Ketogenic diet for drug-resistant epilepsy: Does it work for everyone?
March 15, 2026
The classical ketogenic diet uses fat-to-carbohydrate and protein ratios, including 4:1, 3:1, and 2:1, while the modified ketogenic diet restricts carbohydrates but encourages high fat intake.
Epilepsy is a disabling and common neurological disease that can be successfully controlled in most patients with one or more antiepileptic drugs. Approximately 30–40% of patients with epilepsy have refractory epilepsy, in other words, drug-resistant epilepsy. The definition is basically the failure of adequate trials of two tolerated, appropriately chosen, and properly used antiepileptic drug schedules to achieve sustained relief of seizures.
“Ketogenic diet is one of the lifestyle modifications, especially for those who are also not surgical candidates. In Drug Resistant Epilepsy and Ketogenic Diet: A Narrative Review of Mechanisms of Action by Mishra P., Singh S.C., and Ramadass B, it states that the ketogenic diet is effective in seizure control in drug-resistant epilepsy. The ketogenic diet decreases neuronal excitability,” explains Lau Wai Hong, Assistant Director, Dietetic Service, Sunway Medical Center, Sunway City, at the International Epilepsy Day symposium – Enhancing Epilepsy Awareness and Improving Care in Malaysia. History of ketogenic diet The classical ketogenic diet (CKD) was first introduced in the 1920s by Wilder RM, almost 100 years ago, based on a ratio of fat to carbohydrates and protein. This consists of the four-to-one, three-to-one, and two-to-one classical ketogenic diets. Then in 1971, Huttenlocher PR et al. introduced classical ketogenic diet variant 1, which incorporates 60% of the total energy intake from medium-chain triglyceride (MCT) fat. Because of the high MCT percentage, this caused many gastrointestinal side effects such as diarrhea. In the 1980s, Schwartz RM et al. introduced classical ketogenic diet variant 2, a modified version designed to reduce gastrointestinal side effects. In 2005, Pfeifer HH and Thiele EA introduced the low glycemic index treatment, which is a more liberal low-carbohydrate diet that has a fixed amount of 40 to 60 grams of carbohydrate per day. It selects foods with a glycemic index of less than 50. A year later, in 2006, Kossoff EH et al. introduced the modified Atkins diet (MAD/MKD), which restricts carbohydrate intake throughout the day, allows unrestricted protein intake, and encourages high fat intake. Roadmap of nutritional intervention Lau Wai Hong stressed that before discussing the ketogenic diet, patient selection is very important. “A screening is done for any metabolic contraindications, looking at the serum profiles as well. Important factors to consider include medication, whether they already have poor intake, if they are severe picky eaters, and family support that is crucial in adhering to a classical ketogenic diet (CKD) or a modified ketogenic diet (MKD).” Other factors include language barriers in order to guide them appropriately throughout the journey and for the successful implementation of MKD diets. Financial difficulties are also taken into consideration, as well as pre-existing gastrointestinal disorders, GERD, bone fragility, or other endocrine disorders. Dietetics assessment and preparation During pre-diet preparation, a comprehensive dietary history is taken. This includes evaluating their usual diet intake in terms of feeding method, textures tolerated, pre-existing food allergies or intolerances, and whether there are other special dietary requirements. Personal or cultural preferences are also considered. Baseline anthropometric measurements—weight, length/height, and mid-upper arm circumference (when appropriate)—are taken to determine the patient’s growth history. Laboratory results that support the assessment of the patient’s nutritional status and requirements are also reviewed to inform the diet prescription, such as a full blood count, ferritin, and vitamin D levels, as well as past experiences—whether the patient is currently under, or has previously been under, dietetic care. Factors influencing macronutrient targets include age—whether younger or older—usual diet, the type of epilepsy syndrome, medications and current physical activity levels. All of these affect the calories and protein requirements needed to ensure that a person on a ketogenic diet is able to meet their minimal basic nutritional requirements. Diet initiation Historically, the ketogenic diet was initiated in the inpatient setting. This was usually preceded by a period of fasting lasting about half a day to one day, or 12 to 24 hours. However, both literature and current clinical practices no longer recommend this. Rather, most children and young people can now begin the diet in the comfort of their homes, which also reduces disruption to family life. Exceptions include those who are very young—infants under one year old—and those who are more medically complex, who may still require some form of inpatient monitoring. The diet often begins at a lower ratio or percentage of fat and gradually increases over time. For example, with a two-to-one CKD, you start with that ratio first and gradually increase it over time. This allows for ongoing review of clinical response, ketone levels, and dietary tolerance, facilitating a more personalized and tolerable initiation process. There are one-to-one, two-to-one, three-to-one, and four-to-one ratios. This represents the typical incremental approach. Smaller incremental steps can also be taken, such as 0.2 or 0.5 increments. CKD is often initiated in an outpatient setting with a gradual introduction. For MKD, a gradual introduction usually begins with a targeted calorie intake—often full calorie intake—and then adjusting the macronutrient distribution by reducing carbohydrates slightly and shifting that percentage toward the fat portion. Another approach is to introduce one meal that is low-carbohydrate and high-fat with added protein. It is not strictly one method or the other but depends on the patient and what family members prefer at that point in time. Monitoring Ketones are a useful marker to assess whether the dietary prescription is sufficient to induce and maintain therapeutic ketosis. They may also guide necessary dietary adjustments. “However, individuals following MKDs may exhibit lower ketone levels than those on CKDs. Blood ketone concentrations exceeding 3–4 mmol/L may be most effective for seizure reduction, although the literature is inconclusive.” Blood ketones are recommended to be tested twice daily during the initiation phase, possibly in an outpatient setting. Once the condition stabilizes and the treatment goal is met, ketone monitoring can be reduced. For long-term monitoring, urinary ketone testing can be done, supplemented with blood beta-hydroxybutyrate (BHB) measurements as needed. Glucose monitoring should also be performed when prescribing a low-carbohydrate CKD because there is a recognized risk of hypoglycemia. This risk is particularly present during the initiation phase and during episodes of illness. Although it is rare, most cases occur in younger patients, especially infants receiving a classical ketogenic diet. Therefore, monitoring blood glucose levels or hypoglycemic episodes is necessary so they can be managed in the same way as usual hypoglycemia management. Follow-up assessments every three months are advised. During each follow-up, a full nutritional assessment is conducted, including growth, compliance with the ketogenic diet, challenges faced at home, and whether adjustments are needed to improve compliance, support seizure control, and ensure nutritional status remains adequate. Psychosocial factors identified during the pre-diet phase are also monitored to determine whether fine-tuning the diet is necessary, including macronutrient ratios and energy intake. With additional supplements, there are carbohydrates present in many formulations. When these supplements or medications are added, their carbohydrate content must be accounted for and incorporated into the ketogenic diet plan. Adverse effects should also be managed, including gastrointestinal symptoms, micronutrient status alterations, and episodes of hypoglycemia. Longer-term effects that may occur include hyperlipidemia, renal calculi, growth concerns, and in rare cases, hepatitis. When to consider discontinuing ketogenic diet The ketogenic diet should be discontinued when significant adverse effects occur and cannot be resolved, or when treatment goals are not being achieved. Usually, 75% of children respond to a ketogenic diet within the first 14 days. However, some studies have shown that it may take longer—up to two months—to observe significant benefits. In general recommendations, if the ketogenic diet is not effective after three months, it can be discontinued. For those who started with the MKD diet, they can transition to the stricter CKD regimen to evaluate whether better outcomes can be achieved. They may require lower carbohydrate intake and a higher fat-to-protein ratio to see more benefits. For those responding well—achieving seizure reduction of 50% or more—discontinuation can be considered after two years of treatment. However, there is no defined maximum duration for the ketogenic diet, and there have been documented cases of long-term use up to 20 years in individuals experiencing significant seizure control with minimal side effects. It is also recommended for those with GLUT1-DS to continue dietary therapy until puberty or into adulthood. For those with Pyruvate Dehydrogenase Complex Deficiency (PDHD), extended use beyond two years may be appropriate depending on response and tolerability. How to discontinue a ketogenic diet Discontinuation of the diet is similar to medications and requires a gradual weaning period of four to six weeks, which is both feasible and well tolerated in most cases. For infants on CKD, the ratio should be slowly reduced until ketones are no longer present. For an infant who has not derived any clinical benefit from the diet, a complete weaning within two weeks may be considered. Dietary advice after discontinuation of a ketogenic diet Usually, a person can transition back to their previous pre-ketogenic diet—a regular diet. However, it is recommended to avoid processed and refined sugars initially and slowly reintroduce simple carbohydrates, including processed and refined sugars. |
EXPLORE FURTHER
|
The legal framework governing the rights and responsibilities of people living with epilepsyLegal gaps leave Malaysians with epilepsy vulnerable to workplace discrimination, incapacity
|
|
Optimizing anti-seizure medication management and adherence in epilepsy careCould switching between branded and generic seizure medications affect your control?
|
|
Life after epilepsy: The hidden risks facing patients and familiesAddressing the social, emotional, and psychological challenges of epilepsy
|
|
Seizures and epilepsy: What you need to knowA clear guide to symptoms, diagnosis, risks, and treatment approaches
|
