https://www.cell.com/trends/neurosciences/pdf/S0166-2236(13)00130-6.pdf

Sugar for the brain: the role of glucose in physiological and pathological brain function

Summary Background The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. Methods 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. Findings 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62·0% vs 136·9%, 75% decrease, 95% CI 42.4–107.4%; p Interpretation The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. Funding HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.

https://www.gutbrainaxis.org/pdf/cross%20paper%20KD%20vs%20AEDs.pdf

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial

Nearly a quarter of patients with seizures have drug-resistant epilepsy. This review examines how this diagnosis should be established and how to recognize pseudoresistance. It explains possible mechanisms of drug-resistant epilepsy and presents treatment strategies.

/pdf/drug-resistant-epilepsy-4fqrkkd7mq.pdf

Drug-Resistant Epilepsy

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

/pdf/optimal-clinical-management-of-children-receiving-the-1f3bv61xwx.pdf

Optimal clinical management of children receiving the ketogenic diet: Recommendations of the International Ketogenic Diet Study Group

http://www.paragonhealth.net.au/uploads/2/6/2/4/26246570/the_neuroprotective_properties_of_calorie_restriction_the_ketogenic_diet_and_ketone_bodies.pdf

The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies.

To conduct the first randomized trial on classical and medium-chain triglyceride (MCT) versions of the ketogenic diet, examining efficacy and tolerability after 3, 6, and 12 months.One hundred forty-five children with intractable epilepsy were randomized to receive a classical or an MCT diet. Seizure frequency was assessed after 3, 6, and 12 months. Treatment withdrawals were documented. Tolerability was assessed by questionnaire, and blood ketone levels were measured.Of the 61 children who started a classical diet and the 64 who started an MCT diet, data from 94 were available for analysis: 45 classical and 49 MCT. After 3, 6, and 12 months there were no statistically significant differences in mean percentage of baseline seizures between the two groups (3 months: classical 66.5%, MCT 68.9%; 6 months: classical 48.5%, MCT 67.6%; 12 months: classical 40.8%, MCT 53.2%; all p > 0.05). There were no significant differences between groups in numbers achieving greater than 50% or 90% seizure reduction. Serum acetoacetate and beta-hydroxybutyrate levels at 3 and 6 months were significantly higher in children on the classical diet (p < 0.01); this was the case at 12 months for acetoacetate. There were no significant differences in tolerability except increased reports in the classical group of lack of energy after 3 months and vomiting after 12 months.This study has shown classical and MCT ketogenic diet protocols to be comparable in efficacy and tolerability; both ways of implementing the diet have their place in the treatment of childhood epilepsy.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2008.01870.x

A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy.

OBJECTIVE. The objectives of this study were to examine growth in children on classical and medium-chain triglyceride ketogenic diets and to investigate any association between growth and calorie or protein intake. METHODS. Weight, height, and BMI z scores were recorded for children who were initiated on 1 of 2 ketogenic diets at baseline and after 3, 6, and 12 months, if continued. Mean calorie and protein intakes during treatment were calculated for children who completed 12 months on the diet. Changes in growth were compared between the 2 diets, and the association between growth and dietary intake was examined. RESULTS. Seventy-five children provided growth data. Weight z scores decreased significantly between baseline and 3, 6, and 12 months; height z scores showed no change at 3 months but decreased significantly by 6 and 12 months. This was more significant in the younger and ambulatory children. Subdivision according to diet type showed weight z scores to decrease significantly in the medium-chain triglyceride group only at 3 and 6 months and in both groups at 12 months. Height z scores decreased significantly in both groups by 6 and 12 months. Forty children completed 12 months of treatment; in this group, the slopes of best-fit regression lines of serial z-score measures were used to represent growth trend. There were no significant differences in mean slope between classical and medium-chain triglyceride diet groups for weight, height, or BMI. There was no significant difference in mean calorie intake during the 12 months between the 2 diets, but the medium-chain triglyceride group had significantly higher protein intake. There was no significant correlation between calorie or protein intakes and the slope of the best-fit line for weight, height, or BMI. CONCLUSIONS. Both weight and height z scores decreased during diet treatment. By 12 months, there was no difference in outcome between classical and medium-chain triglyceride protocols despite the increased protein in the latter diet.

Ruby H Schwartz

Papers

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial

A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy.

Growth of children on classical and medium-chain triglyceride ketogenic diets.