Epilepsy: A Nutrition and Natural-Health Reference
1. Definition and Overview
Epilepsy is defined as "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures." The International League Against Epilepsy (ILAE) further specifies that a seizure is "a transient occurrence of signs and/or symptoms due to abnormal synchronous neuronal activity in the brain." Crucially, a single unprovoked seizure does not itself constitute epilepsy; the diagnosis typically requires two or more unprovoked seizures.
Epilepsy is a neurological condition involving the brain that makes people more susceptible to having recurrent seizures. It is one of the most common disorders of the nervous system and affects people of all ages, races, and ethnic backgrounds. With 50 million affected individuals worldwide, epilepsy represents one of the most common neurological disorders, second only to stroke.
Epilepsy is a collective designation for a group of brain disorders consisting of a complex spectrum of different seizure types and syndromes. Epileptic seizures are classified into partial (simple and complex partial seizures) and generalized seizures (absence, tonic-clonic, myoclonic, and atonic seizures).
2. How Epilepsy Presents
During a seizure, nerve cells in the brain send multiple signals at once, much faster than usual. This sudden increase and alternation in electrical activity causes seizure symptoms, such as involuntary movements, behaviors, and altered awareness.
Epileptic seizures may be accompanied by an impairment or loss of consciousness, psychic, autonomic or sensory symptoms, or motor phenomena. Generalized-onset seizures are believed to instantaneously involve almost the entire brain, while focal-onset seizures appear to originate from a circumscribed region of the brain. These simplistic concepts of focal and generalized seizures, however, are being challenged by increasing evidence of seizure onset within a network of brain regions (the epileptic network).
For about 30% of epilepsy patients, seizures remain poorly controlled despite maximal medical management.
3. Body Systems Involved
Central Nervous System
Epilepsy is a neurological (nervous system) disorder that affects the brain, which is part of the central nervous system (CNS). The brain is made up of three main structures: the cerebrum or cerebral hemispheres, the brain stem, and the cerebellum. The cerebrum is the largest and most recognizable of the three structures and is the one most often involved in epilepsy. At a cellular level, hyperexcitability of neurons and hypersynchrony of neural networks are the hallmarks of seizures. Hyperexcitability means that a certain level of excitability, or a threshold, must be exceeded for a seizure to be generated.
The hippocampus, amygdala, frontal cortex, temporal cortex, and olfactory cortex are the common areas involved in seizures. The amygdala plays an important role in temporal lobe epilepsy, while the thalamus plays a crucial role in controlling seizures.
Epileptic seizures result when a sufficient number of neurons fire signals abnormally, leading to an alteration of sensation, behavior, or consciousness. This requires that abnormal cells be able to recruit other normal cells to fire at the same time. Neurologists think that this recruitment is made possible when there is an excess of excitation and/or a lack of inhibition.
Peripheral and Autonomic Nervous Systems
Epilepsy involves episodes of altered electrical activity in the brain. As a consequence of the disrupted brain activity, actions of the peripheral nervous system and autonomic nervous system are also affected. The peripheral nervous system controls purposeful muscle movements, and the autonomic nervous system controls internal organs.
Endocrine, Cardiovascular, and Emotional Systems
Cognitive functions like memory and attention may sometimes be impaired. Emotional well-being can suffer due to unpredictable seizures and societal stigma, potentially leading to depression and anxiety. Hormonal imbalances affecting the endocrine system can emerge. Most seizures have minor cardiovascular and respiratory effects; however, prolonged seizures could impact heart rate and breathing.
4. Contributing and Associated Factors
Genetic Factors
Inconsistent levels of evidence for risk of onset include family history of epilepsy, history of febrile seizures, alcohol consumption, CNS and other infections, brain trauma, head injury, perinatal stroke, and preterm birth, along with several genetic markers. Family history indicates a hereditary inclination for epilepsy, highlighting the importance of genetic counselling and testing in families affected by the condition.
Structural and Acquired Brain Injury
The risk factors described in existing literature include cerebrovascular diseases, brain trauma, and neoplasms. Stroke is one of the leading causes of epilepsy in adults older than age 35. Infections affecting the brain such as meningitis, AIDS, and viral encephalitis can also cause epilepsy.
Perinatal and Early-Life Factors
Premature birth is significantly associated with the risk of epilepsy (pooled OR = 4.36 [95% CI: 1.26–15.09], p = 0.02). Smoking during pregnancy significantly increases this risk by 28% (pooled OR = 1.28 [95% CI:1.1–1.49], p = 0.002). In a large U.S. pediatric database study, the most common risk factors were childhood static encephalopathy, perinatal morbidity, and stroke/cerebrovascular disease. Children with neonatal seizures (odds ratio = 29.0), central nervous system infection (6.5), and childhood static encephalopathy (5.4) had significantly higher risk of developing epilepsy.
Modifiable Risk Factors
Modifiable risk factors that could be targeted by prevention efforts include alcohol consumption, acquired brain injuries, and CNS infections. Limited evidence has shown that high stress or anxiety and lack of sleep decrease the odds of seizure remission.
Gut-Brain Axis
People with epilepsy exhibit altered gut microbiota composition, and bottom-up signals from the gut affect neurotransmission, neuroendocrine, metabolic, and neuroimmune pathways. In a series of studies on rodent models of epilepsy, it has been shown how the microbiota can influence epileptic seizures. Under stressful conditions, animals are more susceptible to developing epileptic seizures; stress is able to alter the gut microbiota, and when the fecal contents of these stressed rats were transplanted into non-stressed animals, the latter developed a greater sensitivity to epilepsy than controls. This emerging research area is still primarily preclinical, and clinical implications in humans remain under investigation.
5. Nutrients Studied in Relation to Epilepsy
5.1 Vitamin B6 (Pyridoxine)
Scientific Evidence: The only vitamin deficiency clearly known to cause or worsen seizures is a deficiency of vitamin B6 (pyridoxine). This deficiency occurs mainly in newborns and infants and causes seizures that are hard to control. A Mendelian randomization analysis published in 2024 found that vitamin B6 was associated with reduced risks of focal epilepsy with hippocampal sclerosis (OR = 0.949; p = 0.020). However, after adjustment using multivariable Mendelian randomization, the causal relationship between vitamin B6 and focal epilepsy with hippocampal sclerosis became non-significant. At the clinical level, supplementation with 80–200 mg/day pyridoxine has been reported to reduce serum phenytoin and phenobarbitone levels in epileptic children, and long-term administration of 500 mg/day or more of pyridoxine has resulted in neurotoxicity in some adults. Evidence is therefore strongest for a clearly defined deficiency state (pyridoxine-dependent epilepsy) in infants; evidence for supplemental benefit in non-deficient individuals is not well established.
5.2 Vitamin D
Scientific Evidence: Using Mendelian randomization analysis, vitamin D was linked to decreased risks of both childhood absence epilepsy (CAE) (OR = 0.976, 95% CI: 0.959–0.993, p = 0.006) and juvenile absence epilepsy (JAE) (OR = 0.986, 95% CI: 0.973–0.999, p = 0.032). These MR estimates provide robust evidence for causal effects of vitamin D on reducing the risk of CAE and JAE, and significant causal relationships between vitamin D and both CAE and JAE remained after MVMR adjustment. Animal models, mechanistic studies, and ecological data provide objective evidence for a direct antiepileptic effect of vitamin D, and human studies appear to confirm this, but there are as yet no controlled studies on large populations. A randomized, double-blind, placebo-controlled multicenter trial has been registered to evaluate vitamin D supplementation in 400 drug-resistant patients to assess effects on seizure frequency. Weak bones are related to inadequate amounts of vitamin D, which is particularly relevant for people with epilepsy taking certain anticonvulsant medications.
5.3 Magnesium
Scientific Evidence: Magnesium has a central nervous system depressant effect by inhibiting the N-methyl-D-aspartate (NMDA) receptor, acting as an antagonist of calcium channels, and increasing the surface tension of the cell membrane. An observational clinical study found that patients with epilepsy who had seizures more than 4 times per week had lower serum magnesium levels than those with seizures less than or equal to once per week, and that a low dose of magnesium added to phenytoin or carbamazepine can reduce seizure frequency. Evidence in this area is based on small observational studies and limited clinical data; large-scale randomized controlled trials are lacking.
5.4 Omega-3 Fatty Acids (EPA and DHA)
Scientific Evidence: There is evidence suggesting that omega-3 fatty acids may have neuroprotective and anticonvulsant effects and, accordingly, may have a potential use in the treatment of epilepsy. Long chain omega-3 fatty acids supplements have been shown to exert beneficial effects in patients with epilepsy through elevation of seizure thresholds and dampening of inflammatory responses. In a triple-blind RCT of 50 patients with refractory epilepsy over 16 weeks, supplementation with 180 mg EPA and 120 mg DHA twice daily resulted in reduced seizure frequency and duration, as well as a significant decrease in TNF-α and IL-6 concentrations.
A 2021 systematic review and meta-analysis found that pooled results indicated that seizure frequency following omega-3 supplementation decreased significantly (WMD: −6.15, 95% CI: −7.78 to −4.53, p < 0.001), with greater benefit from doses of 1500 mg/day or less and intervention durations greater than 16 weeks. The effect of omega-3 intervention was greater in adults than in children. A 2025 meta-analysis reported that larger RCTs (n > 30) with omega-3 supplementation (0.3–1.7 g/day) show moderate-certainty evidence of benefit for drug-resistant epilepsy in adults (a significant reduction of 4.19 monthly seizures), while in the children subgroup no significant difference was found compared with placebo.
Despite these signals, phase II RCT evidence suggests that low-to-moderate doses of omega-3 fatty acids reduce seizures; however, larger multicenter randomized trials are needed to confirm or refute the evidence, and the human data are not yet sufficient to support efficacy in drug-resistant epilepsy at this time.
5.5 Folate and Other B Vitamins
Scientific Evidence: To avoid dietary deficiencies in people with epilepsy, authoritative clinical sources emphasize ensuring adequate intake of folic acid, vitamin B1, vitamin D, vitamin B6, vitamin B12, vitamin E, and vitamin K, as well as inorganic salts including calcium, magnesium, and manganese. Anemia can result from severe folic acid deficiency, and this is clinically relevant since certain antiepileptic drugs interfere with folate metabolism. Evidence for supplementation beyond deficiency correction in epilepsy is limited.
5.6 Zinc and Other Trace Minerals
Scientific Evidence: The 2024 Mendelian randomization study in PMC found that zinc conferred an increased risk of focal epilepsy with hippocampal sclerosis (OR = 1.01; p = 0.045), a counterintuitive finding suggesting complex, possibly dose-dependent and context-dependent relationships between trace minerals and epilepsy subtypes. These findings are novel and require replication; they should not be interpreted as a basis for avoidance or supplementation without further evidence.
6. Herbs and Natural Ingredients: Traditional Use and Scientific Evidence
6.1 Cannabis sativa (Cannabidiol / CBD)
Traditional Use: Medical use of cannabis dates back to 2700 years before the Common Era, and its use for epilepsy was reported in medieval times and in the late 19th century. Over thousands of years, people with epilepsy have used a variety of botanicals and herbs.
Scientific Evidence: This is the most rigorously studied natural compound in epilepsy research. In 2018, the US Food and Drug Administration approved the first phytocannabinoid, cannabidiol (CBD, Epidiolex), now indicated for severe seizures associated with three rare forms of developmental and epileptic encephalopathy: Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In randomized clinical trials, highly purified CBD has demonstrated efficacy with an acceptable safety profile in children and adults with difficult-to-treat seizures.
It has been several years since highly purified CBD was registered as a medication that can be used in children of at least 2 years of age to treat different types of seizures related to LGS, DS, and TSC. During this time, 39 randomized clinical trials (RCTs) and 13 meta-analyses on the efficacy and safety of CBD treatment have been published. A 2018 systematic review and meta-analysis of four RCTs involving 550 patients found that adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of adverse events than placebo. Mechanistically, experimental evidence from in vitro and in vivo studies indicates that CBD reduces neuronal excitability and seizure activity by a wide range of mechanisms including modulation of endocannabinoid, adenosine, GPR55, and TRPV1 receptors, and that CBD's molecular actions trigger immunomodulatory effects and inhibit neuroinflammation. Interpretation of results of RCTs has been complicated by an interaction with clobazam, which leads to a prominent increase in the plasma concentration of the active metabolite N-desmethylclobazam in CBD-treated patients. Overall, the evidence for pharmaceutical-grade purified CBD in specific pediatric epilepsy syndromes is among the strongest for any natural compound in epilepsy.
6.2 Nigella sativa (Black Cumin / Black Seed)
Traditional Use: Traditionally, seeds of Nigella sativa (Ranunculaceae), also known as black seed or black cumin, have been used around the globe for the prevention and management of various conditions. Its use in epilepsy is documented in Islamic traditional medicine and Middle Eastern traditional healing systems.
Scientific Evidence: Nigella sativa and Cannabis sativa are discussed as two of the best documented anticonvulsant herbs in the literature on herbal medicines for seizures. A systematic review of pediatric studies (2004–2024) identified four eligible trials: two studies reported that treatment reduced seizure frequency in their samples, while two studies reported no effect on seizure frequency. The evidence is thus preliminary, mixed, and based on small pediatric pilot studies. Mechanistically, animal studies have demonstrated anticonvulsant effects of thymoquinone, the major active constituent of the seed, but human clinical evidence is insufficient to draw firm conclusions.
6.3 Valeriana officinalis (Valerian)
Traditional Use: Valerian root (Valeriana officinalis) has been used on seizure patients since as far back as ancient Roman and Greek times. Its use continued through the Middle Ages, and by the 16th century, it was documented by both herbalists and physicians, who administered it for seizures, insomnia, and anxiety.
Scientific Evidence: Pharmacology studies have revealed sedative, hypnotic, antispasmodic, analgesic, antidepressant, anxiolytic, anticonvulsant, antiepileptic, and neuroprotective effects of Valeriana. However, rigorous clinical RCT data specifically evaluating valerian's antiseizure effects in human epilepsy are largely absent. Clinical experience suggests that patients may try valerian to reduce AED-related adverse effects or comorbid conditions such as insomnia, rather than as a direct antiepileptic agent. The evidence for valerian as an anticonvulsant in humans is currently weak and primarily derived from preclinical animal studies.
6.4 Traditional Chinese Medicine (TCM) Herbal Formulas
Traditional Use: The treatment of epilepsy using Traditional Chinese Medicine (TCM) dates back a thousand years. TCM herbal formulations exhibit the synergistic activities of multiple components and exert a holistic effect through various targets and pathways. In TCM, the origin of epilepsy is attributed to several internal and external factors including disruptions in organ functions and Yin-Yang imbalances.
Scientific Evidence: The traditional Asian herbal formulas xiǎo chái hú tāng (Minor Bupleurum Decoction), chái hú guì zhī tāng (Bupleurum and Cinnamon Decoction), and related preparations have been reviewed for use in epilepsy. A 2021 review in Frontiers in Neuroscience noted that a review article in 2018 reported eighteen anticonvulsant herbal agents, including Uncaria rhynchophylla, Gastrodia elata, Cannabis, Passiflora incarnata, Withania somnifera, and others. Herbal therapies for epilepsy in developing countries have evolved over the centuries, and nearly 40% of persons in a 1988 survey in China reported they would suggest an herbal medicine doctor or acupuncture for a friend with epilepsy. Overall, the clinical evidence base for specific TCM formulas in epilepsy remains limited by small sample sizes and lack of rigorous blinded trials, though this is an active area of investigation.
6.5 Other Botanicals: Passionflower, Skullcap, and Lavender
Traditional Use and Scientific Evidence: A range of nervine and nootropic herbs that may speculatively have use in seizure disorders includes Scutellaria lateriflora (skullcap), Lavandula angustifolia (true lavender), Passiflora incarnata (passionflower), Valeriana spp. (valerian), Ziziphus jujuba (jujube), Acorus calamus (sweetflag), and Centella asiatica (gotu kola). For all of these, clinical evidence in human epilepsy is limited; most support derives from animal or in vitro models. While some compounds including skullcap and valerian have shown positive effects in laboratory animal assays, the lack of clinical data places constraints on clinical recommendation of herbal medicine.
6.6 Drug–Herb Interaction Considerations
Drug–herb interactions with anti-seizure medications have been reviewed, with specific attention to silymarin, Camellia sinensis (green tea), Hypericum perforatum (St. John's wort), Citrus × paradisi (grapefruit), and Piper spp. (black and long pepper). These interactions are clinically significant and relevant to anyone with epilepsy considering herbal supplementation.
7. Dietary Approaches
7.1 The Ketogenic Diet (KD)
Drug-resistant epilepsy in children poses significant therapeutic challenges. The ketogenic diet (KD), characterized by high-fat and low-carbohydrate content, has emerged as a potential adjunctive treatment. Multiple systematic reviews and meta-analyses now support its efficacy. A 2023 meta-analysis of 21 systematic reviews concluded that KD can be an effective treatment for refractory epilepsy, with a more than 50% reduction in the frequency of seizures and cognitive improvement being achieved in half of pediatric patients. The effectiveness of various types of KD is comparable and the KD can be adapted to the needs of the patient.
A 2025 meta-analysis of nine RCTs in pediatric drug-resistant epilepsy found that for patients achieving >50% seizure reduction, pooled analysis revealed an OR of 7.69 (95% CI [3.42, 17.3]), and analysis of studies reporting >90% seizure reduction yielded an OR of 8.54 (95% CI [3.13, 23.31]). An overview of 24 systematic reviews and meta-analyses found that overall, positive effects of ketogenic diet therapy for epilepsy on seizure frequency reduction, as well as cognition and behavior, were observed.
Concerning cognition, a systematic review found that using subjective assessments, cognitive improvements are frequently reported during KD treatment in the domains of alertness, attention, and global cognition, while studies using objective neuropsychological tests confirmed benefits on alertness but found no improvement in global cognition. There are indications that these improvements are caused by both seizure reduction and direct effects of KD on cognition.
Evidence for the ketogenic diet in epilepsy in previous studies is limited by small sample size, high attrition rates, lack of evidence in adults, and limited number of studies. Adverse effects associated with ketogenic diets such as gastrointestinal problems, weight loss, and cardiovascular complications also remain a limiting factor in studies. The KD also exerts effects on the gut microbiome: recent evidence suggests that KD may influence gut microbiota, which in turn could enhance central GABAergic activity.
7.2 Modified Dietary Approaches
Variants of the classic KD that have been studied in epilepsy include the Modified Atkins Diet (MAD) and the Low Glycemic Index Treatment (LGIT). These are included in major meta-analyses alongside the classic KD, and the effectiveness of the various types of KD is considered comparable. These modified diets generally impose less strict macronutrient ratios and may offer improved adherence.
7.3 Dietary Deficiency Prevention
To avoid dietary deficiencies, authoritative clinical sources recommend ensuring proper intake of nutrients including folic acid, vitamins B1, D, B6, B12, E, and K, inorganic salts (calcium, magnesium, and manganese), and other micronutrients in persons with epilepsy. This is particularly relevant for those on long-term anticonvulsant medications, many of which deplete specific micronutrients.
8. Lifestyle Factors
8.1 Sleep
Significant sleep deprivation is probably the most consistently observed trigger for seizures. Epileptic seizures are often precipitated by a combination of various clinical factors, but sleep loss stands out as an independent seizure trigger. Stress, fatigue, and sleep deprivation are commonly reported precipitants, often coexisting in the same individuals. Sleep deprivation was noted as a precipitant in 28% of patients with idiopathic generalized epilepsy and in 27% of patients with temporal lobe epilepsy.
8.2 Stress
Some individuals with epilepsy have more seizures during times of stress, possibly due to chemical changes that stress can cause in the brain. Among self-reported seizure triggers, emotional stress is the most frequently named. Patients commonly report having more seizures under times of stress, though this connection has proven to be very difficult to prove from a scientific standpoint.
8.3 Alcohol
Alcohol consumption is widely recognized as a significant contributing factor to the occurrence of seizures and can also exacerbate the management of epilepsy. Alcohol may increase the risk of other triggers; for example, consuming alcohol can have a negative effect on sleep quality, which could lead to sleep deprivation, which can also trigger an epileptic seizure.
8.4 Eating Patterns and Caffeine
Some people find they have more seizures when not eating well or going long periods without eating. Excessive coffee or caffeinated beverage consumption may also worsen seizures by disrupting sleep.
8.5 Physical Activity and Sedentary Behavior
Physical activity may play a role in epilepsy through the modulation of the gut microbiota. Epilepsy can lead to more sedentary lifestyles because patients fear having seizures in public, which would adversely affect health outcomes.
References
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