Ketogenic diet therapy is one of the few effective 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. In general, the ketogenic diet will not be the first option for treating epilepsy, except in some special cases.
The ketogenic diet is a high-fat, low-carbohydrate, moderate-protein diet in which the body relies primarily on fat rather than carbohydrates for energy supply. It treats brain disorders by mimicking the metabolic pattern of the body in a starved state. It is used clinically to treat two major groups of diseases, which are epilepsy and inborn metabolic disorders related to glucose utilization disorders, in addition to neurodegenerative diseases such as Alzheimer’s disease, and also spinal cord injuries, tumors, and obesity. This article will briefly review its history, physiology, efficacy, mechanism of action, indications, contraindications, side effects, etc. History of ketogenic diet therapy by Wang Man, Department of Neurology, Shanghai Deji Hospital.
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 method of epilepsy treatment. in 1921, Wilder proposed a high-fat, low-carbohydrate diet to simulate the starvation process, but at that time, this method 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 not treated with epilepsy medication and do not have access to surgical treatment. However, with the introduction of newer antiepileptic drugs, the combination of multiple antiepileptic drugs has not changed the rate of drug-refractory epilepsy.
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 (blood ketones), acetoacetic acid (urinary ketones), and acetone, which are products of the incomplete oxidative breakdown of fat. 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, usually by monitoring the terminal blood of the fingertips with a blood ketone monitor, which can measure 3-5 mmol/L. Although the level of ketone bodies in the blood can be measured, we usually cannot measure the level of ketone bodies in the child on a daily basis. Since ketone bodies are present in a person’s urine when ketone bodies are at high levels in the blood, we can measure the level of ketone bodies in the body roughly by testing the ketone body condition in the urine. Generally, when blood ketone body is 0.8 mmol/L, urine ketone body has +; when blood ketone body reaches 2.0 mmol/L or more, urine ketone body is 4+; Efficacy of ketogenic diet therapy for refractory epilepsy.
Numerous clinical data have reported that the ketogenic diet is effective in treating many types of refractory 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. It is also effective in childhood epilepsy syndromes, including, infantile spasms, Lennox-Gastaut syndrome, Doose syndrome, and Dravet syndrome, a syndrome with multiple forms of seizures. Approximately 1/3 of children with epilepsy have >90% reduction in seizures after 6-12 months of treatment, while 25% 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 for the treatment of glucose transporter protein syndrome due to the inability to transport glucose to the brain, and for the treatment of those disorders with impaired pyruvate metabolism, such as pyruvate dehydrogenase deficiency. It is also effective in the treatment of infantile phosphofructokinase deficiency disorders.
Mechanism of action of the ketogenic diet in the treatment of refractory epilepsy.
The mechanism by which the ketogenic diet reduces seizures is not well understood. Current research focuses on the following.
(1) The ketogenic diet exerts its antiepileptic effect through ketone bodies:
(1) Ketone bodies can inhibit glutamatergic synaptic transmission, reduce glutamate release, and inhibit seizures.
(2) Ketone bodies can also activate mitochondrial adenosine triphosphate (ATP)-sensitive potassium channels, and potassium ion outflow depolarizes or even supercharges nerve cells, thereby reducing cell excitability. Ketone bodies can increase the activity of KATP channels and promote their opening to suppress seizures.
(2) The ketogenic diet exerts antiepileptic effects through pathways other than ketone bodies.
(1) The ketogenic diet exerts its antiepileptic effects by reducing carbohydrate metabolism and decreasing glycolysis.
2) Ketogenic diet inhibits the Mammalian Target of Rapamycin (mTOR) pathway and reduces seizures; 3) Ketogenic diet increases adenosine levels in the brain, activates A1 receptors, decreases adenosine kinase expression, increases adenosine levels, and suppresses seizures by activating A1 receptors.
Indications for ketogenic diet therapy.
There are two basic indications for the ketogenic diet. First, those children whose seizures are not controlled by conventional antiepileptic medication may choose ketogenic diet therapy. Although the ketogenic diet is effective in treating many forms of seizures, it is still not used as a first-line treatment for epilepsy because it is difficult to implement and adhere to, and long-term outcomes are poorly studied. 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, neurologists need to evaluate each patient carefully 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.
Micronutrient deficiencies A ketogenic diet can lead to deficiencies of some micronutrients as well as carnitine. It usually causes deficiencies of vitamin B, vitamin C, vitamin D, calcium, magnesium, and iron. Therefore children on a ketogenic diet need to take timely supplements of these vitamins and minerals.
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 ketogenic diet constitutes more than.
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 carbohydrate 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 diet to be successful, 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 maintain 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.
How to start a ketogenic diet.
Patients who want to be treated with a ketogenic diet need to go through a systematic evaluation with an experienced epilepsy specialist and dietitian. The diet is usually started during hospitalization, which helps monitor the child’s blood ketones, blood glucose, dehydration, and other metabolic parameters. The first step in starting dietary therapy is usually to stop the intake of staple foods right after dinner the day before hospitalization.
The ketogenic diet is generally followed by the Johns Hopkins Medical Institute’s ketogenic diet protocol to begin ketogenic treatment, but people can vary depending on their individual circumstances. In general, there is a choice between a fasting and non-fasting regimen, and if the fasting is generally more than 15 hours, this 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 blood 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 fat, protein, and carbohydrate content of all foods. We need special nutritional tables and software to do this.
What to do if your child becomes ill during ketogenic diet treatment.
When your child has a cold or other illness while on the ketogenic diet, the amount of carbohydrates in any prescription or over-the-counter medication taken must be calculated in the prepared recipe. Almost all chewable tablets and syrups contain sugar, which are prohibited during ketogenic treatment, and need to be replaced with tablets or capsules and some sugar-free oral solutions. If your child has some medical condition that causes an increase in seizures during treatment, he can take a benzodiazepine such as clonazepam for symptomatic management.
Termination of the ketogenic diet.
When your child has been seizure-free for two or more years, the diet can be discontinued after an evaluation by a specialist epilepsy doctor. 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 drugs.
To summarize.
The ketogenic diet is an effective treatment for refractory epilepsy in children and for 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.