Epilepsy

References & Evidence Notes

Each numbered entry below is either a source you can follow or a note setting out what the evidence does and does not support. Both are numbered together so the markers in the text line up.

Last reviewed October 20, 2026. Supplement entries are cross-checked against the NIH National Center for Complementary and Integrative Health and the Linus Pauling Institute Micronutrient Information Center.²⁰ Two things matter more than anything else here. Never stop or change antiseizure medication without your neurologist: abrupt withdrawal is a leading cause of status epilepticus, which is a life-threatening emergency. And a seizure lasting more than five minutes, or repeated seizures without recovery between them, means calling emergency services now. One point stands out: the ketogenic diet is a genuine, long-established medical therapy for drug-resistant epilepsy, not an adjunct. That is exactly why it belongs with a ketogenic diet team and not a website, because it needs monitoring for growth, lipids, kidney stones, bone density and micronutrient status, and it interacts with medication. Anyone who also has diabetes needs that team from the outset: sustained ketosis alongside some diabetes medicines can tip into ketoacidosis at normal blood-sugar readings.

1. On causes and outcomes: WHO states that around 50 million people worldwide have epilepsy, that up to 70% of them could become seizure-free with appropriate use of antiseizure medicines, and that the cause is still unknown in about 50% of cases. Known causes fall into structural, genetic, infectious, metabolic and immune groups and include brain damage around birth, severe head injury, stroke, brain infections such as meningitis, encephalitis or neurocysticercosis, genetic syndromes and brain tumors; an estimated 25% of cases are potentially preventable, WHO, epilepsy fact sheet. ↩
2. On the ketogenic diet as therapy: the classic ketogenic diet has been used for drug-resistant epilepsy since the 1920s, and randomized and controlled evidence supports it, particularly in children. In a randomized trial in 145 children with drug-resistant epilepsy, 38% of those on the diet had their seizures cut by more than half at three months, against 6% of controls; 7% had them cut by more than 90%, PubMed 18456557. The Cochrane review of ketogenic diets for drug-resistant epilepsy covers 13 studies and 932 participants, 711 of them children, and rates every included study at high risk of performance and detection bias because blinding is not possible with a diet (Martin-McGill KJ, et al. Cochrane Database Syst Rev. 2020;6:CD001903. PubMed 32588435). The modified Atkins diet and low glycemic index treatment are less restrictive with broadly comparable results and are more practical in adults. These are prescribed and supervised therapies, initiated with a specialist team and not self-started. ↩
3. On how many people have epilepsy: CDC reports that during 2021 and 2022 about 2.9 million US adults reported having active epilepsy, about 1% of all adults, and that about 456,000 US children have active epilepsy, CDC, epilepsy facts and stats. ↩
4. On drug-resistant epilepsy: the international definition is the failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medicine schedules to achieve sustained seizure freedom, PubMed 19889013. In a cohort of 525 people followed from diagnosis, 63% became seizure-free and more than 30% of people with epilepsy were described as having inadequate control with medicines, PubMed 10660394; in a later 30-⁠year cohort of 1,795 people, 63.7% had been seizure-free for a year or more, and nearly 90% of them reached control on the first or second medicine regimen, PubMed 29279892. ↩
5. On seizure first aid: CDC advises timing a seizure and calling 911 if it lasts longer than 5 minutes, if another seizure follows soon after the first, if the person has trouble breathing or waking afterward, is injured, or the seizure happens in water, and also if it is a first seizure or the person is pregnant, or has diabetes and loses consciousness, CDC, first aid for seizures. ↩
6. On withdrawal and status epilepticus: abrupt discontinuation or missed doses of antiseizure medication are among the most common precipitants of status epilepticus: low antiseizure medicine levels are one of its common, recognized causes, PubMed 22946730, and reported mortality is 15 to 20% in adults and 3 to 15% in children, PubMed 10885737. Status epilepticus is defined operationally by the ILAE at five minutes of continuous seizure activity, with a second threshold at thirty minutes beyond which long-term consequences including neuronal death become likely, PubMed 26336950, and outcome depends on how quickly it is treated. Planned withdrawal, when appropriate after a seizure-free period, is done slowly and under neurological supervision. ↩
7. On SUDEP: sudden unexpected death in epilepsy is a real risk, associated with poorly controlled generalized tonic-clonic seizures and with medication non-adherence. Discussing it is now recommended practice, because the main modifiable factor is seizure control itself. This is the strongest argument against experimenting with medication. A 2017 practice guideline found that SUDEP affects about 1 in 1,000 adults and 1 in 4,500 children with epilepsy each year, that generalized tonic-clonic seizures are the major risk factor, and that seizure freedom, particularly from those seizures, is strongly associated with lower risk, PubMed 28438841. In a case-control study, supervision at night, by someone sharing the bedroom or through a listening device, was protective, PubMed 15824334. ↩
8. On care, safety and when to get help: NHS guidance says epilepsy is often related to inherited genes or gene changes and is sometimes caused by brain damage, that a specialist confirms the diagnosis and the main treatment is antiseizure medicine, sometimes after trying more than one, with checkups at least once a year. It advises medical ID, a diary of possible triggers, showers instead of baths, not missing doses and not changing or stopping medicine without the specialist, who may suggest gradually reducing it after 2 years without seizures. It advises calling emergency services for a first seizure, one lasting longer than usual or longer than 5 minutes, no recovery or another seizure without recovering, or 3 or more seizures in 24 hours, describes status epilepticus as needing urgent treatment to prevent brain damage, and advises getting urgent advice after a possible first seizure that was not seen in the hospital, or a seizure after a long seizure-free time, NHS, epilepsy. ↩
9. On vitamin B6: pyridoxine-dependent epilepsy is a rare genetic condition treated with pharmacological doses under specialist care and is not a reason for general B6 supplementation. High-dose B6 taken long-term causes a predominantly sensory, axonal peripheral neuropathy, PubMed 37447150. That review found patients report improvement after stopping, but the improvement is self-reported and the neurotoxicity at high intakes is not in doubt, so this is a supplement with a real ceiling. ↩
10. On seizure triggers with a dietary or lifestyle component: sleep deprivation, alcohol, particularly withdrawal after binge drinking, and missed meals with hypoglycemia are recognized precipitants, and a prospective study measuring sleep by diary and adherence by drug monitoring found these factors interact strongly rather than acting alone, PubMed 37413785. Photosensitivity affects a minority. Managing these is genuinely useful and requires no supplement. ↩
11. On supplements and interactions, where care is needed: enzyme-inducing antiseizure medications reduce active vitamin D, which raises parathyroid hormone and increases bone resorption, and several of these drugs raise fracture risk, so fracture risk assessment belongs in routine care, PubMed 40889081. Valproate reduces active vitamin D by that route and by others, and carries a teratogenic risk now managed formally when prescribing to girls and women of childbearing age, PubMed 41562644, which is why folate status matters here. Ginkgo biloba has been associated with seizures in case reports, PubMed 11742783, and several herbal products interact with antiseizure drug levels, including St. John's wort, a strong enzyme inducer, so caution applies both when starting it and when stopping it, PubMed 32361205. The effect runs drug by drug rather than across the board: carbamazepine, which already induces its own metabolism, does not appear to be significantly affected, PubMed 22606944. Tell the neurology team before starting or stopping any herbal product. ↩
12. On sleep apnea: a meta-analysis found obstructive sleep apnea in about a third of people with epilepsy, more often than in people without epilepsy, and better seizure control in those treated with continuous positive airway pressure than in those left untreated, PubMed 27473532; NHS guidance lists loud snoring, gasping, snorting or choking noises and breathing that stops and starts during sleep as its signs, NHS, sleep apnoea. ↩
13. On omega-⁠3 supplements: a Cochrane review of three small randomized trials in 155 people with drug-resistant epilepsy found no effect in adults when two trials were pooled and a benefit only in one small trial in children at high risk of bias, and concluded there is not enough evidence to support omega-⁠3 supplements in drug-resistant epilepsy, PubMed 27536971. ↩
14. On driving and swimming: MedlinePlus advises that people with poorly controlled epilepsy should not drive, that each state's law sets which people with a history of seizures may drive, and that swimming alone and other activities needing constant awareness should be avoided because a seizure during them can cause serious injury or death, MedlinePlus, epilepsy in adults. ↩
15. On surgery: in a randomized trial of 80 people with temporal lobe epilepsy, 58% of those who had surgery were free of seizures that impair awareness at one year, against 8% of those who continued on medicines, and 4 of the 40 surgical patients had adverse effects of surgery, PubMed 11484687. ↩
16. On herbs and seizures: many herbs may raise seizure risk, either directly or by changing how the body handles antiseizure medicines, PubMed 17941846. A review of 65 seizure reports linked to dietary supplements judged 20 probably related (19 of them involving ephedra) and named St. John's wort and ginkgo in possibly related cases, PubMed 15732443; two people with well-controlled epilepsy had recurrent seizures within two weeks of starting ginkgo and were seizure-free months after stopping it, PubMed 11742783; and star anise tea given to infants has caused neurotoxicity, often through contamination with the toxic Japanese species, PubMed 34582506. An older concern that evening primrose oil lowers the seizure threshold was re-examined, and the review judged the association spurious, PubMed 17764919. ↩
17. On pregnancy: antiseizure medication in pregnancy is a specialist balance between fetal risk and seizure risk, and the drugs are not interchangeable on this point. In a population cohort, valproate and zonisamide were associated with several neurodevelopmental outcomes, hazard ratios ranging from 1.26 to 4.50, while levetiracetam and phenytoin were not associated with an increased risk of any of them, PubMed 41813017. Folic acid before conception is standard, but the dose is now genuinely contested and belongs with your neurologist rather than being decided alone. In a Nordic cohort of 3.4 million children, among mothers with epilepsy, prenatal exposure to high-dose folic acid was associated with cancer in the child, a hazard ratio of 2.7, with absolute risk rising from 0.6% to 1.4%, PubMed 36156660. No such signal appeared in children of mothers without epilepsy. A later study found a smaller increase in cancer risk in the women themselves, PubMed 39540679, and the finding has been disputed in the literature, PubMed 37452793. None of this is a reason to take no folic acid. It is a reason to agree on the dose with the team managing your epilepsy. Stopping medication on discovering a pregnancy is dangerous and is not the answer. ↩
18. Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of long-term marine omega-⁠3 fatty acids supplementation on the risk of atrial fibrillation in randomized controlled trials of cardiovascular outcomes: a systematic review and meta-analysis. Circulation. 2021;144(25):1981-⁠1990. PubMed 34612056. Seven trials with 81,210 people followed for about 5 years: omega-⁠3 supplements were linked to a higher risk of atrial fibrillation (hazard ratio 1.25), more so in the trials giving higher doses (hazard ratio 1.49), and the risk rose with the dose. ↩
19. On vitamin K and blood thinners: NIH guidance warns that vitamin K can have a serious interaction with the vitamin K antagonist blood thinner, and that anyone taking it should keep the amount of vitamin K from food and supplements about the same every day, because a sudden change can cause dangerous bleeding or blood clots, NIH Office of Dietary Supplements, vitamin K. ↩
20. National Center for Complementary and Integrative Health (NIH), nccih.nih.gov, and the Linus Pauling Institute Micronutrient Information Center, lpi.oregonstate.edu/mic. ↩