stroke, tumors, infections, or birth defects [2]. The manifestation of both clonic and tonic seizures is linked to distinct anatomical features and heightened neuronal activity. Genetic mutations have been linked to a small number of cases and involve multiple genes [3]. Current therapies for epilepsy aim to control seizures and to improve the quality of life for patients. Primary treatment includes antiepileptic drugs (AEDs) like valproate, carbamazepine, and newer agents such as levetiracetam and lamotrigine [4]. For those with drug-resistant epilepsy, surgical options like lobectomy, lesionectomy, or vagus nerve stimulation (VNS) are elective [5]. Recently, responsive neurostimulation and deep brain stimulation have shown promise in some refractory cases [6]. Advances in genetics and personalized medicine are also paving the way for more tailored and effective treatments [7].

Nutrients play a key role in epilepsy, and certain foods, or a lack thereof, increase the risk of epileptic seizures. Dietary approaches, such as the ketogenic diet, involving a high-fat, low-carbohydrate approach, have proven beneficial, particularly for children whose seizures remain unresponsive to anti-seizure medications [8]. About half of children on a ketogenic diet experience a 50% reduction in seizures, and about half achieve a reduction of more than 90% [9]. Caffeine intake may also be a factor to consider when achieving and maintaining seizure control in epilepsy. Coffee has increased seizure susceptibility in animal models, but it has also shown protective effects against seizures. At present, clinical data in humans and the impact of coffee on epileptics is insufficient [10]. Alcohol, when taken responsibly, is safe for most patients with epilepsy [11]. Vitamin D deficiency has been shown to play a role in the pathophysiology of epilepsy [12]. Notably, vitamin B6 (i.e., pyridoxine) provides rapid control in patients with various conditions affecting pyridoxal phosphate (PLP) synthesis and recycling [13]. Additionally, vitamin B6 is effective in conditions where metabolites accumulate and inactivate PLP, such as Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1) deficiency and hyperprolinemia type II. Magnesium deficiency can occasionally cause epilepsy, and recognizing and correcting this deficiency may be life-saving [14]. Gluten sensitivity or celiac disease has been linked to increased seizure activity in susceptible individuals, and these patients may benefit from a gluten-free diet [15]. Omega-3 fatty acid deficiency has also been linked with the risk of epilepsy, and these patients benefit from including omega-3 supplements in their diet [16]. The role of zinc in seizures is controversial because, on one hand, it aids in the synthesis and function of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), but on the other hand, it also inhibits GABA, which can facilitate seizure activity [17]. Vitamin B12 deficiency, and high folate levels, have been shown to cause generalized tonic–clonic seizures in rare cases, highlighting an unusual neurological condition linked to these vitamin imbalances [18]. Finally, electrolyte imbalances, such as hypocalcemia, hyponatremia, and hypomagnesemia, can also manifest with acute symptomatic seizures [19].

Bioinformatics uses a multitude of information to analyze medical data. Bioinformatic techniques, such as text mining and citation counts, are often used to identify trends and patterns in medicine [20]. These are powerful technologies for quickly distilling key information from vast quantities of biomedical literature [21]. Several studies have used text mining, and notably, Bork et al. captured the phenotypic effects of a drug based on the side effects resources published by the Food and Drug Administration (FDA) [22]. In another study, Jensen and coworkers used text mining to associate diseases and genes and to establish a web-based database named DISEASE [23]. In the past, we have used frequency analysis of PubMed citations and have shown that antibiotic resistance is cyclic [24,25]. Furthermore, we have used PubMed frequency analysis to classify autoimmune diseases [26]. Finally, we have used PubMed frequency analysis to find comorbid conditions with Alzheimer’s disease [27]. Currently, some 50 million people worldwide are affected by epilepsy, and more than 225,000 PubMed citations are related to epilepsy, thus providing a wealth of information [28].

In this review, we use citation mining to systematically rank and highlight key compounds associated with epilepsy in the literature. Then, we classify the compounds associated with epilepsy and discuss their potential benefit, or detriment, in the context of epilepsy.