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Formulation of vitamin/mineral supplement used in present study, and comparison to Recommended Daily Allowance (RDA) or Adequate Intake (AI) and Tolerable Upper Limit
Source publication
Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.
This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism...
Contexts in source publication
Context 1
... vitamin/mineral supplement formulation is given in Table 3, for a child of 60 lb; the dosage was adjusted up or down proportionately according to bodyweight (measured at the start of the study), up to a maximum of 100 pounds. As discussed earlier, it is a "second-generation" formula- tion, based on the results of a small unpublished pilot study. ...
Context 2
... is a comprehensive vitamin/mineral supplement, containing most vitamins and minerals. A comparison with the RDA/AI and Tolerable Upper Limit [21] is shown in Table 3. Two essential minerals, iron and cop- per, were not included because our preliminary data sug- gested they were not needed by most children with autism. ...
Context 3
... participants (children and adults) received either the supplement or placebo, and the dosage was adjusted based on baseline measured body weight up to a maxi- mum of 100 pounds (see Table 3). Based on prior stu- dies dosage levels of nutrients in the supplement were chosen to be significantly higher than RDA levels, but either at or below the Tolerable Upper Limit. ...
Context 4
... an Average Change score is computed, based on the average of the individual scores. Finally, the scale is changed from a Table 3 Formulation of vitamin/mineral supplement used in present study, and comparison to Recommended Daily Allowance (RDA) or Adequate Intake (AI) and Tolerable Upper Limit (Continued) Sulfur (MSM) 500 mg n/a n/a Zinc (zinc gluconate) ...
Citations
... Although the role of Cr in neurological function is not wellunderstood, its role in glucose metabolism and improving insulin sensitivity in the hypothalamus is hypothesized to potentially lead to increased synthesis of serotonin and catecholamines (31) . However, the study contrarily found significant decreases in B (RBC), and Se (RBC) and no change in P (serum) and V (RBC) (32) . ...
... A study of adults with ADHD found no change in serum ferritin, serum Fe, plasma Zn, or plasma Cu after 8-or 10-weeks of multinutrients treatment (33) . Similarly, in the study of 53 autistic children (32) . There is additional evidence of this effect from studies in adults without ADHD. ...
Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind RCT of multinutrients for ADHD demonstrated three times as many children (age 6-12) had significantly improved behavior (“treatment responders”) on multinutrients (54%) compared to placebo (18%). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention, and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week 8 from 86 participants (49 multinutrient, 37 placebo). Two-sample t-tests/Mann-Whitney U-tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, chromium (in females only), lithium, molybdenum, selenium, and vanadium, and urinary iodine, lithium, and selenium increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary lithium trended toward moderation: participants with lower baseline urinary lithium were more likely to respond to multinutrients (p=0.058). Additionally, participants with higher baseline iron were more likely to be treatment responders regardless of treatment group (p=0.036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary lithium levels show potential as a non-invasive biomarker of treatment response requiring further study.
... Specific modifiable environmental and lifestyle risk factors for ASD include exposure to environmental toxicants [45][46][47], poor diet [29,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63], disruption of the gut microbiota [64][65][66][67][68][69][70][71][72][73][74], excessive exposure to non-native electromagnetic fields (EMFs) [75][76][77][78][79][80][81][82][83][84], and accumulation of heavy metals. There are limited FDA-approved pharmacological options at present to treat ASD. ...
The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating reversal of autism diagnoses with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which was manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing environmental and lifestyle risk factors.
... The Adams et al. study used an earlier version of the PGIA, the PGI-R, which contained only 11 items on the newer PGIA. The comparison found in the Adams et al. study was that the supplement group had a PGI-R average score of 0.67 ± 0.34 and the placebo group average score of 0.34 ± 0.54 (69). The present study's average PGIA score was 0.36 ± 0.55. ...
... The present study's average PGIA score was 0.36 ± 0.55. Although the survey used in this study is updated compared to the Adams et al. (69) study, the PGIA score average and standard deviation may suggest that the effect of phenotypic improvement is within the placebo range (69). ...
... The present study's average PGIA score was 0.36 ± 0.55. Although the survey used in this study is updated compared to the Adams et al. (69) study, the PGIA score average and standard deviation may suggest that the effect of phenotypic improvement is within the placebo range (69). ...
The efficacy of prebiotics and probiotics (synbiotics when combined) to improve symptoms associated with autism spectrum disorder (ASD) has shown considerable inter-study variation, likely due to the complex, heterogeneous nature of the disorder and its associated behavioral, developmental, and gastrointestinal symptoms. Here, we present a precision synbiotic supplementation study in 296 children and adults diagnosed with ASD versus 123 age-matched neurotypical controls. One hundred seventy ASD participants completed the study. Baseline and post-synbiotic assessment of ASD and gastrointestinal (GI) symptoms and deep metagenomic sequencing were performed. Within the ASD cohort, there were significant differences in microbes between subpopulations based on the social responsiveness scale (SRS2) survey (Prevotella spp., Bacteroides, Fusicatenibacter, and others) and gluten and dairy-free diets (Bifidobacterium spp., Lactococcus, Streptococcus spp., and others). At the baseline, the ASD cohort maintained a lower taxonomic alpha diversity and significant differences in taxonomic composition, metabolic pathways, and gene families, with a greater proportion of potential pathogens, including Shigella, Klebsiella, and Clostridium, and lower proportions of beneficial microbes, including Faecalibacterium compared to controls. Following the 3-month synbiotic supplementation, the ASD cohort showed increased taxonomic alpha diversity, shifts in taxonomy and metabolic pathway potential, and improvements in some ASD-related symptoms, including a significant reduction in GI discomfort and overall improved language, comprehension, cognition, thinking, and speech. However, the open-label study design may include some placebo effects. In summary, we found that precision synbiotics modulated the gut microbiome and could be used as supplementation to improve gastrointestinal and ASD-related symptoms.
IMPORTANCE
Autism spectrum disorder (ASD) is prevalent in 1 out of 36 children in the United States and contributes to health, financial, and psychological burdens. Attempts to identify a gut microbiome signature of ASD have produced varied results. The limited pre-clinical and clinical population sizes have hampered the success of these trials. To understand the microbiome associated with ASD, we employed whole metagenomic shotgun sequencing to classify microbial composition and genetic functional potential. Despite being one of the most extensive ASD post-synbiotic assessment studies, the results highlight the complexity of performing such a case–control supplementation study in this population and the potential for a future therapeutic approach in ASD.
... Multiple studies in humans have also linked sulfate depletion with behavioral problems, particularly autism spectrum disorders. In cohorts of individuals with autism lower serum levels of sulfate have been found compared to age-related controls and higher severity of autism symptoms were correlated with lower serum sulfate levels [60,61]. In a different cohort, individuals with autism had a high prevalence of SLC13A1 variants that were associated with an increased fractional excretion of sulfate [10]. ...
Sulfate is an important anion as sulfonation is essential in modulation of several compounds, such as exogens, polysaccharide chains of proteoglycans, cholesterol or cholesterol derivatives and tyrosine residues of several proteins. Sulfonation requires the presence of both the sulfate donor 3′-phosphoadenosine-5′-phosphosulfate (PAPS) and a sulfotransferase. Genetic disorders affecting sulfonation, associated with skeletal abnormalities, impaired neurological development and endocrinopathies, demonstrate the importance of sulfate. Yet sulfate is not measured in clinical practice. This review addresses sulfate metabolism and consequences of sulfonation defects, how to measure sulfate and why we should measure sulfate more often.
... Conversely, linoleic acid metabolism, alpha-linolenic acid metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and vitamin B6 metabolism were signi cantly downregulated (Fig. 6K). Thiamine (Vitamin B1) and Vitamin B6, both belonging to the B-vitamin group, are synthesized by gut microbiota [40] and have been associated with ASD [41,42]. In female mice, no pathways showed signi cant upregulation. ...
Background
Autism spectrum disorder (ASD) presents a complex neurodevelopmental disorder whose origins remain elusive. Emerging research underscores the potential impact of parental environmental exposures on ASD risk in offspring. While the interplay between the "microbiota-gut-brain axis" and epigenetics is increasingly acknowledged in ASD pathogenesis, their comprehensive effects and regulatory mechanisms have not yet been fully revealed. Our hypothesis posits that parental dysbiosis in gut microbiota may engender transgenerational transmission of DNA methylation abnormalities to offspring, consequently modulating their gut microbiota composition, gene expression profiles, and metabolites levels through the "microbiota-gut-brain axis". This multifaceted interplay potentially triggers ASD-like behaviors.
Results
We conducted fecal microbiota transplantations (FMT) from human donors diagnosed with ASD or typically developing (TD) controls into antibiotic-treated mice, revealing that colonization with ASD microbiota triggered distinct autistic-like behaviors in both male and female offspring. These offspring exhibited pathological changes in both the brain and intestines, alongside significant alterations in their gut microbiota, serum metabolome, and brain transcriptome. Notably, colonization with ASD microbiota induced changes in methylation levels of ASD-related genes in parental mice, with some methylation sites being transmitted transgenerationally to the offspring. Employing a multi-omics sequential mediation network, we elucidated potential mechanisms underlying behavioral differences in mice across genders.
Conclusions
Our findings delineate a link between parental gut microbiota dysbiosis, transgenerational DNA methylation, and the emergence of ASD-like traits, uncovering an epigenetic basis for the clinical observation that parents of children with ASD are typically asymptomatic.
... The role of nutritional and dietary interventions in ASD treatment has been proposed since the last century. Several studies indicate an effect of dietary restrictions and/or supplementations of some vitamins, minerals, amino acids, fatty acids, peptides, probiotics, and prebiotics on ASD symptoms [9][10][11][12]. ...
This paper examines the role of dietary peptides gluten and casein in modulating brain function in individuals with autism spectrum disorder (ASD) from a biochemical perspective. Neurotransmitter systems and neural networks are crucial for brain function, and alterations at the biochemical level can contribute to the characteristic symptoms and behaviors of ASD. The paper explores how dietary peptides influence neurotransmitter systems and neural networks, highlighting their potential as interventions to improve brain function in ASD. The evidence suggests that dietary peptides can impact neurotransmitter synthesis, release, and receptor interactions, disrupting the balance of neurotransmitter systems and affecting neural network function. The findings underscore the potential of dietary interventions in modulating brain function in ASD and call for further research to elucidate the underlying mechanisms and optimize clinical practice. Considering individual dietary sensitivities and preferences, personalized dietary approaches may be necessary for optimal outcomes. Dietary interventions' timing, duration, and integration with other evidence-based treatments are crucial considerations. Safety considerations and regular monitoring are important to ensure the implementation of dietary interventions safely and effectively.
Graphical abstract
... Previous research studies demonstrated that synthetic colorants [e.g. Allura Red AC-E129; E122], are associated with numerous adverse side effects, namely hyperactivity, sleep disorders (Adams et al., 2011), and allergic reactions (Silva, Reboredo, & Lidon, 2022). Furthermore, a notable result of recent trends is that the use of animal-derived colorants, such as carmine, must be reduced due to the increase in vegan nutrition. ...
This research article describes the approach of the electrospinning technique for the development of nanofibers from anthocyanin powder and the possibility of using biodegradable polymers, such as gelatin. The irradiation technique was also examined to improve the technological properties of the AP, which was prepared from black carrot pomace. In the present study, the monomeric anthocyanin content of the anthocyanin powder was reduced from 254.6 to 167.9 mg/g after irradiation treatment. The nano-encapsulated anthocyanin powder with wall material showed stronger color properties compared to those of the irradiated samples. FTIR results revealed that changes in OH stretching and galacturonic acid peaks were observed in anthocyanin powder samples at wave numbers of 3500–3200 cm−1 and 800–1000 cm−1, respectively. The electrospinning technique showed a significant improvement in the thermal stability of the AP compared to that with irradiation. Based on this evidence thus far, it can be concluded that irradiation and electrospinning are promising techniques to develop a natural red colorant from industrial food waste for food, food supplement, and pharmaceutical applications.
... Some micronutrient formulations have shown bene cial effects by improving the nutritional and metabolic status of children with ASD (Adams et al., 2011a). A combination of carnitine, coenzyme Q10, and alpha-lipoic acid targeting mitochondrial function was observed to signi cantly improve the biomarkers related to mitochondrial function and neuro-behavioral performance in children with ASD (Legido et al., 2018). ...
... Some case reports provide evidence for ASD phenotype in patients with molybdenum cofactor de ciency (Huijmans et al., 2017;Lionel et al., 2013). A randomized DBPC trial with a micronutrient containing molybdenum signicantly increased the whole blood molybdenum, urinary sul te, and sulfate levels (Adams et al., 2011a). Interestingly, sul te is well-known to destroy thiamine (Singh et al., 2005). ...
... However, a general multivitamin supplementation can be used in most instances to treat multiple common micronutrient de cits (Trudeau et al., 2019). Several clinical trials lead by Dr. James Adam's group at Arizona State University have provided evidence for this general approach (Adams et al., 2011a(Adams et al., , 2018Adams & Holloway, 2004). ...
Children with autism spectrum disorder (ASD) may exhibit metabolic abnormalities, either with or without an underlying inherited metabolic disorder. Some of these metabolic abnormalities can be targeted by various metabolic therapies. For instance, supplementation with vitamins, minerals, and cofactors can offer therapeutic benefits to ASD associated with nutritional deficiencies resulting from factors such as reduced intake, genetic defects, autoantibodies disrupting vitamin transport, and the accumulation of harmful compounds depleting vitamins. Notably, some nutrients exhibit effects beyond their role as enzyme cofactors, and synergistic effects can be achieved through strategic combinations. This chapter outlines different metabolic therapies with their potential benefits in ASD.
... The data suggested a possible improvement overall (p = 0.02) as well as in receptive language (p = 0.03). Nonsignificant correlations were found in expressive language, play, cognition, GI, sleep, sociability (43). An open label research survey was conducted by the same researchers on their current formulation of the BSM. ...
Psychiatric conditions are inherently multifactorial and must be understood and addressed within a multidimensional framework. Adequate nutritional intake is necessary for optimal mental health and is thus an essential component of any psychiatric treatment plan; this is especially true as many patients have a diet high in ultra-processed foods. However, due to a variety of factors such as individual biological and behavioral contributors, modern farming practices, and climate change, implementing a healthy diet alone may not be sufficient to satisfy nutritional requirements. Research studies on three formulations of broad-spectrum micronutrients (BSMs) have demonstrated significant efficacy in treating a range of mental health disorders. In particular, outcomes associated with emotional regulation via BSMs across a variety of psychiatric illnesses (ADHD, autism, trauma, mood disorders, nicotine dependence, and psychosis) to date have been positive.
... Out of these in 9 studies, 7 studies [14][15][16][17][18][19][20] found the relationship of micronutrient level with ASD symptoms, while 2 studies [10,21] did not find any change in the level of micronutrients by supplementation in ASD patients. In the remaining 17 studies, 12 studies [5,11,13,[22][23][24][25][26][27][28][29][30] showed improvements in the symptoms of ASD patients when they were treated with micronutrient supplements, while 4 studies [31][32][33][34] disagreed. ...
... 20 Beneret al. Min Guo et al. (2) 23Stewart et al.24 Alzghoul et al.25Adam et al.26Mazahahery et al. ...
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by increased developmental, educational, and social demands. Recent evidence suggests that up to 40%–50% of symptom variability may be determined by environmental factors including nutritional deficiency of folate, omega-3 fatty acids, and Vitamin D. Studies exist which advocate the use of micronutrient therapy to improve brain function. However, there is no consensus on their use in ASD and opinions remain divisive. This study aims to identify the role of micronutrients in ASD. We searched PubMed, Google Scholar, and Cochrane Library from the period of January 2010 to January 2022. We excluded animal studies, cross-sectional studies, and less 10 participants in a study. An initial literature search yielded a total of 666 studies, out of which 26 studies were included in the systematic review with a pooled sample of 12086 patients. Twelve studies showed an improvement in the symptoms of ASD patients when they were treated with micronutrients and seven studies found an association between micronutrient levels and ASD symptoms. The results of the meta-analysis in seven studies show that micronutrient therapy has a beneficial effect in reducing the severity of ASD, albeit being statistically insignificant (log odds ratio = −1.03, 95% confidence interval: −2.11–0.05). Our study suggests that in spite of low quality of evidence and randomized data, universal micronutrient supplementation may be started in children diagnosed with ASD due to the potential of reducing the severity of ASD along with a low risk of side effects.
