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Randomized Controlled Trial
, 11, 111

Effect of a Vitamin/Mineral Supplement on Children and Adults With Autism

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Randomized Controlled Trial

Effect of a Vitamin/Mineral Supplement on Children and Adults With Autism

James B Adams et al. BMC Pediatr.

Abstract

Background: Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.

Method: 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 were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.

Results: The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R2 = 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.

Conclusions: Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.

Clinical trial registration number: NCT01225198.

Figures

Figure 1
Figure 1
Study Flow Chart.
Figure 2
Figure 2
Level of vitamins and related substances in neurotypical controls and in the Arizona autism treatment group (pre and post), normalized to the level in the control group. The average values are shown. The number of asterisks indicates the p-value for the t-test of the change in the biomarker from pre-treatment to post-treatment in the autism group (* p < 0.05, ** p < 0.01, *** p < 0.001). Note that the post-treatment value for Vitamin B6 is off the scale.
Figure 3
Figure 3
Level of essential minerals in neurotypical group and in the Arizona autism treatment group (pre and post), normalized to the neurotypical group. The average values are shown. The number of asterisks indicates the p-value for the t-test of the change in the biomarker from pre-treatment to post-treatment in the autism group (* p < 0.05, ** p < 0.01, *** p < 0.001). Note that the post-treatment value for lithium is off the chart. The figures uses standard abbreviations for the minerals, namely: Ca-calcium; I- iodine; Fe-iron; Li - lithium; Mg - magnesium; Mn - manganese; Mo - molybdenum; P-phosphorus; Se - Selenium.
Figure 4
Figure 4
Level of biomarkers in controls and in the Arizona autism treatment group (pre and post), normalized to the level in the neurotypical controls. The average values and the standard deviations are shown. The number of asterisks indicates the p-value for the t-test of the change in the biomarker from pre-treatment to post-treatment in the autism group (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 5
Figure 5
Level of biomarkers in controls and in the Arizona autism treatment group (pre and post), normalized to the level in the neurotypical controls. The average values and the standard deviations are shown. The number of asterisks indicates the p-value for the t-test of the change in the biomarker from pre-treatment to post-treatment in the autism group (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 6
Figure 6
Results for the Parent Global Impressions - Revised, for the Arizona and National groups combined. The supplement group had greater improvements in the PGI-R Average score (p = 0.008), and in the subscores for Receptive Language (p = 0.03), Hyperactivity (p = 0.003), Tantrumming (p = 0.009), and Overall (p = 0.02). The y-axis is from -3 (much worse) to 0 (no change) to +1 (slightly better) to +2 (better) to +3 (much better).
Figure 7
Figure 7
Average Change on the PGI-R vs. Age, for the Arizona and National Treatment group. There is a slight, non-significant correlation of the Average Change vs. age, as indicated by the trendline. The y-axis is from -3 (much worse) to 0 (no change) to +1 (slightly better) to +2 (better) to +3 (much better).
Figure 8
Figure 8
Conversion of Methionine to SAM to SAH to Homocysteine. Homocysteine is then either recycled to methionine or converted into cystathionine.
Figure 9
Figure 9
Reduction of GSSG to GSH (net result of a more complex process which involves FADH).

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