For centuries, starvation and dehydration were reported to improve seizure control. In addition, substances as diverse as mistletoe, turpentine, and marijuana were claimed to be effective for epilepsy. In 1858, Sir Sieveking wrote, “There is scarcely a substance in the world, capable of passing through the gullet of man, that has not at one time or other enjoyed a reputation of being an anti-epileptic.” (Sieveking E.H.: On Epilepsy and Epileptiform Seizures: Their Causes, Pathology, and Treatment.]. Churchill, London, 1858, p. 226) In modern times, various vitamins, mineral, amino acids and nutritional supplements are also promoted for epilepsy patients. The ketogenic and Atkins diets are endorsed by medical authorities and can help control seizures in some patients.
The Ketogenic, Modified Atkins, and Low Glycemic Diets
Research in the 1930s showed that a diet consisting mostly of fats dramatically reduced the frequency of seizures in many children. The diet was named the ketogenic diet because it caused a metabolic change called ketosis, whereby the body produces ketone bodies by metabalozing of fat and protein. After the introduction of phenytoin (Dilantin®) in 1938, the ketogenic diet fell out of use, but new studies during the past several decades confirm its value. Several highly publicized dramatic succeses with the ketogenic diet in children whose seizures were not controlled with medications or surgery renewed interest and use. However, the diet is not without side effects — from problems with the child’s tolerance for the limited menu to kidney stones, growth retardation, and metabolic disorders. These have led to the use of the modified Atkins and low glycemic (South Beach) diets, which also restrict carbohydrates but allow more protein, thereby increasing tolerability and compliance while also decreasing side effects. Early experience with these less restrictive alternatives to the ketogenic diet suggests that they are effective in some patients.
The Ketogenic Diet
Who is a Candidate?
There are no rules about who is and who is not a candidate for the ketogenic diet. The greatest successes are with children between ages 18 months to 6 years whose seizures cannot be controlled by antiepileptic drugs, especially with Lennox-Gastaut and Doose syndromes, who have atonic, tonic, and myoclonic seizures. However, all types of seizures can improve. The diet’s success depends on the child’s previous diet, adaptability, and motivation. After the age of 3-5 years, children have usually been exposed to foods that they are unwilling to part with. Therefore, older children and adolescents need to be highly motivated to stay on the diet. In sensitive patients, “cheating” by eating even small amounts of additional carbohydrates can lead to loss of seizure control. Due to these issues, many parents are hesitant to use the ketogenic diet because their child is a carbohydrate lover or picky eater who barely eats enough. For children with severe epilepsy, however, the potential benefits of a 1- to 3-month trial outweigh the risks. Although this diet can be used successfully in adults, they usually find the modified Atkins or low glycemic diet more tolerable. Infants who are only fed with formula or children who are only fed with a gastrosomy tube can be easily put on the ketogenic diet.
Starting the Diet
The ketogenic diet is most often used in epilepsy centers for children with uncontrolled seizures. The diet should only be started under the co-direction of a physician and a dietician who are familiar with it. Modifications are often needed to make it more effective or tolerable to individual patients. Traditionally (the “Johns Hopkins” approach), the diet is started in the hospital to ensure close supervision and safety During the first 24-48 hours, there is no food and fluids are limited. This initial period of starvation lowers the child’s blood sugar. If the fall in blood sugar is too great, the child may become pale, sweaty, tremulous, irritable, confused, and unresponsive, or may vomit or even have seizures. In such cases, the child requires sugar or other carbohydrate supplementation to prevent more serious side effects. If not monitored closely fluid restriction may result in dehydration. After starvation, the ketones in the blood and urine rise, and ketogenic food is gradually introduced: one third of the diet on the following day, two thirds the next day, and then the full diet.
Many epilepsy centers initiate the diet outside of the hospital, without the initial starvation or fluid restrictions. This more gradual outpatient regimen has fewer side effects, reduced physical and emotional stress on the patient and family, and reduced costs. Further, the inpatient starvation phase is not tolerated by some patients, who may then forgo the diet that could have been very beneficial. The diet can be monitored with urine ketones measured at home with an indicator strip. Urine ketones show that the diet has achieved its metabolic goal of ketosis; higher ketone levels correlate with improved seizure control in many children.
What is the Diet?
The diet consists primarily of foods high in fat, with most of the remaining calories made up of proteins. With the commonly used 3 or 4:1 ratios of fats to carbohydrates and protein, 70-90% of the foods are fats and 10-30% are carbohydrates and protein. The daily diet often consists of 35-45 calories per pound (75-100 calories/kg) and 0.5-1.0 g of protein per pound (i-2g/kg) of body weight. Examples of high-fat foods include mayonnaise, butter, and heavy cream. The foods must be carefully measured and weighed. The child is allowed only small portions of cheese, meat, fish, or poultry each day. Fruit is allowed in modest amounts.
Mixed chain triglyceride (MCT), an alternative source of fat, is a clear, light-colored oil that has no flavor. Its use often allows a slight expansion of nonfat foods in the diet. MCT also has laxative properties, beneficial because the ketogenic diet is often constipating. MCT oil should be introduced gradually to avoid stomach cramps.
Because sugar is prohibited in the diet, parents must be vigilant about their children’s medications, cough syrups, vitamins, toothpaste, and any other nonfoods or foods that may contain sugar. Small amounts of sugar can reverse the effects of the diet and cause a seizure. All adults who may be with the child in the parents’ absence must be informed about the dietary restrictions.
Stopping the Diet
If the diet is well tolerated and effective, the doctor will usually recommend continuing it for 1-3 years. Afterwards, carbohydrates are gradually increased, typically over 2-6 months. Suddenly stopping the diet may cause a temporary increase in seizures.
After the diet is discontinued, some children remain seizure-free without medications. However, seizures may recur, in which case they may be well controlled with medications that were ineffective before the diet. A patient who was seizure-free on a lower ratio of fats to protein and carbohydrates (for example, 2.75:1), but whose seizures recurred when the diet was discontinued, may be helped by continuing the diet at a reduced ratio or trying the modified Atkins or low glycemic diets.
Vitamins, Minerals, and Other Nutritional Supplements
Although many books and websites contain lists of vitamins, amino acids, and other nutritional supplements suggested to control seizures, there is little and often no scientific support for these claims. Unconfirmed reports claim that magnesium, calcium, vitamin E, vitamin B2, melatonin, omega fatty acids, and the amino acids L-taurine, L-tyrosine, or dimethylglycine reduce seizures in some patients. Although patients with deficiencies of some nutrients such as magnesium, calcium, and vitamin B6 (which rarely causes seizures in newborns) can benefit from supplementation, there is no evidence that they are beneficial for other patients with epilepsy. We really just don’t know whether any vitamin, mineral, or other nutritional supplement is generally beneficial or detrimental to seizure control. For example, animal studies suggest that omega fatty acids and melatonin may help control seizures. However, a controlled trial of omega fatty acids in epilepsy patients failed to show any effect. The study does not fully exclude a possible beneficial effect (it may take a longer time or higher dose), but suggests that if such an effect occurs, it is probably small. Some preliminary studies suggest that melatonin may reduce seizure activity in some patients, but controlled studies are lacking. We need more information! One day, researchers may identify a dietary supplement that improves seizure control — we are not there yet.
Nutritional supplements with the amino acids L-taurine and l-tyrosine are recommended for epilepsy patients by many alternative practitioners. Taurine is involved in many cellular functions. It is found naturally in meat, fish, eggs, and dairy products. Taurine is present in many energy drinks and is the ingredient from which Red Bull derives its name. Although taurine may increase inhibitory neurotransmission in some animal studies, the effects of dietary supplementation on the human brain and epilepsy are uncertain. One theoretical concern is if taurine has benefits for epilepsy-that taking it regularly and then missing a dose could cause withdrawal seizures. There are no clearly documented side effects. L-Tyrosine is a critical amino acid in protein synthesis and also forms the building block for several neurotransmitters. There is no evidence that supplementation reduces seizure activity.
There is no nutritional therapy for epilepsy, apart from the ketogenic, modified Atkins and low glycemic diets, for which there is solid evidence for benefits. Western medicine has not studied nutrition as well as it should, and there may well be nutrients that help control seizures. But as of now, there is no proof. However, a multivitamin or specific vitamin or mineral supplement or omega fatty acids in the diet can have other health benefits.
Valproate can deplete the liver’s stores of carnitine, a substance that functions like a vitamin to help in fat metabolism. Carnitine supplementation may help prevent the rare cases of liver damage caused by valproate, but this is unproven. Because serious liver damage from valproate is extremely rare, carnitine supplementation should only be considered for individuals at great risk, such as children under age 2 years. Isolated reports suggest that carnitine supplementation can reduce valproate side effects, such as tremor and tiredness, but other controlled studies show no benefit.
Minerals are essential nutrients. Very low levels of sodium, calcium, and magnesium can alter the electrical activity of brain cells and cause seizures. Deficiency of these minerals in the diet is rare unless there is severe general malnutrition, but other factors may affect the levels in the body. Low sodium levels may be caused by medications such as diuretics or carbamazepine or oxcarbazepine, by excessive water intake, or by hormonal disorders. Low calcium levels can result from kidney disease or hormonal disorders. Because magnesium levels alter the body’s regulation of calcium, low magnesium levels can contribute to or cause low calcium levels. Individuals who chronically abuse alcohol and have poor nutrition often develop low magnesium levels, which can predispose to seizures.
Persons with epilepsy seldom need mineral supplementation for seizure control. Changes in diet or mineral supplements are reasonable for those who have low levels of these minerals.
Antiepileptic drugs that increase liver metabolism (e.g., carbamazepine, phenobarbital, phenytoin, primidone, and valproate) can increase vitamin D metabolism and lead to a deficiency of calcium in the bone. Therefore, combined calcium and vitamin D supplementation may help prevent bone loss. For persons taking these drugs for more than several years, a bone density test can detect this possible complication. If significant reduction of bone density (osteopenia) is found, a consultation with a bone metabolism specialist may be helpful.
Some side effects of valproate may possibly be reduced by mineral supplementation. Inflammation of the pancreas (pancreatitis), which is a rare but serious adverse effect of valproate, may be prevented by selenium supplementation. Selenium at a dose of 100 μg/day was used to prevent valproate-induced pancreatitis in a child who previously had this problem when taking valproate. Selenium (10-20 μg/day) and zinc (30-50 mg/day) also may help to counteract the hair loss that some people experience when taking valproate. These doses are available in many over-the-counter high-potency multivitamins.