Vitamin D and autism, what’s new?
- 1k Downloads
An increasing amount of evidence points to the possibility that gestational and early childhood vitamin D deficiency [25(OH)D < 40 ng/ml] cause some cases of autism. Vitamin D is metabolized into a seco-steroid hormone that regulates about 3% of the 26,000 genes in the coding human genome. It is also a neurosteroid that is active in brain development, having effects on cellular proliferation, differentiation, calcium signaling, neurotrophic and neuroprotective actions; it also appears to have an effect on neurotransmission and synaptic plasticity. Children who are, or who are destined to become, autistic have lower 25(OH)D levels at 3 months of gestation, at birth and at age 8 compared to their unaffected siblings. Two open label trials found high dose vitamin D improves the core symptoms of autism in about 75% of autistic children. A few of the improvements were remarkable. The vitamin D doses used in these children were 300 IU/KG/day up to a maximum of 5000 IU/day (highest final 25(OH)D level reached was 45 ng/ml). The other study used 150,000 IU/month IM as well as 400 IU/day [highest final 25(OH)D level was 52 ng/ml]. These two open label trials were recently confirmed with a randomized controlled trial (RCT) using 300 IU/kg/day with a maximum of 5000 IU/day and resulted in effects similar to the two open label studies. In terms of prevention, a recent small study showed vitamin D supplementation during pregnancy (5000 IU/day) and during infancy and early childhood (1000 IU/day) significantly reduced the expected incidence of autism in mothers who already had one autistic child from 20% to 5%. Vitamin D is safe; for example, over the last 15 years, Poison Control reports there have been approximately 15,000 cases of vitamin D overdose. However only three of these 15,000 people developed clinical toxicity and no one died. Given those facts, practitioners might consider treating autism with 300 IU/kg/day, and seek to prevent autism by supplementing pregnant and lactating women (5000 IU/day) and infants and young children (150 IU/kg/day) checking 25(OH)D levels every 3 months. These doses will increase 25(OH)D blood levels to those recommended by the Endocrine Society. As the American Academy of Pediatrics recommends vitamin D supplementation during infancy and childhood, pediatricians and family practitioners should evaluate the current evidence on autism and vitamin D and act accordingly.
KeywordsAutism ASD Prevention of autism Treatment of autism Vitamin D 25(OH)D CARS
autism spectrum disorder
Childhood Autism Rating Scale
Compliance with ethical standards
Conflict of interest
JJC is president of the non-profit Vitamin D Council; he receives remuneration from Purity Products.
Human and animal studies
No humans or animals were used in this study.
This article does not contain any studies with human participants performed by any of the authors.
- 8.Waldman M, Nicholson S, Adilov N. Does television cause autism? National Bureau of Economic Research Working Group. 12632. 2006. http://www.nber.org/papers/w12632. Accessed 1/19/2017.
- 16.https://www.vitamindcouncil.org/wp-content/uploads/2012/03/Sunlight-for-Babies.pdf. Accessed 1–21-2017.
- 20.Liu L, Zhang D, Rodzinka-Pasko JK, Li YM. Environmental risk factors for autism spectrum disorders. Nervenarzt. 2016. Review.Google Scholar
- 21.Risch N, Hoffmann TJ, Anderson M, Croen LA, Grether JK, Windham GC. Familial recurrence of autism spectrum disorder: evaluating genetic and environmental contributions. Am J Psychiatry. 2014;171(11):1206-13. doi: 10.1176/appi.ajp.2014.13101359.
- 23.Nahum Sacks K, Friger M, Shoham-Vardi I, Abokaf H, Spiegel E, Sergienko R, Landau D, Sheiner E. Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring. Am J Obstet Gynecol. 2016;215(3):380.e1–7.Google Scholar
- 24.Curran EA, O'Neill SM, Cryan JF, Kenny LC, Dinan TG, Khashan AS, Kearney PM. Research review: birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry. 2015;56(5):500–8.CrossRefPubMedGoogle Scholar
- 28.Abbasnezhad A, Amani R, Hajiani E, Alavinejad P, Cheraghian B, Ghadiri A. Effect of vitamin D on gastrointestinal symptoms and health-related quality of life in irritable bowel syndrome patients: a randomized double-blind clinical trial. Neurogastroenterol Motil. 2016;28(10):1533–44.CrossRefPubMedGoogle Scholar
- 29.Garabe’dian M, Jacqz E, Guillozo H, et al. Elevated plasma 1,25-dihydroxyvitamin D concentrations in infants with hypercalcemia and an elfin facies. N Engl J Med 1985;312(15):948–952.Google Scholar
- 33.Holick MF. Vitamin D deficiency. N Engl J Med 2007;357(3):266–281. Review.Google Scholar
- 36.Hallerhan MM. The effect of rickets on the mental development of young children. Arch Psychol. 1938;229:1–67.Google Scholar
- 37.Gilmour A. The mental condition in rickets. School Hygiene. 1912;9:6–16.Google Scholar
- 39.Zaky EA, et al. Prevalence of Autism Spectrum Disorders in Vitamin D Deficient or Insufficient Rickets IJSR. 2015;4:6.Google Scholar
- 49.http://www.strategyr.com/MarketResearch/Sun_Care_Products_Market_Trends.asp. Accessed 1/23/2017
- 50.Council on Scientific Affairs. Harmful effects of ultraviolet radiation. JAMA. 1989;262:380–384.Google Scholar
- 52.Ali A, Cui X, Eyles D. Developmental vitamin D deficiency and autism: putative pathogenic mechanisms. J Steroid Biochem Mol Biol. 2016. doi: 10.1016/j.jsbmb.2016.12.018.
- 57.Patrick RP, Ames BN. Vitamin D Hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J 2014;28(6):2398–2413.Google Scholar
- 58.Smaga I, Niedzielska E, Gawlik M, Moniczewski A, Krzek J, Przegaliński E, Pera J, Filip M. Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacol Rep. 2015;67(3):569–80.CrossRefPubMedGoogle Scholar
- 59.Cortelazzo A, De Felice C, Guerranti R, Signorini C, Leoncini S, Zollo G, et al. Expression and oxidative modifications of plasma proteins in autism spectrum disorders: interplay between inflammatory response and lipid peroxidation. Proteomics Clin Appl. 2016;10(11):1103-1112. doi: 10.1002/prca.201500076.
- 60.Gatti D, Idolazzi L, Fassio A. Vitamin D: not just bone, but also immunity. Minerva Med. 2016;107(6):452-460.Google Scholar
- 63.Krakowiak P, Goines PE, Tancredi DJ. Ashwood P. Hertz-Picciotto I, et al. Neonatal cytokine profiles associated with autism spectrum disorder. Biol Psychiatry: Hansen RL; 2015.Google Scholar
- 70.Shailesh H, Gupta I, Sif S, Ouhtit A. Towards understanding the genetics of Autism. Front Biosci (Elite Ed). 2016;8:412–26.Google Scholar
- 77.Vinkhuyzen AA, Eyles DW, Burne TH, Blanken LM, Kruithof CJ, Verhulst F, et al. Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Mol Psychiatry. 2016. doi: 10.1038/mp.2016.213.
- 83.Olmos-Ortiz A, García-Quiroz J, López-Marure R, González-Curiel I, Rivas-Santiago B, Olivares A, Avila E, Barrera D, Halhali A, Caldiño F, Larrea F, Díaz L. Evidence of sexual dimorphism in placental vitamin D metabolism: testosterone inhibits calcitriol-dependent cathelicidin expression. J Steroid Biochem Mol Biol. 2016;163:173–82.CrossRefPubMedGoogle Scholar
- 85.Jia F, Wang B, Shan L, Xu Z, Staal WG, Du L. core Symptoms of autism improved after vitamin D supplementation. Pediatrics 2015;135(1):e196–e198.Google Scholar
- 86.Saad K, Abdel-Rahman AA, Elserogy YM, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci. 2015;19(8):346-351.Google Scholar
- 87.Feng J, Shan L, Du L. et al. Clinical improvement following vitamin D3 supplementation in autism Spectrum disorder. Nutr Neurosci. 2016. doi: 10.1080/1028415X.2015.1123847.
- 89.Saad K, Abdel-Rahman AA, Elserogy YM. Al-Atram AA. Othman HA, et al. Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. J Child Psychol Psychiatry: El-Houfey AA. 2016. doi: 10.1111/jcpp.12652.
- 92.Við Streym S, Højskov CS, Møller UK, Heickendorff L, Vestergaard P, Mosekilde L, Rejnmark L. Vitamin D content in human breast milk: a 9-mo follow-up study. Am J Clin Nutr 2016;103(1):107–114.Google Scholar
- 97.Wagner CL, McNeil RB, Johnson DD, Hulsey TC, Ebeling M, Robinson C, Hamilton SA, Hollis BW. Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis. J Steroid Biochem Mol Biol. 2013;136:313–20.CrossRefPubMedPubMedCentralGoogle Scholar
- 98.Wagner CL, McNeil R, Hamilton SA, Winkler J, Rodriguez Cook C, Warner G, Bivens B, Davis DJ, Smith PG, Murphy M, Shary JR, Hollis BW. A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. Am J Obstet Gynecol. 2013;208(2):137.e1–13.Google Scholar
- 102.Briefel R, Hanson C, Fox MK, et al. Feeding infants and toddlers study: do vitamin and mineral supplements contribute to nutrient adequacy or excess among US infants and toddlers? J Am Diet Assoc 2006;106(1 Suppl. 1):S52–65.Google Scholar