Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity

James B Adams, Tapan Audhya, Sharon McDonough-Means, Robert A Rubin, David Quig, Elizabeth Geis, Eva Gehn, Melissa Loresto, Jessica Mitchell, Sharon Atwood, Suzanne Barnhouse, Wondra Lee, James B Adams, Tapan Audhya, Sharon McDonough-Means, Robert A Rubin, David Quig, Elizabeth Geis, Eva Gehn, Melissa Loresto, Jessica Mitchell, Sharon Atwood, Suzanne Barnhouse, Wondra Lee

Abstract

Background: The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers.

Method: Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production.

Results: Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges.A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R2 of 0.25-0.57), minerals (adj. R2 of 0.22-0.38), and plasma amino acids (adj. R2 of 0.22-0.39).

Conclusion: The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.

Figures

Figure 1
Figure 1
Vitamins and related substances which were significantly different between the autism and neurotypical groups, rescaled to the average neurotypical values. The average values and the standard deviations are shown. The number of asterisks indicates the p-value (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 2
Figure 2
Minerals which were significantly different between the autism and neurotypical groups, rescaled to the average neurotypical values. The average values and the standard deviations are shown. The number of asterisks indicates the p-value (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 3
Figure 3
Sulfation, methylation, glutathione, and oxidative stress biomarkers which were significantly different between the autism and neurotypical groups, rescaled to the average neurotypical values. The average values and the standard deviations are shown. The number of asterisks indicates the p-value (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 4
Figure 4
ATP, NADH, and NAHPH were significantly different between the autism and neurotypical groups. The average values and the standard deviations are shown, rescaled to the average neurotypical value. The number of asterisks indicates the p-value (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 5
Figure 5
Amino Acids which were significantly different between the autism and neurotypical groups, rescaled to the average neurotypical value. The average values and the standard deviations are shown. The number of asterisks indicates the p-value (* p < 0.05, ** p < 0.01, *** p < 0.001). The standard deviations for beta-amino-isobutyrate and "homocystine + homocysteine" are outside the margins of the figure.

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