An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy

Abstract

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed.

Potassium citrate and metabolic acidosis in children with epilepsy on the ketogenic diet: a prospective controlled study

“…Even if acute metabolic acidosis is known to be anticonvulsive, it is important to diminish its acute symptoms in order to improve adherence to the diet and diminish long-term side-effects of chronic metabolic acidosis, including possible proconvulsive effects. 6 BMI did not differ between participants who developed acidosis and participants treated with citrate who did not develop acidosis. However, among participants not treated with citrate, the risk of developing acidosis was higher in participants with a lower BMI when the ketogenic diet was initiated (p=0.02).…”

“…Potassium citrate supplementation did not affect the serum beta‐hydroxybuturate concentration and the long‐term efficacy of the ketogenic diet in our study. Even if acute metabolic acidosis is known to be anticonvulsive, it is important to diminish its acute symptoms in order to improve adherence to the diet and diminish long‐term side‐effects of chronic metabolic acidosis, including possible proconvulsive effects …”

“…It has been proposed as a substance that can reduce ketogenic-diet induced metabolic acidosis. 6 In renal diseases, potassium citrate is used to prevent metabolic acidosis and to improve bone mineral density. 7,8 Citrate is also used to prevent nephrolithiasis by counteracting urinary acidosis and hypocitraturia induced by the ketogenic diet.…”

“…Citrate is an organic anion that produces bicarbonate when metabolized in the liver, and thus acts as an alkalizing agent. It has been proposed as a substance that can reduce ketogenic‐diet induced metabolic acidosis . In renal diseases, potassium citrate is used to prevent metabolic acidosis and to improve bone mineral density .…”

MELAS reflects a clinical concept with heterogeneous genetic background

“…The ketogenic diet may be particularly effective for seizures and SLEs 9 . The ketogenic diet increases the production of ketone bodies, a side effect of which may be metabolic acidosis, which again increases the propensity of seizures 10 . However, by modifying the diet by monitoring the protein intake and by maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables, metabolic acidosis can be spared 10 .…”