Efficacy of the classic ketogenic and the modified Atkins diets in refractory childhood epilepsy

Kim, Jeong‐A; Yoon, Jung Rim; Lee, Eun Joo; Lee, Joon Soo; Kim, Jeong Tae; Kim, Heung Dong; Kang, Hoon Chul

doi:10.1111/epi.13256

Cited by 134 publications

(152 citation statements)

References 23 publications

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“…Moreover, SWD number and βHB level returned to the control level after both KE and KSMCT treatments (on the PT days). Thus, our results suggest that after ketone supplementation the absence epileptic activity can decrease in correlation with the increase in βHB level, which strengthens the support for nutritional ketosis as a means to suppress absence epileptic seizures (Ross et al, 1985; Groomes et al, 2011; Thammongkol et al, 2012; Clemens et al, 2013; Kim et al, 2016; Lee et al, 2016). …”

Section: Discussionsupporting

confidence: 82%

“…It was previously demonstrated that KD/ketosis may be effective against absence epileptic activity (Ross et al, 1985; Groomes et al, 2011; Thammongkol et al, 2012; Clemens et al, 2013; Kim et al, 2016; Lee et al, 2016). Our results suggest that not only KD, but also sub-chronically applied ketone supplements KE and KSMCT, administered by gavage, can increase βHB levels and decrease SWD number in freely moving WAG/Rij rats ( Figures 3A–D ).…”

Section: Discussionmentioning

confidence: 99%

“…It is well-known that adenosinergic system may be involved not only in the alleviating effect of KD/ketosis on epileptic seizures (mainly by means of A 1 Rs), but also in the modulation of absence epilepsy mechanisms (D’Alimonte et al, 2009; Masino et al, 2011; Kovács et al, 2014; Kim et al, 2016). Thus, we addressed in the present study whether (i) sub-chronically (for 7 days) applied exogenous ketone supplements (KE; KS + MCT: KSMCT) by intragastric gavage can modulate absence epileptic activity and (ii) inhibition of A 1 Rs by its specific antagonist can evoke changes in seizure frequency in WAG/Rij rats.…”

Section: Introductionmentioning

confidence: 99%

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Adenosine A1 Receptor Antagonism Abolished the Anti-seizure Effects of Exogenous Ketone Supplementation in Wistar Albino Glaxo Rijswijk Rats

Kovács

D’Agostino

Dobolyi

et al. 2017

Front. Mol. Neurosci.

104

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The state of therapeutic ketosis can be achieved by using the ketogenic diet (KD) or exogenous ketone supplementation. It was suggested previously that the adenosinergic system may be involved in the mediating effect of KD on suppressing seizure activity in different types of epilepsies, likely by means of adenosine A1 receptors (A1Rs). Thus, we tested in the present study whether exogenous ketone supplements (ketone ester: KE, 2.5 g/kg/day; ketone salt/KS + medium chain triglyceride/MCT: KSMCT, 2.5 g/kg/day) applied sub-chronically (for 7 days) by intragastric gavage can modulate absence epileptic activity in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. The number of spike-wave discharges (SWDs) significantly and similarly decreased after both KE and KSMCT treatment between 3rd and 7th days of gavage. Moreover, blood beta-hydroxybutyrate (βHB) levels were significantly increased alike after KE and KSMCT gavage, compared to control levels. The SWD number and βHB levels returned to the baseline levels on the first day without ketone supplementation. To determine whether A1Rs can modify ketone supplement-evoked changes in absence epileptic activity, we applied a non-pro-epileptic dose of a specific A1R antagonist DPCPX (1,3-dipropyl-8-cyclopentylxanthine) (intraperitoneal/i.p. 0.2 mg/kg) in combination with KSMCT (2.5 g/kg/day, gavage). As expected, DPCPX abolished the KSMCT-evoked decrease in SWD number. Thus, we concluded that application of exogenous ketone supplements may decrease absence epileptic activity in WAG/Rij rats. Moreover, our results suggest that among others the adenosinergic system, likely via A1Rs, may modulate the exogenous ketone supplements-evoked anti-seizure effects.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adenosine A1 Receptor Antagonism Abolished the Anti-seizure Effects of Exogenous Ketone Supplementation in Wistar Albino Glaxo Rijswijk Rats

Kovács

D’Agostino

Dobolyi

et al. 2017

Front. Mol. Neurosci.

104

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“…compared the efficacy of the classic ketogenic and the MADs in refractory childhood epilepsy. [8] The authors reported that overall the efficacy of the two diets was comparable but for patients aged 1–2 years, seizure outcomes were consistently much more favorable in patients consuming the ketogenic diet as compared with those on the MAD.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of the modified Atkins diet in young children with refractory epilepsy: Indian experience

Mehta¹,

Goel²,

Sharma³

et al. 2016

Ann Indian Acad Neurol

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Background:The modified Atkins diet (MAD) has been used predominantly in older children, adolescents, and adults. There is a paucity of data on the use of the MAD in refractory epilepsy in young children.Objectives:This study was planned to evaluate the efficacy and tolerability of the MAD in refractory epilepsy in young children.Methods:This study recruited children aged 9 months to 3 years with refractory seizures. Children received MAD for 6-month with the on-going anticonvulsant medications being continued unchanged. Reduction in seizure frequency was the primary outcome measure. Adverse effects were also studied.Results:Thirty-one children with daily seizures were studied with a median age of 18-month (range 9–30 months). West syndrome was the most common epilepsy syndrome (26, 86.6%). Twenty-one children remained on diet at 3 months and 13 at 6 months. The children who achieved >50% seizure reduction were 17 (54.8%) at 3 months and 9 (29%) at 6 months. Refusal to eat was a significant problem seen in eight children. Three children discontinued the diet due to adverse effects.Conclusion:The MAD was found to be feasible, effective, and well-tolerated.

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“…A recent randomized comparative investigation was performed in 104 children with intractable epilepsy treated with MAD versus classic KD. As a result from the study, MAD may be considered as the primary choice for the treatment of intractable epilepsy in children over KD, but the classic KD recommended as the first line of diet therapy in patients younger than two years of age [40].…”

Section: Diet Therapymentioning

confidence: 99%

Untitled

2017

Cent Asian J Med Sci

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Objectives: Up to one third of epilepsy patients have an unsatisfactory treatment with antiepileptic drugs (AEDs), but advance in neuroimaging, neurophysiologic investigation and treatment modalities have substantially improved the approaches and understanding of intractable childhood epilepsy. Methods: Journal papers, reports, books and government publications on epilepsy treatment were collected and reviewed in chronological order. Results:There are approximately more than 15 newer AEDs developed since 1990, highlighted by the novel mechanism of action with minimal adverse effect, thus they have been frequently used for those who are unresponsive to conventional AEDs. Non-pharmacologic therapies including diet therapy, epilepsy surgery, and neuromodulatory treatment are also effective and should be considered early in the disease course. Diet therapy began to reemerge in mid 1990s, and studies with large data collection allowed to overcome major concerns; its side effects, difficult compliance and doubts on efficacy. And more liberal forms of the diet therapy were introduced to benefit adults and patients in developing counties, where strict supervision is unavailable. The surgical treatment has become increasingly more valuable and it is now accepted for the management of drug resistant focal epilepsy due to major advances in presurgical investigation methods, and surgical techniques. Conclusions: The timely assessment of children with drugresistant epilepsy and active application of advanced treatment modalities were necessary to prevent the effect of uncontrolled seizures on cognitive and behavioral development.

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Efficacy of the classic ketogenic and the modified Atkins diets in refractory childhood epilepsy

Cited by 134 publications

References 23 publications

Adenosine A1 Receptor Antagonism Abolished the Anti-seizure Effects of Exogenous Ketone Supplementation in Wistar Albino Glaxo Rijswijk Rats

Adenosine A1 Receptor Antagonism Abolished the Anti-seizure Effects of Exogenous Ketone Supplementation in Wistar Albino Glaxo Rijswijk Rats

Efficacy and tolerability of the modified Atkins diet in young children with refractory epilepsy: Indian experience

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