Autism is associated with low vitamin D – meta-analysis Oct 2015

Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis

European Child & Adolescent Psychiatry, pp 1-10, online: 29 October 2015 doi: 10.1080/1028415X.2015.1123847
Tiantian Wang, Ling Shan, Lin Du, Junyan Feng, Zhida Xu, Wouter G. Staal, Feiyong Jia erkekangfujia@163.com

Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD).
Vitamin D is regarded as a neuroactive steroid affecting brain development and function.
It plays an essential role in myelination, which is important for connectivity in the brain.
Studies have shown that

  • decreased vitamin D levels in patients,
  • decreased maternal vitamin D levels during pregnancy, and
  • decreased exposure to solar UVB

might increase the risk for ASD.
In addition, autism symptoms and global functioning may improve after vitamin D supplementation.
Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls.
Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.

Summary table from the PDF

Note that all of the trials which had controls with inadequate level of vitamin D had poor results
Imagine how much better the results would have been if the trials with inadequate vitamin D were ignored
Image

VitaminDWiki

  1. Both have strong inheritance features – Vitamin D about 60%
  2. Both have gotten substantially worse in last 30 years
  3. Vitamin D is known to be involved in brain development
  4. All autistic children are VitD deficient, but not all children who are deficient are autistic: genes are involved
  5. When giving vitamin D to cure children of rickets “mental dullness” decreases as well
  6. Children with genes which give them too much (Williams Syndrome) have to reverse of autism – too sociable
  7. Mothers having lots of fish (and thus more vitamin D) give birth to kids with less autistic symptoms
  8. Both associated with weak bones
  9. Both worse around the age of weaning
  10. Autism is more common in rich families – more likely to apply sun screen and stay indoors
  11. Autism increases with drugs which lower levels of vitamin D
  12. Seizures are common with Autism - Vitamin D has been shown to reduce seizures
  13. Fewer autistic symptoms (such as sleep problems) during summer: when child gets more vitamin D from the sun
  14. Both worse with latitude
  15. Both vary with Ultraviolet light
  16. Both vary with time of year (more birth of autistics in March in Northern hemisphere)
  17. 2X more urban autism – less UVB in urban environments
  18. Both worse with pollution
  19. Both worse with increased clouds and rain
  20. Both worse with closely spaced pregnancies
  21. Autistics have abnormal immune response – similar to that of vitamin D deficiency
  22. Low levels of vitamin D in mother animals reduces brain function in offspring
  23. Vitamin deficient rat pups have similar brain abnormalities to that of human autistic children
  24. Autistic children get less vitamin D in their blood for the same amount of sun exposure
  25. The 4 males/1 female ratio - Note estrogen increases vitamin D in the brain (testosterone does not)
  26. Both worse in African Americans (A-A 2-3 increased autism rate)
  27. Both worse in Dark-skinned immigrants in Europe

The TOP articles in Autism and Vitamin D are listed here:


Publisher wants $40 for the PDF

References

  • 1.American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. 5th edn. American Psychiatric Association, Washington DC.
  • 2.Kanner L (1943) Autistic disturbances of affective contact. Nerv Child 2:217–250
  • 3.Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcín C, Montiel-Nava C, Patel V, Paula CS, Wang C, Yasamy MT, Fombonne E (2012) Global prevalence of autism and other pervasive developmental disorders. Autism Res 5:160–179PubMed CentralCrossRefPubMed
  • 4.Atladottir HO, Gyllenberg D, Langridge A et al (2015) The increasing prevalence of reported diagnoses of childhood psychiatric disorders: a descriptive multinational comparison. Eur Child Adolesc Psychiatry 24:173–183CrossRefPubMed
  • 5.Heil KM, Schaaf CP (2013) The genetics of autism spectrum disorders—a guide for clinicians. Curr Psychiatry Rep 15:334CrossRefPubMed
  • 6.Smalley SL, Asarnow RF, Spence MA (1988) Autism and genetics. A decade of research. Arch Gen Psychiatry 45:953–961CrossRefPubMed
  • 7.Schaefer GB, Mendelsohn NJ (2013) Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med Off J Am Coll Med Genet 15:399–407
  • 8.Mendelsohn NJ, Schaefer GB (2008) Genetic evaluation of autism. Semin Pediatr Neurol 15:27–31CrossRefPubMed
  • 9.Posthuma D, Polderman TJ (2013) What have we learned from recent twin studies about the etiology of neurodevelopmental disorders? Curr Opin Neurol 26:111–121CrossRefPubMed
  • 10.Iossifov I, O’Roak BJ, Sanders SJ et al (2014) The contribution of de novo coding mutations to autism spectrum disorder. Nature 515:216–221PubMed CentralCrossRefPubMed
  • 11.De Rubeis S, He X, Goldberg AP et al (2014) Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515:209–215PubMed CentralCrossRefPubMed
  • 12.Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A (2014) The familial risk of autism. Jama 311:1770–1777PubMed CentralCrossRefPubMed
  • 13.Kolevzon A, Gross R, Reichenberg A (2007) Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med 161:326–333CrossRefPubMed
  • 14.Gardener H, Spiegelman D, Buka SL (2009) Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry J Ment Sci 195:7–14CrossRef
  • 15.Munger KL, Levin LI, Massa J, Horst R, Orban T, Ascherio A (2013) Preclinical serum 25-hydroxyvitamin D levels and risk of type 1 diabetes in a cohort of US military personnel. Am J Epidemiol 177:411–419PubMed CentralCrossRefPubMed
  • 16.Ronald A, Hoekstra RA (2011) Autism spectrum disorders and autistic traits: a decade of new twin studies. Am J Med Genet B Neuropsychiatr Genet Off Publ Int Soc Psychiatr Genet 156b:255–274CrossRef
  • 17.Freitag CM, Staal W, Klauck SM, Duketis E, Waltes R (2010) Genetics of autistic disorders: review and clinical implications. Eur Child Adolesc Psychiatry 19:169–178PubMed CentralCrossRefPubMed
  • 18.Uher R (2014) Gene-environment interactions in severe mental illness. Frontiers in psychiatry 5:48PubMed CentralCrossRefPubMed
  • 19.Neggers YH (2014) Increasing prevalence, changes in diagnostic criteria, and nutritional risk factors for autism spectrum disorders. ISRN Nutr 2014:514026PubMed CentralCrossRefPubMed
  • 20.Bakare MO, Munir KM (2011) Autism spectrum disorders (ASD) in Africa: a perspective. Afr J Psychiatry 14:208–210
  • 21.DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC (2013) Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol 39:458–484CrossRefPubMed
  • 22.Cannell JJ (2008) Autism and vitamin D. Med Hypotheses 70:750–759CrossRefPubMed
  • 23.Grant WB, Soles CM (2009) Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermato-endocrinology 1:223–228PubMed CentralCrossRefPubMed
  • 24.Cannell JJ, Grant WB (2013) What is the role of vitamin D in autism? Dermato-endocrinology 5:199–204PubMed CentralCrossRefPubMed
  • 25.Kocovska E, Fernell E, Billstedt E, Minnis H, Gillberg C (2012) Vitamin D and autism: clinical review. Res Dev Disabil 33:1541–1550CrossRefPubMed
  • 26.Becker KG (2011) Autism, immune dysfunction and Vitamin D. Acta psychiatrica Scandinavica 124:74–75CrossRefPubMed
  • 27.Wang TT, Du L, Shan L, Jia FY (2014) Research advances in immunological dysfunction in children with autism spectrum disorders. Chinese journal of contemporary pediatrics (Zhongguo dang dai er ke za zhi) 16:1289–1293
  • 28.Noriega DB, Savelkoul HF (2014) Immune dysregulation in autism spectrum disorder. Eur J Pediatr 173:33–43CrossRefPubMed
  • 29.Meguid NA, Hashish AF, Anwar M, Sidhom G (2010) Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. J Altern Complement Med (New York, NY) 16:641–645CrossRef
  • 30.Humble MB, Gustafsson S, Bejerot S (2010) Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. J Steroid Biochem Mol Biol 121:467–470CrossRefPubMed
  • 31.Mostafa GA, Al-Ayadhi LY (2012) Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation 9:201PubMed CentralCrossRefPubMed
  • 32.Tostes MH, Polonini HC, Gattaz WF (2012) Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism. Trends in Psychiatry and Psychotherapy 3:161–163CrossRef
  • 33.Neumeyer AM, Gates A, Ferrone C, Lee H, Misra M (2013) Bone density in peripubertal boys with autism spectrum disorders. J Autism Dev Disord 43:1623–1629PubMed CentralCrossRefPubMed
  • 34.Gong ZL, Luo CM, Wang L et al (2014) Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. NeuroReport 25:23–27CrossRefPubMed
  • 35.Kocovska E, Andorsdottir G, Weihe P et al (2014) Vitamin d in the general population of young adults with autism in the faroe islands. J Autism Dev Disord 44:2996–3005PubMed CentralCrossRefPubMed
  • 36.Bener A, Khattab AO, Al-Dabbagh MM (2014) Is high prevalence of Vitamin D deficiency evidence for autism disorder?: In a highly endogamous population. J Pediatr Neurosci 9:227–233PubMed CentralCrossRefPubMed
  • 37.Du L, Shan L, Wang B, Feng JY, Xu ZD, Jia FY (2015) Serum levels of 25-hydroxyvitamin D in children with autism spectrum disorders. Chinese journal of contemporary pediatrics (Zhongguo dang dai er ke za zhi) 17:68–71
  • 38.Saad K, Abdel-Rahman AA, Elserogy YM et al. (2015) Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutritional neuroscience. (PMID:25876214)
  • 39.Fernell E, Bejerot S, Westerlund J et al (2015) Autism spectrum disorder and low vitamin D at birth: a sibling control study. Mol Autism 6:3PubMed CentralCrossRefPubMed
  • 40.Molloy CA, Kalkwarf HJ, Manning-Courtney P, Mills JL, Hediger ML (2010) Plasma 25(OH)D concentration in children with autism spectrum disorder. Dev Med Child Neurol 52:969–971PubMed CentralCrossRefPubMed
  • 41.Adams JB, Audhya T, McDonough-Means S et al (2011) Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab 8:32CrossRef
  • 42.Uğur Ç, Gürkan CK (2014) Serum vitamin D and folate levels in children with autism spectrum disorders. Res Autism Spectr Disord 8:1641–1647CrossRef
  • 43.Fernell E, Barnevik-Olsson M, Bagenholm G, Gillberg C, Gustafsson S, Saaf M (2010) Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism. Acta Paediatrica (Oslo, Norway: 1992) 99:743–747
  • 44.Vadeyar S, Shetye S, Somani S, Shah P (2014) Maternal vitamin D deficiency correlation with neonatal vitamin D deficiency. BJOG Int J Obstet Gynaecol 121:165–166
  • 45.Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM (2013) Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord 43:1495–1504CrossRefPubMed
  • 46.Grant WB, Cannell JJ (2013) Autism prevalence in the United States with respect to solar UV-B doses: an ecological study. Dermato-endocrinology 5:159–164PubMed CentralCrossRefPubMed
  • 47.Dealberto MJ (2011) Prevalence of autism according to maternal immigrant status and ethnic origin. Acta Psychiatr Scand 123:339–348CrossRefPubMed
  • 48.Hayashi E (2001) Seasonal changes in sleep and behavioral problems in a pubescent case with autism. Psychiatry Clin Neurosci 55:223–224CrossRefPubMed
  • 49.Adams JB, Audhya T, McDonough-Means S et al (2011) Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 11:111PubMed CentralCrossRefPubMed
  • 50.Cannell JJ (2013) Autism, will vitamin D treat core symptoms? Med Hypotheses 81(2):195–198CrossRefPubMed
  • 51.Jia F, Wang B, Shan L, Xu Z, Staal WG, Du L (2015) Core symptoms of autism improved after vitamin d supplementation. Pediatrics 135:e196–e198CrossRefPubMed
  • 52.Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605CrossRefPubMed
  • 53.Duan XY, Jia FY, Jiang HY (2013) Relationship between vitamin D and autism spectrum disorder. Chinese journal of contemporary pediatrics (Zhongguo dang dai er ke za zhi) 15:698–702
  • 54.Almeras L, Eyles D, Benech P et al (2007) Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics 7:769–780CrossRefPubMed
  • 55.Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29:21–30CrossRefPubMed
  • 56.Eyles DW, Burne TH, McGrath JJ (2013) Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 34:47–64CrossRefPubMed
  • 57.Harms LR, Burne TH, Eyles DW, McGrath JJ (2011) Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab 25:657–669CrossRefPubMed
  • 58.Al-Daghri NM, Al-Attas OS, Alokail MS et al (2014) Lower vitamin D status is more common among Saudi adults with diabetes mellitus type 1 than in non-diabetics. BMC Public Health 14:153PubMed CentralCrossRefPubMed
  • 59.Brance ML, Brun LR, Lioi S, Sanchez A, Abdala M, Oliveri B (2015) Vitamin D levels and bone mass in rheumatoid arthritis. Rheumatol Int 35:499–505CrossRefPubMed
  • 60.Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J (2011) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25:40–45PubMed CentralCrossRefPubMed
  • 61.Jones AP, Tulic MK, Rueter K, Prescott SL (2012) Vitamin D and allergic disease: sunlight at the end of the tunnel? Nutrients 4:13–28PubMed CentralCrossRefPubMed
  • 62.Guillot X, Semerano L, Saidenberg-Kermanac’h N, Falgarone G, Boissier MC (2010) Vitamin D and inflammation. Jt Bone Spine Rev du Rhum 77:552–557CrossRef
  • 63.Mao L, Ji F, Liu Y, Zhang W, Ma X (2014) Calcitriol plays a protective role in diabetic nephropathy through anti-inflammatory effects. Int J Clin Exp Med 7:5437–5444PubMed CentralPubMed
  • 64.Neve A, Corrado A, Cantatore FP (2014) Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis. Clin Exp Med 14:275–283CrossRefPubMed
  • 65.Munoz LE, Schiller M, Zhao Y, Voll RE, Schett G, Herrmann M (2012) Do low vitamin D levels cause problems of waste removal in patients with SLE? Rheumatology (Oxford, England) 51:585–587CrossRef
  • 66.Hayes CE, Nashold FE, Spach KM, Pedersen LB (2003) The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-Grand, France) 49:277–300
  • 67.Masi A, Quintana DS (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20:440–446CrossRefPubMed
  • 68.Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J (2011) Altered T cell responses in children with autism. Brain Behav Immun 25:840–849CrossRefPubMed
  • 69.Sweeten TL, Bowyer SL, Posey DJ, Halberstadt GM, McDougle CJ (2003) Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics 112:e420CrossRefPubMed
  • 70.Croen LA, Grether JK, Yoshida CK, Odouli R, Van de Water J (2005) Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a case-control study. Arch Pediatr Adolesc Med 159:151–157CrossRefPubMed
  • 71.Mostafa GA, Kitchener N (2009) Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol 40:107–112CrossRefPubMed
  • 72.Mostafa GA, Al-Ayadhi LY (2011) Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation 8:39PubMed CentralCrossRefPubMed
  • 73.Al-ayadhi LY, Mostafa GA (2011) Increased serum osteopontin levels in autistic children: relation to the disease severity. Brain Behav Immun 25:1393–1398CrossRefPubMed
  • 74.Mostafa GA, Al-Ayadhi LY (2011) A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children. J Neuroinflammation 8:71PubMed CentralCrossRefPubMed
  • 75.Al-A LY, Mostafa GA (2014) Serum antinucleosome-specific antibody as a marker of autoimmunity in children with autism. J Neuroinflammation 11:69CrossRef
  • 76.Rossignol DA, Frye RE (2012) A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry 17:389–401PubMed CentralCrossRefPubMed
  • 77.Hegazy HG, Ali EH, Elgoly AH (2015) Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model. Cytokine 71:173–180CrossRefPubMed
  • 78.Dringen R (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62:649–671CrossRefPubMed
  • 79.Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D (2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab TEM 13:100–105CrossRefPubMed
  • 80.Garcion E, Thanh XD, Bled F et al (1996) 1,25-Dihydroxyvitamin D3 regulates gamma 1 transpeptidase activity in rat brain. Neurosci Lett 216:183–186CrossRefPubMed
  • 81.Halicka HD, Zhao H, Li J, Traganos F, Studzinski GP, Darzynkiewicz Z (2012) Attenuation of constitutive DNA damage signaling by 1,25-dihydroxyvitamin D3. Aging 4:270–278PubMed CentralPubMed
  • 82.Patrick RP, Ames BN (2014) Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J Off Publ Fed Am Soc Exp Biol 28:2398–2413
  • 83.Crockett MJ, Clark L, Tabibnia G, Lieberman MD, Robbins TW (2008) Serotonin modulates behavioral reactions to unfairness. Science (New York, NY) 320:1739CrossRef
  • 84.Chugani DC, Muzik O, Behen M et al (1999) Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 45:287–295CrossRefPubMed
  • 85.McBride PA, Anderson GM, Hertzig ME et al (1989) Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study. Arch Gen Psychiatry 46:213–221CrossRefPubMed
  • 86.Prufer KJG (1997) 1.25-Dihydroxyvitamin D3 receptor is partly colocalized with oxytocin immunoreac-tivity in neurons of the male rat hypothalamus. Cellular and molecular biology (Noisy-le-Grand, France) 43:543–548
  • 87.Aoki Y, Watanabe T, Abe O et al. (2015) Oxytocin’s neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial. Mol Psychiatry 20:447–453PubMed CentralCrossRefPubMed
  • 88.Dadds MR, MacDonald E, Cauchi A, Williams K, Levy F, Brennan J (2014) Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. J Autism Dev Disord 44:521–531CrossRefPubMed
  • 89.Guastella AJ, Gray KM, Rinehart NJ et al. (2015) The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. J Child Psychol Psychiatry 56:444–452CrossRefPubMed
  • 90.Burne TH, Feron F, Brown J, Eyles DW, McGrath JJ, Mackay-Sim A (2004) Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle. Physiol Behav 81:651–655CrossRefPubMed
  • 91.Vieth R (2006) What is the optimal vitamin D status for health? Prog Biophys Mol Biol 92:26–32CrossRefPubMed
8284 visitors, last modified 04 Apr, 2018,
Printer Friendly Follow this page for updates