OBJECTIVES: To examine the effects of a challenge with monosodium glutamate (MSG) as compared to placebo on the symptoms of fibromyalgia (FM), in participants who initially experienced>30% remission of symptoms on an excitotoxin elimination diet.

METHODS: Fifty-seven FM patients who also had irritable bowel syndrome (IBS) were placed on a 4-week diet that excluded dietary additive excitotoxins including MSG and aspartame. Thirty-seven people completed the diet and 84% of those reported that>30% of their symptoms resolved, thus making them eligible to proceed to challenges. Subjects who improved on the diet were then randomised to a 2-week double-blind placebo-controlled crossover challenge with MSG or placebo for 3 consecutive days each week. The primary outcome measure was total symptom score. Secondary outcome measures included visual analogue pain scales (VAS for FM and IBS), an IBS Quality of Life Questionnaire (IBS QOL) and the Fibromyalgia Impact Questionnaire-Revised (FIQR). Repeated measures ANOVA was used to analyse crossover challenge results.

RESULTS: The MSG challenge, as compared to placebo, resulted in a significant return of symptoms (total symptom score, p<0.02); a worsening of fibromyalgia severity as determined by the FIQR (p<0.03); decreased quality of life in regards to IBS symptoms (IBS QOL, p<0.05); and a non-significant trend toward worsening FM pain based on visual analogue scale (VAS, p<0.07).

CONCLUSIONS: These findings suggest that dietary glutamate may be contributing to FM symptoms in some patients. Future research on the role of dietary excitotoxins in FM is warranted.

This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability [24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% +/- 0.6% (mean +/- SE); normal, less than 3.0%] and by high fecal excretion of 111In-labeled leukocytes (14.2% +/- 1.1%; normal, less than 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% +/- 0.5%; P less than 0.01) and the fecal excretion of 111In (to 5.7% +/- 1.0%; P less than 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease.

The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1 year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12 months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3 ± 4.2 years) were included. Serumselenium levels were measured at baseline and at 3, 6, and 12 months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level<48 μg/L at each visit. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. Mean duration of KD was 15.3 ± 4.3 months. Mean serum selenium levels were significantly lower at 6 and 12 months of KD treatment (66.2 ± 23.3 and 57.2 ± 16.2 μg/L, respectively) compared to pre-treatment levels (79.3 ± 25.7 μg/L) (p = 0.001). On the other hand, selenium levels did not show any significant difference at 3 months of KD treatment (70.0 ± 21.2 μg/L) compared to baseline levels (p = 0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency, and oral selenium medication was initiated for these patients. No relevant clinical findings were detected, and echocardiographic findings were normal in all patients. The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients onthis highly prescriptive dietary treatment need close monitoring of this trace element.

Individual differences in dietary intake are thought to account for substantial variation in cancer incidence. However, there has been a consistent lack of effect for low-fat, high-fiber dietary interventions and risk of colorectal cancer. These inconsistencies may reflect the multistage process of cancer as well as the range and timing of dietary change. Another potential reason for the lack of effect is poor dietary adherence among participants in these trials. The authors examined the effect of strict adherence to a low-fat, high-fiber, high-fruit and -vegetable intervention over 4 years among participants (n = 1,905) in the US Polyp Prevention Trial (1991-1998) on colorectal adenoma recurrence. There was a wide range of individual variation in the level of compliance among intervention participants. The most adherent participants, defined as "super compliers" (n = 210), consistently reported that they met or exceeded each of the 3 dietary goals at all 4 annual visits. Multivariate logistic regression models were used to estimate the association between dietary adherence and adenoma recurrence. The authors observed a 35% reduced odds of adenoma recurrence among super compliers compared with controls (odds ratio = 0.65, 95% confidence interval: 0.47, 0.92). Findings suggest that high compliance with a low-fat, high-fiber diet is associated with reduced risk of adenoma recurrence.

BACKGROUND:Grape seed extract (GSE) is a natural supplement known for its various health benefits, including anti-inflammatory effect. This study aimed to evaluate the effects of GSE supplementation on inflammatory markers, neuropeptide Y, anthropometric measurements, and appetite in obese or overweight individuals.

METHODS AND MATERIALS:A randomized, double-blind clinical trial was performed on 40 obese or overweight subjects who were randomly assigned to receive GSE (300 mg/day) or placebo for a period of 12-weeks. Both groups were under a restricted calorie diet (RCD)(~250 kcal lower than the estimated energy requirement). Anthropometric measurements, biochemical biomarkers and dietary intakes were determined during the study period.

RESULTS:The reductions of body weight, body mass index, waist circumference, and waist to hip ratio were significantly higher in the GSE group compared to the placebo group (P = 0.045, 0.033, 0.029, and 0.021, respectively). Lower levels of neuropeptide Y, tumor necrosis factor alpha, and high sensitivity C-reactive protein were observed in the GSE group in comparison with the placebo group (P = 0.041, 0.001, and 0.034, respectively).

CONCLUSION:GSE supplement with a RCD has favorable effects in reducing anthropometric measurements and inflammatory markers in obese or overweight individuals, and may play an effective role in the treatment of obesity.

OBJECTIVE:To investigate the effects of long-term high-protein, low-carbohydrate diet on body weight and the expression of gastrointestinal hormones in diet-induced obesity rats.

METHODS:Twenty-four diet-induced obesity rat models were established by feeding fat-enriched diet, then were randomly divided into two groups by stratified sampling method by weight: the high-protein diet group (HP, 36.7% of energy from protein), and the normal chow group (NC, 22.4% of energy from protein), 12 rats in each group. The total calorie intake of each rat per day was similar and was maintained for 24 weeks, then body weight, visceral fat mass, fasting plasma ghrelin and glucagon-like peptide-1 (GLP-1) were determined, as well as protein expression of ghrelin in stomach, GLP-1 in ileum were detected by immunohistochemistry.

RESULTS:After 24 weeks, body weight of HP, NC groups were (490.92± 39.47) g and (545.55 ± 31.08) g, respectively (t = -3.664, P<0.01); visceral fat mass were (22.42± 7.04) g and (32.33 ± 9.27) g, respectively (t = -2.503, P<0.05); plasma ghrelin level were (2.36± 0.82) and (1.95 ± 0.64) ng/ml, respectively (t = 1.337, P>0.05), and plasma ghrelin level was negatively correlated to body weight (r = -0.370, t = -1.899, P<0.05), visceral fat mass (r = -0.454, t = -2.52, P<0.01); plasma GLP-1 concentration were (0.52± 0.13) and (0.71 ± 0.19) ng/ml, respectively(t = -2.758, P<0.05); ghrelin protein expression in stomach were 25 473± 8701 and 10 526 ± 6194, respectively (t = 2.501, P<0.05); GLP-1 protein expression in ileum were 27 431± 5813 and 36 601 ± 5083, respectively (t = -1.833, P = 0.081).

CONCLUSION:Long-term isocaloric high-protein, low-carbohydrate diet can reduce body weight and visceral fat, increase the expression of ghrelin, and decline GLP-1 expression in diet-induced obesity rats.

Objectives The purpose of this study was to characterize patients who were diagnosed with glucose transporter protein 1 deficiency syndrome (Glut1D), and also to assess the efficacy of ketogenic diet (KD) therapy on seizure control, cognitive functions, and other neurological disorders. Patients and Methods We studied six unrelated patients with the classical phenotype of Glut1D, focusing on clinical and laboratory features, the KD therapy and outcome over the 25-month follow-up period. Results Five patients became seizure-free with the onset of ketosis, and anticonvulsants were discontinued. Other neurological features such as ataxia, spasticity, and dystonia showed a less striking improvement than seizure control. There was no significant change in the intelligence quotient (IQ) level or microcephaly. In all patients, alertness, concentration, motivation, and activity resulted in a moderate improvement of variable degree. The early-onset adverse effects of KD were observed in five patients. The KD regimen failed in one patient, therefore, his diet was changed with an alternative to KD. Conclusions Treatment with KD resulted in a marked improvement in seizures and cognitive functions but its effect appeared to be less striking on the other neurological disorders of the patients. When the classic KD is not tolerated, an alternative to KD may be helpful.

INTRODUCTION: The phenolic compounds of olive leaves and olive oils in the Mediterranean diet have been associated with a reduced incidence of heart disease. Accordingly, antioxidant-rich diets may prevent the deleterious effects of oxidative metabolism by scavenging free radicals, thus inhibiting oxidation and delaying atherosclerosis. The process involves phospholipase C activation and arachidonic acid metabolism, and is thought to reduce hydrogen peroxide (H(2)O(2)). In our study, an extract of Olea europaea L. leaves was used. The active phenolic compounds in this extract are part of the secoiridoid family, known for their capacity to scavenge H(2)O(2). The results from this study will help to improve our understanding of effects of polyphenol antioxidants in olive leaf extract on platelet function.

METHODS: Full blood examination (FBE), platelet aggregation, and ATP release were performed on samples from fasting, normal, healthy male subjects. Platelet function at increasing concentrations of oleuropein was investigated through measures of platelet aggregation and ATP release from activated platelets.

RESULTS: Blood analysis (n=11) revealed a significant dose-dependant reduction in platelet activity with olive extract concentrations of 1.0% v/v (P<0.001). ATP Release showed a similar pattern (P=0.02).

CONCLUSIONS: Olive leaf polyphenols derived from O. europaea L. leaves inhibited in vitro platelet activation in healthy, non-smoking males. Further bioavailability studies need to be undertaken to determine the in vivo effect of extract on platelet function and to validate the present results.

To evaluate the efficacy and safety of ketogenic diet (KD) in patients with Dravet syndrome (DS).60 DS patients receiving treatment of KD for more than 12 weeks from 2009 to 2018 were analyzed retrospectively. Modified Johns Hopkins protocol was used to initiate KD. Seizure frequency, electroencephalogram (EEG), cognition, language, and motor function of the patients were assessed. Side effects were monitored and adjusted accordingly. SPSS 23.0 software was used for all statistical analysis.In total, 60 DS patients (34 boys, 26 girls) received treatment of KD for more than 12 weeks, and among them 41 (68.3%) patients remained on the diet for more than 24 weeks, 22 (36.7%) patients for more than 48 weeks. Seizures in 35 patients (58.3%) were reduced by over 50% at 12 weeks, and the KD effect was observed within 2 weeks in most of them. At 24 weeks, 61.1% (25/41) of the patients had a>50% seizure reduction. At 48 weeks, 77.3% (17/22) had an over 50% reduction in their seizure frequency. With the treatment of KD in the 60 DS patients, 10 patients had ever been seizure free for 12 months to 24 months (The median duration was 20 months). In 10 KD-effective patients, the background rhythm of their EEG showed obvious improvement, and interictal epileptic discharges decreased significantly. Cognitive function of 22 patients was improved. Language progressed in 14 patients. Motor function was improved in 13 patients. The efficacy of KD in DS patients did not correlate with the seizure onset age, the starting age of KD treatment, themutation and the numbers of antiepileptic drugs combined with KD treatment. The main adverse reactions of KD in the treatment process were gastrointestinal symptoms and metabolic disorders.KD treatment in DS patients has many advantages, including working rapidly, being effective in more than half of the DS patients and tolerable adverse reactions. Pharmoco-resistant DS patients are suggested to receive KD treatment.

A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.

Intestinal microbiota changes may be involved in the development of metabolic syndrome (MetS), which is a multicomponent disorder frequently associated with obesity. The aim of this study was to test the effect of consuming two healthy diets: a Mediterranean diet and a low-fat high-carbohydrate diet, for 2years in the gut microbiota of MetS patients and those in the control group. We analyzed the differences in the bacterial community structure between the groups after 2years of dietary intervention (Mediterranean or low-fat diet) through quantitative polymerase chain reaction using primers, targeting specific bacterial taxa. We observed, at basal time, that the abundance of Bacteroides, Eubacterium and Lactobacillus genera is lower in the control group than in MetS patients, while Bacteroides fragilis group, Parabacteroides distasonis, Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Fusobacterium nucleatum, Bifidobacterium longum, Bifidobacterium adolescentis, Ruminococcus flavefaciens subgroup and Eubacterium rectale are depleted in MetS patients (all P values<.05). Additionally, we found that long-term consumption of Mediterranean diet partially restores the population of P. distasonis, B. thetaiotaomicron, F. prausnitzii, B. adolescentis and B. longum in MetS patients (all P values<.05). Our results suggest that the Mediterranean diet could be a useful tool to restore potentially beneficial members of the gut microbiota, although the stability of these changes over time still remains to be assessed.

Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrationsby casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostatedevelopment and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.

BACKGROUND: The objective of this study was to assess the oral microbiota and clinical data in subjects without access to traditional oral hygiene methods and who ate a diet available in the Stone Age.

METHODS: Ten subjects living in an environment replicating the Stone Age for 4 weeks were enrolled in this study. Bleeding on probing (BOP), gingival and plaque indices, and probing depth (PD) were assessed at baseline and at 4 weeks. Microbiologic samples were collected at the mesio-buccal subgingival aspects of all teeth and from the dorsum of the tongue and were processed by checkerboard DNA-DNA hybridization methods.

RESULTS: No subject had periodontitis. Mean BOP decreased from 34.8% to 12.6% (P <0.001). Mean gingival index scores changed from 0.38 to 0.43 (not statistically significant) and mean plaque scores increased from 0.68 to 1.47 (P <0.001). PD at sites of subgingival sampling decreased (mean difference: 0.2 mm; P <0.001). At week 4, the total bacterial count was higher (P <0.001) for 24 of 74 species, including Bacteroides ureolyticus, Eikenella corrodens, Lactobacillus acidophilus, Capnocytophaga ochracea, Escherichia coli, Fusobacterium nucleatum naviforme, Haemophilus influenzae, Helicobacter pylori, Porphyromonas endodontalis, Staphylococcus aureus (two strains), Streptococcus agalactiae, Streptococcus anginosis, and Streptococcus mitis. Bacterial counts from tongue samples were higher at baseline (P <0.001) for 20 species, including Tannerella forsythia (previously T. forsythensis), Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans; serotype a), and Streptococcus spp.

CONCLUSIONS: The experimental gingivitis protocol is not applicable if the diet (e.g., Stone Age) does not include refined sugars. Although plaque levels increased, BOP and PD decreased. Subgingival bacterial counts increased for several species not linked to periodontitis, whereas tongue bacterial samples decreased during the study period.

In most developed countries, gluten is currently most commonly introduced between 4 and 6 months of age, in spite of little evidence to support this practice. As for infants at risk of developing food allergies, there is clear evidence that introducing solid foods before the end of the 3rd month is detrimental and should be avoided. A recent growing body of evidence however challenges the notion that solids (and among them, gluten-containing foods) should be introduced beyond the 6th month of life. Another important aspect of gluten introduction into the diet has to do with its possible role in causing type-1 diabetes (IDDM). Recently, a large epidemiological investigation in a cohort of children at risk for IDDM found that exposure to cereals (rice, wheat, oats, barley, rye) that occurred early (< or = 3 months) as well as late (> or = 7 months) resulted in a significantly higher risk of the appearance of islet cell autoimmunity compared to the introduction between 4 and 6 months. As for celiac disease, the protective role of breastfeeding can be considered ascertained, especially the protection offered by having gluten introduced while breastfeeding is continued. Evidence is emerging that early (< or = 3 months) and perhaps even late (7 months or after) first exposure to gluten may favor the onset of celiac disease in predisposed individuals. Additionally, large amounts of gluten at weaning are associated with an increased risk of developing celiac disease, as documented in studies from Scandinavian countries. In celiac children observed in our center, we could show that breastfeeding at the time of gluten introduction delays the appearance of celiac disease and makes it less likely that its presentation is predominantly gastrointestinal. Based on current evidence, it appears reasonable to recommend that gluten be introduced in small amounts in the diet between 4 and 6 months, while the infant is breastfed, and that breastfeeding is continued for at least a further 2-3 months.

The prevalence of Alzheimer's disease, a chronic neurodegenerative condition, is increasing as is the need for effective treatments and preventions. The underlying pathology of Alzheimer's is not yet fully understood, so existing research has focused on understanding the prominent features of the disease. These include amyloid plaques, which accumulate in the brains of those with Alzheimer's disease; impaired glucose metabolism; and neuronal cell death. Emerging evidence suggests that a low-carbohydrate, high-fat ketogenic diet may help to mitigate the damage associated with these pathologies. The ketogenic diet could alleviate the effects of impaired glucose metabolism by providing ketones as a supplementary energy source. In addition, this diet may help to reduce the accumulation of amyloid plaques while reversing amyloidβ toxicity. Research has begun to identify early underlying mechanisms in Alzheimer's disease that could be targeted by new prevention strategies. Glycation of the ApoE protein leads to impaired transportation of important lipids, including cholesterol, to the brain, resulting in lipid deficienciesthat could explain progression to the later pathologies of the disease. In this review, we hypothesize that the ketogenic diet could be an effective treatment and prevention for Alzheimer's disease, but both ketone production and carbohydrate restriction may be needed to achieve this.

Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat - or at least ameliorate symptoms of - these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more"natural"treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

The brain aspartate-glutamate carrier (AGC1) is specifically expressed in neurons, where it transports aspartate from the mitochondria to the cytosol, and plays a role in transfer of nicotinamide adenine dinucleotide (NADH)-reducing equivalents into the mitochondria as a part of the malate-aspartate shuttle. Deficient function of AGC1 underlies an inborn error of metabolism that presents with severe hypotonia, arrested psychomotor development, and seizures from a few months of age. In AGC1 deficiency, there is secondary hypomyelination due to lack of N-acetylaspartate (NAA), which is normally generated by acetylation of aspartate in the neuron and required for fatty acid synthesis by the adjacent oligodendrocyte. Based on experiences from AGC2 deficiency, we predicted that reduced glycolysis should compensate for the metabolic defect and allow resumed myelination in AGC1 deficiency. Carbohydrate restriction was therefore initiated in a patient with AGC1 deficiency at 6 years of age by introducing a ketogenic diet. The response was dramatic, clinically as well as radiologically. Psychomotor development showed clear improvement, and magnetic resonance imaging (MRI) indicated resumed myelination. This is the first successful treatment of secondary hypomyelination reported. Because AGC1 is driven by the proton gradient generated by the neuronal mitochondrial respiratory chain, the results have potential relevance for secondary hypomyelination in general.

OBJECTIVE:To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (<1.5 years of age) compared with older children.

METHODS:Patients with complete follow-up data of≥3 months after initiation of the KD were analyzed retrospectively. Infants<1.5 years at initiation of the KD (Group A) were compared with children>1.5 years (Group B).

RESULTS:127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p=0.000). Looking at infants<9 months of age separately (n=42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p=0.005, p=0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p=0.001). No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p=0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.).

SIGNIFICANCE:According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy.

:Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by the recurrence of long-lasting atypical status epilepticus associated with attention impairment and continuous polymorphous jerks, mixed with other complex abnormal movements, in infants suffering from a non-progressive encephalopathy. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies.

PURPOSE:In this study we assess the efficacy and tolerability of the KD in patients with MSNPE.

METHODS:Between March 1, 1980 and August 31, 2013, 99 patients who met the diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins protocol and followed for a minimum period of 24 months.

RESULTS:Twelve months after initiating the diet, three patients had a 75%-99% decrease in seizures, two had a 50%-74% decrease in seizures, and the remaining child had a less than 50% seizure reduction. In five patients with a seizure reduction of more than 50%, the myoclonic status epilepticus disappeared within 6 months after starting the diet. All patients had very good tolerability and no adverse events were identified. In most of the patients AEDs were reduced.

CONCLUSION:The KD is a promising therapy for MSNPE, with most of our patients showing a more than 50% seizure reduction. In patients that responded well to the diet cognitive performance and quality of life also improved.

OBJECTIVE:To document the long-term outcome of the 83 children with difficult-to-control seizures who were enrolled prospectively in a study of the efficacy of the ketogenic diet and who had remained on the diet for 1 year.

METHODS:A total of 150 consecutive children were entered prospectively into a study of the ketogenic diet's efficacy and tolerability. Three to 6 years after diet initiation, all 150 families were sent a survey inquiring about their child's current health status, seizure frequency, and current anticonvulsant medications. They were asked about their experience with the diet and reasons for discontinuation. Several telephone attempts were made to contact those who did not respond to the written questionnaire. Responses were entered in an Access database and analyzed.

RESULTS:In 1999, 3 to 6 years after initiating the diet, 107 of 150 families responded to a questionnaire. Thirty-five additional families were interviewed by telephone, 4 were lost to follow-up, and 4 children had died, unrelated to the diet. Of the original 150 patient cohort, 20 (13%) were seizure-free and an additional 21 (14%) had a 90% to 99% decrease in their seizures. Twenty-nine were free of medications, and 28 were on only 1 medication; 15 remained on the diet. There were no known cardiac complications.

CONCLUSION:Three to 6 years after initiation, the ketogenic diet had proven to be effective in the control of difficult-to-control seizures in children. The diet often allows decrease or discontinuation of medication. It is more effective than many of the newer anticonvulsants and is well-tolerated when it is effective.