A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder.
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ABSTRACT:
SUBMITTER: Lee RWY
PROVIDER: S-EPMC5863039 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder.
Lee Ryan W Y RWY Corley Michael J MJ Pang Alina A Arakaki Gaye G Abbott Lisa L Nishimoto Michael M Miyamoto Rob R Lee Erica E Yamamoto Susan S Maunakea Alika K AK Lum-Jones Annette A Wong Miki M
Physiology & behavior 20180205
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Project description:Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD.
| S-EPMC5293204 | biostudies-literature
Project description:Dietary intervention as a tool for maintaining and improving physical health and wellbeing is a widely researched and discussed topic. Speculation that diet may similarly affect mental health and wellbeing particularly in cases of psychiatric and behavioral symptomatology opens up various avenues for potentially improving quality of life. We examine evidence suggestive that a gluten-free (GF), casein-free (CF), or gluten- and casein-free diet (GFCF) can ameliorate core and peripheral symptoms and improve developmental outcome in some cases of autism spectrum conditions. Although not wholly affirmative, the majority of published studies indicate statistically significant positive changes to symptom presentation following dietary intervention. In particular, changes to areas of communication, attention, and hyperactivity are detailed, despite the presence of various methodological shortcomings. Specific characteristics of best- and non-responders to intervention have not been fully elucidated; neither has the precise mode of action for any universal effect outside of known individual cases of food-related co-morbidity. With the publication of controlled medium- and long-term group studies of a gluten- and casein-free diet alongside more consolidated biological findings potentially linked to intervention, the appearance of a possible diet-related autism phenotype seems to be emerging supportive of a positive dietary effect in some cases. Further debate on whether such dietary intervention should form part of best practice guidelines for autism spectrum conditions (ASCs) and onward representative of an autism dietary-sensitive enteropathy is warranted.
| S-EPMC3540005 | biostudies-literature
Project description:ContextIt has been suggested that a gluten-free and casein-free (GFCF) diet may alleviate the symptoms of autism spectrum disorder (ASD) and facilitate neurodevelopment of children with ASD. Studies to date have been inconclusive.ObjectiveThis study aimed to evaluate (through quantitative meta-analysis) the efficacy and safety of a GFCF diet for children with ASD. To our knowledge, this is the first time such an analysis has been carried out.Data sourcesEight electronic databases were searched, from the establishment of each database up to March 27, 2020: PubMed, Web of Science, Embase (Ovid), PsycINFO (Ovid), Cochrane Library, CNKI, Wanfang, and VIP databases.Data extractionTwo authors independently performed the data extraction and risk-of-bias assessment.Data analysisA quantitative meta-analysis was performed with standard procedures by using Stata SE 15 software. Within the total of 8 studies, with 297 participants, 5 studies reported significant reductions in stereotypical behaviors [standard mean difference (SMD) = -0.41, 95% confidence interval (CI): -0.68 to -0.15], and 3 studies reported improvements in cognition (SMD = -0.46, 95% CI: -0.91 to -0.01) following GFCF dietary intervention . No statistically significant changes were observed in other symptomatic categories (all P > 0.05).ConclusionThe current meta-analysis showed that a GFCF diet can reduce stereotypical behaviors and improve the cognition of children with ASD. Though most of the included studies were single-blind, the benefits of a GFCF diet that have been indicated are promising. Additional studies on a larger scale are warranted.Systematic review registrationPROSPERO registration no. CRD42020177619.
| S-EPMC8990762 | biostudies-literature
Project description:Interventions: Nutrition counseling We provide outpatient nutritional guidance once a month for 30 minutes. It can be calculated once a month as an outpatient nutrition dietary guidance fee. The modified MCT ketogenic diet is 2-3 meals a day, prepared under the supervision of a registered dietitian, and you can cook your own food according to the following rules, or obtain low-carbohydrate foods at the supermarket or the Internet. .. Meal purchase funds will be borne by the patient. Cooking recipes will be distributed at the start of clinical research. 7 rules of dietary intake 1. The target energy intake is 35-40 kcal per body weight. 2. Eat 1.6-2.0 g of protein-rich foods (meat, fish, eggs, soy products) per body weight. 3. Take at least 4g of EPA daily. 4. Limit the amount of sugar to 25 g or less per day (when the body weight is 50 kg). 5. Ingest 60 to 100 g of medium-chain fatty acids per day in terms of MCT oil. 6. The weight of the meal is morning: noon: evening = 4: 10: 6, and the weight is adjusted so that the person feels hungry before going to bed. 7. The target ketone ratio is 1.4 to 1.6: 1. Estimated implementation period and meal contents (see A and B below) 1. First 3 months: Super ketogenic. 2. From 3 months to 1 year: Continue to eat ketogenic diet, mainly super ketogenic. 3. After the above research period is exceeded, we will instruct them to continue ketogenic and semi-ketogenic Level of carbohydrate restriction 1. Semi-ketogenic Ketone ratio Lipid: Sugar + Protein = 1: 1 Sugar intake 80 g / day or less Lipid intake: flaxseed oil 30 g / day, MCT oil 80 mg / day (total fat 110 g) 2. Ketogenic Ketone ratio Lipid: Sugar + Protein = 1.4: 1 Sugar intake 40 g / day or less Lipid intake: flaxseed oil 30 g / day, MCT oil 80 mg / day (total fat 110
Primary outcome(s): Safety Presence or absence of diarrhea or allergic symptoms b. Dehydration, symptomatological hypoglycemia, excessive ketosis, gastrointestinal symptoms Nutritional status (body weight, body composition analysis using In Body (BIA), serum albumin, serum cholinesterase, serum transthyretin, CRP), QOL score (EORTCQLQ-CR38 Japanese version, POMS2 Japanese version)
Study Design: Single arm Non-randomized
| 2723656 | ecrin-mdr-crc
Project description:Background and aimsCeliac disease (CD) is a widespread condition triggered by dietary gluten and treated with a lifelong gluten-free diet (GFD); however, inadvertent exposure to gluten can result in episodic symptoms. A previous trial of latiglutenase (clinicaltrials.gov; NCT01917630), an orally administered mixture of two recombinant gluten-specific proteases, was undertaken in symptomatic subjects with persistent injury. The primary endpoint for histologic improvement was not met, presumably due to a trial effect. In this post hoc analysis, we investigated the efficacy of latiglutenase for reducing symptoms in subgroups of the study participants based on their seropositivity.MethodsThe study involved symptomatic CD patients following a GFD for at least one year prior to randomization. Patients were treated for 12 weeks with latiglutenase or placebo. Of 398 completed patients, 173 (43%) were seropositive at baseline. Symptoms were recorded daily, and weekly symptom scores were compiled. p values were calculated by analysis of covariance.ResultsA statistically significant, dose-dependent reduction was detected in the severity and frequency of symptoms in seropositive but not seronegative patients. The severity of abdominal pain and bloating was reduced by 58 and 44%, respectively, in the cohort receiving the highest latiglutenase dose (900 mg, n = 14) relative to placebo (n = 54). Symptom improvement increased from week 6 to week 12. There was also a trend toward greater symptom improvement with greater baseline symptom severity.ConclusionsSeropositive CD patients show symptomatic improvement from latiglutenase taken with meals and would benefit from the availability of this treatment.
| S-EPMC5709215 | biostudies-literature
Project description:Ketogenic, gluten-free cupcakes containing varying amounts of almond and coconut flours were evaluated for textural and sensory attributes. Coconut-flour particle-size influenced cupcake volume and crumb structure, with smaller flour-particle size resulting in increased volume and decreased crumb density. Although almond-flour particle size itself did not directly influence cupcake properties, volume increases were observed in cupcakes with higher percentages of almond flour. Addition of coconut flour increased cell size and decreased cell density. Mechanical testing showed almond flour resulted in a cupcake that was more tender. Adhesion and cohesion values showed no statistical difference after 24 h and minimal change at subsequent evaluation periods. Quantitative descriptive analysis and consumer acceptance evaluation indicated that cupcakes containing almond flour were more moist and tender, and were preferred over cupcakes made with only coconut flour. Almond and coconut flours may be used in gluten-free, ketogenic cupcakes, with almond flour performing better in evaluated parameters.
| S-EPMC8666506 | biostudies-literature
Project description:There has been a growing interest in the gastrointestinal system and its significance for autism spectrum disorder (ASD), including the significance of adopting a gluten-free and casein-free (GFCF) diet. The objective was to investigate beneficial and safety of a GFCF diet among children with a diagnosis of ASD. We performed a systematic literature search in Medline, Embase, Cinahl, and the Cochrane Library up to January 2020 for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated a GFCF diet compared to a regular diet in children aged 3 to 17 years diagnosed with ASD, with or without comorbidities. The quality of the identified existing reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR). The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool, and overall quality of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified six relevant RCTs, which included 143 participants. The results from a random effect model showed no effect of a GFCF diet on clinician-reported autism core symptoms (standardized mean difference (SMD) -0.31 (95% Cl. -0.89, 0.27)), parent-reported functional level (mean difference (MD) 0.61 (95% Cl -5.92, 7.14)) or behavioral difficulties (MD 0.80 (95% Cl -6.56, 10.16)). On the contrary, a GFCF diet might trigger gastrointestinal adverse effects (relative risk (RR) 2.33 (95% Cl 0.69, 7.90)). The quality of evidence ranged from low to very low due to serious risk of bias, serious risk of inconsistency, and serious risk of imprecision. Clinical implications of the present findings may be careful consideration of introducing a GFCF diet to children with ASD. However, the limitations of the current literature hinder the possibility of drawing any solid conclusion, and more high-quality RCTs are needed. The protocol is registered at the Danish Health Authority website.
| S-EPMC7912271 | biostudies-literature
Project description:ObjectiveTo assess the relationship between self-reported adherence to a gluten-free diet (GFD) and the ability to determine correctly the appropriateness of particular foods in a GFD.MethodsPersons with celiac disease were recruited through clinics and support groups. Participants completed a questionnaire with items related to GFD information sources, gluten content of 17 common foods (food to avoid, food allowed, and food to question), GFD adherence, and demographic characteristics. Diagnosis was self-reported.ResultsThe 82 respondents (88% female) had a median of 6 y GFD experience. Most (55%) reported strict adherence, 18% reported intentional gluten consumption and 21% acknowledged rare unintentional gluten consumption. Cookbooks, advocacy groups, and print media were the most commonly used GFD information sources (85-92%). No participant identified correctly the gluten content of all 17 foods; only 30% identified at least 14 foods correctly. The median score on the Gluten-Free Diet Knowledge Scale (GFD-KS) was 11.5 (interquartile ratio, 10-13). One in five incorrect responses put the respondent at risk of consuming gluten. GFD-KS scores did not correlate with self-reported adherence or GFD duration. Patient advocacy group members scored significantly higher on the GFD-KS than non-members (12.3 versus 10.6; P < 0.005).ConclusionsSelf-report measures which do not account for the possibility of unintentional gluten ingestion overestimate GFD adherence. Individuals who believe they are following a GFD are not readily able to correctly identify foods that are GF, which suggests ongoing gluten consumption may be occurring, even among patients who believe they are "strictly" adherent. The role of patient advocacy groups and education to improve outcomes through improved adherence to a GFD requires further research.
| S-EPMC5457910 | biostudies-literature
Project description:As a journal page for full details. The ketogenic diet (KD) has been established as a treatment for epilepsy, but more recently it has been explored as an alternative or add-on therapy for many other diseases ranging from weight loss to neurological disorders. Animal models are widely used in studies investigating the therapeutic effects of the KD as well as underlying mechanisms. Especially in the context of neurological, psychiatric, and neurodevelopmental disorders essential endpoints are assessed by behavioral and motor tests. Here we summarized research evaluating the influence of the KD on cognition, depressive and anxiety-related behaviors, and social and nutritional behaviors of laboratory rodents. Each section contains a brief description of commonly used behavioral tests highlighting their limitations. Ninety original research articles, written in English, performed on mice or rats, providing measurement of blood beta-hydroxybutyrate (BHB) levels and behavioral evaluation were selected for the review. The majority of research performed in various disease models shows that the KD positively impacts cognition. Almost an equal number of studies report a reduction or no effect of the KD on depressive-related behaviors. For anxiety-related behaviors, the majority of studies show no effect. Despite the increasing use of the KD in weight loss and its appetite-reducing properties the behavioral evaluation of appetite regulation has not been addressed in preclinical studies. This review provides an overview of the behavioral effects of nutritional ketosis addressed to a broad audience of scientists interested in the KD field but not necessarily specializing in behavioral tests.
| S-EPMC10881757 | biostudies-literature
Project description:BackgroundIt has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of people with autism.ObjectivesTo determine the efficacy of gluten and/or casein free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism.Search strategyThe following electronic databases were searched: CENTRAL(The Cochrane Library Issue 2, 2007), MEDLINE (1966 to April 2007), PsycINFO (1971 to April 2007), EMBASE (1974 to April 2007), CINAHL (1982 to April 2007), ERIC (1965 to 2007), LILACS (1982 to April 2007), and the National Research register 2007 (Issue1). Review bibliographies were also examined to identify potential trials.Selection criteriaAll randomised controlled trials (RCT) involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with an autistic spectrum disorder.Data collection and analysisAbstracts of studies identified in searches of electronic databases were assessed to determine inclusion by two independent authors The included trials did not share common outcome measures and therefore no meta-analysis was possible. Data are presented in narrative form.Main resultsTwo small RCTs were identified (n = 35). No meta-analysis was possible. There were only three significant treatment effects in favour of the diet intervention: overall autistic traits, mean difference (MD) = -5.60 (95% CI -9.02 to -2.18), z = 3.21, p=0.001 (Knivsberg 2002) ; social isolation, MD = -3.20 (95% CI -5.20 to 1.20), z = 3.14, p = 0.002) and overall ability to communicate and interact, MD = 1.70 (95% CI 0.50 to 2.90), z = 2.77, p = 0.006) (Knivsberg 2003). In addition three outcomes showed no significant difference between the treatment and control group and we were unable to calculate mean differences for ten outcomes because the data were skewed. No outcomes were reported for disbenefits including harms.Authors' conclusionsResearch has shown of high rates of use of complementary and alternative therapies (CAM) for children with autism including gluten and/or casein exclusion diets. Current evidence for efficacy of these diets is poor. Large scale, good quality randomised controlled trials are needed.
| S-EPMC4164915 | biostudies-literature