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Objective: To investigate incorporating a ready‐to‐use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug‐resistant epilepsy. Methods: Following a three‐day baseline, patients (n = 19; age: 19 years [SD 13], range: 8–46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready‐to‐use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß‐hydroxybutyrate (BHB) concentration, seizure outcomes, health‐related quality of life (HRQoL), acceptability and safety. Results: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). Significance: These findings provide an evidence‐base to support the effective management of children and adults with drug‐resistant epilepsy following a KD with the use of a ready‐to‐use, nutritionally complete, 2.5:1 ratio feed including MCTs. Plain language summary: This study examined the use of a ready‐to‐use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug‐resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively. [ABSTRACT FROM AUTHOR]

Objective: We aimed to find predictors for smartphone application‐based ketogenic diet (KD) treatment effectiveness and safety. Methods: The efficacy was evaluated according to the reduction in seizure frequency after the intervention of KD; safety was evaluated based on adverse effects. The ordinal logistic regression analysis was used to explore the influencing factors of efficacy. Results: The study sample included 116 males and 65 females with a median age of 2.27 years. The baseline frequency of seizure was more than five times/day in 123 children, 50.83% of them received three or more antiepileptic drugs (AEDs). Seventy‐two patients' KD initiation mode was outpatient, and 73 completed the 12‐month follow‐up. A total of 88 (48.62%) patients had reported a reduction in seizure ≥50%. Compared with 12 months, those who had received KD therapy for only 3 (P = 0.009) and 6 months (P = 0.005) were more likely to show negative outcomes. Outpatient initiation had better outcomes (P = 0.029) than inpatient initiation. For the number of AEDs applied, patients on two AEDs were more likely to achieve better outcomes (P = 0.001). Adverse events had been noted among 77 patients; BMI Z‐score at KD initiation was associated with adverse effects (P = 0.003). Significance: Our study suggested that outpatient initiation and long‐term treatment of KD should be encouraged. Plain Language Summary: Our research shows that the KD is a helpful treatment for children with refractory epilepsy, reducing seizures by more than 50% in nearly half of the cases, with some experiencing complete seizure freedom. We used a smartphone app to improve communication between patients and their healthcare teams, resulting in a high retention, and app usage was linked to reduced adverse effects. We recommend early consideration of KD treatment for patients failing two AED, encourage outpatient initiation, and advocate for longer‐term KD use. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) has shown excellent performance in the treatment of refractory epilepsy, but how it works is not yet fully understood. Gut microbiota is associated with various neurological disorders through the brain-gut axis. Different dietary patterns have different effects on the composition and function of gut microbiota. Here, by analyzing fecal samples from some patients with mitochondrial epilepsy before and after KD treatment through 16SrRNA sequencing, we found that KD intervention reduced the abundance of Firmicutes in the patient's gut, while the abundance of Bacteroidota increased in the KD group. LefSe analysis showed that Actinobacteriota, Phascolarctobacterium had significant advantages in the control group, while Bacteroides increased significantly after KD intervention, especially Bacteroides fragilis. Functional analysis showed that there were significant differences in 12 pathways in level 3. These changes suggest that KD can change the composition and diversity of the gut microbiota in patients and affect their function. Changes in specific bacterial groups in the gut may serve as biomarkers for the therapeutic effects of KD on epilepsy. [ABSTRACT FROM AUTHOR]

Background: The ketogenic diet is one of the oldest diets that has been used for more than a centennial in the clinical setting, and it is gaining popularity as a measure to fight obesity, which is a major predisposing factor for many diseases to manifest, including diabetes mellitus, chronic heart disease, cancer, and others. Thus, we designed this retrospective investigation to determine if users of the mobile application KetoCycle achieved statistically significant weight loss outcomes. Methods: The initial study cohort comprised 12,965 consecutive users who started using KetoCycle between January 2020 and December 2020. The final cohort comprised 10,269 users. The main parameters obtained from the database containing all self-reported data were gender, number of active days (AD), total time of use (TT), height, initial weight, and last recorded weight. The primary outcome of the study was weight loss. Statistical analyses were performed using IBM SPSS Statistics, version 26 (IBM Corp., Armonk, NY, USA). In addition, a standard multiple regression model was created to predict weight loss from significant actions. Results: A retrospective analysis of KetoCycle user data showed that 87.3% of KetoCycle users lost some of their initial weight. Of those, 1645 users (18.3%) lost more than 10% of their initial body weight, 3528 (39.3%) users lost between 5 and 10% of their initial body weight, and 3796 (42.3%) users lost less than 5% of their body weight. When user activity was taken into account, it was found that active users lost statistically significantly more weight than non-active users (p < 0.05). App engagement was also associated with losing > 5% of initial weight. Using water tracking, weight tracking, and creation of a meals list within KetoCycle statistically significantly predicted weight loss in a multiple regression model. Conclusions: We concluded that KetoCycle appeared as a promising mobile application suited for weight loss and weight control. Trial registration: This retrospective chart review study was approved by BRANY IRB in January 2022 (registration ID.: 21-08-564-939). [ABSTRACT FROM AUTHOR]

Evidence suggests that low carbohydrate (< 130 g/day of carbohydrate) (LCD) and very low carbohydrate, ketogenic diets (typically < 50 g/day of carbohydrate) (VLCKD) can be effective tools for managing diabetes given their beneficial effects on weight loss and glycemic control. VLCKD also result in favorable lipid profile changes. However, these beneficial effects can be limited by poor dietary adherence. Cultural, religious, and economic barriers pose unique challenges to achieving nutritional compliance with LCD and VLCKD. We review the various methods for assessing adherence in clinical studies and obstacles posed, as well as potential solutions to these challenges. [ABSTRACT FROM AUTHOR]

In the article, the authors present their literature review to determine the effects of ketogenic eating pattern on glycemic management and the impact of ketogenic diet on AIC, fasting blood glucose (FBG), and postprandial glucose (PPG) levels in individuals with type 2 diabetes. Topics include how eating pattern can help achieve nutritional ketosis and how the said diet was used to treat epilepsy and diabetes.

Ketogenic diets (KD) are high in fat and low in carbohydrates, forcing cells to utilize mitochondrial fatty acid oxidation for energy production. Since cancer cells demonstrate increased mitochondrial oxidative stress relative to normal cells, we hypothesized that a KD may selectively enhance metabolic oxidative stress in head and neck cancer cells, sensitizing them to radiation and platinum-based chemotherapy without causing increased toxicity in surrounding normal tissues. This hypothesis was tested in preclinical murine xenografts and in a phase 1 clinical trial (NCT01975766). In this study, mice bearing human head and neck cancer xenografts (FaDu) were fed either standard mouse chow or KetoCal® KD (90% fat, 8% carbohydrate, 2% protein) and exposed to ionizing radiation. Tumors were harvested from mice to test for glutathione, a biomarker of oxidative stress. In parallel, patients with locally advanced head and neck cancer were enrolled in a phase 1 clinical trial where they consumed KD and received radiation with concurrent platinum-based chemotherapy. Subjects consumed KetoCal KD via percutaneous endoscopic gastrostomy (PEG) tube and were also allowed to orally consume water, sugar-free drinks, and foods approved by a dietitian. Oxidative stress markers including protein carbonyls and total glutathione were assessed in patient blood samples both pre-KD and while consuming the KD. Mice bearing FaDu xenografts that received radiation and KD demonstrated a slight improvement in tumor growth rate and survival compared to mice that received radiation alone; however a variation in responses was seen dependent on the fatty acid composition of the diet. In the phase 1 clinical trial, a total of twelve patients were enrolled in the study. Four patients completed five weeks of the KD as per protocol (with variance in compliance). Eight patients did not tolerate the diet with concurrent radiation and platinum-chemotherapy (5 were patient decision and 3 were removed from study due to toxicity). The median number of days consuming a KD in patients who did not complete the study was 5.5 (range: 2–8 days). Reasons for discontinuation included "stress of diet compliance" (1 patient), grade 2 nausea (3 patients), and grade 3 fatigue (1 patient). Three patients were removed from the trial due to dose-limiting toxicities including: grade 4 hyperuricemia (2 patients) and grade 3 acute pancreatitis (1 patient). Median weight loss was 2.95% for the KD-tolerant group and 7.92% for patients who did not tolerate the diet. In conclusion, the ketogenic diet shows promise as a treatment combined with radiation in preclinical mouse head and neck cancer xenografts. A phase 1 clinical trial evaluating the safety and tolerability of KD demonstrated difficulty with diet compliance when combined with standard-of-care radiation therapy and cisplatin chemotherapy. [ABSTRACT FROM AUTHOR]

Pharmacoresistant epilepsy causes serious deleterious effects on the patient's health and quality of life. For this condition, a ketogenic diet (KD) is a treatment option. The KD is a general term for a set of diets that contain high amounts of fat and low content of carbohydrates. The most prominent KD treatments are classical KD (4:1 ratio of fat to carbohydrate), modified Atkins diet (2:1 to 1:1 ratio), medium-chain triglycerides KD (with medium-chain triglyceride as a part of the fat content), and low glycemic index KD (using low glycemic carbohydrates). KD has been widely prescribed for children with epilepsy but not for adult patients. One of the main concerns about adult use of KD is its cardiovascular risk associated with high-fat and cholesterol intake. Therefore, this narrative review provides comprehensive information of the current literature on the effects of KD on lipid profile, glycemic-control biomarkers, and other cardiometabolic risk factors in adult patients with pharmacoresistant epilepsy. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review presents the most current recommendations for providing nutrition to the neurocritical care population. This includes updates on initiation of feeding, immunonutrition, and metabolic substrates including ketogenic diet, cerebral microdialysis (CMD) monitoring, and the microbiome. Recent Findings: Little evidence exists to support differences in feeding practices among the neurocritical care population. New areas of interest with limited data include use of immunonutrition, pre/probiotics for microbiome manipulation, ketogenic diet, and use of CMD catheters for substrate utilization monitoring. Summary: Acute neurologic injury incites a cascade of adrenergic and neuroendocrine events resulting in a pro-inflammatory and hypercatabolic state, which is associated with an increase in morbidity and mortality. Nutritional support provides substrates to mitigate the damaging effects of hypermetabolism. Despite this practice, studies on feeding delivery outcomes remain inconsistent. Guidelines suggest use of early enteral nutrition using standard polymeric formulas. Population heterogeneity, variability in interventions, complexities of the metabolic and inflammatory responses, and paucity of nutrition research in patients requiring neurocritical care have led to controversies in the field. It is imperative that more pragmatic and reproducible research be conducted to better understand underlying pathophysiology and develop interventions that may improve outcomes. [ABSTRACT FROM AUTHOR]

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Rationale: Impaired cerebral glucose metabolism is a core pathological feature of schizophrenia. We recently demonstrated that a ketogenic diet, causing a shift from glycolysis to ketosis, normalized schizophrenia-like behaviours in an acute N-methyl-D-aspartate (NMDA) receptor antagonist model of the illness. Ketogenic diet produces the ketone body, β-hydroxybutyrate (BHB), which may serve as an alternative fuel source in its own right without a strict dietary regime. Objective: We hypothesized that chronic administration of BHB replicates the therapeutic effects of ketogenic diet in an acute NMDA receptor hypofunction model of schizophrenia in mice. Methods: C57Bl/6 mice were either treated with acute doses of 2 mmol/kg, 10 mmol/kg, or 20 mmol/kg BHB or received daily intraperitoneal injections of 2 mmol/kg BHB or saline for 3 weeks. Behavioural testing assessed the effect of acute challenge with 0.2 mg/kg MK-801 or saline on open field behaviour, social interaction, and prepulse inhibition of startle (PPI). Results: Acute BHB administration dose-dependently increased BHB plasma levels, whereas the 2 mmol/kg dose increased plasma glucose levels. The highest acute dose of BHB supressed spontaneous locomotor activity, MK-801-induced locomotor hyperactivity and MK-801-induced disruption of PPI. Chronic BHB treatment normalized MK-801-induced hyperlocomotion, reduction of sociability, and disruption of PPI. Conclusion: In conclusion, BHB may present a novel treatment option for patients with schizophrenia by providing an alternative fuel source to normalize impaired glucose metabolism in the brain. [ABSTRACT FROM AUTHOR]

With the rising demand for ketogenic diet therapy in adult epilepsy, there is a need for research describing the real-life effectiveness, retention, and safety of relevant services. In this 1-year prospective cohort study we present outcomes of the first 100 referrals for modified ketogenic diet (MKD) at the UK's largest tertiary-care epilepsy centre, where patients received dietetic review up to twice per week. Of the first 100 referrals, 42 (31 females, 11 males; mean age 36.8 [SD ± 11.4 years]) commenced MKD, having used a mean of 4 (SD ± 3) previous antiepileptic drugs. Retention rates were: 60% at 3 months, 43% at 6 months, and 29% at 12 months. 60% of patients reported an improvement in seizure frequency, 38% reported a > 50% reduction, and 13% reported a period of seizure freedom; 30% reported a worsening in seizure frequency at some point during MKD therapy. The most common reasons for discontinuing MKD were side effects and diet restrictiveness. The most common side effects were weight loss, gastrointestinal symptoms and low mood. The likelihood of discontinuing MKD was significantly decreased by experiencing an improvement in seizure frequency (p ≤ 0.001). This study demonstrates that MKD can be effective in adults, although, even with regular dietetic support, retention rates remain low, and periods of worsening seizure frequency are common. [ABSTRACT FROM AUTHOR]

Drug-refractory epilepsy is a commonly prevalent pediatric neurological illness of global significance. Ketogenic diet (KD) is a time-tested therapeutic modality for refractory epilepsy, which has reemerged as a robust alternative to anti-epileptic pharmacotherapy. There is a growing body of evidence which supports the anti-seizure efficacy, safety profile and feasibility of KD use in childhood epilepsy. In addition, this modality has been recognized to reduce anti-epileptic exposure, improve cognition and behavioral profile of patients as well as improve the quality-of-life of care-givers. Current indications of KD include refractory epilepsy syndromes, selected metabolic disorders (such as pyruvate dehydrogenase deficiency) and a host of varied neurological entities. KD research has broadened the knowledge-base about its mechanisms of action. Four types of KD are in vogue currently with varying nutritional constitution, palatability, administration protocols and comparable efficacy. KD initiation and maintenance are the result of concerted effort of a team of pediatric neurologist/epileptologist, nutritionist and patient's primary care-giver. Consensus is being formulated about various practical aspects of KD such as patient-selection, parental counseling, baseline work-up, dietary prescription, nutritional supplementation, concurrent anti-epileptic drug administration, follow-up and treatment-duration. Novel applications of KD include its use in neonatal epilepsy and super-refractory status epilepticus and tailor-made formulations such as cooking oil-based KD in predominantly rice-fed populations. Increasing body of clinical experience, improved nutritional designs and translational research are promoting KD as a major therapeutic modality. Currently, KD forms a core essence in the armamentarium against refractory epilepsy. In this review, we summarize the recent advances and current perspectives in the use of KD in refractory epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: Classical ketogenic diet (KD) and modified Atkins diet (MAD) are two types of KD commonly used for the treatment of intractable epilepsy throughout the world. Studies have shown the efficacy of these diets. However, no systematic review and meta-analysis study has to date compared the efficacy of KD and MAD in a time trend. Therefore, the objectives of the present study were to compare the short-term and long-term efficacy of classical KD and MAD in children and adolescents with epilepsy and to determine the efficacy of classical KD and MAD at multiple time points and in a time trend. Methods: Main electronic literature databases, including MEDLINE/PubMed, Web of Science, Scopus, and EMBASE, were searched in November 2016. Rate difference and random effects model were used to compare the efficacy of the classical KD and MAD. Results: Overall, 70 studies were eligible for inclusion. Meta-analysis revealed a non-significant trend toward a higher efficacy of MAD at month-3 and month-6 (P > 0.05). In the classical KD group, the percentage of responder patients achieving ≥50% seizure reduction was 62, 60, 52, 42, and 46% at month-1, 3, 6, 12 and 24 and for the MAD group was 55, 47, 42, and 29% at month-1, 3, 6, and 12, respectively. Discussion: Classical KD does not differ substantially from MAD in ≥50% and ≥90% reduction of seizure frequency at month-3 and month-6. Overall, the number of patients achieving seizure freedom increases over time. [ABSTRACT FROM AUTHOR]

Summary: Objective: Ketogenic diets reduce seizures in children with drug‐resistant epilepsy. Whether adults benefit from similar treatment has not been clarified. We therefore examined the efficacy of the modified Atkins diet in adults with drug‐resistant focal epilepsy. Methods: We performed a randomized clinical trial (RCT) with patients >16 years who had at least 3 seizures per month despite having tried at least 3 antiepileptic drugs. They were randomized to either 12 weeks on the modified Atkins diet (diet group) or habitual diet (control group). Primary endpoint was a change in seizure frequency from baseline to the intervention period, comparing those on diet with controls. Results: We assigned 37 patients to the diet group and 38 to the control group. Nine of the patients in the diet group and 4 controls were excluded. Of those who completed the dietary intervention (n = 24), median seizure change was −1.0 (interquartile range [IQR] −13.7‐8.8), while in the control group (n = 32) the median change was 4.5 (IQR −4.8‐33.5). The median difference between the groups was −7.0 (95% confidence interval [CI] −37.0‐3.0; P = .21). In the intention‐to‐treat analysis, the relative risk (RR) for achieving >50% seizure reduction was 1.8 (95% CI 0.3‐10.2; P = .65), while for achieving >25% seizure reduction RR was 2.43 (95% CI 0.94‐6.28; P = .06). We observed no serious adverse events. Significance: In this RCT investigating the effect of an adjunctive modified Atkins diet on seizure frequency in adults with difficult‐to‐treat focal epilepsy, we found a significant reduction in seizure frequency in the diet group compared to the controls, but only for moderate benefit (>25% seizure reduction) among those who completed the intervention. However, seizure response varied considerably between individuals, perhaps negatively influenced by a drop in serum concentrations of antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Summary: The ketogenic diet (KD) is an effective treatment for children with drug‐resistant epilepsy and has been widely used in young children. Adult patients with intractable epilepsy would also benefit from this dietary treatment. However, only a few studies have been published, and the use of the KD in intractable epilepsy in adults has been limited. This meta‐analysis summarized the findings of the relevant published studies to identify the efficacy of the KD for the treatment of intractable epilepsy in adults. In this meta‐analysis, PubMed, Embase, and Cochrane Library were used for searching studies concerning the effects of the KD and its major subtypes with intractable epilepsy in adults published up to January 10, 2017. The primary outcomes were seizure freedom, seizure reduction by 50% or more, and seizure reduction by <50%. The quality of the methodology of the observational studies was reviewed by using the Newcastle‐Ottawa Scale. We identified 402 articles, of which, 16 studies including 338 patients met the inclusion criteria. The results of the meta‐analysis showed that the combined efficacy rates of all the symptoms of seizure freedom, seizure reduction by 50% or more, and seizure reduction below 50% in adults with intractable epilepsy were 13%, 53%, and 27%, respectively. The adverse reactions of the KD were mild, whereas low glycemic index diet (LGID) and low‐dose fish oil diet (LFOD) may have fewer side effects. Weight loss, high level of low‐density lipoprotein, and elevated total cholesterol were most frequent. The meta‐analysis indicates that the KD for refractory epilepsy in adults is a well‐tolerated treatment and that its side effects are acceptable, which show that the KD is a promising treatment in adult intractable epilepsy. Further research is needed to assess which type of diet or ratio is more effective in the KD treatment. [ABSTRACT FROM AUTHOR]