Nutrients

Editorial

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4 pages, 174 KiB

Open AccessEditorial

Diet in the Treatment of Epilepsy

by Cara J. Westmark

Nutrients 2021, 13(3), 917; https://doi.org/10.3390/nu13030917 - 12 Mar 2021

Viewed by 2215

Abstract

This Special Issue for Nutrients focuses on the effects of diet on brain function with a special emphasis on epileptic disorders [...] Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

Research

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14 pages, 2161 KiB

Open AccessArticle

Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino Glaxo Rijswijk Rats

by Brigitta Brunner, Enikő Rauch, Csilla Ari, Dominic P. D’Agostino and Zsolt Kovács

Nutrients 2021, 13(1), 234; https://doi.org/10.3390/nu13010234 - 15 Jan 2021

Cited by 6 | Viewed by 3642

Abstract

Both uridine and exogenous ketone supplements decreased the number of spike-wave discharges (SWDs) in a rat model of human absence epilepsy Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It has been suggested that alleviating influence of both uridine and ketone supplements on absence epileptic activity [...] Read more.

Both uridine and exogenous ketone supplements decreased the number of spike-wave discharges (SWDs) in a rat model of human absence epilepsy Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It has been suggested that alleviating influence of both uridine and ketone supplements on absence epileptic activity may be modulated by A₁ type adenosine receptors (A₁Rs). The first aim was to determine whether intraperitoneal (i.p.) administration of a specific A₁R antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 0.2 mg/kg) and a selective adenosine A_2A receptor antagonist (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine) (SCH 58261; 0.5 mg/kg) have a modulatory influence on i.p. 1000 mg/kg uridine-evoked effects on SWD number in WAG/Rij rats. The second aim was to assess efficacy of a sub-effective dose of uridine (i.p. 250 mg/kg) combined with beta-hydroxybutyrate salt + medium chain triglyceride (KSMCT; 2.5 g/kg, gavage) on absence epilepsy. DPCPX completely abolished the i.p. 1000 mg/kg uridine-evoked alleviating effect on SWD number whereas SCH 58261 was ineffective, confirming the A₁R mechanism. Moreover, the sub-effective dose of uridine markedly enhanced the effect of KSMCT (2.5 g/kg, gavage) on absence epileptic activity. These results demonstrate the anti-epilepsy benefits of co-administrating uridine and exogenous ketone supplements as a means to treat absence epilepsy. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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18 pages, 1468 KiB

Open AccessArticle

An Examination of Serum Acylcarnitine and Amino Acid Profiles at Different Time Point of Ketogenic Diet Therapy and Their Association of Ketogenic Diet Effectiveness

by Pi-Lien Hung, Ju-Li Lin, Chien Chen, Kai-Yin Hung, Tzu-Yun Hsieh, Mei-Hsin Hsu, Hsuan-Chang Kuo and Ying-Jui Lin

Nutrients 2021, 13(1), 21; https://doi.org/10.3390/nu13010021 - 23 Dec 2020

Cited by 6 | Viewed by 2815

Abstract

Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet [...] Read more.

Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet with non-fasting, gradual KD initiation protocol (GRAD-KD) for 1 year were enrolled. A total of 22 patients remaining in study received blood examinations at baseline, 3rd, 6th, 9th, and 12th months of KDT. β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and non-responders (seizure reduction rate < 50%) to identify the effectiveness of KDT. Results: The 12-month retention rate was 76%. The responders after 12 months of KDT were 59% (13/22). The free carnitine level decreased significantly at 9th months (p < 0.001) but increased toward baseline without symptoms. Propionyl carnitine (C3), Isovaleryl carnitine (C5), 3-Hydroxyisovalerylcarnitine (C5:OH) and methylmalonyl carnitine (C4-DC) decreased but 3-hydroxybutyrylcarnitine (C4:OH) increased significantly at 12th months of KDT. The glycine level was persistently higher than baseline after KDT. KDT responders had lower baseline C3 and long-chain acylcarnitines, C14 and C18, as well as lower C5, C18, and leucine/isoleucine. Conclusions: KDT should be avoided in patients with non-ketotic hyperglycemia. Routine carnitine supplementation is not recommended because hypocarnitinemia was transient and asymptomatic during KDT. Better mitochondrial βoxidation function associates with greater KDT response. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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15 pages, 267 KiB

Open AccessArticle

Soy-Based Infant Formula is Associated with an Increased Prevalence of Comorbidities in Fragile X Syndrome

by Cara J. Westmark, Chad Kniss, Emmanuel Sampene, Angel Wang, Amie Milunovich, Kelly Elver, David Hessl, Amy Talboy, Jonathon Picker, Barbara Haas-Givler, Amy Esler, Andrea L. Gropman, Ryan Uy, Craig Erickson, Milen Velinov, Nicole Tartaglia and Elizabeth M. Berry-Kravis

Nutrients 2020, 12(10), 3136; https://doi.org/10.3390/nu12103136 - 14 Oct 2020

Cited by 12 | Viewed by 2997

Abstract

A large number of adults and children consume soy in various forms, but little information is available regarding potential neurological side effects. Prior work indicates an association between the consumption of soy-based diets and seizure prevalence in mouse models of neurological disease and [...] Read more.

A large number of adults and children consume soy in various forms, but little information is available regarding potential neurological side effects. Prior work indicates an association between the consumption of soy-based diets and seizure prevalence in mouse models of neurological disease and in children with autism. Herein, we sought to evaluate potential associations between the consumption of soy-based formula during infancy and disease comorbidities in persons with fragile X syndrome (FXS), while controlling for potentially confounding issues, through a retrospective case-control survey study of participants with FXS enrolled in the Fragile X Online Registry with Accessible Research Database (FORWARD). There was a 25% usage rate of soy-based infant formula in the study population. We found significant associations between the consumption of soy-based infant formula and the comorbidity of autism, gastrointestinal problems (GI) and allergies. Specifically, there was a 1.5-fold higher prevalence of autism, 1.9-fold GI problems and 1.7-fold allergies in participants reporting the use of soy-based infant formula. The major reason for starting soy-based infant formula was GI problems. The average age of seizure and allergy onset occurred long after the use of soy-based infant formula. We conclude that early-life feeding with soy-based infant formula is associated with the development of several disease comorbidities in FXS. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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7 pages, 556 KiB

Open AccessCommunication

Families’ Perception of Classic Ketogenic Diet Management in Acute Medical Conditions: A Web-Based Survey

by Ludovica Pasca, Costanza Varesio, Cinzia Ferraris, Monica Guglielmetti, Claudia Trentani, Anna Tagliabue, Pierangelo Veggiotti and Valentina De Giorgis

Nutrients 2020, 12(10), 2920; https://doi.org/10.3390/nu12102920 - 24 Sep 2020

Cited by 8 | Viewed by 3352

Abstract

Objective: To describe families’ experiences in managing epileptic patients undergoing ketogenic dietary therapies (KDTs) in acute medical settings. Methods: We conducted a short online survey addressed to the families of patients undergoing a classic ketogenic diet (cKD) for at least three months. The [...] Read more.

Objective: To describe families’ experiences in managing epileptic patients undergoing ketogenic dietary therapies (KDTs) in acute medical settings. Methods: We conducted a short online survey addressed to the families of patients undergoing a classic ketogenic diet (cKD) for at least three months. The survey was composed of 18 questions exploring the following issues: demographic characteristics, epilepsy diagnosis, ketogenic-diet treatment history, the reason for emergency-ward admission and patient management, surgery-procedure management, and outcomes. Results: A sample of 50 families agreed to participate. Out of 50 patients, 33 (66%) had been undergoing a cKD for more than two years. Fifteen (30%) patients had been admitted at least once to the Emergency Room (ER), and 8.2% had undergone surgical procedures during cKD treatment. The causes of ER admission were the following: seizures, infection, trauma, and gastrointestinal or respiratory problems. In 75% of cases, blood ketonemia was not monitored during ER admission, and according to 46% of responders, the medical staff intervening did not have a basic knowledge of KDTs. Conclusions: According to both our experience and caregivers’ reports, it might be useful to search for standardized specific approaches to patients undergoing KDTs in the emergency setting. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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13 pages, 862 KiB

Open AccessArticle

An Open Pilot Study of the Effect and Tolerability of Add-On Multivitamin Therapy in Patients with Intractable Focal Epilepsy

by Hui Hua Chang, Pi-Shan Sung, Wei Chen Liao, Alice Y. W. Chang, Ya-Hsin Hsiao, Tzu-Fun Fu, Chin-Ying Huang and Chin-Wei Huang

Nutrients 2020, 12(8), 2359; https://doi.org/10.3390/nu12082359 - 7 Aug 2020

Cited by 10 | Viewed by 3878

Abstract

Observational studies have investigated the potential modulatory effect of neuronal excitability by vitamins in epilepsy. We aimed to investigate whether the addition of multivitamin therapy (B6/B9, D, E and Q) to regular antiepileptic drug therapy could ameliorate seizures in patients with refractory focal [...] Read more.

Observational studies have investigated the potential modulatory effect of neuronal excitability by vitamins in epilepsy. We aimed to investigate whether the addition of multivitamin therapy (B6/B9, D, E and Q) to regular antiepileptic drug therapy could ameliorate seizures in patients with refractory focal epilepsy. We conducted a prospective cohort open study to investigate the effect and tolerability of add-on multivitamin therapy (daily dose: B6 100 mg, B9 5 mg, D 1000 IU, E 400 IU and coenzyme Q10 100 mg) in patients with intractable focal epilepsy. All patients had effect and safety assessments at baseline and after one, three and six months of the supplementation. Thirty patients (11 men and 19 women) with a mean age of 42.37 ± 9.40 years were recruited and four patients discontinued. The seizure frequency significantly decreased after the six-month supplementation (9.04 ± 18.16/month and 2.06 ± 3.89/month, p = 0.045). At the final visit, 62.5% of the patients showed a ≥50% reduction in seizure frequency, and 12.5% were seizure-free. As to safety and tolerability, most patients did not experience significant adverse events, although three patients reported seizure worsening. In conclusion, this pilot study demonstrated the therapeutic potential and essentially good tolerability of add-on multivitamin therapy in patients with refractory focal epilepsy. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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Review

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19 pages, 565 KiB

Open AccessReview

Diet in the Treatment of Epilepsy: What We Know So Far

by Alberto Verrotti, Giulia Iapadre, Ludovica Di Francesco, Luca Zagaroli and Giovanni Farello

Nutrients 2020, 12(9), 2645; https://doi.org/10.3390/nu12092645 - 30 Aug 2020

Cited by 29 | Viewed by 10939

Abstract

Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5–1% and a lifetime incidence of 1–3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on [...] Read more.

Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5–1% and a lifetime incidence of 1–3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on society and global health. In recent decades, dietary regimens have been used effectively in the treatment of drug-resistant epilepsy, following the path of a non-pharmacological approach. The ketogenic diet and its variants (e.g., the modified Atkins diet) have an established role in contrasting epileptogenesis through the production of a series of cascading events induced by physiological ketosis. Other dietary regimens, such as caloric restriction and a gluten free diet, can also exert beneficial effects on neuroprotection and, therefore, on refractory epilepsy. The purpose of this review was to analyze the evidence from the literature about the possible efficacy of different dietary regimens on epilepsy, focusing on the underlying pathophysiological mechanisms, safety, and tolerability both in pediatric and adult population. We believe that a better knowledge of the cellular and molecular biochemical processes behind the anticonvulsant effects of alimentary therapies may lead to the development of personalized dietary intervention protocols. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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23 pages, 835 KiB

Open AccessReview

Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned

by Iwona Maria Zarnowska

Nutrients 2020, 12(9), 2616; https://doi.org/10.3390/nu12092616 - 27 Aug 2020

Cited by 47 | Viewed by 10227

Abstract

Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic changes occurring during starvation. Except for classic KD, its modified counterparts, including modified Atkins diet and low-glycemic-index treatment, have [...] Read more.

Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic changes occurring during starvation. Except for classic KD, its modified counterparts, including modified Atkins diet and low-glycemic-index treatment, have gained grounds to increase palatability and adherence. Strong evidence exists that the KD offers protection against seizures in difficult-to-treat epilepsy and possesses long-lasting anti-epileptic activity, improving long-term disease outcome. The KD can also provide symptomatic and disease-modifying activity in a wide range of neurodegenerative diseases. In an era of highly available new anti-seizure medications (ASMs), the challenge of refractory epilepsy has still not been solved. This metabolic therapy is increasingly considered due to unique mechanisms and turns out to be a powerful tool in the hands of a skillful team. Despite decades of extensive research to explain the mechanism of its efficacy, the precise mechanism of action is to date still largely unknown. The key feature of this successful diet is the fact that energy is derived largely from fat but not from carbohydrates. Consequently, fundamental change occurs regarding the method of energy production that causes alterations in numerous biochemical pathways, thus restoring energetic and metabolic homeostasis of the brain. There are barriers during the use of this special and individualized therapy in many clinical settings worldwide. The aim of this review is to revisit the current state of the art of therapeutic application of KD in refractory epilepsy. Full article

(This article belongs to the Special Issue Diet in the Treatment of Epilepsy: What We Know So Far)

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