Ketogenic diet therapies as a non-pharmacological adjuvant in resistant epilepsy: retrospective analysis of adult outpatients in Colombia.

Twelve patients between 18 and 53 years of age were included. MAD plus nutritional supplementation was administered to 75% (n = 10) of the participants, one (8.3%) received MAD alone, and 16.7 (n = 2) received Classic Ketogenic Diet (cKD) plus nutritional supplementation. Oral nutritional supplementation, administered in the outpatient setting, provided patients with between 31 and 55% of the total caloric value. In the first month of KDT treatment, 83.3% (n = 10) of patients reduced the number of weekly seizures by 40% (median). At six months of treatment, 75% of patients had at least halved the number of weekly seizures. At 12 months of treatment, the number of weekly seizures had been reduced by 85.7% (median). KDT was well tolerated, and there was no need to discontinue treatment. This study provides real-world information on the use of KDT, particularly MAD in adults, in developing countries. Future studies in larger cohorts will provide further information on different types of KDT, adherence, and patient-reported outcomes.

Keto Clarity: A Comprehensive Systematic Review Exploring the Efficacy, Safety, and Mechanisms of Ketogenic Diet in Pediatric Epilepsy.

Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population. Antiepileptic drugs (AEDs) constitute the primary treatment; however, drug-resistant epilepsy (DRE), especially in children, poses a therapeutic challenge. Alternative interventions, such as surgery, vagus nerve stimulation, and the ketogenic diet (KD), have been explored. This systematic review aims to investigate various types of KDs, their distinctions, their effectiveness, and their safety concerning the reduction of seizure frequency, achieving seizure freedom, and the occurrence of adverse events. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was conducted using databases such as PubMed Central (PMC), MedLine, and Science Direct to identify relevant articles. Eligibility criteria and quality assessment tools were applied to evaluate the potential risk of bias and select 11 articles for inclusion in this review. The selected articles encompassed four randomized controlled trials (RCTs), two systematic reviews, and five narrative reviews. The data collected for this review was completed on October 2, 2023. Challenges, such as palatability, cultural factors, and adherence difficulties, were identified. Family or caregiver involvement plays a pivotal role in treatment success. Despite numerous RCTs and reviews, information gaps persist, hindering conclusive outcomes. Evaluating the risk-benefit ratio is crucial, considering potential side effects. The highly individualized nature of KD therapy, influenced by diverse seizure types and syndromes, necessitates a trial-and-error approach monitored by a multidisciplinary team. Long-term safety and efficacy demand continuous real-life patient data review. In summary, while KD presents a promising alternative for DRE, its success relies on meticulous planning, individualized implementation, and ongoing research to address existing challenges and information gaps.

A randomized feasibility trial of the modified Atkins diet in older adults with mild cognitive impairment due to Alzheimer's disease.

Background: Alzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action. Methods: We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time. Results: A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: -0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen's D = 0.57, 95% CI: -0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids. Conclusions: Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

The impact of ketogenic diet on drug-resistant epilepsy in children: A comprehensive review and meta-analysis.

The ketogenic diet (KD), characterized by high-fat and low-carbohydrate intake, is currently gaining widespread popularity as a treatment for drug-resistant epilepsy (DRE). In addition to the traditional ketogenic diet, several variants have been introduced to enhance compliance and flexibility, such as the modified Atkins diet (MAD) and the low glycemic index diet (LGID). These adaptations aim to provide patients with more manageable and sustainable options while harnessing the potential therapeutic benefits of DRE. The objective of this study is to evaluate the efficacy and safety of the KD in pediatric patients who exhibit DRE. In this study, we conducted a thorough review of existing literature by searching Cochrane, Embase, Medline, and PubMed. Our approach involved predefined criteria for data extraction and the assessment of study quality. Eleven RCTs with 788 participants were included in this study. The pooled effect estimates revealed a significant association between dietary interventions and seizure frequency reduction of > 50% (OR 6.68, 96% CI 3.52, 12.67) and > 90% (OR 4.37, 95% CI 2.04, 9.37). Dietary interventions also increased the odds of achieving seizure freedom (OR 4.13, 95% CI 1.61, 10.60). The common adverse effects included constipation (39.07%) and vomiting (10%). In conclusion, dietary interventions, notably the KD, hold promise for pediatric DRE, reducing seizures and achieving freedom. These non-pharmacological options improve the quality of life of non-responsive and non-surgical patients. The KD has emerged as a potential therapeutic approach. Further research is needed to address the limitations and investigate their long-term effects.

Modified Atkins diet for drug-resistant epilepsy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE). METHODS: In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively. RESULTS: Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM. SIGNIFICANCE: This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.

Age-Related Changes in Epilepsy Characteristics and Response to Antiepileptic Treatment in Autism Spectrum Disorders.

Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD), there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an online survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities, potential etiologies, and ASD diagnosis were collected from individuals with ASD and seizures. We previously reported overall general patterns of treatment effectiveness but did not examine the effect of seizure characteristics or age on antiepileptic treatment effectiveness. Such information would improve the personalized medicine approach to the treatment of seizures in ASD. Survey data from 570 individuals with ASD and clinical seizures were analyzed. Seizure severity (seizure/week) decreased with age of onset of seizures, plateauing in adolescence, with a greater reduction in generalized tonic-clonic (GTC) seizures with age. Seizure severity was worse in those with genetic disorders, neurodevelopmental regression (NDR) and poor sleep maintenance. Carbamazepine and oxcarbazepine were reported to be more effective when seizures started in later childhood, while surgery and the Atkins/modified Atkins Diet (A/MAD) were reported to be more effective when seizures started early in life. A/MAD and the ketogenic diet were reported to be more effective in those with NDR. Interestingly, atypical Landau-Kleffner syndrome was associated with mitochondrial dysfunction and NDR, suggesting a novel syndrome. These interesting findings need to be verified in independent, prospectively collected cohorts, but nonetheless, these data provide insights into novel relationships that may assist in a better understanding of epilepsy in ASD and provide insight into personalizing epilepsy care in ASD.

A case-control evaluation of Spasm control and Tolerability of the Modified Atkins diet versus classic ketogenic diet in Chinese Children with infantile epileptic spasms syndrome.

OBJECTIVE: This study was conducted to compare the efficacy, tolerability and safety of the modified Atkins diet (MAD) and the classic ketogenic diet (KD) in Chinese children with infantile epileptic spasms syndrome. METHODS: We retrospectively recruited and analyzed 56 children with infantile epileptic spasms syndrome started on the MAD (n = 21) and classic KD (n = 35) at our institution from June 2016 to July 2022. RESULTS: The MAD group had exhibited comparable rates of spasm reduction (>50%) as the classic KD group at the time point of 3 months (66.7% for MAD, 75% for KD; p = 0.510), 6 months (75% for MAD, 82.6% for KD; p = 0.694), and 12 months (84.6% for MAD, 90.9% for KD; p = 1.000). The probability of patients remaining on the MAD was higher (p = 0.048) than those consuming the classic KD. By analyzing discontinuation reasons, we found that the MAD patients had a lower rate of poor compliance than the classic KD patients (p = 0.014). Response to the diet at 1 month and fewer anti-seizure medicines (ASMs) had tried before KD initiation were possible factors in regard to likelihood of spasm-free response to the diet therapy at 3 months (p = 0.001 and p = 0.014, respectively). CONCLUSIONS: The efficacy of spasm control was similar in the MAD, with better tolerability and higher compliance compared to the classic KD. Therefore, MAD could be the primary treatment for children in China with- infantile epileptic spasms syndrome. Additionally, an earlier beginning of the diet treatment may have significant advantages.

Modified Atkins diet in children with epilepsy with eyelid myoclonia (Jeavons syndrome).

BACKGROUND: Epilepsy with eyelid myoclonia(EEM) or Jeavons syndrome is considered a genetic generalized epilepsy with a typical age of onset in childhood. Many types of seizures can be observed, including eyelid myoclonia, absence, generalized tonic-clonic, and myoclonic seizures. Seizures tend to be difficult to control requiring polypharmacy treatment or become drug-resistant. Dietary therapy, particularly with Modified Atkins Diet (MAD), as a treatment of seizures in this syndrome has rarely been studied. We report efficacy and tolerability of MAD in children with epilepsy with eyelid myoclonia. METHODS: We reviewed medical records of children with EEM treated at the University of Chicago Ketogenic Diet program from 2017 to 2022. Patient's demography, seizure characteristics, EEG findings, response to treatment, and adverse effects were reviewed. RESULT: Six patients with EEM were identified. Average age of seizure onset was 6 (2-11) years and an average age when the MAD started was 10.7 (6-15) years. All patients were started on MAD and completed at least 6 months on the diet at the time of report. An average of 4 (0-9) anti-seizure medications (ASM) had been tried prior to the MAD. All patients achieved ketosis with an average level of serum beta-hydroxybutyrate of 1.9 (1.03-3.61) mmol/L. At the 6-month follow-up visit, all patients (100%) experienced a greater than 50% seizure reduction, 3/6 patients (50%) had more than 90% seizure reduction, 1/6 patients (17%) became seizure-free. All seizure types demonstrated a greater than 80% reduction in frequency.Absence and myoclonic seizures showed the greatest reduction with 100% seizure reduction. Eyelid myoclonia and generalized tonic-clonic seizures showed more than 80% seizure reduction.Moreover, all patients reported improvement in alertness, mood, and concentration. Initial weight loss and mild gastrointestinal disturbances were reported in 2/6 patients (33%) and corrected with dietary adjustment. CONCLUSION: The Modified Atkins Diet has shown to be effective and welltolerated for children with EEM in our study. Cognitive improvement has also been subjectively reported in all patients. Adverse effects are tolerable and correctable. The MAD, therefore, may be considered as a treatment option for patients with epilepsy with eyelid myoclonia.

Role of nutritional adjuncts in the management of gliomas: A systematic review of literature.

BACKGROUND: A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug. METHODOLOGY: A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts. RESULTS: The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas. CONCLUSION: While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions.

The effect of anti-seizure medications on lipid values in adults with epilepsy.

PURPOSE: Certain anti-seizure medications (ASMs) adversely impact lipid values. Here, we explored the impact of ASMs on lipid values in adults with epilepsy. METHODS: A total of 228 adults with epilepsy were divided into four groups based on ASMs used: strong EIASMs, weak EIASMs, non-EIASMs, and no ASMs. Demographic information, epilepsy-specific clinical history, and lipid values were obtained through chart review. RESULTS: While there was no significant difference in lipid values between groups, there was a significant difference in the proportion of participants with dyslipidemia. Specifically, more participants exhibited elevated low-density lipoprotein (LDL) level in the strong EIASM group compared to the non-EIASM group (46.7% vs 18%, p < 0.05). In addition, more participants showed elevated LDL level in the weak EIASM group compared to the non-EIASM group (38% vs 18%, p < 0.05). Users of strong EIASMs showed greater odds of high LDL level (OR 5.734, p = 0.005) and high total cholesterol level (OR 4.913, p = 0.008) compared to users of non-EIASMs. When we analyzed the impact of individual ASMs used by more than 15% of the cohort on lipid levels, participants using valproic acid (VPA) showed lower high-density lipoprotein (p = 0.002) and higher triglyceride levels (p = 0.002) compared to participants not using VPA. CONCLUSION: Our study demonstrated a difference in the proportion of participants with dyslipidemia between ASM groups. Thus, adults with epilepsy using EIASMs should have careful monitoring of lipid values to address the risk of cardiovascular disease.

Prospective study of the modified Atkins diet in adult drug-resistant epilepsy: effectiveness, tolerability, and adherence.

INTRODUCTION: Drug-resistant epilepsy presents high worldwide prevalence and is difficult to control despite the wide variety of available antiepileptic drugs (AED). The modified Atkins diet (MAD) is an additional treatment alternative. Several studies have addressed the use of the ketogenic diet and MAD in children with drug-resistant epilepsy, but insufficient research has been conducted into adults with the same condition. OBJECTIVE: To evaluate the effectiveness and tolerability of, and adherence to, the MAD in adults with drug-resistant epilepsy. MATERIAL AND METHODS: We conducted a 6-month pre-post prospective study at a reference hospital. Patients were prescribed the MAD with limited carbohydrate intake and unlimited fat intake. We conducted clinical and electroencephalographic follow-up according to the relevant guidelines, and assessed adverse effects changes in laboratory findings, and adherence. RESULTS: Thirty-two patients with drug-resistant epilepsy were included in the study. Patients' mean age was 30 years, mean disease progression time was 22 years, and all patients had focal or multifocal epilepsy. Thirty-four percent of patients presented > 50% decreases in overall seizure frequency (P =  .001); seizure control was greater in the first month and subsequently declined. These patients presented weight loss (RR: 7.2; 95% CI, 1.3-39.5; P = .02), good to fair adherence only in the first and third months (RR: 9.4; 95% CI, 0.9-93.6; P = .04 and RR: 0.4; 95% CI, 0.30-0.69; P = .02, respectively). Tolerability data showed that the MAD is safe: adverse effects were minor and short-lived in most cases, with the exception of mild to moderate hyperlipidaemia in one-third of patients. The adherence rate was 50% at the end of the study. CONCLUSIONS: In adults with drug-resistant focal epilepsy, the MAD showed adequate tolerability and moderate but decreasing effectiveness and adherence, probably due to a preference for a carbohydrate-based diet.

Does the ketogenic ratio matter when using ketogenic diet therapy in pediatric epilepsy?

The ketogenic diet (KD) is a widely used therapeutic option for individuals with medically refractory epilepsy. As the diet's name implies, ketosis is a historically important component of the diet, but it is not well understood how important ketosis is for seizure control. The ketogenic ratio is defined as the ratio of fat to carbohydrate plus protein by weight in the diet (grams). Traditionally, the classic KD contains a 4:1 ratio, and a very high proportion of fat in the diet. The classic KD, with its high proportion of fat and limited carbohydrate intake can be restrictive for patients with epilepsy. Recently, there is experience with use of lower ketogenic ratios and less-restrictive diets such as the modified Atkins diet and the low glycemic index treatment. In this narrative review, we examine the role of ketosis and ketogenic ratios in determining the efficacy of the KD in children with epilepsy.

Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet.

Introduction: Previous studies have demonstrated the safety and efficacy of the modified Atkins diet (MAD) in attenuating seizures in patients with intractable epilepsy. MAD works by achieving ketosis, which is heavily dependent on the metabolic compound, carnitine, to facilitate the transport of long-chain fatty acids across the mitochondria for beta-oxidation. The effect of carnitine on ketogenic diet therapy is not well-defined in the current literature. Thus, the purpose of our study is to investigate the effects of hypocarnitinemia on the efficacy of MAD. Methods: A retrospective chart review was conducted, and 58 adults with epilepsy undergoing MAD were evaluated. Generalized linear mixed effects models were used to compare the low carnitine status with normal carnitine group in patient measures of body mass index, seizure frequency and severity, number of anti-seizure medications, beta-hydroxybutyrate, triglyceride, and carnitine levels across baseline, 3-9-month follow-up (timepoint 1), 1-2-year follow-up (timepoint 2), and 2+ year follow-up (timepoint 3). Results: Our study revealed that 38.3% of adult patients with epilepsy following MAD experienced low free carnitine at some point through the course of diet therapy. Patients with hypocarnitinemia at timepoint 2 showed a significant percent seizure increase while seizures continued to decrease in the normal carnitine group. Fasting triglyceride levels at timepoint 1 were significantly increased in the low carnitine group compared to normal carnitine group. Change in BHB, BMI, seizure severity, and number of ASMs showcased no significant differences between the low and normal carnitine groups. Discussion: It may be important for clinicians to monitor for hypocarnitinemia in adults on MAD and provide carnitine supplementation when low. Further investigations into carnitine and MAD may inform clinical decisions on carnitine supplementation to maximize the efficacy of MAD therapy.

Modified Atkins diet versus ketogenic diet in children with drug-resistant epilepsy: A meta-analysis of comparative studies.

INTRODUCTION: The modified Atkins diet (MAD), a less restrictive form of the ketogenic diet (KD), has gained popularity and is proposed to be an alternative to the traditional KD in the management of drug-resistant epilepsy (DRE). However, the evidence to support this hypothesis remains limited. In this meta-analysis, we aimed to evaluate the efficacy and tolerability of MAD compared to traditional KD in children with DRE. METHOD: We systematically searched multiple databases through March 2022 for all the studies that evaluated the clinical utility of MAD versus KD for DRE in a pediatric population. The primary outcome was the proportion of children who had seizure frequency reduction (SFR) > 50%. The secondary outcomes were SFR >90%, seizure freedom, and diet-related side effects. All measurements were taken 6 months after starting the regimens. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using random-effects model meta-analysis. RESULTS: Six studies, with 397 patients with DRE (201 followed MAD vs. 196 with KD), were included. There was a significant difference in the proportion of patients who attained SFR >50% favoring the traditional KD (RR: 0.63; 95% CI: 0.47-0.83; P = 0.001). However, there was no significant differences in SFR >90% (RR: 0.73; 95% CI: 0.49-1.10; P = 0.13) or the proportion of patients who had seizure freedom (RR: 0.83; 95% CI: 0.49-1.41; P = 0.49). Furthermore, both regimens had comparable safety profiles (RR: 1.00; 95% CI: 0.95-1.05; P = 0.96). CONCLUSIONS: Our meta-analysis demonstrated the superiority of traditional KD over MAD in achieving SFR > 50% at 6 months in pediatric patients with DRE. However, SFR > 90% and seizure freedom were comparable between KD and MAD at 6 months. The tolerability profile between the two regimens was similar as well. Large-scale RCTs are necessary to validate our findings.

Modified Atkins diet versus levetiracetam for non-surgical drug-resistant epilepsy in children: A randomized open-label study.

BACKGROUND: This study was undertaken to compare the efficacy of modified Atkins diet (MAD) among children with non-surgical drug-resistant epilepsy (DRE) to levetiracetam, when added to on-going anti-seizure medications. METHODS: An open-label, randomized controlled trial among children aged 2-12 years with non-surgical DRE was conducted. Eligible children were randomized in a 1:1 ratio to receive add-on MAD or levetiracetam. Baseline and post-intervention seizure frequency at 12 weeks was determined from seizure logs maintained by parents. The primary outcome was the proportion of responders, i.e., patients who achieved > 50% seizure reduction from baseline. Adverse events were compared. Analysis was intention-to-treat. (NCT04172311) RESULTS: One hundred and one children were enrolled (MAD-51, levetiracetam-50). The majority of the enrolled children had generalized seizures of mixed types secondary to structural brain lesions and Lennox-Gastaut syndrome was the most common electroclinical syndrome (46%). The proportion of children with >50% seizure reduction at 12 weeks was significantly higher in the MAD arm compared to the levetiracetam arm (27/51(52.9%) vs 11/50(22%); p < 0.001). At 12-weeks post-intervention, the change in mean seizure frequency compared to baseline was -47.33 ± 39.57% in the MAD arm and -31.15 ± 32.18% in the levetiracetam arm (p = 0.03). Constipation (41.1%) was the most frequent adverse effect with MAD. Sedation/lethargy (18%) and anxiety and irritability (14%) were the most frequent adverse effects in the levetiracetam group. CONCLUSION: Addition of MAD was found to be superior to levetiracetam among children with non-surgical DRE with predominant generalized seizures in achieving seizure reduction at 12 weeks. Both treatments were well tolerated. Adverse effects, although higher with MAD, were expected side effects.

Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier.

The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits-mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1-defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving.

A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy.

Ketogenic diets (KDs) are highly effective in the treatment of epilepsy. However, numerous complications have been reported. During the initiation phase of the diet, common side effects include vomiting, hypoglycemia, metabolic acidosis and refusal of the diet. While on the diet, the side effects involve the following systems: gastrointestinal, hepatic, cardiovascular, renal, dermatological, hematologic and bone. Many of the common side effects can be tackled easily with careful monitoring including blood counts, liver enzymes, renal function tests, urinalysis, vitamin levels, mineral levels, lipid profiles, and serum carnitine levels. Some rare and serious side effects reported in the literature include pancreatitis, protein-losing enteropathy, prolonged QT interval, cardiomyopathy and changes in the basal ganglia. These serious complications may need more advanced work-up and immediate cessation of the diet. With appropriate monitoring and close follow-up to minimize adverse effects, KDs can be effective for patients with intractable epilepsy.

Evaluation of ketogenic diet therapy in children diagnosed with drug-resistant epilepsy: a single-center experience.

BACKGROUND: We evaluate here the effect of the ketogenic diet (KD) on children with drug-resistant epilepsy (DRE) in terms of clinical effectiveness, anthropometric measurements, and some electroencephalogram (EEG) and biochemical findings. METHODS: Included in the study were 18 children (median age 70 months, 61.1% female) who received the classical KD and modified Atkins diet (MAD) for at least one year due to DRE. The patients` demographic and laboratory data; weight, height and body mass index values; EEG and electrocardiographic findings; abdominal ultrasonography findings; and biochemical parameters were recorded at baseline and at 12 months after the initiation of the diet. A reduction of ≥50% in the number of seizures was accepted as a response to KD. RESULTS: Classic KD was chosen for 14 patients (77.8%), and MAD for four patients (22.2%). The response to KD therapy (≥50% reduction) was 55.5% (n = 10) (p = 0.008), and one patient even became seizure-free. By the 12th month of treatment, 10 patients had experienced a reduction of more than 50% in epileptiform discharges, as indicated by EEG findings. There was no difference in seizure reduction between the patients who received classical KD and MAD. A total of 11.1% of the children lost weight during KD treatment. The most common side effect was constipation (n = 10, 55.6%). At the end of one year of treatment, total cholesterol and low density lipoprotein cholesterol (LDL-C) LDL-C levels had increased dramatically, while fasting blood glucose levels had decreased significantly. CONCLUSIONS: Our study suggests that KD treatment provides good clinical efficacy in the treatment of pediatric DRE, and can significantly reduce the frequency of epileptic discharges. Also, total cholesterol and LDL-C levels increased significantly, and fasting blood glucose levels decreased significantly compared to the baseline levels.

Effect of Atkins versus a low-fat diet on gut microbiota, and cardiometabolic markers in obese women following an energy-restricted diet: Randomized, crossover trial.

BACKGROUND AND AIMS: There is controversy about effects of the Atkins diet on cardiometabolic markers in previous studies. No study compared effects of Atkins versus a low-fat diet on gut microbiota in obese women during a weight-loss program up to date. METHODS AND RESULTS: A 6-week, randomized, crossover trial was conducted. Twenty-four healthy women with obesity (BMI≥30 kg/m2) were randomly assigned to receive the Atkins (55%, 25%, and 20% of total daily calories from fat, protein, and carbohydrates), or low-fat (20%, 15%, and 65% of total daily calories from fat, protein, and carbohydrates) diets while following a weight-loss program. Vegetable oils were used as the main source of dietary fat. Dietary groups were switched after two weeks of washout period with a weight maintenance low-fat diet. The effects of the two diets did not differ for the most endpoints. However, Gut Actinobacteria residency and serum total antioxidant capacity significantly increased in the Akins diet group compared with the low-fat one (p = 0.02 and p = 0.04). Adjusting for all parameters, gut Actinobacteria residency 1.48- and 2.5-folds decreased the serum LDL.C/HDL.C ratio and non-HDL.C levels (95%CI: 3.1, -0.22; p = 0.03 and -0.07, -0.002; p = 0.04), respectively. Decrease in gut Proteobacteria residency showed a significant reduction in serum total oxidant status (95%CI: 7.4, -0.07; p = 0.04). CONCLUSIONS: The Atkins diet, based on vegetable oils, alters gut microbiota composition, atherogenic and antioxidant parameters. REGISTRATION NUMBER FOR CLINICAL TRIAL: IRCT20200929048876N3.

Quantitative Three-Dimensional Gait Evaluation in Patients With Glucose Transporter 1 Deficiency Syndrome.

BACKGROUND: Of the patients with glucose transporter 1 deficiency syndrome (GLUT1-DS), 90% have a pathologic gait. Ataxic-spastic and ataxic gaits are seen in 35% of patients each. A ketogenic diet and modified Atkins diet (MAD) are effective therapy in GLUT1-DS in terms of both the seizures and movement disorder. A three-dimensional gait analysis (3DGA) system can be used to evaluate gait quantitatively using spatiotemporal data and gait kinematics. We performed 3DGA in three ambulatory patients with GLUT1-DS to evaluate the characteristics of their gait pathology, and we compared the gait variables before and after enhancing the MAD in one patient. METHODS: After examination by pediatric neurologists and pediatric orthopedic surgeons, 3DGA was performed. We assessed walking speed, step length, step width, gait variability, Gait Deviation Index (GDI), Gait Profile Score (GPS), and Gait Variable Score (GVS). RESULTS: All three patients had a low GDI and high GPS, comprehensive indices of gait pathology. The unstable gait pattern featured a wide step width in one patient and high gait variability in two patients. In the sagittal plane, the patients had increased GVSs in the knee and ankle joints due to excessive knee flexion or extension and excessive ankle plantarflexion. In the horizontal plane, the patients had increased GVSs in the pelvis, hips, and foot due to excessive rotation during walking. After enhancing the MAD, GDI, GPS, and GVSs improved. CONCLUSIONS: 3DGA has potential for quantifying the characteristics of gait pathology and its improvement with dietary therapy in patients with GLUT1-DS.