Ketogenic Diet Therapy Research Articles

The effects of ketogenic dietary therapies on sleep: A scoping review.

Sleep problems are common in neurological conditions for which ketogenic dietary therapies (KDTs) are recognised as an effective intervention (drug-resistant epilepsy, autism spectrum disorder, and migraine). Given the composite framework of action of ketogenic dietary therapies, the prevalence of sleep disturbance, and the importance of sleep regulation, the present scoping review aimed at identifying and mapping available evidence of the effects of ketogenic dietary therapies on sleep. A comprehensive web-based literature search was performed retrieving publications published to June 2023 using PubMed and Scopus, yielding to 277 records. Twenty papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study design and sleep outcome evaluation among the selected studies. Several changes in sleep quality and sleep structure under ketogenic dietary therapies were found, namely an improvement of overall sleep quality, improvement in the difficulty falling asleep and nighttime awakenings, improvement in daytime sleepiness and an increase of REM sleep. The relevance and possible physiological explanations of these changes, clinical recommendations, and future directions in the field are discussed.

Nutritional treatment with the ketogenic diet in children with refractory epilepsy: a narrative review

The two mainstays of therapy for refractory epilepsy are medication and surgery. Child behavioral and cognitive aspects of epilepsy can be improved by using a specialized dietary regimen such as the ketogenic diet (KD). The purpose of this review is to expand our understanding of KD as a nutritional therapy for children with refractory epilepsy and to provide insight into the physiological aspects of its efficacy as an alternative to anti-seizure medication. Either directly or indirectly, ketones, glucose restriction, and polyunsaturated fatty acids regulate epileptic seizures. For KD to be effective, all three of these components must be present, even though the exact mechanism is unknown. Increasing gamma-aminobutyric acid, mitochondrial biogenesis, and oxidative phosphorylation levels can also serve as a means of promoting stable synaptic function while also decreasing neural activity and excitability. Most side effects of KD are caused by mild metabolic abnormalities such as acidosis, hyperuricemia, hypercholesterolemia, hypocalcemia, and hypomagnesemia. Since medium-chain triglycerides (MCTs) produce more ketones per calorie than long-chain triglycerides, individuals who consume MCTs can consume more carbohydrates and protein. This review demonstrated that KD therapy led to positive outcomes for patients with refractory epilepsy. Further study is needed to evaluate whether less restrictive and easier-to-follow diets, such as the modified Atkins diet and MCT diets, have a similar effect on seizure treatment as the standard KD.

Ketogenic diet may improve sleep quality and daytime somnolence in patients affected by multiple sclerosis. Results of an exploratory study

Objective/backgroundPatients with multiple sclerosis (MS) frequently report sleep complaints. The ketogenic diet (KD) is safe and tolerable in MS patients. Our aim was: 1) to investigate the effects of KD on sleep complaints in patients affected by relapsing-remitting MS and 2) to verify if sleep changes can positively impact on psychological status and quality of life (QoL) in these patients. Patients/methodsFrom January 2020 to November 2022, we consecutively enrolled 21 non-disabled or minimally disabled MS patients. We collected information regarding: 1) anthropometric measures; 2) psychological status by the Depression Anxiety Stress Scale-21; 3) QoL by the Multiple Sclerosis Quality of Life-54 (MSQOL-54); 4) subjective sleep complaints, i.e. sleep quality, by the Pittsburgh Sleep Quality Index (PSQI), and excessive daytime sleepiness (EDS), by the Epworth Sleepiness Scale (ESS). ResultsAfter 6 months of KD therapy, anthropometric measures considerably changed, psychological status significantly improved, and almost all the MSQOL-54 subscales ameliorated. Regarding sleep, we observed that the global PSQI (T0: 7.7 ± 3.1 versus T1: 4.4 ± 3.1, p = 0.002) and the ESS (T0: 7.5 ± 3.9 versus T1: 4.9 ± 3.2, p = 0.001) scores significantly decreased after KD therapy. At T1, only the global PSQI score was an independent predictor of anxiety, stress, and mental health. ConclusionsFor the first time, we demonstrated that KD may improve sleep complaints in MS patients. In addition, KD seems to have a positive impact on psychological status and QoL of MS patients, mainly through improving sleep quality. Further controlled studies with larger sample sizes are needed to confirm these preliminary results.

Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study.

The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, β-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy. Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.

Long-term effectiveness and seizure recurrence risk factors of ketogenic diet for pediatric refractory epilepsy: Experience from a tertiary care center in China.

This study aimed to assess the long-term effectiveness and seizure recurrence risk in children with drug-resistant epilepsy who achieved seizure freedom on a ketogenic diet (KD). Predictors associated with seizure recurrence were also evaluated. Patients with drug-resistant epilepsy who received KD therapy for at least 3 months between May 2011 and April 2020 were included. The clinical efficacy of the KD was evaluated. Patients who achieved seizure freedom for at least 3 months on the KD were focused. Multivariate Cox regression models were used to explore the risk factors of seizure relapse in patients who achieved seizure freedom. This study included 288 patients (163 males, 125 females). The seizure-free rates of the KD at 3, 6, 12, and 24 months were 9.7%, 16.7%, 14.2%, and 9.0%, respectively. Additionally, the seizure reduction rates between 50% and 99% were 46.5%, 39.9%, 30.2%, and 20.5%, respectively. Patients with Angelman syndrome (AS) showed the highest efficacy rate, followed by those with Dravet syndrome (DS). 51 patients achieved at least 3 months of seizure freedom on the KD. Seizures recurred in 24 (47.1%) patients. None of the patients with AS relapsed, while those with DS had the highest recurrence rate. The etiology of epilepsy, KD maintenance treatment period, and electroencephalography (EEG) abnormalities during follow-up differed significantly between patients with and without recurrence. However, multivariate Cox regression analysis indicated that a KD maintenance treatment period of less than 12 months and the presence of EEG abnormalities during follow-up were significantly correlated with a higher risk of relapse. Epilepsy control was restored in 3 of the 24 (12.5%) patients who experienced relapse. KD appears to be effective in children with various types of drug-resistant epilepsy. A short KD maintenance treatment period and EEG abnormalities during follow-up were associated with an increased risk of seizure recurrence.

Evaluation of Families’ Views on Disease Management by Applying Telemedicine During the COVID-19 Pandemic

The Coronavirus disease-2019 pandemic has led to the spread of telemedicine management of ketogenic diet therapy (KDT) in children with drug-resistant epilepsy (DRE). In this study, we evaluated the views and satisfaction of families about telemedicine and KDT management. Families of 25 children who underwent KDT for DRE were included in the 17-item questionnaire. Nearly half of the families had a primary education level. Most children with DRE were in the process of maintaining KDT. 88% of the families were applying KDT with telemedicine due to the pandemic. 60% of families found it difficult to start KDT via telemedicine, but 96% reported that reaching the KDT team via telemedicine was sufficient. The necessity of laboratory analyzes and evaluation of the results of the KDT team was evaluated as good in 72%, and their response when dietary changes or vitamin addition was required was evaluated as good in 68%. All families were satisfied with the management of the KDT team in emergencies. 60% of the family recommended others to follow the KDT with telemedicine at all times and 40% recommended them during the pandemic period. According to the results of our study, in selecting patients who will be started with telemedicine and KDT, it should be noted that the families have sufficient education levels. The use of the telemedicine method may be a good option in the presence of an experienced and trained team in KDT management.

Evaluation of Families’ Views on Disease Management by Applying Telemedicine During the COVID-19 Pandemic

The Coronavirus disease-2019 pandemic has led to the spread of telemedicine management of ketogenic diet therapy (KDT) in children with drug-resistant epilepsy (DRE). In this study, we evaluated the views and satisfaction of families about telemedicine and KDT management. Families of 25 children who underwent KDT for DRE were included in the 17-item questionnaire. Nearly half of the families had a primary education level. Most children with DRE were in the process of maintaining KDT. 88% of the families were applying KDT with telemedicine due to the pandemic. 60% of families found it difficult to start KDT via telemedicine, but 96% reported that reaching the KDT team via telemedicine was sufficient. The necessity of laboratory analyzes and evaluation of the results of the KDT team was evaluated as good in 72%, and their response when dietary changes or vitamin addition was required was evaluated as good in 68%. All families were satisfied with the management of the KDT team in emergencies. 60% of the family recommended others to follow the KDT with telemedicine at all times and 40% recommended them during the pandemic period. According to the results of our study, in selecting patients who will be started with telemedicine and KDT, it should be noted that the families have sufficient education levels. The use of the telemedicine method may be a good option in the presence of an experienced and trained team in KDT management.

Management of Status Epilepticus by Different Pediatric Departments: Neurology, Intensive Care, and Emergency Medicine

Introduction: The aim of this study was to explore the differences in status epilepticus (SE) management among pediatric neurology, emergency medicine, and intensive care specialists in Turkey. Methods: A 22-item questionnaire regarding first-, second-, and third-line management strategies of SE including demographic characteristics and common etiologies according to the specialty of participants was mailed to 370 specialists working in Turkey. Results: A total of 334 participants (response rate 90%) comprising 136 pediatric neurologists, 102 pediatric emergency medicine specialists, and 96 pediatric intensive care specialists completed the survey. While intensive care specialists frequently managed SE due to metabolic and autoimmune reasons, the most common etiologies encountered by emergency medicine specialists were epilepsy and infections. More than half of the intensive care specialists (64.6%) reported using non-BZD antiseizure medications in the 5th minute of the seizure. Most of the neurologists (76.4%) preferred to administer intravenous (IV) levetiracetam infusion as a second-line agent. About half of intensive care specialists and neurologists tried immunomodulatory therapies in super-refractory SE. Intensive care and emergency medicine specialists were less likely to favor ketogenic diet and pyridoxine therapy for the treatment of super-refractory SE. The rate of requesting EEG monitoring to recognize nonconvulsive SE (NCSE) was found to be very low except for neurologists. Conclusion: There was no consensus among neurologists, intensive care specialists, and emergency medicine specialists in the management of SE in Turkey. Familiarity with particular antiseizure medications and the etiologies they manage seem to be the most important factors influencing the attitudes.

Validation of an Italian Questionnaire of Adherence to the Ketogenic Dietary Therapies: iKetoCheck.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rates and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by 61 drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. The test-retest reliability was evaluated using Pearson's correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software version 12.03.02. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p = 0.284). In conclusion, despite the small sample size, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

Factor Analysis of the Brazilian Questionnaire on Adherence to Ketogenic Dietary Therapy: Keto-Check.

several strategies are used to assess adherence to ketogenic dietary therapies (KDTs), the most commonly used being ketonemia or ketonuria, despite their limitations. The purpose of this article is to carry out an exploratory and confirmatory factor analysis on the proposed Keto-check (adherence's KDT Brazilian questionnaire). there was a methodological study of a quantitative nature, complementary to the analysis realized previously, with a complimentary sample. The factorial analysis was performed with Factor software for parallel exploratory analysis, replicability, and confirmatory factor analysis. Graphical representation was created according to the number of factors resulting from the analysis. 116 questionnaires were reached by complementary data collection (n = 69 actual data, complementing n = 47 previous data) through online forms. A polychoric correlation matrix suitability analysis resulted in a significant Bartlett statistic (p = 0.0001) and a Kaiser-Meyer-Olkin (KMO) test of 0.56. The parallel factorial analysis resulted in two factors, graphically represented as "efficacy" and "adherence". A confirmatory factor analysis, considered fair, indicated an RMSEA of 0.063, NNFI resulted in 0.872, CFI in 0.926, and GFI in 0.897. this study confirms the validity of Keto-check through a more detailed analysis. Adherence is the key to improving the effectiveness of KDTs; therefore, improving knowledge about it can lead to a better healthcare approach.

Feasibility of ketogenic diet therapy variants for refractory epilepsy in neonates to infants under 2 years old

BackgroundKetogenic diet Therapy (KDT) has been reported as a possible beneficial management strategy for controlling seizures in infants aged <2 years, but the safety and efficacy of this therapy remain to be investigated. We investigated the achievability, tolerability, efficacy, and safety of KDT for patients under 2 years old. Materials and methodsInfants younger than 2 years old with pharmacoresistant epilepsy were enrolled in this prospective study. We divided cases into three age groups: I) neonates; II) infants aged 1–12 months; III) infants aged 12–24 months. KDT initiation protocol were administration through parenteral route, enteral route or oral feeding. Seizure reduction rate, physical growth, and adverse effects were assessed at monthly visit. ResultsThirteen patients who completed 6 months of KDT were recruited. There was one neonate in group I, 9 infants in group II, and 3 infants in group III. Eleven of them (11/13, 84.6%) were responders to KDT. All infants with underlying genetic etiology were seizure free after treating with KDT. The starting keto ratio was 1.1 mmol/L in group I, 2.3 mmol/L in group II, and 2.8 mmol/L in group III, which gradually approached 3:1–4:1 over 5–7 days. There were no symptomatic adverse effects or growth retardation in any of the study subjects. ConclusionsKDT is a promising alternative therapy with high feasibility, safety, and efficacy for pharmacoresistant epilepsy in infants under 2 years old, especially for those with genetic etiology. The starting keto ratio should be lower, and the keto ratio titration period should be longer than for children older than 2 years.

Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet.

Ketogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors. Possible variations in glycemia and ketone bodies blood levels according to the menstrual cycle have not been systematically assessed yet, but this time window deserves special attention because of hormonal and metabolic related changes. This study aims at searching for subtle changes in KBs blood level during menstrual cycle in female patients undergoing a stable ketogenic diet, by analyzing 3-months daily measurement of ketone bodies blood levels and glucose blood levels throughout the menstrual cycle. We report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet. A significant increase in glucose blood levels during menstruation was found in the entire cohort. As far as the ketone bodies blood levels, an inversely proportional trend compared to glycemia was noted. Exploring whether ketonemia variations might occur according to the menstrual cycle is relevant to determine the feasibility of transient preventive diet adjustments to assure a continuative treatment efficacy and to enhance dietary behavior support. clinicaltrials.gov, identifier NCT05234411.

Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against Epilepsy Dietary Therapy Study Group.

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.

Efficacy and safety of the ketogenic diet therapy in Pakistani children with refractory epilepsy

Efficacy and safety of the ketogenic diet therapy in Pakistani children with refractory epilepsy

Factors Associated With Growth in Patients Treated With the Classic Ketogenic Diet for Drug-Resistant Epilepsy

BackgroundSuboptimal growth and malnutrition are often cited as complications of ketogenic diet therapy in patients with drug-resistant epilepsy; however, there is conflicting evidence on the factors that contribute to growth. MethodsThis is an observational, case-based study to evaluate growth in patients with drug-resistant epilepsy treated with the classic ketogenic diet for at least 12 months. Age, gender, height, weight, and body mass index (BMI) were collected at baseline and epilepsy clinic standard-of-care visits (one month, six months, and 12 months after diet initiation). Dietary intake and laboratory measures including glucose, bicarbonate, and beta-hydroxybutyrate were also collected. Results119 patients were included. After ketogenic diet initiation, there was a significant fall in height z score from baseline to 12 months (−0.15, P = 0.001) but no other significant changes in weight, weight-for-length/BMI, or height z scores were noted between any time points within the 12 months after diet initiation. When separated by age, height z score changes were limited to those aged zero to three years. This was accompanied by a significant decrease in energy intake 12 months after treatment in this age group. When separated by diet route, weight z scores at each time point were significantly lower in the group eating by mouth than tube. ConclusionsOur study provides further evidence that the classic ketogenic diet impacts growth. Our population demonstrated restriction in linear growth in those aged zero to three years, which correlated with declines in energy intake, and weight declines limited to patients fed by mouth.

Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group.

Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.

Kidney Stones in Epileptic Children Receiving Ketogenic Diet: Frequency and Risk Factors.

Although it is a valuable option for children with drug-resistant epilepsy, ketogenic diet (KD) therapy is associated with several side effects. The frequency of kidney stones and risk factors for their development in epileptic children receiving KD is unclear. The aim of this study was to determine the frequency and risk factors for the development of renal stones in children receiving KD therapy. A total of 95 patients receiving KD were identified. Of these, seven patients were excluded from the study due to the duration of KD being less than 12 months. The remaining 88 children were enrolled in the study. Renal stones were detected in 15 patients (17%), of which 12 (73.3%) received potassium citrate treatment. Two (13.3%) patients needed lithotripsy despite receiving potassium citrate treatment, and one of these, who received potassium citrate treatment for 5 months, developed acute vesicourethral reflux and underwent surgery. No patient discontinued KD due to renal stone development. The serum uric acid concentrations and urine calcium/creatinine ratio did not change significantly over the 24-month follow-up period. Age, gender, etiology, age at seizure onset, duration of KD, mobility status, use of topiramate or zonisamide, and the number of antiepileptic drugs used were not significantly different between patients with and without kidney stones. Renal stone appears to be a common adverse effect of KD therapy. Although adequate hydration and potassium citrate treatment are effective in most patients, lithotripsy and surgery may be required in a minority of patients.

Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control

Objective/backgroundMigraine patients are frequently affected by sleep complaints. The ketogenic diet (KD) is an option for the treatment of migraine. Our aim was: 1) to assess the effects of KD on sleep complaints in patients affected by migraine and 2) to verify if sleep changes were related to the effects of the diet on headache symptoms. Patients/methodsFrom January 2020 to July 2022 we consecutively enrolled 70 migraine patients who were treated with KD as a preventive therapy. We collected information regarding: 1) anthropometric measures; 2) migraine intensity, frequency and disability; 3) subjective sleep complaints, i.e. insomnia, sleep quality, by the Pittsburgh Sleep Quality Index (PSQI), and excessive Daytime Sleepiness (EDS), by the Epworth Sleepiness Scale (ESS). ResultsAfter 3 months of KD therapy, anthropometric measures considerably changed, i.e. body mass index and free fat mass, and migraine significantly improved, i.e. lower intensity, frequency and disability. Regarding sleep, we observed that insomnia affected a decreased rate of patients (T0: 60% versus T1: 40%, p < 0.001). Similarly, patients with poor sleep were significantly less after KD therapy (T0: 74.3% versus T1: 34.3%, p < 0.001). Finally, EDS prevalence declined at the follow-up (T0: 40% versus T1: 12.9%, p < 0.001). Sleep features modifications were not correlated with migraine improvements and with anthropometric changes. ConclusionsFor the first time we demonstrated that KD may improve sleep complaints in migraine patients. Interestingly, the positive effect of KD on sleep is independent of migraine improvements and anthropometric modifications.

A Review of Ketogenic Dietary Therapies for Epilepsy and Neurological Diseases: A Proposal to Implement an Adapted Model to Include Healthy Mediterranean Products.

Based on the growing evidence of the therapeutic role of high-fat ketogenic dietary therapies (KDTs) for neurological diseases and on the protective effect of the Mediterranean diet (MD), it could be important to delineate a Mediterranean version of KDTs in order to maintain a high ketogenic ratio, and thus avoid side effects, especially in patients requiring long-term treatment. This narrative review aims to explore the existing literature on this topic and to elaborate recommendations for a Mediterranean version of the KDTs. It presents practical suggestions based on MD principles, which consist of key elements for the selection of foods (both from quantitative and qualitative prospective), and indications of the relative proportions and consumption frequency of the main food groups that constitute the Mediterranean version of the KDTs. We suggest the adoption of a Mediterranean version of ketogenic diets in order to benefit from the multiple protective effects of the MD. This translates to: (i) a preferential use of olive oil and vegetable fat sources in general; (ii) the limitation of foods rich in saturated fatty acids; (iii) the encouragement of high biological value protein sources; (iv) inserting fruit and vegetables at every meal possible, varying their choices according to seasonality.

Comprehensive study of metabolic changes induced by a ketogenic diet therapy using GC/MS- and LC/MS-based metabolomics

ObjectiveThe ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a subset of patients with drug-resistant epilepsy, although the mechanisms of the KD have not been fully elucidated. The aims of this observational study were to investigate comprehensive short-term metabolic changes induced by the KD and to explore candidate metabolites or pathways for potential new therapeutic targets. MethodsSubjects included patients with intractable epilepsy who had undergone the KD therapy (the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil). Plasma and urine samples were obtained before and at 2–4 weeks after initiation of the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). ResultsSamples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively. The KD increased ketone bodies, various fatty acids, lipids, and their conjugates. In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA, including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric acid and lactic acid, were elevated. ConclusionsThe metabolites that were significantly changed after the initiation of the KD and related metabolites may be candidates for further studies for neuronal actions to develop new anti-seizure medications.