Title: The ketogenic diet and epilepsy
Key words: cardiovascular risk, serum lipids, triglycerides, renal calculi, fluid intake, uric acid, haematuria, growth centiles, energy requirements, nutrient deficiencies, optic neuropathy, vomiting, starvation, constipation, sodium valproate, acidosis, ketoacidosis
Date: Jan 2001
Category: Special diets
Author: Kate Neil (NS3)
The ketogenic diet and epilepsy
Patients and/or their parents must be made aware of the full implications of the diet and agree prior to implementation1.
Evidence does not bear out the theoretical risk that the high-fat ketogenic diet is a risk factor for cardiovascular disease, though it is fair to say that the long-term effects have not been extensively evaluated2,3,4. Regularly monitoring serum lipids would seem pertinent. Even though it was successful, the ketogenic diet has had to be stopped in one individual with seriously high levels of triglycerides, to prevent a possible life-threatening pulmonary embolism5.
Renal calculi have been documented in some patients2,3,4. Increased levels of plasma uric-acid have been found in patients following both long-chain triglyceride LCT and medium-chain triglyceride MCT diets, possibly as a result of altered renal tubular function3.
Adequate fluid intake can help minimise this side-effect3. However, too much fluid can dilute ketones, reducing the efficacy of the diet1. Ideally, liquid intake should be restricted to about 75% of normal6. Decreased fluid intake serves to compound the effects of the profoundly ketotic state by producing more acidic urine7. Plasma uric-acid levels should be regularly monitored2,3. Screening for haematuria may alert practitioners to possible stone formation8.
Physical growth is moderately retarded in most patients following the diet4. This appears a temporary disturbance as re-examination of patients 15-20 years later found all of them to be within limits of normal for their chronological age4. Others have found that growth was not affected in the short-term and most measurements of stature continued to follow normal centile lines3.
Energy requirements should be carefully calculated and re-evaluated every few months and the diet adjusted accordingly9. Regularly monitor growth measurements.
Various vitamin and mineral deficiencies might occur including: calcium4,6, folate6, zinc5,6, iron5,6, B complex4,6 vitamin C4,6 and water-soluble vitamin D5.
Routine supplementation with a quality, sugar-free multi-nutrients and calcium should be given4 particularly as optic neuropathy has been reported in patients not receiving vitamins2,6 and can lead to blindness10.
Vomiting can occur during the preliminary starvation period and at any point during the diet4. The starvation period should be interrupted and resumed at a later date4. If the patient does not respond to symptomatic treatment whilst on the diet then it is advisable to discontinue all foods for 24-48 hours and give only water4. Nausea, vomiting and abdominal discomfort is more common whilst establishing the MCT diet2,3 and can be overcome by temporarily reducing the amount of MCT oil before gradually increasing again2,3.
Constipation can arise as the diet provides less bulk5. An enema, mineral oil, unsweetened agar, Epsom salts or unsweeted fluid extract of cascara may be prescribed when indicated4. An adequate intake of fluid helps6.
Diet and Medication
Valproate, a common anti-epileptic drug, has been shown to inhibit ketogenesis and deplete glycogen stores in mice8,11. Diets consisting mainly of ketogenic substances, may drive the body into the breakdown of proteins for energy, which could become life-threatening8,11.
Considerations if on valproate: Regularly assess blood urea levels. 24 hour amino acid analysis as pattern can be indicative of excessive protein breakdown and may pre-empt a case of acute renal failure.
Ketosis and Acidosis
Untreated ketosis may lead to ketoacidosis, coma and death. Ketoacidosis is characterised by: fruity breath odour, mental confusion, dyspnoea, nausea, vomiting, dehydration, weight loss. Patients/parents/staff should be aware of symptoms and urgent medical treatment sought10.
Impaired Neutrophil Function
This has been documented in children with seizures treated with the ketogenic diet8,12. Consideration should be given to stopping iatrogenic causes of ketosis in patients if a bacterial infection develops12.
Medium or Long Chain acyl-CoA dehydrogenase deficiency
The ketogenic diet is contraindicated in such cases, as it can kill within hours5. Routine biochemical testing for raised levels: acylcarnitine:free carnitine ratio, octanoate and Cis-4-decenoate to identify sufferers prior to implementing the diet5. Cell culture of skin fibroblasts can also be used13.
Cessation of Diet
It is imperative to release the dietary restrictions slowly over 1-2 weeks. Sudden sugar consumption might precipitate a seizure, due to the likely anti-convulsive action of ketones1.