EXPERT ANALYSIS FROM AES 2016
HOUSTON (FRONTLINE MEDICAL NEWS) – The ketogenic diet is usually thought of as a solution of near-last resort for pediatric epilepsy, but some adolescents and adults with epilepsy can also benefit from a very low carbohydrate diet.
There are also limited data to suggest that more palatable adaptations of the diet may provide benefit while improving adherence, said Mackenzie C. Cervenka, MD, speaking at the annual meeting of the American Epilepsy Society.
“Ketogenic diets are a reasonable option for older adolescents and adults with drug-resistant epilepsy that’s not amenable to surgical intervention,” said Dr. Cervenka, director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore.
Dr. Cervenka said that a review paper found that of 206 adolescents and adults who had seizures and received a ketogenic (or related) diet, 100 (49%) experienced at least a 50% reduction in seizures, and of those, 13 were seizure-free ( Epilepsia. 2011 Nov;52:1941-8 ). These numbers are not that different, she said, than the results for many antiepileptic drugs in some populations. Overall, “patients with symptomatic generalized epilepsies may have greater seizure reduction, as may patients with multiple seizure types,” Dr. Cervenka said.
The antiepileptic benefit of a diet that induces ketogenesis, forcing the brain to utilize ketone bodies rather than glucose for energy, has been known since the 1920s, with benefit seen for adolescents and adults in studies completed in the 1930s. These diets mimic a starvation state, but provide enough calories through fat or protein to maintain weight. Calories in the traditional ketogenic diet, Dr. Cervenka said, are about 90% fat. Food for patients on this diet should be weighed on a gram scale, and those preparing meals should aim for a ratio of 3 to 4 grams of fat for each gram of carbohydrate and protein combined. A modified version uses a 1:1 or 2:1 ratio, a more appealing configuration for some patients.
Weighing each bite of food is cumbersome, and palatability can be a major problem as well, contributing to adherence problems with such a high-fat diet. However, for patients who are so ill that they are tube-fed, commercially available ketogenic formulas are available. Necessary supplementation on a traditional ketogenic diet includes calcium, vitamin D, multivitamins, and oral citrates to prevent kidney stone formation, she said.
However, ketogenic diets are known to be anti-inflammatory: Animal models have shown less inflammation, pain, and fever when rats are fed a ketogenic diet. Also, proinflammatory cytokines and chemokines are reduced on a ketogenic diet in a rodent model of Parkinson’s disease and multiple sclerosis. Particularly for patients with autoimmune encephalopathies, the ketogenic diet has been shown to be of benefit.
One option with promising, but limited, results is a low-carbohydrate diet rich in medium-chain triglycerides. Medium chain triglyceride (MCT) oil is available in a commercial preparation derived from coconut or palm kernel oil. On this diet, 30%-60% of calories should come from MCTs, which is usually sufficient to induce ketosis. However, gastrointestinal side effects such as bloating and diarrhea can be pronounced, especially if the diet is begun abruptly. It’s best to ramp up slowly with MCTs, so this diet would not be appropriate for the patient who needs quick improvement in seizure control, Dr. Cervenka said.
A modified Atkins diet provides 15-20 grams of net carbohydrates daily, after dietary fiber is subtracted. Using this strategy, adolescents and adults don’t have to weigh foods. Rather, food tables are used to track carbohydrates and fiber, and ketosis is assessed by measuring urine ketones on a test strip. The goal, Dr. Cervenka said, is to achieve moderate to large ketosis (40-160 ng/mL urine ketones).
Finally, low glycemic index treatment (LGIT) is an option worth considering. This diet takes advantage of certain carbohydrate-rich foods that do not raise blood sugar quickly, such as fiber-rich vegetables or legumes with some fat content. Patients on the LGIT diet can have from 40 to 60 grams of carbohydrate daily, and the diet has been used with some success in drug-resistant childhood epilepsy as well as Angelman syndrome, she said.
Though sample sizes are small and efficacy may be modest, Dr. Cervenka said, “the effect is quick.” Finding less-restrictive modifications of these diets may help patients stay on the diet over the long term, increasing real-world effectiveness.
But long-term adherence to a ketogenic or other high-fat, low-residue diet comes with a host of unknowns about cardiovascular, metabolic, and renal health; ongoing study of these patients may yield answers about whether theoretical concerns are borne out, and whether the risk is worth it in terms of seizure benefit.
Dr. Cervenka reported receiving grant support from Nutricia North America, Vitaflo, and the BrightFocus Foundation. She has also received an honorarium for speaking from LivaNova.
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