The ketogenic diet (KD), popular in the United States as a method for weight loss, was originally developed in the early 20th century as a therapy for seizures, particularly refractory pediatric epilepsy.1 KD is a treatment traditionally used for people with epilepsy, especially children, who do not respond sufficiently to medication. The goal of the diet is for the body to use fat, rather than carbohydrates or glucose (the body’s preferred energy sources), as a source of metabolic energy (Figure). To achieve ketosis, which is the metabolic state resulting from fat burning, a person must consume a diet that is very low in carbohydrate content and relatively high in fat content (Table). This diet essentially mimics the fasting state without fasting, resulting in the production of metabolites called ketone bodies.1
The mechanisms underlying the therapeutic effects of ketosis in people with epilepsy are incompletely understood but are believed to be associated with bypassing certain stages in glucose metabolization. There are likely multiple mechanisms responsible for the effects. KD therapy does not resolve the underlying cause of seizures but is helpful in reducing seizure frequency.
KD has become popular as a weight-loss method because people tend to consume fewer calories when adhering to a KD, as fats are satiating and take longer to digest than carbohydrates. However, the KD used to treat epilepsy is more restrictive than the popular weight-loss versions.
How Does Ketogenic Diet Therapy Fit in With Other Epilepsy Therapies?
KD therapy is a broad-spectrum treatment for epilepsy. Anyone who is not responding well to medications is a potential candidate for KD therapy; however, it is typically recommended that people try traditional medications first before committing to diet therapy. In practice, KD therapy is usually used as an adjunct to medications, although there are certain specific genetic syndromes (eg, Glut-1 transporter deficiency, pyruvate dehydrogenase deficiency) in which the KD addresses the key metabolic defect and therefore should be considered the treatment of choice. In addition, there are other epilepsy syndromes in which the KD may be more effective than many medications, including Dravet syndrome, epilepsy with myoclonic atonic seizures (previously known as Doose syndrome), Angelman syndrome, super-refractory status epilepticus, and early infantile developmental and epileptic encephalopathy (previously known as Ohtahara syndrome or early myoclonic encephalopathy). KD also may be helpful for people who experience intolerable side effects from antiepileptic medications.1
There is a popular perception that KD therapy is a natural alternative to medication, which is not entirely accurate. People on the KD typically take supplements, such as multivitamins, citrates, and carnitine, among others, so the diet is not a “pill-free” option. In addition, it can take weeks to find the correct diet ratio and achieve transition to a ketogenic metabolism—much longer than the amount of time it takes for many medications to take effect. Therefore, considering the safety and effectiveness of epilepsy medications, medical treatment is the primary approach, which can be used in combination with KD therapy.
Challenges With Ketogenic Diet Therapy
Challenges associated with KD therapy are mainly attributable to following the diet. Swallowing a pill is simple; KD therapy entails a major lifestyle change. Challenges differ on a case-by-case basis. For a person who is fed primarily by feeding tube, adhering to the diet is as easy as switching out the enteral formula for a ketogenic option. However, for a person who consumes a regular diet, adhering to KD therapy requires more discipline than medication use.1
Unlike with a diet for weight loss, there are no “cheat days” with KD therapy. For a person with epilepsy, compromising their KD is comparable to skipping a day of medication; seizures can return and there can be lasting effects, followed by the need to readjust to the diet and await the return of its therapeutic effects.1
These challenges illustrate why KD therapy is especially useful for children and adolescents: a parent or caregiver can control the food that is available to the child. In addition, it is easier for a child to achieve ketosis because of the specifics of their nutritional needs and their smaller size.
Whereas restaurants and prepared meal manufacturers have begun to offer ketogenic-friendly menu options, “keto” in these cases is often used as a buzzword for weight loss–oriented diets, rather than KD therapy. Popularization of the KD has relieved much of the social stigma associated with KD therapy and sparked renewed interest in the KD, but, in some respects, has created more communication obstacles for individuals and physicians because of misinformation and misleading labeling.
Strategies to Help Maintain Ketogenic Diet Therapy
Beginning KD therapy slowly and initiating treatment in steps will ease the transition to a KD and assist with adherence to this therapy, especially for children and adolescents. The practitioner must keep in mind that KD therapy does not work for everyone.
As with any healthy diet, fluid intake is vital to KD therapy. As a first step, physicians can set a daily fluid goal for their patients. Most people do not drink enough to meet their maintenance fluid needs on a daily basis, which can serve as a predictor for therapy success: difficulty drinking enough water each day may be an indicator that the person will have difficulty adhering to a restrictive diet.1
The next step is to eliminate processed foods and sweets. A more wholesome diet that eliminates processed foods and added sugar is a healthier diet in general, and, after this step, some people may already notice improvements in their seizure frequency and epilepsy symptoms. In addition, focusing on whole foods can help address potential side effects associated with nutritional deficits.2
The third step is to initiate the complete KD. At this point, the individual has developed the discipline needed to alter their food intake. If a person is having difficulty achieving ketosis, they can work with their physician to record diet histories to pinpoint which foods might contain hidden carbohydrates. Devices such as urine ketone sticks and blood glucose and ketone monitors can be used to measure ketone levels and help further refine individual diets accordingly.1
If a person is having an especially difficult time adhering to a KD, an alternative strategy is the modified Atkins diet, which sets a specific gram limit for carbohydrate intake, rather than prescribing specific food allowances. This is still a major adjustment from regular eating habits but provides more flexibility for people to choose their own foods.1
Vegetarians, Vegans, and People With Food Allergies or Intolerances
KD therapy is compatible with vegetarian or vegan diets, although food choices will be more limited. Plant sources of fat (eg, avocados, nuts and seeds, coconut oil, olive oil) can be substituted for animal sources of fat. Most food intolerances and allergies are also manageable in KD therapy. Often, these dietary restrictions are not problematic. KD therapy is particularly compatible with gluten-free diets.
In general, people should speak to a dietitian to ensure that they are meeting their nutrition needs. A dietitian will be well-suited to assist in altering the KD based on specific circumstances.
Beneficial Effects and Outcomes Expected With Ketogenic Diet Therapy
The ideal outcome of KD therapy is the cessation of all seizures. However, as with all therapies, the extent of the benefit varies from person to person. As mentioned previously, certain seizure syndromes respond better to KD therapy than others, and it is important for physicians to encourage people with those syndromes to attempt the KD. For other individuals, the goal is to reduce seizure frequency or intensity. An additional goal for people who are experiencing side effects of medication may be to decrease medication use.
Side Effects of Ketogenic Diet Therapy
A range of side effects are associated with KD therapy. Some of these side effects are associated with the diet itself. For example, KD can cause hypoglycemia, which is associated with nausea, jitteriness, and lethargy. Nausea can also be caused by too much acidity in the blood, which is a consequence of the acidic chemistry of ketone bodies. In urine, high acidity increases the likelihood of calcium crystal formation, increasing the risk of kidney stone development. High blood acidity also leaches calcium from the bones, which can accelerate the long-term process of osteopenia. Side effects can be mitigated through adjustments to fluid intake, diet composition, and supplementation with citrates to reduce acid levels.1
As individuals transition from childhood to adulthood, they may experience the activation of certain hereditary risk factors. The high fat content of the diet can be problematic during this transition, especially for people with a history of familial hypercholesterolemia or metabolic syndromes. Physicians should monitor weight and cholesterol levels and provide appropriate intervention as needed.3
Dietitians can play a major role in helping individuals identify healthy sources of fat, manage side effects, and tailor the KD to meet nutritional needs.
Other Applications for the Ketogenic Diet
Use of the KD in other conditions is an active area of research. Brain tumors constitute one of the major areas under investigation. In neuro-oncology, PET scans are used to detect the glucose metabolism taking place within brain tumors. Brain tumor cells are known to divide rapidly because of their efficient use of glucose as a source of energy. These cancerous cells have difficulty switching from glucose metabolism to ketogenic metabolism so they have access to less energy when the body is in a state of ketosis. For this reason, researchers are investigating whether a KD can be used to weaken brain tumors, thereby increasing the effectiveness of chemotherapy, radiation therapy, and other interventions for brain cancer.4
KD are also being explored for potential benefits in people who have experienced a traumatic brain injury. Results from studies in animal models have suggested that ketogenic metabolism may promote more efficient repair, faster recovery, and, ultimately, better cognitive functioning after traumatic brain injury.5
Researchers are also investigating the potential applications of KD therapies in certain mood disorders and schizophrenia as well as neurodegenerative conditions, such as Alzheimer disease and Parkinson disease.6
Additional Resources
The Charlie Foundation, Matthew’s Friends, and the International Neurological Ketogenic Society are valuable sources of information about KD therapy. The Charlie Foundation and Matthew’s Friends are charitable, advocacy-oriented organizations dedicated to the dissemination of information about diet therapies for epilepsy and other conditions. The International Neurological Ketogenic Society is a physician-oriented organization that hosts symposia, supports research, and offers training and education to professionals.
In 2009, Kossoff et al7 reported important recommendations from the International Ketogenic Diet Study Group for the optimal use of KD therapy for children and adolescents with epilepsy. A follow-up article in 20181 updated and expanded upon these treatment guidelines. Both articles are a valuable resource for physicians treating individuals who are candidates for KD therapy.
Conclusion
Certain seizure syndromes respond particularly well to KD therapy. Individuals with these seizure syndromes should be encouraged to attempt KD therapy. KD therapy is a major commitment, but can provide substantial benefit, especially for people with epilepsy that is not responding well to medication.
