Efficacy and tolerability of the modified Atkins diet in children with drug-resistant genetic generalized epilepsy.

OBJECTIVE: The ketogenic diet therapy is a time-tested and potent non-pharmacologic treatment for epilepsy. However, the study of the ketogenic diet in patients with genetic generalized epilepsy (GGE) is not widely established. The aim of this study was to evaluate the efficacy and tolerability of the modified Atkins diet, a variation of the ketogenic diets, as a treatment for drug-resistant GGE. METHODS: A retrospective chart review was performed in patients with epilepsy treated with the modified Atkins diet at the University of Chicago from 2017 to 2020. For three months following diet initiation, participants were monitored for diet tolerability and effect on seizures. Response to the treatment was recorded by self-reporting patients and guardians. RESULTS: Thirteen patients with a diagnosis of drug-resistant GGE were identified. An average of 3.8 anti-seizure medications (ASMs) had been tried and 3.4 years had elapsed from seizure onset before dietary therapy was attempted. Patients were receiving a mean of 2.2 ASMs at the time of diet initiation. After undergoing dietary treatment for three months, 12/13 (92%) patients experienced a greater than 50% reduction in seizure frequency, 6/13 (46%) patients became seizure-free, and 7/13 (54%) were able to discontinue at least one ASM. All patients completed at least three months of dietary therapy with an average duration of 9.3 months at the time of report. One patient reported side effects of fatigue which may be attributed to the diet. SIGNIFICANCE: The modified Atkins diet has shown to be an effective and well-tolerated treatment for children with drug-resistant GGE. The diet provides the additional benefit of aiding to discontinue ASMs and, therefore, minimize the side effects from polypharmacy. Given these results, it seems reasonable to consider the modified Atkins diet as an alternative and possibly earlier treatment option for patients with drug-resistant GGE.

Tratamiento de la epilepsia refractaria. Comparación entre la dieta cetogénica clásica y la de Atkins modificada en cuanto a eficacia, adherencia y efectos indeseables / Treatment of refractory epilepsy. A comparison between classic ketogenic diet and modified Atkins diet in terms of efficacy, adherence, and undesirable effects

Introducción: la dieta cetogénica (CD) es un tratamiento no farmacológico efectivo, ya establecido para la epilepsia refractaria en la infancia. Objetivo: el objetivo de este estudio fue comparar la eficacia, la presencia de efectos indeseables y la adherencia entre la dieta cetogénica clásica (DCC) y la dieta de Atkins modificada (DAM).Materiales y métodos: se realizó una investigación retrospectiva y comparativa, evaluando las historias clínicas de todos los pacientes que iniciaron tratamiento con dieta cetogénica a cargo de un mismo equipo de trabajo entre 2008 y 2018. Se incluyeron 57 pacientes que iniciaron una dieta DAM y 19 pacientes con dieta DCC. Resultados: se observó que tanto la dieta Atkins como la clásica fueron igualmente eficaces (80 %, aproximadamente; p = 0,252). En relación a la adherencia, se registró un porcentaje significativamente mayor de adherencia a la dieta Atkins que a la clásica (p = 0,018). Se observaron menos efectos adversos con la DAM que con la dieta CC (p = 0,012). El 21 % de los pacientes con DAM presentaron efectos desfavorables (12/57), mientras que el 52.63 % de los pacientes en DCC tuvieron complicaciones (10/19). Conclusión: se describe una efectividad equiparable en cuanto al control de crisis entre la DAM y la DCC. Sin embargo, la DAM presenta una adherencia mucho mejor que la observada con la DCC y sus efectos indeseables son más leves y más infrecuentes. Es por eso que, de acuerdo con otros trabajos, la DAM probablemente sea la primera elección para los pacientes con epilepsia refractaria en un gran porcentaje de los casos. (AU)

Background: the ketogenic diet (CD) is an established, effective non-pharmacological treatment for refractory epilepsy in childhood. Aim: the objective of this study was to compare the efficacy, the presence of undesirable effects, and adherence between the classic ketogenic diet (DCC) and the modified Atkins diet (DAM). Materials and methods: a retrospective and comparative investigation was carried out to evaluate the medical records of all the patients who started treatment with a ketogenic diet by the same team between 2008 and 2018. In all, 57 patients were started on a DAM diet and 19 patients were given a DCC diet. Results: it was observed that both the Atkins and the classic diets were equally effective (approximately, 80 %; p = 0.252). Regarding adherence, there was a significantly higher percentage of adherence to the Atkins diet than to the classic diet (p = 0.018). Fewer adverse effects were observed with DAM than with DCC (p = 0.012). In all, 21 % of patients under DAM had unfavorable effects (12/57), while 52.63 % of patients on DCC had complications (10/19). Conclusion: a comparable effectiveness in terms of crisis control was found between DAM and DCC. However, DAM exhibits a much better adherence than DCC, and its undesirable effects are milder, less common. That is why, according to other works, it is likely that DAM should be first-choice for patients with refractory epilepsy in a large percentage of cases. (AU)

[Treatment of refractory epilepsy. A comparison between classic ketogenic diet and modified Atkins diet in terms of efficacy, adherence, and undesirable effects]. / Tratamiento de la epilepsia refractaria. Comparación entre la dieta cetogénica clásica y la de Atkins modificada en cuanto a eficacia, adherencia y efectos indeseables.

INTRODUCTION: Background: the ketogenic diet (CD) is an established, effective non-pharmacological treatment for refractory epilepsy in childhood. Aim: the objective of this study was to compare the efficacy, the presence of undesirable effects, and adherence between the classic ketogenic diet (DCC) and the modified Atkins diet (DAM). Materials and methods: a retrospective and comparative investigation was carried out to evaluate the medical records of all the patients who started treatment with a ketogenic diet by the same team between 2008 and 2018. In all, 57 patients were started on a DAM diet and 19 patients were given a DCC diet. Results: it was observed that both the Atkins and the classic diets were equally effective (approximately, 80 %; p = 0.252). Regarding adherence, there was a significantly higher percentage of adherence to the Atkins diet than to the classic diet (p = 0.018). Fewer adverse effects were observed with DAM than with DCC (p = 0.012). In all, 21 % of patients under DAM had unfavorable effects (12/57), while 52.63 % of patients on DCC had complications (10/19). Conclusion: a comparable effectiveness in terms of crisis control was found between DAM and DCC. However, DAM exhibits a much better adherence than DCC, and its undesirable effects are milder, less common. That is why, according to other works, it is likely that DAM should be first-choice for patients with refractory epilepsy in a large percentage of cases.

INTRODUCCIÓN: Introducción: la dieta cetogénica (CD) es un tratamiento no farmacológico efectivo, ya establecido para la epilepsia refractaria en la infancia. Objetivo: el objetivo de este estudio fue comparar la eficacia, la presencia de efectos indeseables y la adherencia entre la dieta cetogénica clásica (DCC) y la dieta de Atkins modificada (DAM). Materiales y métodos: se realizó una investigación retrospectiva y comparativa, evaluando las historias clínicas de todos los pacientes que iniciaron tratamiento con dieta cetogénica a cargo de un mismo equipo de trabajo entre 2008 y 2018. Se incluyeron 57 pacientes que iniciaron una dieta DAM y 19 pacientes con dieta DCC. Resultados: se observó que tanto la dieta Atkins como la clásica fueron igualmente eficaces (80 %, aproximadamente; p = 0,252). En relación a la adherencia, se registró un porcentaje significativamente mayor de adherencia a la dieta Atkins que a la clásica (p = 0,018). Se observaron menos efectos adversos con la DAM que con la dieta CC (p = 0,012). El 21 % de los pacientes con DAM presentaron efectos desfavorables (12/57), mientras que el 52.63 % de los pacientes en DCC tuvieron complicaciones (10/19). Conclusión: se describe una efectividad equiparable en cuanto al control de crisis entre la DAM y la DCC. Sin embargo, la DAM presenta una adherencia mucho mejor que la observada con la DCC y sus efectos indeseables son más leves y más infrecuentes. Es por eso que, de acuerdo con otros trabajos, la DAM probablemente sea la primera elección para los pacientes con epilepsia refractaria en un gran porcentaje de los casos.

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma.

OBJECTIVE: To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma. METHODS: Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8. RESULTS: Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (ß-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB R s = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria. CONCLUSION: The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02286167.

Beneficial Effects of a Specially Designed Home Meal Replacement on Cardiometabolic Parameters in Individuals with Obesity: Preliminary Results of a Randomized Controlled Clinical Trial.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes.

We previously observed beneficial effects of a carbohydrate-reduced, high-protein (CRHP) diet on cardiovascular risk markers in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, when all food was provided to subjects as ready-to-eat meals. Here, we report the results from a 6-month open label extension: 28 patients with T2DM were instructed to self-prepare the CRHP diet with dietetic guidance. At weeks 0, 6, 12, and 36, fasting and postprandial (4-h meal test) blood samples were collected for measurements of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triacylglycerol (TG), apolipoproteins A1 and B, non-esterified fatty acids (NEFA), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6. Diurnal blood pressure and heart rate were also assessed. At the end of the study (week 36), concentrations of fasting total and LDL-cholesterol, fasting and postprandial NEFA and TG, and fasting apolipoprotein-B, CRP and TNF-α concentrations were significantly lower compared with week 0 (p < 0.05). A significant decrease in diurnal heart rate was also observed. From week 12 to 36, an increase in HDL-cholesterol and apolipoprotein-A1 concentrations and a further reduction in fasting and postprandial NEFA (p < 0.05) were found. These changes were independent of minor fluctuations in body weight. We conclude that the substitution of dietary carbohydrate for protein and fat has beneficial effects on several cardiovascular risk markers in patients with T2DM, which are maintained or augmented over the next 6 months when patients select and prepare the CRHP diet on their own in a dietitian-supported setting.

Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases.

BACKGROUND: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. METHODS: An observational descriptive study was conducted to describe 18 children (January 2009-August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. RESULTS: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. CONCLUSIONS: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.

Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial.

OBJECTIVES: We aimed to evaluate the efficacy of the modified Atkins diet in children with epileptic spasms who had failed hormonal therapy. METHODS: Children aged 9 months to 3 years having daily epileptic spasms despite a trial of ACTH or oral prednisolone and 1 additional anticonvulsant medication were enrolled. Children were randomly assigned to receive the modified Atkins diet either immediately or after a delay of 4 weeks. The ongoing anticonvulsant medications were continued unchanged. The primary outcome variable was the proportion of children who achieved spasm freedom as per parental reports at 4 weeks. Secondary outcomes included time to spasm cessation, proportion of children with electroclinical remission, the proportion of children with >50% reduction of spasms at 4 weeks, and adverse effects of the diet. (ClinicalTrials.gov Identifier: NCT03807141). RESULTS: A total of 91 children were enrolled in the study; 46 in the diet group and 45 in the control group. At the end of 4 weeks, 11 children in the diet group were spasm free compared with none in the control group (P ≤ .001). The median time to achieve spasm cessation was 10 days (interquartile range 9-20). Nine of these had resolution of hypsarrhythmia on electroencephalography (EEG). Thirty (65.2%) in the diet group had >50% reduction in spasms, compared with none in the control group (P < .001). The most common side effect was constipation, noted in 34.8% of the children. CONCLUSIONS: The modified Atkins diet was found to be effective and well tolerated in children with epileptic spasms refractory to hormonal therapy.

The efficacy comparison of classic ketogenic diet and modified Atkins diet in children with refractory epilepsy: a clinical trial.

Dietary therapy has an important role in the therapeutic process in children suffering refractory epilepsy. There are two kinds of dietary therapy which are the most common in children with refractory epilepsy: The classic ketogenic diet (KD) and the modified Atkins diet (MAD). The purpose of the present study was to compare the efficacy, tolerability, and compliance of these two dietary therapies in the children who have refractory epilepsy during 6 months of treatment. From March 2017 to November 2018, 45 children aged 2-15 years who had refractory epilepsy were randomly allocated in KD or MAD group. The intervention period was 6 months in both groups. The frequencies of seizures were determined from parental reports and were compared between the groups. The patients with upper than 50% reduction in seizure frequency were deemed as responders to the diets. Twenty-four patients were assigned to the KD and 11 patients to the MAD. Overall, 45.8% of children treated with the KD and 45.5% of children treated with MAD had over than 50% response to the diet therapies. The difference was not statistically significant (P = 0.437). The MAD was more advantageous regarding better tolerability and fewer side effects. There is not much difference regarding the efficacy between the MAD and classic KD. The MAD with fewer side effects may be more suitable as the first line of dietary therapy in children with refractory epilepsy.

Dietary Management, Clinical Status and Outcome of Patients with Citrin Deficiency in the UK.

BACKGROUND: Little is known about the optimal dietary treatment for citrin deficiency. Our aim is to describe the management of UK citrin deficiency patients. METHODS: A longitudinal retrospective review was performed. Data were collected from medical records on presenting signs and symptoms, dietary management and clinical outcome. RESULTS: data were collected on 32 patients from 21 families. 50% were females (16/32). Median age at diagnosis was 4 y (5 days-35 y) with 12 patients diagnosed in the neonatal period with neonatal intrahepatic cholestasis (NICCD), eight later in childhood (FTTDCD) and 12 by family screening based on index cases from five families. No patient had adult-onset type II citrullinemia. The patient age at the time of data collection was a median of 11 y (1-44 y). 91% (29/32) of patients had normal physical and neurological development, 47% (15/32) experienced recurrent unexplained abdominal pain and 9% (3/32) episodes of hypoglycaemia. Siblings had different phenotypes (5 families had > 1 affected patient). Most patients preferred high protein foods, limiting sugar-containing foods. Only 41% (13/32) were prescribed a low CHO, high protein, high fat diet (restriction varied) and two used medium chain triglyceride (MCT) supplements. No patient was prescribed drug therapy. Twenty-five per cent (8/32) of patients were underweight and 41% (13/32) had height <-1 z-scores. CONCLUSIONS: patients presented with various phenotypes, symptoms and suboptimal growth. Symptoms and biochemical markers improved with age, but height remained low in some. More research is necessary to assess the effectiveness of dietary approaches in improving clinical outcomes and symptoms in citrin deficiency.

Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial.

Importance: The ketogenic diet (KD) has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet compared with the KD are scarce. Objective: To determine whether the MAD and LGIT diet are noninferior to the KD among children with drug-resistant epilepsy. Design, Setting, and Participants: One hundred seventy children aged between 1 and 15 years who had 4 or more seizures per month, had not responded to 2 or more antiseizure drugs, and had not been treated previously with the KD, MAD, or LGIT diet were enrolled between April 1, 2016, and August 20, 2017, at a tertiary care referral center in India. Exposures: Children were randomly assigned to receive the KD, MAD, or LGIT diet as additions to ongoing therapy with antiseizure drugs. Main Outcomes and Measures: Primary outcome was percentage change in seizure frequency after 24 weeks of dietary therapy in the MAD cohort compared with the KD cohort and in the LGIT diet cohort compared with the KD cohort. The trial was powered to assess noninferiority of the MAD and LGIT diet compared with the KD with a predefined, noninferiority margin of -15 percentage points. Intention-to-treat analysis was used. Results: One hundred fifty-eight children completed the trial: KD (n = 52), MAD (n = 52), and LGIT diet (n = 54). Intention-to-treat analysis showed that, after 24 weeks of intervention, the median (interquartile range [IQR]) change in seizure frequency (KD: -66%; IQR, -85% to -38%; MAD: -45%; IQR, -91% to -7%; and LGIT diet: -54%; IQR, -92% to -19%) was similar among the 3 arms (P = .39). The median difference, per intention-to-treat analysis, in seizure reduction between the KD and MAD arms was -21 percentage points (95% CI, -29 to -3 percentage points) and between the KD and LGIT arms was -12 percentage points (95% CI, -21 to 7 percentage points), with both breaching the noninferiority margin of -15 percentage points. Treatment-related adverse events were similar between the KD (31 of 55 [56.4%]) and MAD (33 of 58 [56.9%]) arms but were significantly less in the LGIT diet arm (19 of 57 [33.3%]). Conclusions and Relevance: Neither the MAD nor the LGIT diet met the noninferiority criteria. However, the results of this study for the LGIT diet showed a balance between seizure reduction and relatively fewer adverse events compared with the KD and MAD. These potential benefits suggest that the risk-benefit decision with regard to the 3 diet interventions needs to be individualized. Trial Registration: ClinicalTrials.gov Identifier: NCT02708030.

Effects of modified Atkins diet on thyroid function in adult patients with pharmacoresistant epilepsy.

INTRODUCTION: The use of ketogenic diet as a supplement to antiseizure medication (ASM) in refractory epilepsy has increased the past decades. This high-fat, low-carbohydrate diet mimics the metabolic state of fasting and is generally well-tolerated. However, the long-term adverse effects of the diet are unclear. The purpose of this study was to investigate whether the modified Atkins diet (MAD), a variant of the ketogenic diet, may have an impact on thyroid hormone levels. METHODS: We assessed thyroid function by measuring thyroid stimulation hormone (TSH), fT4, T3, fT3, and rT3 before diet start (baseline) and after 12 weeks on the diet in 53 adult patients with drug-resistant epilepsy. Further, we examined the correlation between the changes in thyroid function during dietary treatment and type of (i) change in seizure frequency, (ii) drugs in use, and (iii) degree of ketosis. RESULTS: After 12 weeks on the diet, we found a significant reduction in T3 and fT3 values (13.4% and 10.6%, respectively) and a significant increase in fT4 values (12.1%) compared with baseline. In addition, there was an insignificant increase in TSH and rT3. These changes were similar in women and men, and there was no correlation to drugs in use (enzyme-inducing vs. nonenzyme-inducing drugs), changes in seizure frequency, or level of ketosis. CONCLUSION: This study indicates that dietary treatment for epilepsy may bring about a modest fall in thyroid hormone levels. This could be relevant for those patients with low thyroid hormones and those treated with ASMs known to lower thyroid hormone levels. A cumulative effect of ASMs, low basal thyroid hormone levels, and ketogenic diet may therefore be of clinical importance in the case of thyroid hormones when treating patients with MAD.

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa.

INTRODUCTION: Glycogen storage disease Type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme, encoded by the AGL gene. Two clinical types of the disease are most prevalent: GSD IIIa involves the liver and muscle, whereas IIIb affects only the liver. The classical dietetic management of GSD IIIa involves prevention of fasting, frequent feeds with high complex carbohydrates in small children, and a low-carb-high-protein diet in older children and adults. Recently, diets containing high amount of fat, including ketogenic and modified Atkins diet (MAD), have been suggested to have favorable outcome in GSD IIIa. METHODS: Six patients, aged 3-31 years, with GSD IIIa received MAD for a duration of 3-7 months. Serum glucose, transaminases, creatine kinase (CK) levels, capillary ketone levels, and cardiac parameters were followed-up. RESULTS: In all patients, transaminase levels dropped in response to MAD. Decrease in CK levels were detected in 5 out of 6 patients. Hypoglycemia was evident in 2 patients but was resolved by adding uncooked cornstarch to diet. CONCLUSION: Our study demonstrates that GSD IIIa may benefit from MAD both clinically and biochemically.

Ketogenic diets for drug-resistant epilepsy.

BACKGROUND: Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with drug-resistant epilepsy. This is an update of a review first published in 2003, and last updated in 2018. OBJECTIVES: To assess the effects of ketogenic diets for people with drug-resistant epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies. SELECTION CRITERIA: RCTs or quasi-RCTs of KDs for people of any age with drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta-analysis. We utilised an intention-to-treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over). We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty. Ketogenic diets versus usual care for children Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low-certainty evidence) and seizure reduction (RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low-certainty evidence) favoured KDs (including: classic KD, medium-chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low-certainty evidence). Ketogenic diet versus usual care for adults In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low-certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low-certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported. Ketogenic diet versus ketogenic diet for children Up to 55% of children achieved seizure freedom with a classical 4:1 KD after three months whilst up to 85% of children achieved seizure reduction (very low-certainty evidence). One trial reported a greater incidence of seizure reduction with gradual-onset KD, as opposed to fasting-onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction. Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD) and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low-certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD, whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate. Ketogenic diet versus ketogenic diet for adults One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate. Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low-certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported. AUTHORS' CONCLUSIONS: The evidence suggests that KDs could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associated risk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty. More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug-resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug-resistant epilepsy.

A low-carbohydrate protein-rich bedtime snack to control fasting and nocturnal glucose in type 2 diabetes: A randomized trial.

In type 2 diabetes, liver insulin resistance and excess hepatic glucose production results in elevated fasting glucose. A bedtime snack has been recommended to improve fasting glucose, yet there is little evidence supporting this recommendation. Moreover, the optimal composition of a bedtime snack is unknown. PURPOSE: To determine whether a low-carbohydrate protein-rich bedtime snack (Egg) could reduce fasting plasma glucose levels in people with type 2 diabetes when compared to a high-carbohydrate protein-rich bedtime snack (Yogurt) or a No Bedtime Snack condition. Secondary outcomes included glucose control assessed by continuous glucose monitoring (CGM) and fasting insulin sensitivity markers. METHODS: Using a randomized crossover design, participants with type 2 diabetes (N = 15) completed three separate isocaloric conditions: i) Egg, ii) Yogurt, and iii) No Bedtime Snack, each lasting three days. CGM was collected throughout and duplicate fasting blood samples were obtained on the morning of day 4 in each condition. RESULTS: Fasting plasma glucose (P = 0.04, d = 0.68), insulin (P = 0.04, d = 0.45), and nocturnal glucose (P = 0.02, d = 0.94) were significantly lower, and quantitative insulin sensitivity check index (QUICKI; P = 0.003) was improved, in the Egg compared to the Yogurt bedtime snack. There were no significant differences between either bedtime snack and No Bedtime Snack. CONCLUSION: In the short-term, a low-carbohydrate bedtime snack (Egg) lowered fasting glucose and improved markers of insulin sensitivity when compared to a high-carbohydrate protein-matched bedtime snack (Yogurt). However, consuming a low- or high-carbohydrate bedtime snack did not appear to lower fasting glucose compared to consuming an isocaloric diet with no bedtime snack. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (NCT03207269).

Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (-56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = -0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.

Different effects of high-protein/low-carbohydrate versus standard hypocaloric diet on insulin resistance and lipid profile: Role of rs16147 variant of neuropeptide Y.

BACKGROUND AND AIMS: Few studies have assessed the effect of the NPY gene rs16147 variant on metabolic response following a dietary intervention. We evaluated the effect of rs16147 on body weight and biochemical changes after a high-protein/low-carbohydrate hypocaloric diet compared with a standard severe hypocaloric diet over 9 months. MATERIALS AND METHODS: A population of 270 obese individuals was enrolled. At baseline, participants were randomly allocated to one of two hypocaloric diets, high protein (Diet HP) or standard (Diet S), for a period of 9 months. RESULTS: After both diets, all genotypes showed decreased body mass index, weight, fat mass, waist circumference, and leptin levels. Participants with the minor allele (A) assigned to the HP diet showed decreases in total cholesterol (-6.5 ±â€¯4.8 vs 10.1 ±â€¯4.1 mg/dL; p < 0.05), LDL cholesterol (-5.9 ±â€¯3.8 vs 9.6 ±â€¯2.4 mg/dL; p < 0.05), triglycerides (-1.0 ±â€¯4.8 vs 16.2 ±â€¯4.1 mg/dL; p < 0.05), insulin (-0.5 ±â€¯2.8 vs 1.7 ±â€¯2.1 UI/L; p < 0.05), HOMA-IR (-0.2 ±â€¯2.1 vs 0.5 ±â€¯2.0 units; p < 0.05), and CRP (-0.3 ±â€¯0.4 vs 1.3 ±â€¯0.2 mg/dL; p < 0.05). Participants with the minor allele assigned to diet S also showed decreases in total cholesterol (-6.1 ±â€¯4.1 vs 14.4 ±â€¯3.1 mg/dL; p < 0.05), LDL-cholesterol (-3.1 ±â€¯2.8 vs 15.0 ±â€¯3.1 mg/dL; p < 0.05), triglycerides (-6.9 ±â€¯4.1 vs 13.2 ±â€¯4.0 mg/dL; p < 0.05), insulin (-0.3 ±â€¯2.1 vs. -1.2 ±â€¯0.2 UI/L: p < 0.05), HOMA-IR (-0.3 ±â€¯2.1 vs. -1.6 ±â€¯1.1 units: p < 0.05), and CRP (-0.4 ±â€¯0.1 vs 1.1 ±â€¯0.2 mg/dL; p < 0.05). CONCLUSION: In obese Caucasians, the presence of the A allele of the rs16147 genetic variant produces a better metabolic response that is secondary to weight loss with two different hypocaloric diets.

Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet.

PURPOSE: The modified Atkins diet (MAD) is a less restrictive treatment option than the ketogenic diet (KD) for intractable epilepsy and some metabolic conditions. Prolonged KD treatment may decrease bone mineralization and affect linear growth; however, long-term studies of MAD treatment are lacking. This study was designed to assess growth, body composition, and bone mass in children on MAD treatment for 24 months. METHODS: Thirty-eight patients, mean age (SD) 6.1 years (4.8 years), 21 girls, with intractable epilepsy (n = 22), glucose transporter type 1 deficiency syndrome (n = 7), or pyruvate dehydrogenase complex deficiency (n = 9) were included. Body weight, height, body mass index (BMI), bone mass, and laboratory tests (calcium, phosphorus, magnesium, alkaline phosphatase, cholesterol, 25-hydroxyvitamin D, insulin-like growth factor-I and insulin-like growth factor binding protein 3) were assessed at baseline and after 24 months of MAD treatment. RESULTS: Approximately 50% of the patients responded with more than 50% seizure reduction. Weight and height standard deviation score (SDS) were stable over 24 months, whereas median (minimum - maximum) BMI SDS increased from 0.2 (-3.3 to 4.5) to 0.7 (-0.9 to 2.6), p < 0.005. No effects were observed for bone mass (total body, lumbar spine and hip) or fat mass. CONCLUSIONS: The MAD was efficient in reducing seizures, and no negative effect was observed on longitudinal growth or bone mass after MAD treatment for 24 months.

Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease.

Ketone bodies, the products of fat metabolism, are a source of energy for the brain and are available even when glucose supplies are inadequate (such as with severe carbohydrate deprivation) or its metabolism is faulty (as it is in Alzheimer's disease). This phase I/II randomized clinical trial examined the feasibility of using a modified Atkins diet (MAD) to induce ketogenesis in persons with mild cognitive impairment (MCI) or early AD, and the effect of this diet on memory and other clinical outcomes. In the first 2.5 years of active recruitment, only 27 eligible and willing patients enrolled. After extensive assessment and education, they and their study partners were randomly assigned for 12 weeks to either the MAD or the National Institute on Aging (NIA) recommended diet for seniors. As of April 2018, 9 patients in the MAD arm and 5 in the NIA arm have completed the trial. In spite of extensive teaching, coaching, and monitoring, adherence to both diets was only fair. Among those in the MAD arm who generated at least trace amounts of urinary ketones, there was a large (effect size = 0.53) and statistically significant (p = 0.03) increase in Memory Composite Score between the baseline and week-6 assessment. MAD participants also reported increased energy between baseline and week-6 assessment. Despite challenges to implementing this trial, resulting in a small sample, our preliminary data suggest that the generation of even trace ketones might enhance episodic memory and patient-reported vitality in very early AD.