Monthly Research Review June 2017

This month I have included some research into melatonin, intestinal permeability and vitamin D, as well as the usual ASD research review.


Dietary Sources and Bioactivities of Melatonin. Full pdf. “Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. Eggs and fish are higher melatonin-containing food groups in animal foods, whereas in plant foods, nuts are with the highest content of melatonin. This review summaries the dietary sources and bioactivities of melatonin, with special attention paid to the mechanisms of action.”

Melatonin for the prevention and treatment of cancer. Full pdf. “The epidemiological studies have indicated a possible oncostatic property of melatonin on different types of tumors.  Melatonin could be an excellent candidate for the prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer. This review summarized the anticancer efficacy of melatonin, based on the results of epidemiological, experimental and clinical studies, and special attention was paid to the mechanisms of action.”

Intestinal Permeability

Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes. Full pdf. “Increased intestinal permeability has been implicated in various pathologies, has various causes, and can develop during vigorous athletic training. Colostrum bovinum is a natural supplement with a wide range of supposed positive health effects, including reduction of intestine permeability. We assessed influence of colostrum supplementation on intestinal permeability related parameters in a group of 16 athletes during peak training for competition. Colostrum bovinum supplementation was safe and effective in decreasing of intestinal permeability in this series of athletes at increased risk of its elevation.”

Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Full pdf. “Levels of inflammatory mediators in circulation are known to increase with age. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts. These data suggest that aging-associated microbiota promote inflammation and that reversing these age-related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity.”

Vitamin D

Association Between Serum Vitamin D and All-Cause and Cause-Specific Death in a General Japanese Population. Full pdf. “Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations. The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.”

Autism Spectrum Disorder

Characterization of Medication Use in a Multicenter Sample of Pediatric Inpatients with Autism Spectrum Disorder.Nearly 11% of youth with Autism Spectrum Disorder (ASD) undergo psychiatric hospitalization, and 65% are treated with psychotropic medication. Here we characterize psychotropic medication usage in subjects enrolled in the Autism Inpatient Collection. Participant psychotropic medication usage rates topped 90% at admission and discharge, though there was a decline at 2-month follow-up. Antipsychotics, ADHD medications, and sleep aids were the most commonly reported classes of medications.”

Evaluation of behavioral change after adenotonsillectomy for obstructive sleep apnea in children with autism spectrum disorder.Behavioral problems were significantly improved following AT [adnotonsillectomy] in ASD children with OSA [obstructive sleep apnoea]. Early detection and treatment of children with OSA is essential to prevent behavioral problems and to support mental development.”

Sleep in Children with Autism Spectrum Disorder.Approximately two thirds of children with ASD have chronic insomnia, and to date, the strongest evidence on promoting sleep is for sleep education, environmental changes, behavioral interventions, and exogenous melatonin.”

Association between autism spectrum disorder and epilepsy in children.There is a significant association between ASD and epilepsy in children. The possibility of the comorbidity between ASD and epilepsy may be assessed according to the status of growth and development before the age of one year, sensory responses and behavioral competencies, and the presence or absence of epileptic seizures.”

The Gut Microbiota and Autism Spectrum Disorders. Full text. “Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD.”

Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects.Serum levels of zonulin, which regulates tight junctions between enterocytes and is a physiological modulator controlling intestinal permeability, in patients with autism spectrum disorders (ASDs). Serum zonulin levels were significantly higher in the patients with ASD compared with the healthy controls. There was a positive correlation between zonulin levels and Childhood Autism Rating Scale score when all subjects were assessed. This study suggests that zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD.”

Blood Mercury, Arsenic, Cadmium, and Lead in Children with Autism Spectrum Disorder.Environmental factors have been implicated in the etiology of autism spectrum disorder (ASD); however, the role of heavy metals has not been fully defined. This study investigated whether blood levels of mercury, arsenic, cadmium, and lead of children with ASD significantly differ from those of age- and sex-matched controls. Data showed that the children with ASD had significantly higher levels of mercury and arsenic and a lower level of cadmium. The levels of lead did not differ significantly between the groups. The results of this study are consistent with numerous previous studies, supporting an important role for heavy metal exposure, particularly mercury, in the etiology of ASD.”

Maternal experience raising girls with autism spectrum disorder: a qualitative study.Mothers reported a sense of exclusion from the neurotypical population and male-dominant ASD population and transformation in relationship. Themes identified were skepticism and delayed diagnosis, disbelief from others, lack of information about girls with ASD, higher social demands in adolescence, puberty challenges around hygiene, disappointment about physical appearance, vulnerability in relationships and worries about future functioning. The mother-daughter relationship started with an early expectation of a close and intimate relationship that then underwent a transformation, which challenged maternal competence, reshaped expectations and created a different bond between mother and daughter.”

Autism, epilepsy, and synaptopathies: a not rare association.ASD are often associated with neurological conditions: the co-occurrence of epilepsy is well documented and there is also evidence of a higher prevalence of EEG abnormalities with 4-86% of individuals with ASD presenting epileptiform or not epileptiform EEG abnormalities. The presence of epilepsy in people with ASD may be determined by several structural alterations, genetic conditions, or metabolic dysfunctions, known to play a role in the emergence of both epilepsy and autism.”

EEG abnormalities and long term seizure outcome in high functioning autism.Electroencephalographic abnormalities may occur in autistic spectrum disorders (ASD) even in the absence of clinical seizures. These abnormalities may vary from nonspecific changes to epileptiform abnormalities and are more common compared to the overall population. In this study we investigated the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD. EEG recording was performed for at least 2 h and included at least 90 min of sleep activity. While none of the patients had clinical seizures, 5 patients (31.3%) were detected to have EEG abnormalities. Four of these were epileptiform (25%), and one patient developed seizure during follow-up. Our results support the fact that EEG abnormalities are observed at a higher rate also in ASD with a better functionality. The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients.”

Gestational vitamin D deficiency and autism spectrum disorder. Full text. “Based on a sample of 4334 children and their mothers, of whom 68 children were diagnosed with ASD, we show that gestational 25OHD deficiency is associated with a higher risk of being diagnosed with ASD. The finding from this study lends weight to the growing body of epidemiological and animal model-based research linking gestational vitamin D deficiency and altered brain development.”

The effect of dietary supplements on clinical aspects of autism spectrum disorder: A systematic review of the literature.Types of dietary supplements evaluated in these studies included amino acids, fatty acids and vitamins/minerals. N-acetylcysteine was shown to exert a beneficial effect on symptoms of irritability. On the other hand, literature data about the efficacy of d-cycloserine and pyridoxine-magnesium supplements was controversial. No significant effect was identified for fatty acids, N,N-dimethylglycine and inositol. Literature data about ascorbic acid and methyl B12 was few, although some encouraging results were found. No serious adverse events were reported in the vast majority of the studies, while the prevalence of adverse reactions was similar between treatment and placebo groups. The use of dietary supplements in children with autism seems to be a safe practice with encouraging data about their clinical efficacy.”

Melatonin and circadian rhythms in autism: Case report.Among the most co-occurring conditions in autism spectrum disorders (ASD), there are sleep disorders which may exacerbate associated behavioral disorders and lead to intensification of existing autistic symptoms. Several studies investigating the use of melatonin in the treatment of sleep disorders in ASD have shown comparative efficiency in sleep with little or no side effects.”

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism. Full text. “The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.”

Vitamin D-related genes are subjected to significant de novo mutation burdens in autism spectrum disorder.Vitamin D deficiency is a putative environmental risk factor for autism spectrum disorder (ASD). Besides, de novo mutations (DNMs) play essential roles in ASD. However, it remains unclear whether vitamin D-related genes (VDRGs) carry a strong DNM burden. We provide straightforward genetic evidences for the first time that VDRGs with a strong degree of DNM burden in ASD and DNMs of VDRGs could be involved in the mechanism underlying in ASD pathogenesis.”

Whose Expertise Is It? Evidence for Autistic Adults as Critical Autism Experts. Full pdf. “Autistic and non-autistic adults’ agreement with scientific knowledge about autism, how they define autism, and their endorsement of stigmatizing conceptions of autism has not previously been examined. Autistic participants exhibited more scientifically based knowledge than others. They were more likely to describe autism experientially or as a neutral difference, and more often opposed the medical model. As one autistic participant stated, “everybody is an expert bar the person with a diagnosis. That needs to change”.”

Gingival bleeding in a patient with autism spectrum disorder: A key finding leading to a diagnosis of scurvy.This case reports a patient with ASD in which gingival bleeding was the key finding that led to a diagnosis of scurvy. The literature review discusses behavioral food aversions in patients with ASD that lead to significant nutritional deficiencies, such as scurvy. Through this case report, the objective is to raise clinical awareness to consider relatively rare diseases in patients with ASD who have atypical feeding patterns.”

Vitamin-D Deficiency As a Potential Environmental Risk Factor in Multiple Sclerosis, Schizophrenia, and Autism. Full pdf. “Several studies found lower vitamin-D levels in children with autism compared to their siblings, parents, and non-family controls. Low vitamin-D levels were already present at birth in children later diagnosed with ASD but not in their healthy siblings. Subsequent research demonstrated that the vitamin-D status of mothers corresponded with their offspring’s vitamin-D status at birth. Low levels of vitamin-D during pregnancy impacted negatively on the cognitive status, early development, and ASD diagnosis.”

Clinical clues for autoimmunity and neuroinflammation in patients with autistic regression.The charts of 206 children with ASD and 33 diagnosed with autistic regression variant were reviewed. The incidence of febrile illness in the 6 months prior to initial parental concern was significantly higher in the children with autistic regression compared with those with ASD. The overall prevalence of familial autoimmunity was also higher in children with autistic regression compared with those with ASD. Type 1 diabetes and autoimmune thyroiditis were both more common in families with children with autistic regression.”

For more research into ASD that your medical professional is not reading. Just follow the link to my Autism page, and scroll down to Current Research – Selected research articles of interest.

Be informed, NOT misinformed!