Medium Chain Triglyceride Ketogenic Diet Research Articles

Efficacy and safety of modified medium-chain triglyceride ketogenic diet in patients with drug-resistant epilepsy

BackgroundMedium-chain triglyceride ketogenic diet (MCTKD) is previously less commonly used in China. This study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese patients.MethodsPatients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September 2022. The modified MCTKD contained fat that provided 50–70% of the total energy, as well as proteins and carbohydrates that provided 20–30% and 20% of energy, respectively. The fat component was composed of 20–30% medium-chain triglycerides (MCTs) and 30–40% long-chain triglycerides. The efficacy and safety of the diet were assessed at 1, 3 and 6 months.ResultsA total of 123 patients aged 2.5 to 65 years, were included in this study. The response rates at 1, 3 and 6 months were 49.6%, 43.1%, and 30.9%, respectively. The seizure freedom rates at 1, 3 and 6 months were 12.2%, 10.6%, and 6.5%, respectively. The retention rates at 1, 3 and 6 months were 98.4%, 65.0% and 33.3% respectively. Side effects occurred in 21.14% of patients, which were predominantly gastrointestinal symptoms such as abdominal pain, diarrhea, vomiting, and constipation, and most of them resolved after dietary adjustments. A total of 82 patients (66.7%) discontinued the treatment with the reason of refusing to eat (8.1%), poor efficacy (35.0%), poor compliance (4.9%), and inability to follow-up (9.8%). Only 4 patients (3.3%) withdrew the diet due to side effects.ConclusionsThe modified MCTKD with MCTs providing 20–30% of energy has a good safety in patients with drug-resistant epilepsy, but its effectiveness needs to be enhanced. Further modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.

Potential benefits of medium chain fatty acids in aging and neurodegenerative disease.

Neurodegenerative diseases are a large class of neurological disorders characterized by progressive dysfunction and death of neurones. Examples include Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Aging is the primary risk factor for neurodegeneration; individuals over 65 are more likely to suffer from a neurodegenerative disease, with prevalence increasing with age. As the population ages, the social and economic burden caused by these diseases will increase. Therefore, new therapies that address both aging and neurodegeneration are imperative. Ketogenic diets (KDs) are low carbohydrate, high-fat diets developed initially as an alternative treatment for epilepsy. The classic ketogenic diet provides energy via long-chain fatty acids (LCFAs); naturally occurring medium chain fatty acids (MCFAs), on the other hand, are the main components of the medium-chain triglyceride (MCT) ketogenic diet. MCT-based diets are more efficient at generating the ketone bodies that are used as a secondary energy source for neurones and astrocytes. However, ketone levels alone do not closely correlate with improved clinical symptoms. Recent findings suggest an alternative mode of action for the MCFAs, e.g., via improving mitochondrial biogenesis and glutamate receptor inhibition. MCFAs have been linked to the treatment of both aging and neurodegenerative disease via their effects on metabolism. Through action on multiple disease-related pathways, MCFAs are emerging as compounds with notable potential to promote healthy aging and ameliorate neurodegeneration. MCFAs have been shown to stimulate autophagy and restore mitochondrial function, which are found to be disrupted in aging and neurodegeneration. This review aims to provide insight into the metabolic benefits of MCFAs in neurodegenerative disease and healthy aging. We will discuss the use of MCFAs to combat dysregulation of autophagy and mitochondrial function in the context of "normal" aging, Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease.

The efficacy of a medium-chain triglyceride ketogenic diet for drug-resistant epilepsy with PIGA germline variant

The efficacy of a medium-chain triglyceride ketogenic diet for drug-resistant epilepsy with PIGA germline variant

Neuroprotective effect of a medium-chain triglyceride ketogenic diet on MPTP-induced Parkinson’s disease mice: a combination of transcriptomics and metabolomics in the substantia nigra and fecal microbiome

The ketogenic diet (KD) is a low carbohydrate and high-fat protein diet. It plays a protective role in neurodegenerative diseases by elevating the levels of ketone bodies in blood, regulating central and peripheral metabolism and mitochondrial functions, inhibiting neuroinflammation and oxidative stress, and altering the gut microbiota. However, studies on ketogenic therapy for Parkinson’s disease (PD) are still in their infancy. Therefore, we examined the possible protective effect of KD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, examined the mouse gut microbiota and its metabolites, and performed transcriptomics and metabolomics on the substantia nigra of mice. Our results showed that a long-term medium-chain triglyceride KD (MCT-KD) significantly reduced MPTP-induced damage to dopaminergic (DA) neurons, exerted antioxidant stress through the PI3K/Akt/Nrf2 pathway, and reversed oxidative stress in DA neurons. The MCT-KD also reduced mitochondrial loss, promoted ATP production, and inhibited the activation of microglia to protect DA neurons in MPTP-induced PD mice. MCT-KD altered the gut microbiota and consequently changed the metabolism of substantia nigra neurons through gut microbiota metabolites. Compared to the MPTP group, MCT-KD increased the abundance of gut microbiota, including Blautia and Romboutsia. MCT-KD also affects purine metabolism in the substantia nigra pars compacta (SNpc) by altering fecal metabolites. This study shows that MCT-KD has multiple protective effects against PD.

Experience with the use of a ketogenic diet with type 1 glucose transporter deficiency (De Vivo disease)

De Vivo disease is characterized by early epileptic encephalopathy, delayed psychomotor development, spasticity, the formation of microcephaly, ataxia, dysarthria, alternating hemiplegia, and a decrease in glucose and lactate levels in the cerebrospinal fluid. Epilepsy is pharmacoresistant and the therapy for this syndrome is the ketogenic diet (until the time when will development of genetic targeted therapy). In GLUT1 deficiency syndrome, mutations are found in the SLC2A1 gene that lead to a decrease in glucose transport across the cell membrane. The “classic” ketogenic diet is a special high-fat, low-carbohydrate diet that helps to control seizures in some people with epilepsy. It is prescribed by a physician and carefully monitored by a dietitian. It is usually used in children with seizures that do not respond to medications. It is stricter than the modified Atkins diet, requiring careful measurements of calories, fluids, and proteins. Foods are weighed and measured. Normal dietary fats, which are used predominantly in the classical ketogenic diet, consist of a mixture of mainly long chain triglyceride (LCT) fats with a small amount of short and medium chain triglyceride (MCT) fats. The MCT ketogenic diet uses a fat supplement that consists only of MCT fats (MCT oil).

Decanoic Acid Stimulates Autophagy in D. discoideum.

Ketogenic diets, used in epilepsy treatment, are considered to work through reduced glucose and ketone generation to regulate a range of cellular process including autophagy induction. Recent studies into the medium-chain triglyceride (MCT) ketogenic diet have suggested that medium-chain fatty acids (MCFAs) provided in the diet, decanoic acid and octanoic acid, cause specific therapeutic effects independent of glucose reduction, although a role in autophagy has not been investigated. Both autophagy and MCFAs have been widely studied in Dictyostelium, with findings providing important advances in the study of autophagy-related pathologies such as neurodegenerative diseases. Here, we utilize this model to analyze a role for MCFAs in regulating autophagy. We show that treatment with decanoic acid but not octanoic acid induces autophagosome formation and modulates autophagic flux in high glucose conditions. To investigate this effect, decanoic acid, but not octanoic acid, was found to induce the expression of autophagy-inducing proteins (Atg1 and Atg8), providing a mechanism for this effect. Finally, we demonstrate a range of related fatty acid derivatives with seizure control activity, 4BCCA, 4EOA, and Epilim (valproic acid), also function to induce autophagosome formation in this model. Thus, our data suggest that decanoic acid and related compounds may provide a less-restrictive therapeutic approach to activate autophagy.

Using Dictyostelium to Advance Our Understanding of the Role of Medium Chain Fatty Acids in Health and Disease.

Ketogenic diets have been utilized for many years to improve health, and as a dietary approach for the treatment of a range of diseases, where the mechanism of these low carbohydrate and high fat diets is widely considered to be through the production of metabolic products of fat breakdown, called ketones. One of these diets, the medium chain triglyceride ketogenic diet, involves high fat dietary intake in the form of medium chain fatty acids (MCFAs), decanoic and octanoic acid, and is commonly used in endurance and high intensity exercises but has also demonstrated beneficial effects in the treatment of numerous pathologies including drug resistant epilepsy, cancer, and diabetes. Recent advances, using Dictyostelium discoideum as a model, have controversially proposed several direct molecular mechanisms for decanoic acid in this diet, independent of ketone generation. Studies in this model have identified that decanoic acid reduces phosphoinositide turnover, diacylglycerol kinase (DGK) activity, and also inhibits the mechanistic target of rapamycin complex 1 (mTORC1). These discoveries could potentially impact the treatment of a range of disorders including epilepsy, cancer and bipolar disorder. In this review, we summarize the newly proposed mechanisms for decanoic acid, identified using D. discoideum, and highlight potential roles in health and disease treatment.

Ketonuria and Seizure Control in the Medium Chain Triglyceride and Classic Ketogenic Diets.

We hypothesized that children receiving medium-chain triglyceride ketogenic diet (MCTKD) experience similar seizure reduction despite lower ketosis compared with classic ketogenic diet (CKD). Children initiating CKD or MCTKD were enrolled in a prospective observational study. Forty-five children completed 6 months of KD (n = 17 MCTKD, n = 28 CKD). The proportion achieving ≥50% seizure reduction was 71% CKD group and 59% MCTKD group; ≥90% reduction was 32% and 36% in CKD and MCTKD groups, respectively. CKD had higher urine ketones (≥8mmol/L: 79% vs. 36%, p = 0.005). Children receiving MCTKD experience similar seizure control to CKD despite lower urine ketone measures.

Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone

Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

The Effects of a Ketogenic Medium-Chain Triglyceride Diet on the Feces in Dogs With Idiopathic Epilepsy

Consumption of diets containing medium chain triglycerides have been shown to confer neuroprotective and behavior modulating effects. We aimed to identify metabolic and microbiome perturbations in feces that are associated with consumption of a medium chain triglyceride ketogenic diet (MCT-KD) in dogs with idiopathic epilepsy. We used 16S rRNA gene sequencing to generate microbiome profiles and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to generate lipidomic profiles of canine feces. We made comparisons between the MCT-KD, standardized placebo diet and baseline pre-trial diet phases. Consumption of the MCT-KD resulted in a significant increase in the species richness (α-diversity) of bacterial communities found in the feces when compared to the baseline diet. However, phylogenetical diversity between samples (beta-diversity) was not affected by diet. An unnamed Bacteroidaceae species within genus 5-7N15 was identified by LEfSe as a potential biomarker associated with consumption of the MCT-KD, showing an increased abundance (p = 0.005, q = 0.230) during consumption of MCT-KD. In addition, unclassified members of families Erysipelotrichaceae (p = 0.013, q = 0.335) and Fusobacteriaceae (p = 0.022, q = 0.358) were significantly increased during MCT-KD consumption compared to baseline. Blautia sp. and Megamonas sp. instead were decreased during consumption of either placebo or MCT-KD (p = 0.045, q = 0.449, and p = 0.039, q = 0.449, respectively). Bacteroidaceae, including genus 5-7N15, have previously been associated with non-aggressive behavior in dogs. In addition, 5-7N15 is correlated in humans with Akkermansia, a genus known to be involved in the neuroprotective effect of ketogenic diets in mice models of seizures. Five metabolite features, tentatively identified as long chain triglycerides, were significantly higher after consumption of the placebo diet, but no unique features were identified after consumption of the MCT-KD. The data presented in this study highlight significant changes shown in both the fecal microbiome and lipidome as a result of consumption of the MCT-KD. Elucidating the global canine gut response to MCT consumption will improve our understanding of the potential mechanisms which confer anti-seizure and behavior modulating effects. Further studies should aim to characterize the gut microbiome of both dogs with epilepsy and healthy controls.

Ketogenic diet: A nutritional remedy for some metabolic disorders

Background: Ketogenic diets (KD) consist of high fat, moderate protein and low carbohydrates.Aim: This review explores the effect of ketogenic diet and its mechanism of actions in disease management.Methods: Recent information on ketogenic diets and disease management were retrieved from academic journals using scientific search engines and popular library databases such as PubMed, Scopus, Web of Science, JSTOR amongst others.Commentary: Ketogenic diet means a high fat, low-carbohydrate diet, with enough protein content, which makes the body utilize fat, rather than carbohydrate, as a preferred energy source. There are four different types of ketogenic diet, the traditional classic ketogenic diet, medium chain triglyceride (MCT) ketogenic diet, the modified Atkins diet (MAD), and the low glycemic index treatment (LGIT). The classic ketogenic diet, also known as long-chain fats consist of 16-20 carbon atoms. Its peculiarity is the low carbohydrate content, which could be difficult to maintain. The MCT was developed as an alternative to classic ketogenic diet. It has a fat composition of 60% octanoic acid (eight-carbon fatty acid) and 40% decanoic acid (10-carbon fatty acid). The MCT provides about 45% of energy when compared with the classic ketogenic diet. The MAD though strongly encourages the intake of high fat, it allows for 10-20 g of carbohydrate per day. The LGIT permits only low glycemic index foods. Ketogenic diets have been a therapeutic strategy for several diseases such as obesity, dyslipidemia, cancer and a broad range of neurological disorders.Conclusion: The ketogenic diet, an effective and age-long treatment for epilepsy in children, is gradually gaining acceptance as a therapeutic modality for many other diseases.

Ketogenic diets for drug-resistant epilepsy.

Ketogenic diets for drug-resistant epilepsy.

Efficacy and Safety of a Ketogenic Diet in Children and Adolescents with Refractory Epilepsy-A Review.

Epilepsy in the pediatric and adolescent populations is a devastating condition where individuals are prone to recurrent epileptic seizures or changes in behavior or movement that is the direct result of a primary change in the electrical activity in the brain. Although many children with epilepsy will have seizures controlled with antiseizure medications (ASMs), a large percentage of patients are refractory to drug therapy and may consider initiating a ketogenic diet. The term Ketogenic Diet or Ketogenic Diet Therapy (KDT) refers to any diet therapy in which dietary composition results in a ketogenic state of human metabolism. Currently, there are 4 major Ketogenic diet therapies—the classic ketogenic diet (cKD), the modified Atkins diet (MAD), the medium chain triglyceride ketogenic diet (MCTKD) and the low glycemic index treatment (LGIT). The compositions of the 4 main KDTs differ and limited evidence to distinguish the efficacy among different diets currently exists. Although it is apparent that more randomized controlled trials (RCTs) and long-term studies are needed to evaluate efficacy, side effects and individual response to the diet, it is imperative to study and understand the metabolic profiles of patients with epilepsy in order to isolate which dietary restrictions are necessary to maximize clinical benefit.

M-Current Suppression, Seizures and Lipid Metabolism: A Potential Link Between Neuronal Kv7 Channel Regulation and Dietary Therapies for Epilepsy.

Neuronal Kv7 channel generates a low voltage-activated potassium current known as the M-current. The M-current can be suppressed by various neurotransmitters that activate Gq-coupled receptors. Because the M-current stabilizes membrane potential at the resting membrane potential, its suppression transiently increase neuronal excitability. However, its physiological and pathological roles in vivo is not well understood to date. This review summarizes the molecular mechanism underlying M-current suppression, and why it remained elusive for many years. I also summarize how regulation of neuronal Kv7 channel contributes to anti-seizure action of valproic acid through inhibition of palmitoylation of a Kv7 channel binding protein, and discuss about a potential link with anti-seizure mechanisms of medium chain triglyceride ketogenic diet.

Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study

PurposeWe conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients’ quality of life and health; (iii) patients’ perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials.MethodsA single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modified ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n = 15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo.ResultsKEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n = 3; MKD n = 1). Participants’ decisions were intuitive and emotional; caregivers supported diet implementation and influenced the patients’ decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew.ConclusionRecruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregivers should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.

Ketogenic diets as an adjuvant therapy in glioblastoma (KEATING): A mixed methods randomised feasibility study

Abstract Background There is increasing interest in the use of ketogenic diets (KD) as adjuvant therapy for glioblastoma (GBM). Trial aims: i) investigate protocol feasibility; ii) assess patient/carer acceptability; iii) explore the decision-making of patients’ invited to participate in KEATING; and iv) inform phase III trial design. Methods Prospective, feasibility study, with embedded qualitative design randomised 12 newly-diagnosed GBM patients to three months of medium chain triglyceride ketogenic diet (MCTKD) or the modified ketogenic diet (MKD) during chemoradiotherapy. Primary outcome was retention; secondary outcomes included recruitment rate, dietary acceptability, progression free survival (PFS) and overall survival (OS). Semi-structured interviews were conducted with a representative sample of patients and relatives (n=15). Results Recruitment targets were achieved, but recruitment rate was low (28.6%). Retention was poor; only 4 of 12 completed the three-month diet (MCTKD n=3; MKD n=1). Median duration until discontinuing was 5.2 weeks (0–7 weeks; n=8). Participants made instantaneous decisions without deliberation: relatives supported diet implementation. Decliners made considered decisions factoring diet burden and quality of life. A three-month diet was undesirable to these patients. Median PFS was 11.4 weeks and OS was 67.3 weeks. Conclusion Recruitment to a ketogenic-glioblastoma trial is possible. To assess effectiveness in a phase III clinical trial, a six week intervention period is proposed. Future trials should optimise and adequately support the decision-making of patients. The role of relatives should not be underestimated.

Absence of increased blood decanoic acid levels in children with epilepsy treated with classic ketogenic diet.

Recently, decanoic acid (C10), a medium-chain fatty acid, was shown to be a direct inhibitor of the AMPA receptor. Accordingly, C10 has been suggested as a potential anticonvulsant factor in the ketogenic diet (KD) or the medium-chain triglyceride KD. Here, we tested whether C10 serum levels correlate with the response to KD in five children (1.5 ± 0.6 years of age) with epilepsy. The serum levels of C10 were measured before and after KD initiation (n=2 at one month, n=3 at three months, and n=1 at six months after initiation) by gas chromatography-mass spectrometry. After three months on KD, two patients were found to be responders. The mean serum level before KD initiation was 63.2μM. Only one patient, who was a non-responder, showed an increase (5%) in C10 serum level after a month of KD. The remaining four patients (two responders) showed a decrease in the C10 level from -5.3% to -75.5%. Our preliminary data show that KD does not lead to an increase in C10 serum levels, suggesting that increased concentration of C10 might not be directly involved in the anticonvulsant effects of classic KD.

Differential Metabolism of Medium-Chain Fatty Acids in Differentiated Human-Induced Pluripotent Stem Cell-Derived Astrocytes.

Medium-chain triglyceride (MCT) ketogenic diets increase ketone bodies, which are believed to act as alternative energy substrates in the injured brain. Octanoic (C8:0) and decanoic (C10:0) acids, which produce ketone bodies through β-oxidation, are used as part of MCT ketogenic diets. Although the ketogenic role of MCT is well-established, it remains unclear how the network metabolism underlying β-oxidation of these medium-chain fatty acids (MCFA) differ. We aim to elucidate basal β-oxidation of these commonly used MCFA at the cellular level. Human-induced pluripotent stem cell-derived (iPSC) astrocytes were incubated with [U-13C]-C8:0 or [U-13C]-C10:0, and the fractional enrichments (FE) of the derivatives were used for metabolic flux analysis. Data indicate higher extracellular concentrations and faster secretion rates of β-hydroxybutyrate (βHB) and acetoacetate (AcAc) with C8:0 than C10:0, and an important contribution from unlabeled substrates. Flux analysis indicates opposite direction of metabolic flux between the MCFA intermediates C6:0 and C8:0, with an important contribution of unlabeled sources to the elongation in the C10:0 condition, suggesting different β-oxidation pathways. Finally, larger intracellular glutathione concentrations and secretions of 3-OH-C10:0 and C6:0 were measured in C10:0-treated astrocytes. These findings reveal MCFA-specific ketogenic properties. Our results provide insights into designing different MCT-based ketogenic diets to target specific health benefits.

Investigating the effect of chemotherapy combined with ketogenic diet on stage IV colon cancer.

e15182 Background: The effectiveness of carbohydrate restriction to limiting cancer growth has often been observed in in vitro and in vivo experiments; however, few cases of clinical efficacy have been reported. We examined the clinical effectiveness of chemotherapy with ketogenic diet for advanced cancer treatment. Methods: We administered chemotherapy with a modified medium-chain triglyceride (MCT) ketogenic diet at a ratio of 1.4:1 in 10 patients with stage IV recurrent colon cancer for one year and performed a conversion surgery in five of the cases. We followed-up for the next 3 years, compared the overall survival (OS) of the chemotherapy-only group of the stage IV colon cancer patients, and investigated the factors contributing to an improved OS. Results: Evaluations in the first year revealed a response rate of 21% and disease control rate of 64% for patients in the chemotherapy-only group. Patients in the ketogenic diet-chemotherapy combination group exhibited a response rate of 60%, disease control rate of 70%, and complete response rate of 50% for the five conversion surgeries. The time to conversion surgery was 4.0±0.9 months and the time to postoperative recurrence was 6.2±2.6 months. Regarding the duration of overall survival, there was no significant difference ( p value = 0.98) upon comparing the ketogenic diet group with the chemotherapy-only group (32.5 months and 37.9 months, respectively). However, overall survivals were 50 months, 23.0 months, and 32.5 months for the ketogenic diet-chemotherapy combination response group, ketogenic diet-chemotherapy combination non-response group, and chemotherapy-only group, respectively ( p value = 0.07). The ketogenic diet-chemotherapy combination response group tended to have a longer OS than the chemotherapy-only group. In addition, in the ketogenic diet-chemotherapy combination response group, introduction time was earlier than the ketogenic diet-chemotherapy combination non-response group for 5.7 months, with high serum ketone body levels and low blood sugar levels. Conclusions: Chemotherapy with ketogenic diet resulted in higher response and disease control rates than chemotherapy alone. Additionally, the conversion surgery rate was high and an improved OS could be expected. Therefore, ketogenic diet may be a supportive therapy to chemotherapy. Clinical trial information: 000029527.

Dietary Therapies: Emerging Paradigms in Therapy of Drug Resistant Epilepsy in Children : Based on 6th Dr. I. C. Verma Excellence in Research Award Oration.

About one-third of childhood epilepsy ultimately becomes drug resistant epilepsy. Only about one-third of drug resistant epilepsy is amenable for epilepsy surgery. Epilepsy surgery and vagal nerve stimulation is still beyond the reach of huge proportion of children with pharmacoresistant epilepsy. Ketogenic diet (KD) has been in use for almost a century now all over the world for drug resistant epilepsy, although in between there was a decline in its popularity with advent of newer antiepileptic drugs like valproate, phenytoin and carbamazepine. Again from 1990s there was resurgence of interest in KD for pharmacoresistant epilepsy and in the last two decades several randomized controlled trials and systemic reviews have proved its efficacy beyond any suspicion. Ketogenic diet is a high fat low carbohydrate and low protein diet, which has been found to reduce epileptogenesis in body most probably by production of ketone bodies. Modified Atkin's Diet (MAD) first introduced in 2003 and Low Glycemic Index Treatment (LGIT) first introduced in 2005 are another two dietary therapies, which are less restrictive, more palatable with fewer adverse effects and comparable efficacy. MAD is also a high fat, low carbohydrate diet, in which high sugar foods are discouraged and protein and fluids are unrestricted. In LGIT, only carbohydrates with Glycemic Index <50 are allowed and carbohydrate intake is restricted to 40-60g per day. Medium Chain Triglyceride KD (MCT KD) is another alternative, in which there are more food choices as compared to classic KD, with comparable efficacy.