Modified Atkins Diet Research Articles

Efficacy and safety of modified Atkins diet therapy for drug‐resistant epilepsy in children and adults: A systematic review and meta‐analysis

AbstractIntroductionDiet‐based treatments have been proposed for drug‐resistant epilepsy (DRE), and the Modified Atkins Diet (MAD) is an alternative. This study aimed to assess the efficacy and safety of MAD as an adjunctive therapy for reducing seizures in patients with drug‐resistant epilepsy.MethodsA literature search was done on six databases. Randomized controlled trial (RCT) studies were included, comparing DRE patients of all ages on standard antiseizure medications (ASD) who received MAD compared to no‐dietary or other dietary interventions. The outcomes are the seizure frequency reduction and the adverse events. Cochrane risk‐of‐bias tool and GRADE were used to assess study quality and the overall certainty of evidence. The effect size of the efficacy of MAD was computed as risk ratio (95% CI). Subgroup analysis based on each type of comparator was done.ResultsTen RCT studies (905 participants) were included, comparing MAD to no dietary intervention, ketogenic diet (KD), and low glycemic index treatment (LGIT). Overall, MAD is constantly and significantly more efficacious than no dietary intervention in reducing seizures ≥50% (RR 7.90, 95% CI 4.59–13.62), ≥90% (RR 4.61, 95% CI 2.05–10.36), and inducing complete seizure‐free (RR 7.79, 95% 2.61–23.22) with high certainty. Other dietary therapies and MAD did not differ significantly from one another in terms of efficacy. The risk of adverse events in MAD is insignificantly higher than in others (RR 1.19, 95% 0.92–1.55).ConclusionThe Modified Atkins Diet has better seizure reduction than no diet intervention but is comparable to other dietary interventions with a negligible increased risk of adverse events.

Predictors of elevations in fasting lipid levels in adults with epilepsy on a modified Atkins diet

BackgroundKetogenic diet therapies can improve seizure control in patients with drug-resistant epilepsy (DRE). The current study investigated whether dietary fat composition is associated with elevations in serum lipid levels in adults with epilepsy who began a modified Atkins diet (MAD). MethodsAdults with DRE were instructed to follow the MAD. Food records collected at baseline and follow-up were analyzed to extract median daily macro- and micronutrient composition. Total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, triglyceride (TG), high-density lipoprotein (HDL) cholesterol, non-HDL and TC/HDL ratio were measured at baseline and follow-up. ResultsStudy participants initiating MAD showed higher fat intake at 1 month (p<0.001) and 2 months (p<0.001) and lower carbohydrate intake at 1 month (p<0.001) and 2 months (p<0.001) compared to baseline. Study participants also showed higher intake of cholesterol (p<0.001), saturated fatty acid (p<0.001) and monounsaturated fatty acid (p<0.001) over time. Following MAD initiation, study participants showed significant increases in levels of TC (p = 0.007), LDL (p<0.001), and non-HDL (p = 0.009) over time. Dietary intake variables, including cholesterol and fat subtypes, were significantly associated with difference in 1 month TC and LDL levels from baseline but not absolute 1 month lipid values. In a sub-analysis, participants with baseline dyslipidemia showed smaller changes in lipid values during diet use. ConclusionsAdults with DRE starting MAD increased fat intake, particularly saturated and monounsaturated fat subtypes, and reduced carbohydrate intake. Changes in TC and LDL levels 1 month after MAD initiation are associated with dietary intake of cholesterol and fat.

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.

Stress biomarkers in adult patients with drug-resistant epilepsy on a modified Atkins diet: A prospective study.

Ketogenic diets like the modified Atkins diet (MAD) are increasingly used in patients with refractory epilepsy. For epilepsy patients, stress is a well-known seizure-precipitating factor. New possibilities for measuring biomarkers of stress are now available. The purpose of this study was to investigate the impact of MAD on endocrine stress biomarkers. Forty-nine patients with drug-resistant epilepsy were investigated at baseline and after 12 weeks on MAD. Cortisol and cortisol-binding globulin (CBG) were measured and free cortisol index (FCI) calculated. We also measured metanephrine, normetanephrine, and methoxytyramine, all markers of epinephrine, norepinephrine, and dopamine, respectively. Changes were analyzed according to sex and antiseizure medications. The different markers at baseline and after 12 weeks of MAD treatment were correlated with seizure frequency and weight loss, respectively. The change in total cortisol was modest after 12 weeks on the diet (from 432.9 nmol/L (403.1-462.7)) to 422.6 nmol/L (384.6-461.0), P = 0.6). FCI was reduced (from 0.39 (0.36-0.42) to 0.34 (0.31-0.36), P = 0.001). CBG increased during the study (from 1126.4 nmol/L (1074.5-1178.3) to 1272.5 nmol/L (1206.3-1338.7), P < 0.001). There were no changes in the metanephrines after 12 weeks on the diet. The decrease in FCI was significant only in women, and only observed in patients using nonenzyme-inducing ASMs. We did not find any correlation between cortisol, CBG, or FCI levels and seizure frequency. After being on MAD for 12 weeks, FCI decreased significantly. The reduction in FCI may reflect reduced stress, but it may also be an effect of increased CBG. The reasons behind these alterations are unknown. Possibly, the changes may be a result of a reduction in insulin resistance and thyroid hormone levels. Treatment with MAD does not seem to influence "fight or flight" hormones.

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

ObjectiveTo 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). MethodsIn 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. ResultsSix 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. SignificanceThis 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.

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

BackgroundEpilepsy 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. MethodsWe 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. ResultSix 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. ConclusionThe 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.

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

ObjectiveThis 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. MethodsWe 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. ResultsThe 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). ConclusionsThe 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.

Brain Glutathione Increase and Seizure Burden Decrease in Patients with Intractable Epilepsy on Ketogenic Diet.

Ketogenic diet (KD) improves seizure control in patients with drug-resistant epilepsy. As increased mitochondrial levels of glutathione (GSH) might contribute to a change in seizure susceptibility, we quantified changes of absolute GSH levels in the brain by in vivo 1H magnetic resonance spectroscopy (1H MRS) and correlate that with degree of seizure control in patients on KD. Five cognitively normal adult patients with drug-resistant epilepsy were initially included and 2 completed the study. Each patient was evaluated by a neurologist and registered dietitian at baseline, 1, 3, and 6 months for seizure status and diet adherence after initiation of a modified atkins diet. Multiple metabolites including GSH were quantified using LCModel (version 6.3-1P; Stephen Provencher, Oakville, ON, CA) on a short echo time single-voxel 1H MRS in parieto/occipital grey matter and parietal white matter on a 3 Tesla General Electric magnet prior to starting the ketogenic diet and at 6 months. Both patients (42-years-old male and 35-years-old female) demonstrated marked increases in absolute GSH level in both gray matter (0.12 to 1.40 and 0.10 to 0.70 international unit [IU]) and white matter (0.65 to 1.50 and 0.80 to 2.00 IU), as well as 50% improvements in seizure duration and frequency. Other metabolites including ketone bodies did not demonstrate consistent changes. Markedly increased levels of GSH (7-fold and 14-fold) were observed in longitudinal prospective study of two adult patients with intractable epilepsy with 50% seizure improvement after initiation of ketogenic diets. This pilot study supports the possible anticonvulsant role of GSH in the brain.

#5187 GREASE II: A PHASE II RANDOMIZED, 24-MONTH, PARALLEL-GROUP, SUPERIORITY STUDY TO EVALUATE THE EFFICACY OF A KETOGENIC DIET IN ADPKD PATIENTS

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the 4th cause of end-stage renal disease in Western Countries, nevertheless still represents an illness with a significant unmet medical need. In recent years, deregulation in glucose metabolism in ADPKD has been identified. Data suggest that cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis. Preclinical experiences show beneficial effects in terms of cystic size reduction, interstitial fibrosis and disease progression, targeting these deregulated metabolic pathways by ketosis induction. A ketogenic diet treatment approach, such as a Modified Atkins Diet (MAD), to ADPKD represents an interesting therapeutic strategy, because of its low cost, tolerability and safety [1]. The Primary Endpoint of this study is the evaluation of the effect of the MAD protocol on the modification of the Total Kidney Volume (TKV), formally qualified, both by FDA and by EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline. Method the initial protocol [2] has been modified in a multicentric study that involves the Divisions of Nephrology of AOU Policlinico di Modena (Modena, Italy) and Policlinico di Sant'Orsola (Bologna, Italy). GREASE II is supported by the Italian Ministry of Health (Ricerca Finalizzata grant no. RF-2021-12374522). During the run-in period, 90 patients will follow a Balanced Normocaloric Diet (BND). In the week preceding the randomization, patients will perform a baseline MRI. Patients will be then randomized to MAD or BND according to a stratified 1:1 ratio. Patients will be followed for 12 months at scheduled clinical and dietetic visits. In the 12ve month, the patients on the MAD arm will be switched to BND and a second MRI will be performed after a month (± 7 days). After the MRI, the patients will be switched again to their original MAD. Patients will be followed for further 12 months at scheduled clinical and dietetic visits. At the 24th month, patients of the MAD arm will be switched once again to BND and after a month (± 7 days) a final visit will be performed (Fig. 1). As co-primary endpoint tolerability and safety will be assessed. Furthermore, as secondary outcomes, the study will evaluate renal function decline, total liver volume (TLV) and the impact of the diets on urinary and serum markers β2MG and MCP-1. Results we expect to obtain a reduction of the TKV in the group of patients treated by the MAD protocol. Safety and tolerability are coprimary endpoints of the study. As secondary exploratory outcomes, the study will evaluate the effect of the diet on the TLV and quality of life (ADPKD-IS and SF-12 questionnaires). This clinical trial will allow us to evaluate the proof of concept of the therapeutic efficacy of MAD in the ADPKD clinical setting. Conclusion GREASE II represents the first multicenter RCT evaluating the reduction of the TKV in ADPKD and renal function decline. The identification of a coordinated reduction of TKV and renal function decline in the patients randomized to the MAD compared to the BND will suggest a protective role of the ketogenic diet against disease progression of ADPKD.

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.

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

IntroductionDrug-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. ObjectiveTo evaluate the effectiveness and tolerability of, and adherence to, the MAD in adults with drug-resistant epilepsy. Material and methodsWe 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. ResultsThirty-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. ConclusionsIn 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.

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.

Impact of two ketogenic diet types in refractory childhood epilepsy

BackgroundKetogenic diet (KD) refers to any diet in which food composition induces a ketogenic state of human metabolism.ObjectiveTo assess short- and long-term efficacy, safety, and tolerability of KD [classic KD and modified Atkins diet (MAD)] in childhood drug-resistant epilepsy (DRE) and to investigate the effect of KD on electroencephalographic (EEG) features of children with DRE.MethodsForty patients diagnosed with DRE according to International League Against Epilepsy were included and randomly assigned into classic KD or MAD groups. KD was initiated after clinical, lipid profile and EEG documentation, and regular follow-up was done for 24 months.ResultsOut of 40 patients with DRE, 30 completed this study. Both classic KD and MAD were effective in seizure control as 60% in classic KD group and 53.33% in MAD group became seizure free, and the remaining showed ≥50% seizure reduction. Lipid profile remained within acceptable levels throughout the study period in both groups. Adverse effects were mild and managed medically with an improvement of growth parameters and EEG during the study period.ConclusionsKD is an effective and safe non-pharmacologic, non-surgical therapy for the management of DRE with a positive impact on growth and EEG.ImpactBoth common types of KD (classic KD and MAD) are effective for DRE, but unfortunately, nonadherence and dropout rates are frequent.High serum lipid profile (cardiovascular AE) is often suspected in children following a high-fat diet, but lipid profile remained in the acceptable level up to 24 months. Therefore, KD constitutes a safe treatment.KD had a positive impact on growth, despite inconsistent results of the KD’s effect on growth.In addition to showing strong clinical effectiveness, KD also considerably decreased the frequency of interictal epileptiform discharges and enhanced the EEG background rhythm.

Keto Is Not Just for Kids: A Randomized Trial of a Modified Atkins Diet for Adolescents and Adults With Anti-Seizure Medication-Resistant Epilepsy.

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Modified Atkins Diet Delayed the Onset of Epileptogenesis, Improved Motor Coordination and Enhanced Learning Memory in Mice

Modified Atkins diet is a high fat, moderate protein and carbohydrate diet that has long been used to manage intractable epilepsy in developed countries. However, the use of this diet for same condition is uncommon in most low- and middle-income countries including Nigeria. In a previous research, we formulated modified Atkins diet using cheap and locally-available food materials in Nigeria. This research is thus, aimed at evaluating the effect of the formulated modified Atkins diet on seizure plasticity using the PTZ-induced kindling model of seizure. We also investigated the effect of sub-chronic use (60 days) of the diet on motor coordination using positional sense test and on visual-spatial reference and learning memory using Morris-water maze. The result revealed that the formulated modified Atkins diet significantly (<i>p<0.05</i>) increased seizure plasticity by reducing the severity of seizure as well as delaying the onset of tonic-clonic seizure and death. The diet also enhanced motor coordination, and improved learning memory, but not reference memory in mice. We therefore concluded that the formulated modified Atkins diet may be of benefit in the management of intractable/treatment-resistant epilepsy, especially in patients who are already suffering from amnesia and/or postural instability since the diet was able to offer protection against seizure-induced memory loss and motor-incoordination in mice.

Застосування кетогенної дієти в педіатрії: спектр можливостей

Purpose - to describe the possibilities of using a ketogenic diet (KD) in the pediatric population for therapeutic purposes in refractory seizure syndrome and congenital metabolic disorders. The historical aspects of the development of special medical nutrition to achieve stable ketosis in children for the treatment of seizures of various genesis are briefly highlighted; the development of the evidence base for the effectiveness of the KD in children is presented. A review of current data on the multifactorial mechanisms of neuroprotective effects of KD is carried out. In particular, individual ways of modulating fundamental biochemical pathways, presynaptic and postsynaptic changes in vesicular transport and release of excitotoxic and inhibitory substrates at synapses are considered. Four types of diets are described according to the distribution of proteins, fats, and carbohydrates: the classic, modified Atkins diet, medium-chain triglyceride diet, and low glycemic index diet. The indications and contraindications for the appointment of medical ketogenic dietary therapy are considered. The most appropriate age periods of childhood for the type of KD are outlined to achieve maximum effectiveness. The authors describe in detail the main objectives of the stages of preparation of the child and family for the start of dietary treatment, the principles of initiation of KD, laboratory and instrumental monitoring and discontinuation of ketogenic dietary therapy. Particular attention is paid to the issue of counseling a child before starting a KD, the main steps in calculating the proportion of macronutrients and the principles of daily nutrition. The possibilities of prescribing medical ketogenic dietary therapy outside of refractory seizures, in particular, in glucose transaminase 1 deficiency syndrome, pyruvate dehydrogenase deficiency, mitochondrial disorders, heart failure, and brain injury, are analyzed. Available special products for medical purposes (clinical nutrition) for the organization of medical ketogenic therapy in pediatric patients, especially in the first years of life, are presented. No conflict of interests was declared by the authors.

Metabolomic, proteomic, and transcriptomic changes in adults with epilepsy on modified Atkins diet.

High-fat and low-carbohydrate diets can reduce seizure frequency in some treatment-resistant epilepsy patients, including the more flexible modified Atkins diet (MAD), which is more palatable, mimicking fasting and inducing high ketone body levels. Low-carbohydrate diets may shift brain energy production, particularly impacting neuron- and astrocyte-linked metabolism. We evaluated the effect of short-term MAD on molecular mechanisms in adult epilepsy patients from surgical brain tissue and plasma compared to control participants consuming a nonmodified higher carbohydrate diet (n= 6 MAD, mean age=43.7 years, range=21-53, diet for average 10 days; n= 10 control, mean age=41.9 years, range=28-64). By metabolomics, there were 13 increased metabolites in plasma (n= 15 participants with available specimens), which included 4.10-fold increased ketone body 3-hydroxybutyric acid, decreased palmitic acid in cortex (n= 16), and 11 decreased metabolites in hippocampus (n= 6), which had top associations with mitochondrial functions. Cortex and plasma 3-hydroxybutyric acid levels had a positive correlation (p= .0088, R2 = .48). Brain proteomics and RNAseq identified few differences, including 2.75-fold increased hippocampal MT-ND3 and trends (p< .01, false discovery rate > 5%) in hippocampalnicotinamideadeninedinucleotide(NADH)-related signaling pathways (activated oxidative phosphorylation and inhibited sirtuin signaling). Short-term MAD was associated with metabolic differences in plasma and resected epilepsy brain tissue when compared to control participants, in combination with trending expression changes observed in hippocampal NADH-related signaling pathways. Future studies should evaluate how brain molecular mechanisms are altered with long-term MAD in a larger cohort of epilepsy patients, with correlations to seizure frequency, epilepsy syndrome, and other clinical variables. [Clinicaltrials.gov NCT02565966.].

Modified Atkins Diet Proves Effective as an Adjuvant Therapy for Refractory Epilepsy in Adults and Teens

Modified Atkins Diet Proves Effective as an Adjuvant Therapy for Refractory Epilepsy in Adults and Teens

A bibliometric analysis of the global trends and hotspots for the ketogenic diet based on CiteSpace.

The ketogenic diet (KD) is a potential nutritional therapy that is frequently utilized in various conditions. More and more studies are being done on KD in recent years. However, as far as we know, few studies have made an effort to offer a thorough synthesis and assessment of this topic. This paper aims to do a rigorous and thorough evaluation of the knowledge structure, development trend, and research hotspot of scientific outputs connected to KD. The bibliographic records connected to KD from January 1, 2001 to April 22, 2022 were collected using the core collection database of Web of Science. The complex data input, that consisted of the amount of publications, journals, authors, institutions, countries, keywords and cited references, was generated and analyzed visually using CiteSpace. A total of 2676 literatures on the KD were published between 2001 and 2022. The most KD-related publications were found in Epilepsia and Epilepsia Research. The authors with the most KD-related papers are Kossoff EH and Rho J. The United States is the country with the most publications, and Johns Hopkins University, Johns Hopkins University Hospital, and Johns Hopkins Medical Institutions are the institutions with the most articles. The high frequency keywords are "KD," "ketone body," "children," "efficacy," "weight loss," "low carbohydrate diet," "metabolism," "epilepsy," "beta hydroxybutyrate," and "modified atkins diet." The 2018 study by Kossoff EH on epilepsia and the 2017 study by Puchalska P on ketone body metabolism earned 127 and 114 citations, respectively. The results of this bibliometric analysis provide information on the state and trends in KD and may be used by researchers to pinpoint hot issues and discover new areas of study.

Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy

Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions. To evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy. Systematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy. Randomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers. Data extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve. Short-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes. Of 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event-related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes. This study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.