Practical guidelines for addressing common questions and misconceptions about the ketogenic diet

“The Proof is in the Pudding”: Do SGLT2 Inhibitors Cause Diabetic Ketoacidosis?

The ketogenic diet has been successfully used in the last 100 years in the treatment of epilepsy and other neurological disorders. In recent decades, it gained wider application in the treatment of obesity, metabolic syndrome, and type 2 diabetes. However, there have been only a few studies on its use in children with obesity and associated metabolic disorders. To determine the clinical and metabolic effects of a well-formulated low-carbohydrate (ketogenic) diet in children with obesity. One hundred children with obesity and metabolic disorders underwent initial anthropometric, laboratory, and ultrasound examinations. They were placed on a well-formulated ketogenic diet and monitored for 4 months. The 58 patients who completed the study underwent follow-up examinations to assess the effects of the diet on anthropometric, clinical, and laboratory markers of metabolic syndrome and insulin resistance, cardiovascular risk factors, and certain hormone levels. Compliance with the diet, common difficulties in adhering to it, side effects, and positive changes in the patients' health were analyzed. At the end of the study, the average weight loss for the entire group was 6.45 kg, with a reduction in BMI of 3.12 kg/m2. Significant improvements were also observed in insulin resistance indicators, including fasting insulin levels, HOMA-IR index, QUICKI (p < 0.0001), and adiponectin (p = 0.04). The cases of hepatosteatosis decreased twofold, the number of patients with arterial hypertension was significantly reduced, as well as the number of children receiving antihypertensive therapy. Additionally, the number of patients meeting the criteria for metabolic syndrome decreased threefold. A well-formulated short-term ketogenic diet is effective in treating obesity, metabolic syndrome, and related comorbidities, and can be part of a comprehensive approach for these patients.

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1month, 3months, 6months, 1year, and 2years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology.

Traditional weight loss and dukan diets as to nutritional and laboratory results

(1) Background: The ketogenic diet (KD) was developed in the 1920s as a treatment for pediatric epilepsy and is emerging as a possible treatment option for certain mental health disorders. There is a link between certain mental health disorders and epilepsy, suggesting some commonality among underlying mechanisms. (2) Methods: The literature relating to mental disorders and the KD is sparse. The authors attempt to a narrative review of the existing literature to show that there may be validity to studying the KD as a treatment for certain mental health disorders. (3) Results: Various types of mitochondrial dysfunction and impaired oxidative metabolism have been identified in many mental health disorders (bipolar disorder, major depressive disorder, autism, schizophrenia, and others). Mitochondrial deficits may affect neuroplasticity and cause synaptic dysfunction, which could change brain structure and function in a way that might affect behavior. The KD has been associated with epigenetic changes in the genes associated with mitochondrial function. Chronic oxidative stress and inflammation have also been implicated in mental health disorders and may be reduced by the KD. The KD regulates glutamatergic transmission and may initiate extracellular changes as well, in a manner similar to pharmacological agents used to stabilize moods. The KD may be difficult for patient adherence and has been associated with many and potentially severe adverse effects. The role of the KD in addressing treatment-resistant pediatric epilepsy is established and epilepsy is comorbid with a number of mental health conditions. (4) Conclusions: There is a paucity of literature on this subject and there is no robust clinical evidence in support of the use of the KD for treating mental disorders but there are indications that the KD can reduce systemic inflammation, improve cerebral mitochondrial metabolism, and enhance endogenous antioxidation, all of which may be helpful in treating certain mental health conditions. The KD is also associated with serious health risks and clinicians must weigh risks versus benefits.

Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown.1 Mossy fiber sprouting in the inner molecular layer of the dentate gyrus causes the synaptic reorganization in the hippocampus, which is an important cause of temporal lobe epilepsy in animals and humans.1,2 It is also essential to the genesis and development of epilepsy. As the predominant excitatory neurotransmitter in the central nervous system, glutamate plays a role in synaptic reorganization and development of epilepsy. In recent years, the role of glutamate receptor 5 (GluR5) in the genesis of seizures has attracted more and more attention of researchers and this receptor has become a candidate target of new antiepileptic drugs.3,4 In this study, we investigated the possible antiepileptic mechanism of KD in terms of synaptic reorganization and GluR5 expression, attempting to provide a theoretical basis for the development of new antiepileptic drugs. METHODS KA-induced epileptic model Male Sprague-Dawley rats obtained from the Experimental Animal Center of Shandong University were divided into four groups: kainic acid (KA) + normal diet (ND), KA + KD, saline (NS) + ND, and NS + KD. On day 28 after birth, the rats of the experimental groups received KA (10 mg/kg, i.h., Sigma, USA), and the saline control groups received an equivalent volume of saline. All rats were fasted for 24 hours, after which on day 30 they had free access to their respective diet. The experimental KD resembled the classic 4:1 diet used clinically (fat 70%, protein 20%, and carbohydrates 0%).5 The diet was given for the next 8 weeks. At the end of the experiment, the number of animals in each group was 13 (KA + ND group), 12 (KA + KD group), 4 (NS + ND group), and 4 (NS + KD group). Behavior observation During the 8-week dietary treatment, spontaneous recurrent seizure (SRS) was recorded by observing each KA-induced animal for 1 hour everyday. SRS was defined as an unprovoked seizure involving unilateral or bilateral forelimb clonus, with or without loss of posture. Material extraction and brain slice preparation At the end of the experiment, 3 ml blood was withdrawn from the heart of the animal after deep anesthesia. β-hydroxybutyrate (β-OHB) level was assessed with a commercially available kit (Randox, UK). After blood extraction, brains were removed from some rats, and bilateral hippocampus was immediately dissected, put in liquid nitrogen, then stored for later use in a -80°C freezer. The other rats were perfused transcardially with 200 ml sodium sulfide medium (2.925 g Na2S, 2.975 g NaH2PO4/H2O in 500 ml H2O) followed by 200 ml 4% phosphate buffered paraformaldehyde (PFA, 0.1 mol/L, pH 7.4). The brains were postfixed in 4% PFA overnight and then placed in a 30% sucrose phosphate buffer until they sank to the bottom of the vial. The fourth coronal section of 25 μm was used for Timm staining and the adjacent section was for Nissl staining. Timm staining and Nissl staining Sections were developed in the dark for 60 minutes in a 12:6:2 mixture of 50% gum arabic, 5.6% hydroquinone, and citric acid-sodium citrate buffer with 1.5 ml 17% AgNO3 solution. Toluidin blue was used for Nissl staining. All images were processed with Image-pro plus 5.0 software. For Timm stained sections, the mean density (A) of Timm granules in the inner molecular layer (IML) of the dentate gyrus and Timm granules in the stratum pyramidal and stratum orient of the CA3 region was calculated. For Nissl stained sections, A of neurons in the hilus, CA3 and CA1 regions was analyzed. Five brain slices of the bilateral hippocampus for each rat were examined. Protein extracts and Western blot analysis One side of the hippocampus was homogenized. The cell lysates were cleansed by a centrifugation at 15 000 r/min for 20 minutes at 4°C, and protein concentration was determined by BCA assay (Pierce, Rockford, USA). For immunoblots, 40 μl of protein extract was loaded on a 10% SDS-PAGE and transferred onto nitrocellulose membranes. Blots were detected with 1:50 primary antibody against GluR5, and specific signals were detected with 1:1000 horseradish peroxidase secondary antibodies by a chemiluminescence reaction (Santa Cruz, California, USA). RNA preparation and RT-PCR The other side of the hippocampus was used for RNA isolation by the guanidinium thiocyanatephenol-chloroform method. The RT-PCR procedure was performed according to the manufacturer's recommendation (RT-PCR Kit, Fermentas Life Science, Ontario, Canada). The primers used in this study were as follows: GluR5: 5′-GGTATAACCCCC ACCCATGCAACC-3′ (forward), 5′-GAAGGTCATCG TCGAGCCATCTCTG-3′ (Reverse); β-actin: 5′-AAGA TCCTGACCGAGCGTGG-3′ (Forward), 5′-CAGCAC TGTGTTGGCATAGAGG-3′ (Reverse). PCR procedures (50 μl) contained 30 cycles, with each cycle of 40 seconds at 94°C, 40 seconds at 56°C, and 40 seconds at 72°C. The products were GluR5 313 bp, and β-actin 326 bp. Statistical analysis Differences between means of the two groups were compared by Student's t/t' test. The comparison of GluR5 mRNA and protein used Wilcoxon's rank-sum test. Significance level was 0.05 for all comparisons. RESULTS Behavior observation Three weeks after KA injection, KA-induced rats started SRS in succession. Eleven rats in the KA + ND group experienced SRS, while eight rats in the KA + KD group had SRS. SRS frequency per rat was significantly less in the KD-fed animals (1.40±1.03) than in the controls (7.36±3.75, t' =5.024, P<0.05). No SRS was observed in saline injected animals. β-OHB determination In KD-fed (KA + KD and NS + KD groups) rats, β-OHB rose to the level [(4.51 ± 2.32) mmol/L] significantly higher than that in standard diet-fed (KA + ND and NS + ND groups) rats [(0.11 ± 0.03) mmol/L, t=6.83, P<0.05]. Histology Timm staining reflects mossy fiber sprouting into the dentate IML. The A of Timm granules in the IML of the dentate gyrus in the KA-induced groups (KA + KD and KA + ND) was respectively higher than that in the saline control groups (NS + KD and NS + ND) (P<0.01, Fig. 1A-1D, Table 1), but no significant difference was found between the KD-fed groups (KA + KD and NS + KD) and the normal diet control groups (KA + ND and NS + ND) (Table 1). There was no statistically significant difference in Timm staining of the CA3 region between the groups (t values were 0.35 and 0.08, both P>0.05, Fig. 1E). Granular cells and pyramidal cells were densely arranged in the dentate and CA3, CA1 regions, as demonstrated in toluidin blue stained sections. There was no significant difference between gross neuron damages in subfields of the CA3, CA1, and hilus (Fig. 1F).Fig. 1.: Examples of Timm staining and Nissl staining in the hippocampus. A and B: Mossy fiber sprouting in IML of the dentate gyrus of rats from the KA + ND group. C and D: Timm-stained sections reveal a normal pattern of staining in the NS + ND group. E: The distribution of Timm granules in the stratum pyramidale and stratum oriens of the CA3 region of rats from the KA + KD group. F: The distribution of neurons in the CA3 region of rats from the KA + ND group. The magnification of A, C, E, and F is 100 and that of B and D is 200.Table 1: Comparison of Timm stained granular density in IML of dentate gyrusGluR5 mRNA and its expression The results of Western blot indicated that GluR5 expression in KA+ KD rats was significantly higher than that in KA +ND rats (Fig. 2, Table 2), although there was no significant difference in GluR5 mRNA between the two groups, shown by RT-PCR (Fig. 3, Table 2).Fig. 2.: Western blot detection of GluR5.Table 2: Hippocampus GluR5 mRNA and its protein in KA-induced different diet fed groupsFig. 3.: RT-PCR detection of GluR5 mRNA. Lanes 1 and 4: GluR5; Lanes 3 and 6: β-actin.DISCUSSION In recent years, a number of new antiepileptic drugs have been used in the treatment of epilepsy, but about 25% -30% patients are intractable to conventional medications and can be considered to have refractory epilepsy. Because of its special effect on this group of patients, KD has become popular since the 1970s of the last century.6 KD action is age-dependent since several studies have shown that KD is more efficient in fetuses, infants and children than in adults.7 In this study, KA-induced on day 28, young rats were used and results showed KD-fed rats had significantly fewer SRS than did standard diet-fed rats, indicating the definite antiepileptic effect of KD on KA-induced animals. MFS refers to the synaptic reorganization of the mossy-fiber axons of dentate granule cells into the inner molecular layer of the dentate gyrus of the hippocampus.8 The formation of recurrent excitatory synapses between dentate granule cells, as is thought to occur after MFS, may transform the dentate granule cells into an epileptogenic population of neurons and could promote seizure initiation.9 Muller-Schwarze et al1 found in KA-induced adult rats, KD could decrease the frequency of SRS and prevent MFS in the dentate gyrus, suggesting that KD might play an antiepileptogenic role by suppressing MFS. Although in our study, MFS in the dentate gyrus was different between KA-induced and saline control groups, no significant difference was found in KD-fed groups and standard diet-fed groups. Both MFS in the CA3 region and neuron damage in different regions of the hippocampus were similar in different groups. These data were in accord with the results reported by Zhao,10 which were drawn from experiments of pilocarpine-induced animals on day 20. Therefore, MFS may be responsible for epileptogensis in KA-induced rats, but for young rats, impeding MFS is not the antiepileptic mechanism of KD. The difference in antiepileptic mechanism between young and adult rats may be due to the characterization of the developing brain. Thus, we propose that for young rats, KD's antiepileptic effect may be age-dependent and related to neurogenesis and synaptic plasticity. Glutamate plays a crucial role in the ontogeny of the nervous system and synaptic formation. As a type of ionotropic glutamate receptor, KA receptors can be divided into five types of KA1–2 and GluR5–7, and they modulate synaptic transmission by pre- and post-synaptic mechanism.11 It was reported that in KA induced adult rats, GluR5 mRNA and protein increased significantly at 72 hours and 180 days.12 The study on temporal lobe epilepsy patients found decreased GluR5 mRNA densities per pyramid cell and increased GluR5 hybridization densities per granule cell in patients with hippocampus sclerosis (HS). Mathern et al13 hypothesized that the former change was a consequence of seizures and the latter was in association with MFS and/or hippocampal neuronal loss. The results of our study showed increased GluR5 expression in KA induced KD-fed rats although no difference was found of GluR5 mRNA in the hippocampus. The different expression of GluR5 and its mRNA in the hippocampus may be due to their different expression phases and different factors regulating the transcription and translation processes. In addition, the different expression may also be related to the neuron protection effect of KD. According to Noh's findings,14 KD has an antiepileptic effect via a neuroprotective action involving the inhibition of caspase-3-mediated apoptosis of hippocampal neurons. Despite no significant neuron damage of the hippocampus found between different diet-fed groups may result from neurogenesis after repetitive seizures or KD's neuroprotective effect, further investigation is required to clarify whether there are differences in GluR5 expression between neurons from neurogenesis and those protected from seizure through KD. GluR5 mRNA is confined predominantly to hippocampal interneurons.15 In GluR6-deficient animals, currents mediated by kainate receptors in CA1 interneurons are not eliminated, supporting the role of GluR5 in interneuronal kainate receptors.16 Our findings indicate that KD can not inhibit MFS in KA-induced young rats. The high expression of GluR5 does not result from MFS, otherwise it might be the reason for decreased SRS in KD-fed animals since the activation of GluR5 on GABAergic interneurons can lead to an increased inhibition in the hippocampus to prevent the propagation of seizure from one hemisphere to the other.17,18 In conclusion, in young rats, KD may increase GluR5 expression in interneurons in the CA1 region as well as the inhibitory transmission in the hippocampus to play its antiepileptic action. Acknowledgement: This study was accomplished in Cardiovascular Reorganization and Function Key Lab in Shandong University of the Ministry of Education. We deeply appreciate LIU Chun-xi, JIANG Hong and FENG Jin-bo for their technical assistance.

ObjectiveTo assess early signs of atherosclerosis following long‐term treatment with the ketogenic diet therapy due to concerns regarding the impact of this low‐carbohydrate, high‐fat diet on cardiovascular health.MethodIn this cohort study, 28 patients aged 6 to 49 years who had been treated with ketogenic diet therapy for more than five years and 28 age‐ and gender‐matched controls underwent ultrasound assessment of carotid intima media (cIMT). Measurements were compared between the two groups. Traditional cardiovascular risk factors were recorded in the patient group.ResultsWe found increased cIMT in patients treated with the ketogenic diet compared with controls (median 0.62 mm (IQR 0.12) vs. 0.53 mm (IQR 0.14), p < 0.001). This difference increased with age (median 0.69 (IQR 0.18) vs. 0.60 mm (IQR 0.12), p = 0.029). The type of ketogenic diet (classical or modified) did not affect cIMT. Blood pressure, body mass index (BMI), and blood lipids in patients treated with the ketogenic diet for more than 5 years were within the normal range.SignificancecIMT may be an early biomarker for cardiovascular risk and be warranted in the standard follow‐up of patients with long‐term ketogenic diet treatment.Plain Language SummaryThis study documents increased thickness of the inner layers of the carotid artery (carotid intima media) (cIMT) in 28 patients treated with a high‐fat, low‐carbohydrate, and adequate protein (ketogenic) diet for more than 5 years compared with controls and that this difference increased with age. The type of ketogenic diet (classical or modified) did not affect cIMT. Blood pressure, body mass index, and blood lipids in patients treated with the ketogenic diet for more than 5 years were within the normal range.

PCOS is the most prevalent female endocrine disorder and is characterized by polycystic ovaries, hyperandrogenism, and protracted anovulation. In PCOS, obesity, low-grade chronic inflammation, and insulin resistance (IR) frequently coexist. The Mediterranean diet (MD) and Ketogenic diet act as an anti-inflammatory eating plan that is high in complex carbohydrates, fiber, and monounsaturated fat, whereas the Keto diet is high in fat content. PCOS is associated with obesity, low-grade chronic inflammation, insulin resistance, and hormonal imbalances. The aim of the present study was to measure the metabolic and endocrine effects of a ketogenic and hypocaloric Mediterranean diet in women with polycystic ovarian syndrome. For this purpose, 80 participants were divided into two groups. Group 1 was on the ketogenic diet and Group 2 was on the Mediterranean diet for 9 weeks. The result of the present study showed that significant weight was reduced among the keto group (−10.9 kg) as compared to the Mediterranean group (−5.1 kg). Total cholesterol and Low-Density Lipoprotein among the keto group was 181. 5 ± 22.2 and 85.3 ± 16.2 U/L whereas, in the Mediterranean group 190.3 ± 22.7 and 91.3 ± 15.9 U/L were observed. Blood glucose levels among the Keto and Mediterranean groups reduced significantly 83.47 ± 5.81 and 91.7 ± 5.8 (mg/dl). C-peptide, LH, and FSH also improved more significantly as compared to the Mediterranean group respectively. This study revealed that a ketogenic diet is superior to a hypocaloric Mediterranean diet for lowering Triglyceride, Cholesterol, LDL, blood glucose, insulin, C peptide, HOMA-IR, LH/FSH, Serum Albumin, Facilitating Hormone, and Sex hormone-binding globulin levels. Females having PCO may improve health with the ketogenic diet

Background: The ketogenic diet (KD), a high-fat low-carbohydrate diet, has gained in popularity in recent years, which is reflected by an increasing number of scientific articles, books, websites, and other publications related to low carbohydrate (LC) diets and KDs. Numerous preclinical studies in different animal models of cancer have examined the effect of KDs on cancer growth, but no large randomized controlled studies or prospective cohort studies are available for human cancer patients. Evidence supporting the use of KDs as an adjunct to traditional cancer therapy has come predominantly from anecdotes and case reports. The first KD clinical trials in patients with glioblastoma revealed good acceptance and a possible anti-tumor effect. Metabolic therapy options such as the KD are not yet part of the standard of care in cancer patients. However, many cancer patients have begun implementing a KD or LC diet on their own. The aim of the present study was to gather information, via an online questionnaire, about how cancer patients go about implementing a KD or LC diet, what resources they rely on, whether they perceive benefits from the diet on quality of life (QoL), and what factors influence feasibility and adherence to the diet.Method: Recruitment of participants was carried out via social media platforms, forums and cooperating physicians (April 2018 through November 2018). To be eligible for the study, participants had to be diagnosed with cancer and on a KD or LC diet at the time of participating in the study or been on a KD or LC diet during cancer treatment. Study participants were asked to fill out an online questionnaire. The questionnaire was divided into four parts and contained a total of 64 questions. The questions were focused on the current health status of the participant, type of cancer, time since diagnosis, and treatment regimen. In addition, questions addressed social support, extent of professional counseling, food preferences and QoL.Results: A total of 96 participants (77 F, 17 M) submitted the questionnaire, of which 94 were included in the final data analysis. Ages ranged between 24 and 79 years (mean 50.1 ± 12.1 years). In 73.4% of the participants, the tumor had not formed metastases at the time of initial diagnosis. Twenty-four (26%) participants had a PET-positive tumor, 8 (9%) a PET-negative tumor, and the remainder (66.0%) did not report a PET scan. Eighty seven percent had undergone surgery in the course of their cancer treatment. The most frequent tumor type was breast cancer, followed by cervical cancer, prostate cancer, colorectal cancer and melanoma. Fifty nine percent of the study participants stated that they followed a KD during cancer therapy, 21% followed a low carbohydrate/high fat (LCHF) diet and 12% followed a low glycemic index (LOGI) diet. Sixty nine percent reported an improvement of QoL because of the diet. Almost half of the study participants sourced their initial information on KDs and LC diets from the internet. We found a significant correlation between weight loss upon implementation of a KD and the extent of overweight (p < 0.001). Weight loss in already lean participants was not reported. Overall, 67% of the participants found long-term adherence to the diet to be “easy” and 10.6% described it as being “very easy.” Participants who like fatty foods tended to perceive the diet as being easier to follow (p = 0.063).Conclusion: The KD or LC diet improved self-reported QoL in more than two-thirds of study participants. The KD had a normalizing effect on body weight. The majority of the participants rated the diet as easy or very easy to follow long term. There was an obvious gap between patients' desire for professional dietary counseling and what is currently offered by health care providers. In the future, efforts should be made to invest in nutrition experts who are trained in the KD to support cancer patients with implementation of a KD.

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

The Ketogenic Diet (KD) has been used in treatment of epilepsy in mainland China since 2004.Clinical indications of KD include: Glucose Transporter Type 1 (GLUT-1) deficiency, Pyruvate Dehydrogenase Deficiency (PDHD, myoclonus-astatic epilepsy (Doose syndrome), tuberous sclerosis complicated with or without epilepsy, Rett syndrome, Dravet syndrome, infantile spasms, and Landau-Kleffner syndrome, Lafora disease, and super-refractory status epilepticus.The contraindications of KD include: Inborn error of lipid metabolism, porphyria, and patients who are unable to cooperate with the KD.There should be standardized clinical consultation and evaluation before starting KD treatment; and special attention should be paid to selection and preparation of food, and to indication of age and geographic area etc.During the KD treatment, the transition time from ordinary diet to KD often takes 1-2 weeks; and a final 2: 1-4: 1 ketogenic diet ratio will normally produce ketosis of clinical therapeutic effect.The KD could be combined with anticonvulsant treatment.A qualified ketogenic diet therapy means: (1) Proper nutrition and growth with normal nutrition biomarkers; (2) Tasty foods: patients are willing to accept the therapeutic diet; (3) Ideal state of ketosis: urine ketone remains above (+++), blood ketone at about 4.0 mmol/L, blood sugar is controlled at 4.0 mmol/L, ratio of blood sugar/blood ketone is about 1: 1-2: 1; (4) Reasonable balanced food composition, defecate daily and naturally without constipation; (5) No remarkable complication(s).It is recommended that KD could be tried at least for three months continuously.Good responders should maintain the KD therapy for 2 yrs.or so.It often needs to take 3-6 months to return back to a regular diet.KD therapy should be monitored with close follow-ups and assessments.Our extensive experience has confirmed that it is safe in clinical practice.

PO-305 An 8-week, low carbohydrate, high fat, ketogenic diet enhanced exercise capacity through improved ketolysis and lipolysis in mice

Although a larger number of antiepileptic drugs became available in the last decades, epilepsy remains drug-resistant in approximately a third of patients. Ketogenic diet (KD), first proposed at the beginning of the last century, is complex and has anticonvulsant effects, yet not completely understood. Over the last decades, different types of ketogenic diets (KDs) have been developed, namely classical KD and modified Atkins diet (MAD). They offer an effective alternative for children and adults with drug-resistant epilepsies. We review several papers on KDs as an adjunctive treatment of refractory epilepsy of children and adults, discussing its efficacy and adverse events. Because of the heterogenous, uncontrolled nature of the studies, we analyzed all studies individually, without a meta-analysis. KDs may be considered first choice treatment in some specific metabolic conditions, such as glucosetransporter type 1 and pyruvate dehydrogenase deficiencies, and mitochondrial complex I defects. Preliminary findings indicate that KDs may be specifically effective in some epileptic syndromes, such as West syndrome, severe myoclonic epilepsy of infancy, myoclonic-astatic epilepsy, febrile infection related epileptic syndrome, and drug-resistant idiopathic generalized epilepsies or refractory status epilepticus. Short term adverse events are usually mild in both children and adults, including gastrointestinal symptoms, hyperlipidemia, and hypercalciuria; potential long term adverse effects include nephrolitiasis, decreased bone density, and liver steatosis. Possible atherosclerotic effects remain a concern. Patients on KDs should be carefully monitored in specialized centers during initiation, maintenance and withdrawal periods, in order to minimize such adverse events, and to improve compliance. Although the majority of KD trials on children and adults with drug-resistant epilepsies are openlabel, uncontrolled studies based on small samples, an increasing number of randomized controlled trials have provided better quality evidence on its efficacy in recent years. There is a need for future randomized clinical trials aimed to confirm the efficacy of KDs in specific epileptic syndromes, and to provide further information about some practical unsolved problems, i.e. for how long KD treatment should be continued.

S2-3 Function of microglia on the process of neuronal repair

The ketogenic diet, being high in fat and low in carbohydrates, has been suggested to reduce seizure frequency. It is currently used mainly for children who continue to have seizures despite treatment with antiepileptic drugs. Recently there has been interest in less restrictive ketogenic diets including the Atkins diet and the use of these diets has extended into adult practice. To review the evidence from randomised controlled trials regarding the effects of ketogenic and similar diets. We searched the Cochrane Epilepsy Group's Specialised Register (June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2 of 4), MEDLINE (1948 to May week 4, 2011) and EMBASE (1980 to March 2003). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. Studies of ketogenic diets and similar diets for people with epilepsy. Three review authors independently applied pre-defined criteria to extract data and also assessed study quality. We identified four randomised controlled trials which generated five publications.These included Kossoff 2007, Bergqvist 2005, Seo 2007, Neal 2008 and Neal 2009. All trials applied the intention-to-treat analysis with varied randomisation method. The four studies recruited a total of 289 children and adolescents and no adults. Meta-analysis could not be conducted due to heterogeneity of the studies. Seven prospective studies and four retrospective studies were also identified. Our review update included data from four new randomised studies of the ketogenic diet. Although none were blinded, some were of good quality. These studies suggest that in children, the ketogenic diet results in short to medium term benefits in seizure control, the effects of which are comparable to modern antiepileptic drugs. However, one study of long term outcome reports a high attrition rate for the diet. This would suggest that many children find the diet difficult to tolerate. The main reasons for drop-outs in the included studies included gastrointestinal side effects and dislike for the diet.We found just three studies on the use of the diet in adults and none of these were randomised. There has been less research involving other diets. We found one randomised study of reasonable quality of the Atkins diet. This study showed similar benefits in seizure control with a less restrictive diet.For those with medically intractable epilepsy or those in whom surgery is unsuitable, a ketogenic diet could improve seizure control, but tolerability is poor. One observational study suggested that the Atkins diet may have a similar effect on seizure control, but this requires more investigation.