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History

Fasting as a treatment for epilepsy has been known since biblical times. In the 1920ties the principle of the ketogenic diet was established as a systematic approach to treat intractable childhood epilepsy. It was an established therapy until the discovery of anticonvulsants led to decreased use of the diet. Recent years have seen a resurgence of the interest in the ketogenic diet, in particular as novel indications such as GLUT1 deficiency syndrome emerged.

Indications

Approximately 70% of children with epilepsy will respond effectively to an anticonvulsant drug. 30% of children will need a second anticonvulsant, which will control seizures in yet again 70% of children. Epilepsy in the remaining 30% will usually respond poorly to further anticonvulsant treatment. In these patients the ketogenic diet is a therapeutic option that has regained the interest of pediatricians.There is ample evidence that in these children the ketogenic diet is effective.
A metaanalysis of 11 studies on the ketogenic diet (Lefevre, Pediatrics 2000) showed - independent of age and seizure frequency – complete seizure control in 16%, a major seizure reduction in 32% and a moderate seizure reduction in 33% of patients.

The ketogenic diet can be used effectively in:

intractable childhood epilepsy

Seizures that respond well to a single drug or a combination of anticonvulsants are not an indication of a ketogenic diet. Regarding epileptic seizures that are difficult to treat or intolerable drug side effects, the ketogenic diet can be very successful: an analysis of 11 studies on the ketogenic diet (Lefevre, Pediatrics 2000) found seizure freedom in 16% of treated children regardless of the type and frequency of seizures. In one third of the patients seizures were reduced by more than 90%, in more than half of the patients by more than 50%.

(rare) disorders of brain energy metabolism

In the resting state the human brain requires about 20% of total body energy consumption. In infants this can increase up to 80%.

These diseases are caused by disturbances of the energy metabolism in the brain.

  • In GLUT1 deficiency syndrome  the supply of glucose to the brain is impaired due to a transport defect of the glucose transporter GLUT1 in the blood-brain barrier. This “energy crisis” in brain results in early-onset epilepsy, developmental delay and a complex movement disorder. The ketogenic diet provides ketones as an alternative fuel to the brain restoring energy metabolism in the developing brain. Seizures are controlled effectively within weeks, the impact on developmental delay and the movement disorder respond to a lesser extent.
  • Pyruvate dehydrogenase deficiency is a severe disorder of brain energy metabolism resulting in hypotonia, epilepsy, episodic apneas, and death in infancy. Glucose can not be metabolized into acetyl-CoA fueling the citrate cycle and the respiratory chain for energy production. The ketogenic diet provides ketones potentially restoring acetyl-CoA to fuel energy production.
Principle

The ketogenic diet is a normocaloric, high-fat, low-carbohydrate diet for the treatment of intractable childhood epilepsy and specific defects of brain energy metabolism (see Principle).

The ketogenic diet simulates the body’s response to starvation by shifting the metabolism from carbohydrate to fat utilization for fuel. In starvation, ketones are formed from the breakdown of body fat. They readily pass the blood-brain barrier and provide the brain with energy.

Applying a ketogenic diet follows the same principle but prevents weight loss by providing nutritional fat to maintain ketosis.

Application of the diet

The application of the ketogenic diet follows these steps:

  • Preparation
  • Starting the dietc
  • Follow-up


1. Preparation

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Before initiating a ketogenic diet, a careful history needs to be taken and clinical examination performed. Contraindications of the ketogenic diet such as defects of fat metabolism or ketone production must be excluded. (Ketoneogenese-/ Ketolysedefects) such as mitochondrial diseases (fatty-acid-oxidation-disorders and Pyruvat-Carboxylase-desease). The ketogenic diet in infancy is reserved for experienced centers!

2. Starting the diet

For the initiation of the ketogenic diet the patient should be hospitalized for roughly 5 days.

Patients are fasted initially (except for Pyruvat-Carboxylase-desease) and metabolic parameters such as blood glucose are monitored closely. Water or sugar-free beverages are allowed.
When ketosis is achieved, the ketogenic diet is initiated.
After establishing the maintenance of the diet and the dietary education the patient can be discharged once he and his caretakers feel confident to prepare and monitor the diet at home.

Zunächst wird gefastet (Ausnahme: Pyruvat-Dehydrogenase-Mangel), bis der Körper Ketone produziert.
Dies kann je nach Alter des Kindes 1-3 Tage dauern. The ketogenic diet is started usually after 72 hours.
Blood pressure, pulse, respiration, blood sugar and the rise of ketones in the blood and urine are closely monitored.

Occasional vomiting, due to high levels of ketosis, can be well resolved by a small sip of orange juice and continued fasting.
When evidence of a clear ketosis is started in stages with food intake.
If the diet is tolerated without complications and the patient / family is familiar with the calculation of the diet, it can be discharged into the outpatient care.

3. follow-up

After discharge the patient needs to be followed up closely at outpatient clinics.
Frequent phonecalls and initial appointments at weekly intervals can gradually be extended to regular follow-up appointments every 3-6 months.

Maintaining the diet in kindergarten and at school often takes some getting used to for the child and carers.
For this purpose, it is advisable to involve the caregivers and to take the "fear" of the diet and disease.

The ketogenic diet is only a balanced diet, if daily carbohydrate-free multivitamins, trace elements and minerals, especially calcium are taken. Biannual controls of blood counts are required.

Control of ketosis:

The development of ketosis is during the fasting phase every 4-6 hours by the direct measurement
of the ketone β-hydroxybutyrate (target range> 2 mmol / L) and
glucose (target range> 40 mg / dl) in the blood.
The effectiveness of the diet, or the required ketone ß-hydroxybutyrate concentration can be very individual.

After successful conversion to the ketogenic diet, daily, then weekly, measurements of the β-hydroxybutyrate in the blood make sense. In the course of this, the monitoring of ketosis in the urine can then be carried out by means of test strips (target range: 80-160 mg / dl).

In special situations (eg, seizures, infections, dietary errors, etc.) the measurement of ß-hydroxybutyrate in the blood should be carried out again - this indicates the current metabolic situation and gives the supervising physician important information for the further course of action.

duration

To be able to assess the ketogenic diet, you must consistently perform it for at least three months.
If it shows no effect despite detectable constant ketosis, it can be stopped again within a short time.

If the diet is successful in patients with epilepsy and the child is seizure-free, consider stopping the ketogenic diet after two to three years.
This should be done over a year by gradually changing the ratio of fat: non-fat (from 4: 1 to 3: 1 over 2: 1 to normal diet) so as not to provoke seizures.

For pyruvate dehydrogenase deficiency, the ketogenic diet is likely to be life-long.
The duration of the diet is currently unclear for glucose transporter (GLUT1) deficiency - due to the increased energy expenditure in the brain of the child, the ketogenic diet should definitely be maintained until puberty.

 

 

Contraindications and adverse effects

The ketogenic diet must not be used in defects of fatty acid oxidation nor in defectsof ketone body production or ketolysis. These diseases are rare but need to be excluded before starting the ketogenic diet to avoid severe hypoglycemia andmetabolic decompensation in the fasting situation.

An acylcarnitine profile in blood and an organic acid profile in urine should be determined, but do not generally rule out these diseases. For this reason children should be admitted for the initial fast. A further contraindication is pyruvate carboxylase deficiency. Of note, expected non-compliance of patients and/or caretakers also is a contraindication to the ketogenic diet. Glycogen storage diseases are discussed controversially.

Potential side effects associated with the ketogenic diet are change in bowel habits, renal stones, and potentially hyperlipidemia. Because patients on the ketogenic diet are in a chronic acidotic state, bone-demineralization is a risk and supplements need to be strictly adhered to. Sporadic complications of the ketogenic diet have been reported in single patients.

 

 

 

Calculation

The ketogenic diet is an individually calculated restricting diet that should only be administered under the care of physicians experienced with the diet. The amount of fat to non-fat (in gram, not in calories) is expressed as a ratio, e.g. 3:1 :

3 : 1
3 gram fat : 1 gram (protein + carbohydrates)

The ratio should be strictly adhered to in every meal. Adequate protein needs to be provided for sufficient growth. Every food item needs to be weighed and calculated into the meal plan. The dieticians will help to select and calculate the ketogenic meals.

 

Questions and answers to the ketonic diet