Ketogenic Diet Therapy Research Articles

The Ketogenic Diet Revisited: Beyond Ketones.

Epilepsy is a neurological disease characterized by seizures, which affects up to 65 million people worldwide (1). About two-thirds of patients with epilepsy are able to achieve seizure control with current antiseizure medication (ASM) (2), whereas one-third of epilepsy patients are difficult to treat, i.e., patients with drug-resistant epilepsy (DRE). In addition, ASM can induce (serious) adverse events and a significant reduction of the quality of life (QoL), leading to ASM retention rates around 50% (3). DRE can induce neurobiochemical alterations and emotional and physical dysfunctions. The multifaceted status of DRE patients underscores the emphasis on non-pharmacological options, and therapies that target multiple mechanisms are likely to be more effective to treat DRE (4), thereby acting as a “magic shotgun” rather than a “magic bullet.” If epilepsy surgery is not an option in a patient with DRE, vagus nerve stimulation (VNS) (5) or dietary treatments, such as the ketogenic diet (KD), are valuable alternative options (5–7). Initial studies with dietary treatments report on the classical KD, consisting of 80% fat and 20% protein plus carbohydrate (4:1 KD) or 75% fat and 25% protein plus carbohydrate (3:1 KD) (8). A KD using medium-chain triglycerides (MCTs) leads to more ketones/kcal of energy and a more efficient absorption (9). Therefore, the MCT diet is less restrictive since it consists of a lower amount of fat and a higher intake of protein and carbohydrate (10). The modified Atkins diet (MAD) (11) and the low-glycemic index treatment (LGIT) (12) are other dietary therapies mimicking the seizure reduction result of the KD, but they are less restrictive. Clinical studies show that both modalities (VNS and KD) lead to a seizure frequency reduction (SFR) by at least 50% in half of the DRE patients. A recent study proposed a treatment algorithm for pediatric DRE, including non-pharmacological treatment options such as VNS and the KD (13). Interestingly, the KD therapy has some advantages in comparison to VNS: the SFR is slightly higher for patients on the KD (14); the KD is non-invasive, and there are few to no neurotoxic effects when compared to multiple ASM (6). Nevertheless, there are barriers and disadvantages in putting the KD into practice, such as palatability issues, compliance issues, side effects (usually mild), variable response rates, and restrictions to the daily life of the patient (15). Overall, a multidisciplinary team (pediatric neurologist, dietician/nutritionist, and a primary care-giver) is indispensable when dietary treatments are initiated and also during maintenance (16). Currently, we are unable to pinpoint the mechanism(s) of action of the KD, and it is possible that dietary therapies will be classified as “magic shotguns” (17–20). Therefore, our aim was to elaborate on the newest pathways involved, such as the gut microbiome and serine synthesis.

Is the antiseizure effect of ketogenic diet in children with drug-resistant epilepsy mediated through proinflammatory cytokines?

In order to understand whether the antiseizure mechanism of ketogenic diet (KD) is mediated through its anti-inflammatory effect, we measured the serum concentrations of cytokines IL- 1β and IL-6 in 21 children with drug-resistant epilepsy. We found a significant reduction in the levels of serum IL- 1β and IL-6 levels at one-year of KD therapy compared to baseline. However, we did not find any correlation between decrease in the serum concentrations of these interleukins with the reduction in seizure frequency at one-year of KD therapy, which may be due to the small sample size and heterogeneous patient population we studied. Future studies should try to overcome these limitations.

Efficacy, tolerability, and safety of zonisamide in children with epileptic spasms: A systematic review and meta-analysis.

Background: Valproate, levetiracetam, benzodiazepines, and topiramate are antiseizure medications (ASMs) considered to have definite efficacy in reducing the frequency of epileptic spasm frequency, apart from ketogenic dietary therapies. Although zonisamide has also been shown to have efficacy as second-line ASM for epileptic spasms, various studies have conflicting results in literature. This systematic review aims to summarize clinical studies regarding the efficacy of zonisamide for epileptic spasms. Methods: We conducted a systematic literature search collating all available literature. The primary objective was to determine efficacy in terms of proportion with complete spasm resolution, we also intended to determine proportion with at least 50% spasm reduction, hypsarrhythmia resolution, and nature/frequency of adverse effects. All prospective/retrospective, controlled/uncontrolled studies describing the use of zonisamide with epileptic spasms were included in the qualitative review excluding case reports, but for metanalysis pertaining to key outcomes, we included studies with at least 10 participants. Results: A total of nineteen publications were found eligible for inclusion in the qualitative review, out of 101 search items. A total of 401 children with epileptic spasms were tried up to a maximum of 9.9-35 mg/kg/day dose with only mild adverse effects in a few patients. Total 20.8% (95% CI-11.4%-29.2%) and 23.4% (95% CI-17.8%-29.1%) patients had complete cessation of spasms and at least a 50% reduction in total spasm frequency as compared to baseline after starting zonisamide. Similarly, 20.3% (95% CI-10.1%-30.5%) had resolution of hypsarrhythmia in EEG after starting zonisamide. Conclusion: Zonisamide can reduce spasms in 21% of children with epileptic spasms, without major adverse effects. But there are only limited studies on epileptic spasms of sufficient quality to give high confidence in meta-analysis. Large controlled trials are needed in this regard to provide high-quality evidence favoring/disfavoring its use in patients with epileptic spasms.

Challenges faced by people with epilepsy on ketogenic diet therapy and their caregivers during the COVID-19 pandemic in Brazil

BackgroundAlthough ketogenic diet therapy (KDT) is a well-established, nonpharmacologic therapeutic option for patients with pharmacoresistant epilepsy, its availability is still not widespread. The COVID-19 pandemic may have further restricted the access of people with pharmacoresistant epilepsy (PWE) to KDT. Thus, we evaluated the experiences of Brazilian PWE and their caregivers during the first year of the pandemic. MethodsAn online self-assessed survey containing 25 questions was distributed via social media to be answered by PWE treated with KDT or their caregivers through Google Forms from June 2020 to January 2021. Mental health was assessed using the DASS and NDDI-E scales. ResultsFifty adults (>18 yo), of whom 68% were caregivers, answered the survey. During the pandemic, 40% faced adversities in accessing their usual healthcare professionals and 38% in obtaining anti-seizure medication (ASM). Despite these issues, 66% of those on KDT could comply with their treatment. Those struggling to maintain KDT (34%) named these obstacles mainly: diet costs, social isolation, food availability, and carbohydrate craving due to anxiety or stress. An increase in seizure frequency was observed in 26% of participants, positively associated with difficulties in obtaining ASM [X2 (1, N = 48) = 6.55; p = 0.01], but not with KDT compliance issues. ConclusionsPeople with pharmacoresistant epilepsy and undergoing KDT, as well as their caregivers, faced additional challenges during the COVID-19 pandemic, not only difficulties in accessing healthcare and KDT maintenance but also on seizure control and mental health.

Ketogenic Diet Therapy for Epilepsy Associated With Aicardi Syndrome.

Aicardi syndrome is a rare neurodevelopmental disorder associated with epilepsy in females. Ketogenic diet therapy represents a possible nonpharmacologic treatment in Aicardi syndrome patients. All patients with Aicardi syndrome seen at Johns Hopkins Hospital (Baltimore, MD) and Johns Hopkins All Children's Hospital (St Petersburg, FL) treated with ketogenic diet therapy since 1994 were evaluated retrospectively. Fifteen patients, ages 4 months to 34 years, were identified. Ten (67%) patients experienced a ≥50% seizure reduction after 3 months, with 3 (20%) having a ≥90% reduction. Only 1 patient was seizure-free for a short period of time. The number of drugs tried prior to ketogenic diet therapy initiation was correlated with ≥50% seizure reduction at 3 months, 5.8 vs 2.6 in responders versus nonresponders (P = .01). In addition, the mean number of drugs actively received also correlated, 3.0 vs 1.2, P = .005. Ketogenic diet therapy was slightly more successful in those without infantile spasms, 78% vs 50%, P = .33. Ketogenic diet therapy was helpful in Aicardi syndrome, although seizure freedom was rare. It was especially helpful for those who were more drug-resistant and did not have infantile spasms at ketogenic diet therapy onset.

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.

The Feasibility and Tolerability of Medium Chain Triglycerides in Women with a Catamenial Seizure Pattern on the Modified Atkins Diet.

Ketogenic diet therapy (KDT), particularly modified Atkins diet (MAD), is increasingly recognized as a treatment for adults with epilepsy. Women with epilepsy (WWE) comprise 50% of people with epilepsy and approximately one in three have catamenial epilepsy. The purpose of this study was to determine whether adding a medium chain triglyceride emulsion to MAD to target catamenial seizures was feasible and well-tolerated. This was a prospective two-center study of pre-menopausal WWE with a catamenial seizure pattern on MAD. After a 1-month baseline interval with no changes in treatment, participants consumed betaquik® (Vitaflo International Ltd.) for 10 days each menstrual cycle starting 2 days prior to and encompassing the primary catamenial seizure pattern for five cycles. Participants recorded seizures, ketones, and menses, and completed surveys measuring tolerability. Sixteen women aged 20–50 years (mean 32) were enrolled and 13 (81.2%) completed the study. There was 100% adherence for consuming betaquik® in the women who completed the study and overall intervention adherence rate including the participants that dropped out was 81.2%. The most common side effects attributed to MAD alone prior to starting betaquik® were constipation and nausea, whereas abdominal pain, diarrhea, and nausea were reported after adding betaquik®. The high adherence rate and acceptable tolerability of betaquik® shows feasibility for future studies evaluating KDT-based treatments for catamenial seizures.

Ketogenic Dietary Therapies in Patients with Autism Spectrum Disorder: Facts or Fads? A Scoping Review and a Proposal for a Shared Protocol.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing incidence. An expanding body of literature is examining connections between ASD and dietary interventions. Existing reports suggest a beneficial effect of ketogenic dietary therapies (KDTs) in improving behavioral symptoms in ASD. In this context, the purpose of this scoping review was to identify and map available evidence in the literature about the feasibility and potential efficacy of KDTs in pediatric patients with ASD and to inform clinical practice in the field. Moreover, based on the resulting data from the literature review, we aimed to provide a shared protocol to develop a personalized KDT intervention in patients with ASD. A comprehensive and structured web-based literature search was performed using PubMed and Scopus and it yielded 203 records. Seven papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study designs and dietary aspects emerged among selected studies. Results supported the effectiveness of KDTs in promoting behavioral improvements. Clinical recommendations on which patients may benefit most from KDTs implementation and difficulties in dietary adherence were discussed.

Ketogenic Diet Therapy for the Treatment of Post-encephalitic and Autoimmune-Associated Epilepsies.

Introduction: Acute Encephalitis is associated with a high risk of acute symptomatic seizures, status epilepticus, and remote symptomatic epilepsy. Ketogenic diet therapies (KDT) have been established as a feasible and safe adjunctive management of refractory- and super-refractory status epilepticus. However, the role of KDT in the chronic management of Post-encephalitic epilepsy (PE) and autoimmune-associated epilepsy (AE) is unknown. This study aims to investigate the use of KDT in patients with PE and AE.Methods: A retrospective single-center case series examining adult patients with PE and AE treated with the modified Atkins diet (MAD), a KDT commonly used by adults with drug-resistant epilepsy.Results: Ten patients with PE and AE who were treated with adjunctive MAD were included. Four patients had either confirmed or presumed viral encephalitis, five patients had seronegative AE, and one patient had GAD65 AE. The median latency between starting MAD and onset of encephalitis was 6 years (IQR: 1–10). The median duration of MAD was 10 months (IQR: 3.75–36). Three patients (30%) became seizure-free, one patient (10%) achieved 90% seizure freedom, and three patients (30%) achieved a 50–75% reduction in their baseline seizure frequency, while three patients (30%) had no significant benefit. Overall, seven patients (70%) achieved ≥50% seizure reduction.Conclusion: In addition to its established role in the treatment of RSE, KDT may be a safe and feasible option for the treatment of chronic PE and AE, particularly in those with prior history of SE. Prospective studies are warranted to explore the efficacy of KDT in management of patients with PE and AE.

Ketogenic diet therapy in Alzheimer's disease: an updated review.

Ketogenic diets (KD) are validated treatments of pharmacoresistant epilepsy. Their interest in neurodegenerative diseases such as Alzheimer's disease (AD) has been suggested, because ketone bodies may reduce neuroinflammation, improve neurotransmitters transport pathway, synaptic maintenance, and reduce brain β-amyloid deposition. In this updated review, we aimed at critically examining the evidence of the past 2 years regarding KD or ketogenic supplements (KS) on cognitive and biological/neuropathological outcomes. We conducted our search in preclinical studies (animal models of AD) or in humans with or without cognitive impairment. Overall, 12 studies were included: four in animal models of AD and eight in humans. In preclinical studies, we found additional evidence for a decrease in cerebral inflammation as well as in specific features of AD: β-amyloid, aggregates of tau protein under KD/KS. Several AD mouse models experienced clinical improvements. Human studies reported significant cognitive benefits, improved brain metabolism and biomarkers change under KD/KS, despite rather short-term interventions. Adherence to KD or KS was acceptable with frequent, but minor gastrointestinal adverse effects. The present review gathered additional evidence for both pathophysiological and clinical benefits of KS/KD in AD. Further studies are warranted with a biomarker-based selection of AD participants and long-term follow-up.

The effect of ketogenic diet on thyroid functions in children with drug-resistant epilepsy.

Ketogenic diet (KD) remains a valuable treatment option for children with drug-resistant epilepsy. However, it may cause many well-known adverse effects such as dyslipidemia or kidney stones. But, its effects on thyroid functions are largely unknown. The aim of this study was to investigate the effects of the KD on thyroid functions in children with drug-resistant epilepsy. A total of 66 children (35 females) aged 3-193 months (median, 52 months) with drug-resistant epilepsy who received a KD for at least 12 months were enrolled in the study. All children were started on KD with 3:1 ratio which was then adjusted as clinically necessary. Serum free-thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations were measured before starting treatment and at the first, sixth and twelfth months of treatment. Changes in FT4 and TSH concentrations over 12 months were analyzed. Median serum FT4 and TSH concentrations, and the frequencies of patients with low FT4 and high TSH concentrations did not change significantly in the study sample over the 12-month study period. Serum FT4 levels increased significantly and TSH concentrations decreased insignificantly in four patients receiving L-thyroxine replacement therapy. During the 12-month treatment period, BMI-SDS increased, and the number of antiepileptic drugs decreased significantly. It appears that KD therapy does not impair thyroid functions in children with drug-resistant epilepsy. KD can be used safely along with L-thyroxine replacement even in children with pre-existing subclinical hypothyroidism.

Efficacy of the ketogenic diet on ACTH- or corticosteroid-resistant infantile spasm: a multicentre prospective control study.

To determine the efficacy of ketogenic diet (KD) therapy on adrenocorticotropic hormone- (ACTH) or corticosteroid-resistant infantile spasm (IS), and identify relevant associated factors. A prospective controlled study was undertaken at 10 tertiary children's medical centres in mainland China. Participants were non-randomly assigned to KD therapy or control (adjustment of antiepileptic drugs). The primary outcome was the reduction in spasms and remission of hypsarrhythmia at the 16th week, divided into Grade I (spasm-free for at least one week with hypsarrhythmia remission), Grade II (≥50% spasm reduction and/or hypsarrhythmia remission) and Grade III (<50% spasm reduction with hypsarrhythmia). In total, 227 patients were recruited and assigned to the KD (135 patients) and control (92 patients) groups. The efficacy in the KD group was superior to that in the control group (Grade I: 13.4% vs. 10.9%; Grade II: 40.7% vs. 20.7%, p=0.025). Patients with a ketogenic ratio <3:1 had a higher rate of Grade I than those with ketogenic ratio ≥3:1 (66.7% vs. 33.3%, p=0.037). No significant correlation was found between the efficacy of KD and level of serum ketosis, aetiology of IS, or age. The efficacy of KD therapy was superior to adjustment of oral antiepileptic drugs in children with ACTH- or corticosteroid-resistant infantile spasms.

Pan-Cancer Analysis of Glycolytic and Ketone Bodies Metabolic Genes: Implications for Response to Ketogenic Dietary Therapy

Background: The Warburg effect is one of the most remarkable and ubiquitous metabolic characteristics exhibited by cancer cells, representing a potential vulnerability for tumor therapy. Ketogenic diets (KDs), composed of high-fat, moderate-protein and low carbohydrates, are aimed at targeting the Warburg effect for cancer treatment, which have recently gained considerable attention. However, the efficiency of KDs was inconsistent, and the genotypic contribution is still largely unknown. Methods: The bulk RNA-seq data from The Cancer Genome Atlas (TCGA), single cell RNA sequencing (scRNA-seq) and microarray data from Gene Expression Omnibus (GEO) were collected. A joint analysis of glycolysis and ketone bodies metabolism (KBM) pathway was performed across over 10,000 samples and nearly 1,000 cell lines. A series of bioinformatic approaches were combined to identify a metabolic subtype that may predict the response to ketogenic dietary therapy (KDT). Mouse xenografts were established to validate the predictive utility of our subtypes in KDT. Findings: We first provided a system-level view of the expression pattern and prognosis of the signature genes from glycolysis and KBM pathway across 33 cancer types. Analysis by joint stratification of glycolysis and KBM revealed four metabolic subtypes, which correlated extensively but diversely with clinical outcomes across cancers. The glycolytic subtypes were driven by TP53 mutations, whereas the KB-metabolic subtypes may be mediated by CTNNB1 mutations. The glycolytic subtypes had better response to KDs compared to other three subtypes. We preliminarily confirmed the idea by literature review and further performed a proof-of-concept experiment to validate the predictive value of the metabolic subtypes using xenografts model. Interpretation: Our findings identified a metabolic subtype based on glycolysis and KBM that may serve as a promising biomarker to predict the clinical outcomes and therapeutic responses to KDT. Funding: This work was supported by grants from the Nature Science Foundation of China (No. 82002509, 81871967, 81903147), China Postdoctoral Science Foundation (No. 2019M661803, 2018M642223), Social Development Foundation of Jiangsu Province of China (No. BE2018604), Jiangsu Provincial Medical Talent, the Nanjing Science and Technology Project (No. 201803028). Declaration of Interest: The authors have declared that no competing interest exists. Ethical Approval: All experimental procedures using animals were in accordance with the guidelines provided by the Animal Ethics Committee of the Affiliated Drum Tower Hospital of Medical School of Nanjing University.

DDRE-31. FEASIBILITY AND BIOLOGIC ACTIVITY OF A KETOGENIC / INTERMITTENT FASTING DIET IN GLIOMA PATIENTS

BACKGROUNDThere has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma.METHODS25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following 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 gm/day) 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, IGF-1, and MR spectroscopy at baseline and week 8.RESULTS21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% 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. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria.CONCLUSIONSThe GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.

41502 Does dietary fat composition predict short-term elevations in lipid levels in adults on a modified Atkins diet?

ABSTRACT IMPACT: Our work provides guidance on whether dietary fat intake influences serum cholesterol levels in response to ketogenic diet therapy in adults with epilepsy. OBJECTIVES/GOALS: The modified Atkins diet (MAD) is used in the management of drug-resistant epilepsy in adults. Some patients on MAD show an increase in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. We explored whether dietary fat composition predicts short-term elevations in serum lipid levels in diet-naive adults who begin MAD. METHODS/STUDY POPULATION: Participants self-reported their diet intake with 3-day food records at baseline, 1 month and 2 months. Food records were analyzed using Nutrition Data System for Research software. Fasting serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides were also collected and LDL level calculated at baseline, 1 month, and 2 months. RESULTS/ANTICIPATED RESULTS: 38 patients submitted complete food records at each study visit (baseline, 1 month, and 2 month). Compared to baseline diet intake, there was a significant reduction in daily carbohydrate intake at 1 and 2 months (p&lt;0.001) and a significant increase in daily fat intake at 1 and 2 months (p&lt;0.001). There was also a significant increase in daily saturated fatty acid (SFA) intake at 1 and 2 months (p&lt;0.001), daily mono-unsaturated fatty acid (MUFA) intake at 1 and 2 months (p&lt;0.001), and daily cholesterol intake at 1 month (p&lt;0.05) and 2 months (p&lt;0.001), but no change in daily poly-unsaturated fatty acid (PUFA) intake over time. Compared to baseline, there was a significant increase in serum LDL at 1 month (p&lt;0.001) and 2 months (p&lt;0.01) and an increase in serum TC at 1 month (p&lt;0.01) but not 2 months. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite a significant increase in total fat, saturated fat and mono-unsaturated fat intake as well as an increase in total cholesterol and LDL levels following MAD initiation, dietary fat composition appears to minimally predict serum lipid values in the short term.

The psychiatric effects of ketogenic diet therapy on adults with chronic epilepsy

ObjectivesPatients with epilepsy are known to exhibit high rates of comorbid psychiatric disorders such as depression, anxiety, and other mood disorders. Little is known about the psychiatric effects of a ketogenic diet therapy (KDT) on adults with epilepsy. The objective of this study was to better understand the relationship between KDT and psychological state based on depressive and anxiety symptoms in adults with chronic epilepsy. MethodsAdults at the Johns Hopkins Adult Epilepsy Diet Center on a modified Atkins diet (MAD) for at least one month were surveyed retrospectively. Adults who were diet naïve were given a baseline survey and an additional survey after 3 months or more on MAD. Surveys included validated measures of depressive and anxiety symptoms as well as their severity. Participant demographics, seizure frequency, and use of concomitant antiseizure drugs (ASDs), chronic anxiolytics (excluding as-needed benzodiazepines for seizure rescue only), and/or antidepressant drugs were extracted from electronic medical records. ResultsOne-hundred participants aged 19–75 enrolled in the study. Sixty participants filled out a single retrospective survey. Of 40 diet naïve participants who filled out a baseline prospective survey, 19 completed a follow-up survey while on MAD and 21 participants were lost to follow-up. Longer diet duration was significantly associated with fewer anxiety and depressive symptoms, based on psychiatric measure scores, in retrospective study participants. Lower seizure frequency was also significantly associated with less anxiety symptoms in the retrospective cohort. Prospective study participants did not experience significant change in anxiety or depressive symptoms on the diet. There was a significant correlation between higher ketone level and responder rate (≥50% seizure reduction) in the prospective cohort, although no correlation between ketone level and change in psychiatric symptoms was seen. SignificancePsychiatric comorbidity among patients with epilepsy is quite common and can be influenced by multiple factors such as seizure frequency, the use of various ASDs, social factors, and underlying etiology. Although ketogenic diet therapies have been in clinical use for one century, the psychiatric impacts have been insufficiently explored. This study provides preliminary evidence that KDT may have a positive impact on psychological state independent of seizure reduction or ketone body production and may be influenced by longer duration of diet therapy. These results support further investigation into specific effects and potential therapeutic benefits on various psychiatric disorders.

Efficacy of low glycemic index diet therapy (LGIT) in children aged 2–8 years with drug-resistant epilepsy: A randomized controlled trial

BackgroundA classic ketogenic diet, even though effective in children with drug-resistant epilepsy is not tolerated well by them and cumbersome to prepare. Low glycemic index therapy (LGIT), the least restrictive with minimal adverse effects among ketogenic dietary therapies has been proven effective in uncontrolled trials, but a placebo-controlled trial in this regard is still lacking. MethodsIn this open-label randomized controlled study, we randomized children above age two years with drug-resistant epilepsy into two groups (LGIT and control groups). Patients in the LGIT group received an add-on low glycemic index diet for 3 months along with the ongoing antiepileptic drugs and the patients in the control group did not receive any dietary intervention. Seizure frequency was assessed from the seizure diary maintained by the parents. Diet compliance was assessed using the diet diary that was maintained by the parents for three days just before the scheduled monthly visits of the patients. ResultsForty children with drug-refractory epilepsy (20 in each group) were enrolled. While 6/20 children in the LGIT arm have >50 % reduction in seizure frequency, none achieved this in the control arm (p = 0.02). The overall compliance with the low glycemic diet in the intervention group was 88.5 %. Out of six responders to LGIT, one child achieved seizure freedom and one achieved >90 % seizure reduction. Five continued LGIT further for a median duration of 8 months (range-4−12 months) successfully. The number needed to treat for more than 50 % seizure reduction was 3 and for more than 90 % seizure reduction was 10. The mean frequency of seizures for the intervention and control groups at three months of follow-up was not significantly different (p = 0.16), but the change in seizure frequency as compared to baseline was better in the intervention arm (p = 0.01). Three patients in the LGIT arm had non-serious adverse events (lethargy in two, vomiting in one). ConclusionIn children aged 2−8 years with drug-refractory epilepsy, the administration of LGIT along with ongoing anti-seizure medications (ASM) is more efficacious in reducing seizure frequency as compared to ASM alone.

Successful implementation of classical ketogenic dietary therapy in a patient with Niemann-Pick disease type C

BackgroundNiemann-Pick disease type C (NP-C) is a neurodegenerative disease for which only palliative treatment exists, and only miglustat is effective in stabilizing neurological manifestations of NP-C. Ketogenic dietary therapies (KDT) are successfully used in patients with seizure disorders, including those associated with various inherited metabolic diseases (IMD), to reduce seizure frequency and medication requirement as well as to confer neuroprotection. Since patients with NP-C suffer pharmacorefractory seizures associated with ongoing neurodegeneration, KDT might be beneficial. The concomitant use of miglustat and KDT in patients with NP-C has not been reported. Case presentationWe describe our experience in a now 17-year-old female with NP-C manifest early in childhood who has been successfully and continuously treated with miglustat and KDT in a palliative care setting for 3y. Although the neurodegeneration of NP-C progressed, she benefited from a reduction in seizure activity, fewer hospital stays related to seizure exacerbation, and increased alertness. ConclusionKDT could be safely deployed in our patient with NP-C, in whom its effects have been beneficial. Generally KDT is demonstratedly efficacious in patients with epilepsy and IMD. It reduces seizure activity and medication requirements and confers neuroprotection. Intracellular cholesterol trafficking and regulation of cholesterol biosynthesis are impaired in NP-C, which may prompt caution with respect to dietary lipid intake.

Six-month effects of modified Atkins diet implementation on indices of cardiovascular disease risk in adults with epilepsy

ABSTRACT Background/Aims Ketogenic diet therapies (KDTs) offer a needed therapeutic option for patients with drug-resistant epilepsy. The current study investigated biochemical and anthropometric indices of cardiovascular disease (CVD) risk in adults with epilepsy treated with KDT over 6 months. Method 65 adults with epilepsy naïve to diet therapy were enrolled in a prospective longitudinal study and instructed on modified Atkins diet (MAD) use. Seizure frequency, anthropometric measures, blood levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 and B, and lipoprotein sub-fractions were assessed at baseline, 3 months, and 6 months. Results Subsequent to study enrollment, 34 participants were lost to follow-up, elected not to start, or stopped MAD prior to study completion, leaving a total of 31 participants in the study at 6 months. Compared to baseline, participants on MAD showed significant reductions in median seizure frequency/week, weight, body mass index, waist and hip circumference, and percent body fat at 3 and 6 months. Compared to baseline, participants on MAD for 3 months showed significantly increased levels of total, small and medium LDL particles, ApoB and ApoB/A1 ratio. At 6 months, only small LDL particles and ApoB levels remained elevated and levels of ApoA1 had risen, suggesting possible compensatory adaptation over time. Conclusions This study provides evidence demonstrating the efficacy and cardiovascular safety of 6 months of MAD use by adults with epilepsy. It also highlights an index of CVD risk – small LDL particles - that should be closely monitored.. Trial registration: ClinicalTrials.gov identifier: NCT02694094..

Neutropenia in Children Treated With Ketogenic Diet Therapy

The objectives were to investigate the relationship between ketogenic diet therapy and neutropenia in children with epilepsy. A retrospective chart review of children who initiated ketogenic diet at the Hospital for Sick Children between January 1, 2000, and May 1, 2018 was performed. Factors associated with the development of neutropenia during ketogenic diet therapy were evaluated and the relationship between development of a significant or suspected infection and neutrophil count was analyzed. One hundred two children met inclusion criteria and were followed on the diet for up to 24 months. Thirteen of 102 (13%) children were neutropenic at diet initiation. In the remaining 89 children, 27 developed neutropenia. Developing neutropenia was significantly associated with the ketogenic diet at 6 (13%), 12 (23%), and 24 (25%) months follow-up. Developing neutropenia was associated with higher urinary ketones (OR = 4.26, 95% CI: 1.27, 14.15) and longer duration of ketogenic diet therapy (OR = 3.29, 95% CI: 1.42, 7.96). There was no significant association between development of a clinically significant infection and neutropenia. Ketogenic diet therapy is associated with neutropenia in children with epilepsy, however, it does not have a significant clinical impact. Concern regarding neutropenia should not discourage the use of the ketogenic diet in children.