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

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

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

BACKGROUND: Ketogenic 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). METHODS: Adults 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. RESULTS: Study 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. CONCLUSIONS: Adults 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.

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

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

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE: 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.

The Modified Atkins Diet for Epilepsy: Two Decades of an "Alternative" Ketogenic Diet Therapy.

In 2003, the first case series of six patients treated with an Atkins diet for epilepsy was published in the journal Neurology. The concept was a simple, outpatient-initiated diet in which ketosis could be maintained by eating high-fat foods while tracking and limiting daily carbohydrate counts based on food ingredient labels. Twenty years later, after dozens of studies encompassing hundreds of patients, including several randomized controlled trials, the Modified Atkins Diet is a proven method of providing ketogenic dietary therapy for epilepsy. It is a diet therapy of choice for adolescents and adults, is being investigated for new-onset epilepsy, and is researched for neurological conditions other than epilepsy. Adverse effects do exist but may be less common than the classic ketogenic diet. This review will cover the history, clinical trials, implementation, current utilization, and future directions of this "alternative" ketogenic diet therapy on its 20-year anniversary.

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

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

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

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

Modified Atkins Diet vs. Ketogenic Diet in the Management of Children with Epileptic Spasms Refractory to First Line Treatment: An Open Labelled, Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy and tolerability of modified Atkins diet (mAD) and ketogenic diet (KD) among children aged 9 mo to 3 y with epileptic spasms refractory to the first line treatment. METHODS: An open labelled, randomized controlled trial with parallel group assignment was conducted among children aged 9 mo to 3 y with epileptic spasms refractory to the first line treatment. They were randomized to either receive the mAD along with conventional anti-seizure medications (n = 20) or KD with conventional anti-seizure medications (n = 20). Primary outcome measure was proportion of children who achieved "spasm freedom" at 4 wk and 12 wk. Secondary outcome measures were proportion of children who achieved >50% and >90% reduction in spasms at 4 wk and 12 wk, nature and proportion of the adverse effects as per parental reports. RESULTS: Proportion of children achieving spasm freedom [mAD {4 (20%)} vs. KD {3 (15%)}: OR (95% CI) 1.42 (0.27-7.34); P = 0.67], >50% spasm reduction [mAD {3 (15%)} vs. KD {5 (25%)}: OR (95% CI) 0.53 (0.11-2.59); P = 0.63] and >90% spasm reduction [mAD {4 (20%)} vs. KD {2 (10%)}: OR (95% CI) 2.25 (0.36-13.97); P = 0.41] was comparable between the two groups at 12 wk. The diet was well tolerated in both the groups with vomiting and constipation being the most common reported adverse effect. CONCLUSIONS: mAD is an effective alternative to KD in the management of children with epileptic spasms refractory to first line treatment. However, further studies with adequately powered sample size and longer follow-up are required. TRIAL REGISTRATION: CTRI/2020/03/023791.

Health-related quality of life in adults with drug-resistant focal epilepsy treated with modified Atkins diet in a randomized clinical trial.

Ketogenic diet, a high-fat, low-carbohydrate diet, is an established treatment for patients with severe epilepsy. We have previously reported a moderate reduction in seizure frequency after treatment with a modified Atkins diet. This study aimed to see whether dietary therapy impacts patients' health-related quality of life (HRQOL). In a randomized controlled design, we compared the change in self-reported HRQOL among adults with difficult-to-treat epilepsy after a 12-week diet intervention. Thirty-nine patients with drug-resistant focal epilepsy (age = 16-65 years) were randomized to eat a modified Atkins diet with maximum 16 g of carbohydrate per day (diet group, n = 19) or to continue eating habitual diet (control group, n = 20). No changes to the other epilepsy treatments were allowed. Patient-reported HRQOL was assessed with the Quality of Life in Epilepsy Inventory-89 (QOLIE-89). The diet group experienced a statistically significant improvement in mean total score of QOLIE-89 of 10 points compared to controls (p = .002). Moreover, although not statistically significant when using a cutoff of 50% seizure reduction, our data suggest an association between diet-induced reduction in seizure frequency and improvement in HRQOL. The improvement in HRQOL was not associated with diet-induced weight reduction.

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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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 hippocampal nicotinamide adenine dinucleotide (NADH)-related signaling pathways (activated oxidative phosphorylation and inhibited sirtuin signaling). SIGNIFICANCE: 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.].

Safety, Efficacy, and Tolerability of Modified Atkins Diet in Persons With Drug-Resistant Epilepsy: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Modified Atkins diet (MAD) has emerged as an adjuvant therapy in drug-resistant epilepsy (DRE). Most studies are in children; there is limited evidence for DRE in adults. This study aimed to investigate whether MAD along with standard drug therapy (SDT) was indeed more effective than SDT alone in reducing seizure frequency and improving psychological outcomes at 6 months in adolescents and adults with DRE (nonsurgical). METHODS: A prospective randomized controlled trial was conducted at tertiary care referral center in India. Persons with DRE aged 10-55 years attending outpatient epilepsy clinics between August 2015 and April 2019, who had more than 2 seizures per month despite using at least 3 appropriate antiseizure medications (ASMs) at their maximum tolerated doses and had not been on any form of diet therapy for the past 1 year, were enrolled. Patients were assessed for the eligibility and randomly assigned to receive SDT plus MAD (intervention arm) or SDT alone (control arm). The primary outcome was >50% reduction in seizure frequency, and the secondary outcomes were quality of life (QOL), behavior, adverse events, and rate of withdrawal at 6 months. Intention-to-treat analysis was performed. RESULTS: A total of 243 patients were screened for eligibility; 160 patients (80 adults and 80 adolescents) were randomized to either the intervention or control arm. Demographic and clinical characteristics in both groups were comparable at baseline. At 6 months, >50% seizure reduction was seen in 26.2% in the intervention group vs 2.5% in the control group (95% CI 13.5-33.9; p < 0.001). Improvement in QOL was 52.1 ± 17.6 in the intervention group vs 42.5 ± 16.4 in the control group (mean difference, 9.6; 95% CI 4.3 to 14.9, p < 0.001). However, behavior scores could be performed in 49 patients, and improvement was seen in the intervention vs control group (65.6 ± 7.9 vs 71.4 ± 8.1, p = 0.015) at the end of the study. One patient had weight loss; 2 patients had diarrhea. DISCUSSION: The MAD group demonstrated improvement in all aspects (reduction in seizure frequency and behavioral problems) compared with the control group at the end of the study. MAD is an effective modality in controlling seizures; further research is required to assess its efficacy in terms of biomarkers along with descriptive metabolomics studies. TRIAL REGISTRATION INFORMATION: The clinical trial registry of India: CTRI/2015/07/006048. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the MAD increases the probability of seizure reduction in adolescents and adults with DRE.

Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy: A Systematic Review and Network Meta-analysis.

Importance: Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions. Objective: To evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy. Data Sources: 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. Study Selection: 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 and Synthesis: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Effects of a low-carbohydrate/high-protein diet on metabolic health in individuals with chronic spinal cord injury: An exploratory analysis of results from a randomized controlled trial.

We explored the impact of a low-carbohydrate/high-protein diet (LC/HP, ~30% energy from protein, 40% energy from carbohydrate) on indices of metabolic function and body composition in individuals with chronic spinal cord injury (SCI). Adults with SCI (≥3 years post-injury, C4-L2, AIS A-D) and insulin resistance or pre-diabetes were randomly assigned to an 8-week iso-caloric LC/HP diet group (n = 11) or control group (n = 14). All LC/HP meals were delivered weekly to participants' homes, and participants in the control group consumed their habitual diet. Each participant underwent an oral glucose tolerance test (OGTT) to assess glucose tolerance, insulin, area under the curve (AUC) for glucose and insulin, Matsuda Index, glucose-stimulated insulin secretion (GSIS), disposition index, and hepatic insulin extraction (HIE). Fasting blood lipid and inflammation were assessed, and body composition was estimated using dual-energy x-ray absorptiometry. A linear mixed model was used to evaluate the main effect of diet, time, and their interaction. Compared to the control group, participants in the LC/HP group had reduced total body fat mass (LC/HP: -5.9%, Control: 0.7%), visceral fat mass (LC/HP: -16.2%, Control: 5.2%), total- (LC/HP: -20.1, Control: 3.7 mg/dl), and LDL-cholesterol (LC/HP: -13.9, Control: 3.1 mg/dl) (pdiet*time < 0.05 for all). Regardless of group, AUCinsulin and peak insulin during the OGTT decreased, and HIE increased over time (ptime < 0.05). A trend for diet*time interaction was observed for glucoseOGTT120min (LC/HP: -20.7, Control: 3.0 mg/dl, pdiet*time  = 0.09) and peak C-peptide (LC/HP: -2.1, Control: 0.0 ng/ml, pdiet*time  = 0.07). HDL-cholesterol, lean body mass, Matsuda Index, fasting glucose, insulin, insulinOGTT120min , AUCglucose , pancreatic beta cell function (GSIS, disposition index), and inflammation (C-reactive protein, IL-6, IL-8, IL-10, TNF-α) did not change over time. In conclusion, our results suggest that individuals with SCI and insulin resistance may adopt an LC/HP diet to improve body composition and lipid profiles. Its impact on glucose metabolism and inflammation remains inconclusive and warrants future investigations.

Effect of the modified Atkins diet in adults with drug-resistant epilepsy: A controlled study.

The objective of this study was to be a proof of concept of an analysis strategy to assess the effectiveness of the modified Atkins diet (MAD) in adults with drug-resistant epilepsy (DRE). This retrospective cohort study included participants aged >16 years with at least two failed antiseizure medications (ASMs). The variables were self-reported and gathered from medical records or phone calls. Two groups are compared: MAD adjuvant to ASM (diet group) and ASM only (control). To make both groups comparable, diet and control groups were matched (1:2) by predictors of seizure remission (PSR) in adults with DRE. A systematic review of the literature was conducted to establish PSR. A total of 127 patients were eligible. Forty-six participants (36 %) initiated the MAD, but only 28 (22 %) continued the diet after 3 months. The number of past and new ASMs, epilepsy type, and follow-up time were selected as PSR. Twelve patients were included in the diet group and 24 in the control group, matched by PSR. Compared with the control group, the diet group had 4.5 greater odds of achieving ≥50 % seizure frequency reduction at 1-3 months (OR 5.5; 90 % confidence interval 1.1-26.65). Mean seizure frequency and other secondary outcomes did not differ significantly between the groups. In summary, the MAD showed a modest effect over seizure control compared with only ASM. Matching by PSR could be an alternative analysis approach to determine the effectiveness of the ketogenic diet in controlled studies. Additional studies are required to validate the analysis proposed.

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

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

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

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

Factors associated with initiation of the modified Atkins diet in adults with drug-resistant epilepsy.

Ketogenic diets are promising therapies for drug-resistant epilepsy (DRE). Diet adherence is a major concern in adults, so a less restrictive diet like the modified Atkins diet (MAD) is preferred. The objective of this study was to explore factors associated with MAD initiation in adults with DRE. It is a retrospective cohort study that includes participants aged ≥ 16 years with at least two failing antiseizure medications (ASM). We compared clinical and demographic variables between those patients who initiated the MAD and those who did not. A total of 136 patients were included and 52 participants initiated a MAD. After 3 months, only 28 patients (58%) continued on the MAD. For those who initiated a MAD trial: 1) the average number of current ASMs (3 ±â€¯1 vs 2 ±â€¯1, p < 0.008) and the average lifetime ASMs (6 ±â€¯3 vs 5 ±â€¯2, p < 0.008) was higher, 2) they had an earlier age of epilepsy onset (9 vs 13 years, p < 0.006) and 3) there was a greater proportion of patients with a history of status epilepticus (OR = 3.89, 95% CI = 1.16-13.01). In contrast, temporal lobe epilepsy onset had a negative association with MAD trial initiation (OR = 0.32, 95% CI = 0.12-0.88). In conclusion, five factors are associated with MAD initiation in adults with DRE. Chronic DRE may be the major motivation for MAD initiation. Nonetheless, adults with a history of status epilepticus could be a target population to initiate the MAD early.

Substantial early changes in bone and calcium metabolism among adult pharmacoresistant epilepsy patients on a modified Atkins diet.

OBJECTIVE: The aim of this study was to investigate whether the modified Atkins diet (MAD), a variant of the ketogenic diet, has an impact on bone- and calcium (Ca) metabolism. METHODS: Two groups of adult patients with pharmacoresistant epilepsy were investigated. One, the diet group (n = 53), was treated with MAD for 12 weeks, whereas the other, the reference group (n = 28), stayed on their habitual diet in the same period. All measurements were performed before and after the 12 weeks in both groups. We assessed bone health by measuring parathyroid hormone (PTH), Ca, 25-OH vitamin D (25-OH vit D), 1,25-OH vitamin D (1,25-OH vit D), phosphate, alkaline phosphatase (ALP), and the bone turnover markers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide collagen type 1 (CTX-1). In addition, we examined the changes of sex hormones (estradiol, testosterone, luteinizing hormone, follicle-stimulating hormone), sex hormone-binding globulin, and leptin. RESULTS: After 12 weeks of MAD, we found a significant reduction in PTH, Ca, CTX-1, P1NP, 1,25-OH vit D, and leptin. There was a significant increase in 25-OH vit D. These changes were most pronounced among patients <37 years old, and in those patients with the highest body mass index (≥25.8 kg/m²), whereas sex and type of antiseizure medication had no impact on the results. For the reference group, the changes were nonsignificant for all the analyses. In addition, the changes in sex hormones were nonsignificant. SIGNIFICANCE: Twelve weeks of MAD treatment leads to significant changes in bone and Ca metabolism, with a possible negative effect on bone health as a result. A reduced level of leptin may be a triggering mechanism. The changes could be important for patients on MAD, and especially relevant for those patients who receive treatment with MAD at an early age before peak bone mass is reached.