The ketogenic diet is one of the few treatments for epilepsy. Other treatments include: antiepileptic drugs, epilepsy surgery, and vagus nerve stimulation. For a child with epilepsy, most neurologists will first choose medication. Generally speaking, except for some special cases, ketogenic diet will not be the first choice option for treating epilepsy. Shenzhen Children’s Hospital has pioneered the ketogenic diet treatment method in China and has successfully achieved similar efficacy as abroad. The ketogenic diet is a high-fat, low-carbohydrate, low-protein diet regimen in which the body relies primarily on fat rather than carbohydrates for energy supply. It is used to treat brain disorders by simulating starvation therapy. It is used clinically to treat two main types of disorders, which are epilepsy and inborn metabolic disorders related to glucose utilization disorders. This article will briefly review its history, physiology, efficacy, mechanism of action, indications, contraindications, pitfalls, side effects, and some practical issues in the initiation and maintenance of treatment. History: The ketogenic diet began with the observation that starvation reduced seizures. Very early on, Hippocrates used starvation therapy to treat epilepsy, and Bible mentioned starvation therapy as a treatment for epilepsy. in 1921, Wilder proposed a high-fat, low-carbohydrate diet to mimic the starvation process, but at the time, this approach was not practically applied. Interest in diet therapy waned when phenobarbital, as well as phenytoin sodium, became effective in the treatment of epilepsy. Recently, however, there has been a renewed interest in ketogenic diet therapy, as 20-30% of children with epilepsy are treated ineffectively with epilepsy medication. New drugs invented in the 1990s have still not changed the rate of drug-refractory epilepsy. Physiology: Ketogenic diet therapy is based on the brain’s ability to use ketone bodies as a source of energy. Ketone bodies include beta-hydroxybutyric acid, acetoacetic acid, and acetone, which are products of lipolysis. Under normal conditions, the brain obtains its primary energy from glucose. When in a state of starvation, hormonal changes cause fat cells to release fat, which is then metabolized in the liver, which converts the energy in the fat into ketone bodies, which are then released into the bloodstream and transported to the brain. On a ketogenic diet, the child will be in a state of ketosis and the level of ketone bodies in the body will be elevated. Ketone levels in the blood can be measured, but we usually cannot measure ketone levels in children every day. Since ketone bodies are present in the urine when they are high in the blood, we can monitor the level of ketone bodies in the body by testing the urine for ketone bodies. Treatment: Many studies have reported that the ketogenic diet is effective in treating many types of epilepsy in children and adults, including: atonic seizures, myoclonic seizures, generalized tonic seizures, generalized clonic seizures, generalized tonic-clonic seizures, simple partial seizures, complex partial seizures, and partial seizures generalized to generalized seizures. It may be most effective for myoclonic seizures, atonic seizures or burst seizures, and atypical aphasic seizures. And it is also effective in children with epilepsy, a syndrome of multiple forms of seizures, including Lennox-Gastaut syndrome. About 1/3 of children with epilepsy have >90% reduction in seizures after 6-12 months of treatment, while 5% have complete seizure control, another 1/3 have 50-90% reduction in seizures after treatment, and the remaining 1/3 have no significant improvement. In addition, in some children with epilepsy, although seizures do not improve, ketogenic diet treatment can reduce the number of antiepileptic drugs, increase the cognitive function of the child, and improve the motor behavior of the child. Treatment of inborn metabolic disorders: The ketogenic diet is an alternative treatment for some inborn metabolic disorders and is also used to treat children with glucose transporter protein syndrome due to inability to transport glucose to the brain, and for the treatment of those with disorders of pyruvate metabolism, such as pyruvate dehydrogenase deficiency. It is also effective in the treatment of infantile phosphofructokinase deficiency disorders. Mechanism of action: The mechanism by which the ketogenic diet reduces seizures is not well understood. Indications: There are two basic indications for the ketogenic diet. First, those children whose seizures are not controlled with conventional antiepileptic medication may choose to be treated with a ketogenic diet. Although the ketogenic diet is effective in treating many forms of seizures, it is still not a first-line treatment for epilepsy because it is difficult to implement and adhere to, and long-term outcomes lack good research. Second, certain children with inborn metabolic defects, such as glucose transporter syndrome and pyruvate dehydrogenase deficiency, are also indications for the ketogenic diet. Although ketogenic diet therapy may be beneficial in epilepsy, pediatric neurologists need to carefully evaluate each child before recommending ketogenic diet therapy. Contraindications: Internal contraindications to the ketogenic diet include various disorders of lipid and ketone body metabolism or mitochondrial disease. These include beta-oxidation deficiency, primary or secondary carnitine deficiency, carnitine cycle disorders, electron transport chain disorders, ketogenesis and ketolytic disorders, pyruvate carboxylase deficiency, pyruvate dehydrogenase, and phosphorylase deficiency disorders. Some antiepileptic drugs may exacerbate some of the side effects of the ketogenic diet, so when on a ketogenic diet, we need to be aware of these drugs. They include acetazolamide, tolterol, and zonisamide, all of which may cause acidosis as well as kidney stones. Another drug that needs close attention is sodium valproate. Finally, some children or adults who can find their own food as well as those who do not understand the restrictions of this diet are also not candidates for the ketogenic diet. These individuals will not adhere to this diet without close monitoring, which is often impractical. Micronutrient deficiencies: A ketogenic diet can lead to deficiencies of some micronutrients as well as carnosine. It usually causes deficiencies of vitamin B, vitamin C, vitamin D, calcium, magnesium, and iron. Children on a ketogenic diet therefore need timely supplementation of these vitamins and minerals. Carnitine supplementation can also be helpful in some children, but this is usually not needed. Side effects: As with other antiepileptic drugs, the ketogenic diet may have a variety of mild and severe side effects. Common ones include vomiting, diarrhea, indigestion, and anorexia. Less common ones include slow growth, kidney stones, and cardiac arrhythmias. The function of white blood cells and platelets may also be impaired. While white blood cells help us fight infections, platelets help us stop bleeding. In rare cases, it can be fatal. Ketogenic diet composition ratio: Just as each child needs a different dose of anti-seizure medication, they also need different strengths of ketogenic diet. The ratio of fat to protein plus carbohydrates is the strength of the ketogenic diet. So a 3:1 ketogenic diet means that for every gram of protein and carbohydrates this diet contains, it also contains 3 grams of fat. Since each gram of fat provides 9 calories and each gram of protein and carbohydrate provides only 4 calories, 87% of the calories on a 3:1 ketogenic diet will be provided by fat. In comparison, in the average American child’s diet, fat provides 25-40% of calories, protein provides 10-20%, and carbohydrates provide 40-60% of calories. A common ketogenic diet ratio is 3-4.5:1. For the success of the diet, you and your child will have to adhere strictly to this ratio, as any deviation could result in your child losing ketosis. If your child does not remain in ketosis, the ketogenic diet may not control seizures. So everything your child eats, including the amount of fat, protein and carbohydrates in the medication, should be accounted for. In short, if your child is on a dietary violation, the diet will not be successful. Case selection: Before your child can receive the ketogenic diet for epilepsy, your child must be systematically evaluated by a pediatric neurologist or epilepsy specialist who is familiar with the ketogenic diet. This evaluation must take into account numerous medical factors, such as your child’s type of epilepsy, the cause of the epilepsy, age, growth level, and any other medical conditions. All of these factors will help determine whether your child will be able to adhere to a ketogenic diet. Obviously, those children who are very young or who need to be fed will not be in violation. In addition, this evaluation must also take into account psychosocial factors such as your commitment to the success of the diet, the willingness of your child’s babysitter or school to adhere to the diet, and the interactions between your child and his or her siblings. Finally, you must be willing to adhere to the diet for at least two months, except when terminating the diet for medical reasons. Start of treatment: If your child has been systematically evaluated and is ready for the ketogenic diet, his pediatric neurologist or epilepsy specialist will refer you to a pediatric epilepsy center with experienced epilepsy specialists and nutritionists. Most epilepsy centers start the diet during the hospital stay, which helps monitor the child’s blood sugar, dehydration, and other metabolic parameters. The first step of diet therapy – fasting – usually begins after dinner the day before hospitalization. Your child’s bedside doctor will obtain blood and urine specimens from your child to perform basic laboratory tests. Your child will also need an EEG and ECG. Off-hospital treatment with a ketogenic diet will likely result in death. While many people follow the ketogenic diet protocol provided by Johns Hopkins Medical Institute to begin ketogenic treatment, people can vary depending on their individual circumstances. Generally speaking, the fast will last 1-2 days, which is sufficient to produce ketosis. During the fast, your child’s epilepsy specialist as well as the nurse will closely monitor his vital signs. They will also monitor blood glucose and urinary ketone bodies. According to the ketogenic diet protocol offered by Johns Hopkins Medical Institute, the ketogenic diet can begin with dinner the day after admission to the hospital. However, your child will first receive only one-third of the planned food portions, as well as breakfast and lunch on the third day. Starting with dinner on the third day, your child can receive two-thirds of the planned food portion. Starting with dinner on the fourth day, your child will receive the full amount of food. During your stay, the dietitian will teach you how to prepare foods for the ketogenic diet. You will also learn how to design recipes based on planned ratios and calories and how to calculate your child’s ketones in the urine. Calculation of the ketogenic diet: The ketogenic diet requires a detailed calculation of the amount of fat, protein and carbohydrates in all foods. We need special nutrition tables and software to do the calculation. Shenzhen Children’s Hospital has compiled our own intellectual property rights and ketogenic diet meal preparation software that is in line with Chinese eating habits. If your child is sick: When your child has a cold or other illness while on the ketogenic diet, the amount of carbohydrates in the prescription or over-the-counter medications taken must be calculated in the prepared recipes. Almost all chewable pills and syrups contain sugar. If your child is having an increase in seizures due to some medical condition he has during treatment, he may take a benzodiazepine such as clonazepam. Discontinuation of the ketogenic diet: Your child’s pediatric neurologist or epilepsy specialist may discontinue the diet when your child has been seizure-free for two or more years. In addition, your child’s specialist may also discontinue the diet if treatment is not working well or if there are serious side effects. Generally, your child will need to slowly reduce the ketogenic diet over a period of weeks or months, just like slowly withdrawing other antiepileptic medications. In summary: The ketogenic diet is an effective treatment for children with intractable epilepsy and certain inborn metabolic disorders. However, your child should only begin this diet in an epilepsy center staffed by a neurologist or epilepsy specialist, dietitian, or nurse. An experienced treatment team can avoid many serious complications through a thorough and systematic pre-treatment evaluation, while carefully ensuring the implementation and adherence to the ketogenic diet.