HomeMedicinePediatricsCan Vitamin A Supplements Help Alleviate Autism Symptoms in Children?

Can Vitamin A Supplements Help Alleviate Autism Symptoms in Children?

A new Chinese study determines whether vitamin A supplements for children with autism spectrum disorders can help alleviate autism symptoms.

Autism spectrum disorders are characterized by difficulties in social communication, repetitive motions of arms, fingers, or head, unusually intense and prolonged emotional interactions, and developmental delays. A number of studies indicate altered gut microbiota in children with autism spectrum disorders.1-4 Retinoic acid, a metabolite formed from dietary vitamin A, is important for intestinal immunity and the integrity of the mucosal epithelium.5,6 The gut microbiome is known to be altered by a deficiency of vitamin A.7,8 A number of studies have also reported a deficiency of vitamin A in children with autism spectrum disorders9 and vitamin A levels were found to be negatively correlated with autism scores.10 A new study attempted to delineate the link between vitamin A supplements for children, changes in the gut microbiota, and autism. The results of the study were published recently in BMC Microbiology.11

The study included 64 children with autism spectrum disorders between one and eight years of age in the Chongqing province of China. The children were evaluated for autism using a modified version of the Autism Behavior Checklist (ABC), the Childhood Autism Rating Scale (CARS), and the Social Responsiveness Scale (SRS) before and after six months of vitamin A supplementation. Additionally, the levels of retinoic acid in their plasma were determined before and after supplementation. Also evaluated were the mRNA levels of two genes that are biomarkers of autism, CD38 and RORA (retinoic acid receptor-related orphan receptor alpha), using the real-time PCR technique after extracting the RNA from the white blood cells in the plasma. The expression of both genes is reduced in autism spectrum disorders. Stool samples were collected from 20 of the 64 children before and after vitamin A supplementation for the analysis of gut microbiota. The children received a single vitamin A dose of 200,000 IU orally.

The results showed that plasma retinoic acid levels increased significantly after vitamin A supplementation. There were also significant increases in the mRNA levels of CD38 and RORA after vitamin A supplementation. Significant differences were also observed in the gut bacteria after vitamin A supplementation. Notably, the proportion of Bacteroidetes/Bacteroidales was significantly increased while the proportion of Bifidobacterium was significantly reduced after vitamin A supplementation. However, there were no significant changes in the ABC, CAR, and SRS scores that quantitated autism.

One limitation of this study is its single-blind nature and the small sample size, especially for the evaluation of gut microbiota. Also, partly due to the very nature of autism, follow-up by the participants was less than ideal. Another was the presence of vitamin A deficiency (48.4%) or marginal vitamin A deficiency (48.4%) in children even after vitamin A administration.  In fact, because vitamin A deficiency was discovered in every single participant, this study lacked the control group of autistic participants who did not have vitamin A deficiency. This very limitation emphasizes the immediate need for more research into the effects of vitamin A deficiency.

One thing that is very clear is the immediate need for increased vitamin A supplements for children with autism in China. While vitamin A supplements could be linked to changes in gut microbiota profiles and autism linked biomarkers, there were no changes in the symptoms of autism. While this study did find that vitamin A levels play a role in autism, the nature of the role is still unclear. This underlines the need for future placebo-controlled studies to understand the role of vitamin A and the gut microbiome in the development of autism.

Written by Usha B. Nair, Ph.D.

1) De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One. 2013 Oct 9;8(10):e76993. doi: 10.1371/journal.pone.0076993. eCollection 2013. PubMed PMID: 24130822; PubMed Central PMCID: PMC3793965.

2) Kang DW, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown  R. Reduced incidence of Prevotella and other fermenters in intestinal microflora  of autistic children. PLoS One. 2013 Jul 3;8(7):e68322. doi: 10.1371/journal.pone.0068322. Print 2013. PubMed PMID: 23844187; PubMed Central PMCID: PMC3700858.

3) Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011 Mar 16;11:22. doi:  10.1186/1471-230X-11-22. PubMed PMID: 21410934; PubMed Central PMCID: PMC3072352.

4) Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut  microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91. PubMed PMID: 16157555.

5) Cassani B, Villablanca EJ, De Calisto J, Wang S, Mora JR. Vitamin A and immune regulation: role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance. Mol Aspects Med. 2012 Feb;33(1):63-76. doi: 10.1016/j.mam.2011.11.001. Epub 2011 Nov 22. Review. PubMed PMID: 22120429; PubMed Central PMCID: PMC3246074.

6) McCullough FS, Northrop-Clewes CA, Thurnham DI. The effect of vitamin A on epithelial integrity. Proc Nutr Soc. 1999 May;58(2):289-93. Review. PubMed PMID:  10466169.

7) Amit-Romach E, Uni Z, Cheled S, Berkovich Z, Reifen R. Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet. J Nutr Biochem. 2009 Jan;20(1):70-7. doi: 10.1016/j.jnutbio.2008.01.002. Epub 2008 May 20. PubMed PMID: 18495461.

8) Cha HR, Chang SY, Chang JH, Kim JO, Yang JY, Kim CH, Kweon MN. Downregulation of Th17 cells in the small intestine by disruption of gut flora in the absence of retinoic acid. J Immunol. 2010 Jun 15;184(12):6799-806. doi: 10.4049/jimmunol.0902944. Epub 2010 May 19. PubMed PMID: 20488794.

9) Hyman SL, Stewart PA, Schmidt B, Cain U, Lemcke N, Foley JT, Peck R, Clemons T, Reynolds A, Johnson C, Handen B, James SJ, Courtney PM, Molloy C, Ng PK. Nutrient intake from food in children with autism. Pediatrics. 2012 Nov;130 Suppl 2:S145-53. doi: 10.1542/peds.2012-0900L. PubMed PMID: 23118245; PubMed Central PMCID: PMC4536585.

10) Liu X, Liu J, Xiong X, Yang T, Hou N, Liang X, Chen J, Cheng Q, Li T. Correlation between Nutrition and Symptoms: Nutritional Survey of Children with Autism Spectrum Disorder in Chongqing, China. Nutrients. 2016 May 14;8(5). pii: E294. doi: 10.3390/nu8050294. PubMed PMID: 27187463; PubMed Central PMCID: PMC4882707.

11) Liu J, Liu X, Xiong XQ, Yang T, Cui T, Hou NL, Lai X, Liu S, Guo M, Liang XH, Cheng Q, Chen J, Li TY. Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders – a pilot study. BMC Microbiol. 2017 Sep 22;17(1):204. doi: 10.1186/s12866-017-1096-1. PubMed PMID: 28938872.

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