Protein Nutrition in Autism.

Autism is a developmental disorder that affects communication and behavior. Although autism can be diagnosed at any age, it is said to be a "developmental disorder" because symptoms generally appear in the first 2 years of life. The primary cause of autism is still not clear and therapy is currently restricted to controlling behavioral abnormalities. However, emerging studies have shown a link between mitochondrial dysfunction and autism. Dietary supplements that promote mitochondrial biogenesis and inhibit the production of oxidative stress have been used to treat autism patients. Dietary adjustments in treating autism is a novel approach to suppress autistic symptoms. Supplementation with antioxidants has been found to not only inhibit cognitive decline but also improve behavioral symptoms in autism. Dietary supplements fortified with vitamins should only be given under the supervision of a physician. A wide range of nutraceuticals are under clinical trials to understand whether they physiologically target mitochondrial pathways and improve the quality of life in autism.

Evaluation and Clinical Course of Keratomalacia With Descemetocele in a Child With Autism and Vitamin A Deficiency.

Autistic children with selective diets have an elevated risk for vitamin A deficiency. The authors present the case of a 7-year-old boy with keratomalacia resulting from dietary vitamin A deficiency. Optical coherence tomography and ultrasound biomicroscopy can provide useful details of the cornea and underlying structures. Vitamin A supplementation can result in significant resolution, obviating the need for surgical intervention. [J Pediatr Ophthalmol Strabismus. 2020;57:e1-e3.].

Round Table Discussion.

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).

Gastrointestinal microbiota in children with autism in Slovakia.

Development of Autism Spectrum Disorders (ASD), including autism, is based on a combination of genetic predisposition and environmental factors. Recent data propose the etiopathogenetic role of intestinal microflora in autism. The aim of this study was to elucidate changes in fecal microbiota in children with autism and determine its role in the development of often present gastrointestinal (GI) disorders and possibly other manifestations of autism in Slovakia. The fecal microflora of 10 children with autism, 9 siblings and 10 healthy children was investigated by real-time PCR. The fecal microbiota of autistic children showed a significant decrease of the Bacteroidetes/Firmicutes ratio and elevation of the amount of Lactobacillus spp. Our results also showed a trend in the incidence of elevated Desulfovibrio spp. in children with autism reaffirmed by a very strong association of the amount of Desulfovibrio spp. with the severity of autism in the Autism Diagnostic Interview (ADI) restricted/repetitive behavior subscale score. The participants in our study demonstrated strong positive correlation of autism severity with the severity of GI dysfunction. Probiotic diet supplementation normalized the Bacteroidetes/Firmicutes ratio, Desulfovibrio spp. and the amount of Bifidobacterium spp. in feces of autistic children. We did not find any correlation between plasma levels of oxytocin, testosterone, DHEA-S and fecal microbiota, which would suggest their combined influence on autism development. This pilot study suggests the role of gut microbiota in autism as a part of the "gut-brain" axis and it is a basis for further investigation of the combined effect of microbial, genetic, and hormonal changes for development and clinical manifestation of autism.

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.

Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.

Impact of nutrition on serum levels of docosahexaenoic acid among Omani children with autism.

OBJECTIVES: Autism is a lifelong neurodevelopmental disorder of early childhood. Dietary supplementation of the ω-3 fatty acid (docosahexaenoic acid [DHA]) during prenatal and postnatal life is considered a protective dietary intervention strategy to minimize the risk for autism spectrum disorder (ASD). To our knowledge, no relevant studies have been conducted in the Middle East investigating the status of DHA among children with autism during early childhood. The aim of this study was to investigate the serum levels and dietary intake status of DHA among Omani children recently diagnosed with ASD. METHODS: The present case-control study involved 80 Omani children (<5 y), 40 cases and 40 controls matched for age and sex. A semi-quantitative food frequency questionnaire was used to assess dietary intake of all the participants, while serum levels of DHA were measured using high-performance liquid chromatography. RESULTS: Our results showed that children with ASD had lower dietary consumption of foodstuff containing DHA, as well as lower serum levels of DHA than controls. CONCLUSION: The present finding from Oman supports the view of other studies that there are low serum levels of DHA among children with ASD.

Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy.

Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.

Vitamin supplementation reduces the level of homocysteine in the urine of autistic children.

Significant differences in homocysteine levels in the urine of autistic children are observed. We hypothesized that vitamin supplementation might reduce the level of urinary homocysteine. To rationalize such a hypothesis, analyses were performed using the gas chromatography/mass spectrometry method. The homocysteine level in the urine of autistic children was measured twice: (1) before vitamin supplementation (group C, 30 autistic children) and (2) after supplementation, with either folic acid and vitamins B(6) and B(12) (group A1, 24 autistic children) or vitamins B(6) and B(12) alone (group A2, 6 autistic children). The homocysteine level in the urine of autistic children before vitamin supplementation was 2.41 ± 1.10 mmol/mol creatinine (mean ± SD difference). After treatment, the homocysteine level was reduced to 1.13 ± 0.44 and 1.33 ± 0.39 mmol/mol creatinine for A1 and A2 groups, respectively. The intake of vitamins B(6) and B(12), together with folic acid, was found to be more effective in lowering the levels of urinary homocysteine than the intake of vitamins B(6) and B(12) alone. Our findings may lead to the recommendation of including vitamins B(6) and B(12) together with folic acid supplementation in the diets of children with autism.

The review of most frequently occurring medical disorders related to aetiology of autism and the methods of treatment.

The medical understanding of autism has changed since it was first defined by Kanner. Nowadays medicine identifies many medical abnormalities and diseases, which may underline or aggravate the cognitive aspect, behavioural issues and general health in autists. This includes chronic inflammation of gastrointestinal tract, dysbiosis, maldigestion, malabsorption, malnutrition, food intolerance, allergies, chronic viral, fungal and bacterial infections, impaired kidney function, impaired detoxification of endo- and exotoxins, disorders of metal ion transportation. Treatment of the above mentioned conditions combined with improving detoxification mechanisms, followed by a special diet and individually customized supplementation of nutritional deficiencies may lead to the improvement of the functioning of these patients, changing their level of functioning and self-dependence. The aim of this paper is to present medical problems of children with autism which may be identified and treated by general practitioners as a review of current medical papers related to Autism Spectrum Disorder, in the context of author's professional experience, based on the medical cases from author's practice.

Neurofeedback for autistic spectrum disorder: a review of the literature.

There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.

Role of polyunsaturated fatty acids in the management of Egyptian children with autism.

OBJECTIVE: Estimation of free polyunsaturated fatty acids (PUFAs) in blood and evaluation of behavior of autistic children before and after taking fish oil (Efalex) were performed. DESIGN AND METHODS: 30 autistic children (18 males and 12 females) aged 3-11 years and 30 healthy children as control group were included in this study. Tandem mass spectrometry and CARS were used to estimate the free PUFAs from dried blood spot and to evaluate the autistic behavior respectively. RESULTS: Before taking Efalex, linolenic acid showed a significant reduction (71%), followed by docosahexaenoic acid (65%) and arachidonic acid (45%), while linoleic acid was the least affected PUFA (32%). After taking Efalex, 66% of autistic children showed clinical and biochemical improvement, linolenic acid and docosahexaenoic acid showed the highest levels after Efalex supplementation. CONCLUSION: PUFA supplementation may play an important role in ameliorating the autistic behavior.

Gluten- and casein-free diets for autistic spectrum disorder.

BACKGROUND: It 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. OBJECTIVES: To 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 STRATEGY: The 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 CRITERIA: All 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 ANALYSIS: Abstracts 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 RESULTS: Two 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' CONCLUSIONS: Research 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.

Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.

The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.

Children and autism--Part 2--management with complementary medicines and dietary interventions.

BACKGROUND: Complementary and alternative medicines (CAMs) and dietary interventions are widely used in the management of autistic disorders as pharmacological treatments offered by mainstream medicine are limited and often associated with significant adverse effects. OBJECTIVE: In this article, the rationale, safety and efficacy of a range of CAMs and dietary interventions used in the management of autistic disorders are discussed. DISCUSSION: Despite many anecdotal reports supporting the efficacy of CAMs, evidence for their use in autistic disorders is either unclear or conflicting, and available data comes from a limited number of small studies. Large randomised controlled trials have not yet been conducted to examine efficacy in this population. Although most interventions are associated with only mild adverse effects, there is a lack of long term safety data. General practitioners need to be aware that the use of CAMs in autism is not risk free and often lacks sound clinical evidence. On the other hand, there may be subtle benefits to the child, especially if interventions are coupled with intensive behavioural and/or educational intervention.

Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study.

BACKGROUND: There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders. METHODS: We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks. RESULTS: We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group. CONCLUSIONS: The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.

Elimination diets in autism spectrum disorders: any wheat amidst the chaff?

The use of complementary or alternative treatment approaches in children with autism spectrum disorders (ASDs) is increasing, and the most popular of such approaches are diets that eliminate either gluten or casein, or both. The popularity of these diets indicates a need for more rigorous research into their efficacy. Owing to significant methodological flaws, the currently available data are inadequate to guide treatment recommendations. The purpose of this review is to examine the available trials of gluten/casein diets in children with ASDs regarding the strength of their findings and also concerning points that may be useful in the design of future studies. Seven trials of these diets in ASD are critically reviewed; 6 of these were uncontrolled trials and 1 used a single-blind design. All reported efficacy in reducing some autism symptoms, and 2 groups of investigators also reported improvement in nonverbal cognition. Design flaws in all of the studies weaken the confidence that can be placed in their findings. Careful double-blind, placebo-controlled studies are needed to evaluate whether actual benefit undergirds the diets' popularity and to provide better guidance to clinicians and caregivers. The literature currently available suggests that diets eliminating both gluten and casein (rather than either alone) should be studied first and that outcome measures should include assessments of nonverbal cognition.