Research Provides New Insight Into Diet and Epilepsy

Many children with certain forms of epilepsy achieve seizure control through a stringent medically supervised diet, either the ketogenic diet (KD) or a Modified Atkins Diet (MAD). When to use these diets and the mechanisms underlying their anticonvulsant effect are not well defined. Research presented here at the 64th American Epilepsy Society annual meeting provides new insight into when and how these diets work.

In a retrospective study involving four institutions in Denmark, Germany, South Korea, and the United States, researchers sought to determine the likelihood of achieving additional seizure control from a switch from the Modified Atkins Diet to the ketogenic diet. Of 28 patients who made this dietary change, nine (32%) had >10% additional seizure reduction with KD above the MAD, of which five became seizure free.
(Abstract 2.230)

Lead author Eric Kossoff, M.D., of Johns Hopkins University, and his international colleagues, also found that children in the study who did not improve while on the MAD did not respond when switched to the KD. However, there was an increased likelihood of improvement if the patient had myoclonic-astatic epilepsy compared to all other etiologies combined.

The investigators report, “These results suggest that KD probably represents a ‘higher dose’ of dietary therapy compared to the MAD, rather than unique diets. The switch from MAD to KD may particularly benefit those with myoclonic-astatic epilepsy.”

In another study of the ketogenic diet, researchers here in the U.S. and Sweden, tested the hypothesis that adenosine plays a key role in the diet’s anticonvulsant effect. The investigators used three types of transgenic mice, all with spontaneous electrograph seizures that are due to decreased adenosine receptor (A1R) signaling. The first group had a complete absence of A1Rs. Group two had 50% of normal AIR levels, while group three had normal A1R levels but an over expression of an enzyme that negatively influences adenosine binding at these receptors. (Abstract 1.019)

After maintenance on a ketogenic diet, the investigators found that animals with intact A1Rs (group three) had a near cessation of seizures. In contrast, animals with a reduction of A1Rs (group two) and those with an absence of these receptors (group one) were partly or completely resistant to the ketogenic diet therapy. The antiseizure effects were reversed with either an injection of glucose or a substance that blocked A1Rs.

These results suggest that a ketogenic diet reduces seizures by increasing the inhibitory ability of adenosine receptors, and that this effect depends on the low carbohydrate nature of the diet, according to the investigators.

“Our study provides new insight into the mechanisms underlying the anticonvulsant effects of the ketogenic diet,” reports lead author Susan Masino, of Trinity College in Hartford, CT. “These results suggest that ketogenic diet metabolism increases the activity of adenosine at the A1 receptor subtype, and could offer insight into therapies for other clinical conditions where adenosine is known to have direct clinical benefit.”