Sunshine in Greece (Photo credit: Guillaume Cattiaux)
Vitamin D, the “sunshine vitamin”, is considered a hormone by most experts. Following exposure to the sun’s ultraviolet B (UVB) radiation, the skin produces significant quantities of Vitamin D in a relatively short period of time. However, Vitamin D production in the skin is affected by many environmental factors, including the following:
- Latitude 
- Air pollution [2, 3]
- Cloud cover 
- Season 
- Skin pigmentation 
- Age 
- Body mass index 
- Sun screen use 
- Various medications, including anti-epileptic and steroid medications 
Unfortunately, very little Vitamin D is obtained in our modern day diet. Although Vitamin D can be obtained through dietary sources, such as fatty fish or fortified foods, the quantity of Vitamin D in these sources is quite variable and most people today do not obtain a sufficient quantity of Vitamin D through diet [10, 11]. As a result, Vitamin D deficiency and insufficiency among adults and children are considered a pandemic by some experts [12, 13], particularly in certain populations such as those with darker skin pigmentation [14, 15]. Vitamin D deficiency and insufficiency appears to be associated with increased risks for a number of diseases, including hypertension, diabetes, allergies, cancer, and depression [16-21].
In addition to its well-known effects on bone health and prevention of rickets, Vitamin D has wide-ranging extra-skeletal effects, including, but not limited to, the immune system [22-24], brain development and function [25-28], and gene regulation . Thorough reviews of Vitamin D and its effects are freely available from the National Institutes of Health, Office of Dietary Supplements (http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/) and the Vitamin D council, a non-profit organization whose mission is to increase public and professional awareness of the health benefits of Vitamin D (http://www.vitamindcouncil.org). Additionally, thousands of peer-reviewed publications can be accessed through the U.S. National Library of Medicine’s PubMed search engine (http://www.ncbi.nlm.nih.gov/pubmed) (my personal favorite!), including hundreds of papers that have been published by Michael F. Holick from Boston University Medical Center (for review, see  and evidence-based recommendations from the Endocrine Society’s Clinical Practice Guidelines ). Currently, the optimal dose of Vitamin D for a given population is under debate among medical and scientific experts [32, 33], so don’t be surprised to hear more about this “vitamin” in the future and its importance for other diseases, including, but not limited to, cancer, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and autoimmune diseases.
So, what does Vitamin D have to do with autism spectrum disorders (ASD)? Current evidence has not established Vitamin D as a cause for ASD, but findings from epidemiological studies, associative studies, small clinical studies, and some case reports do indicate that maternal Vitamin D deficiency is associated with the development of ASD in some cases (note that “associated” with autism is different than “causes” autism). The theory that Vitamin D deficiency may play a role in ASDs was first proposed by Dr. John Cannell in the May 2007 Vitamin D Council newsletter (www.vitamindcouncil.org; Accessed December 2012) and later reviewed by Dr. Cannell in peer-reviewed papers published in 2008  and 2010 . His reviews provide a compelling argument and describe data from a variety of associative and epidemiological studies that indicate that Vitamin D deficiency, particularly maternal Vitamin D deficiency, contributes to the development of ASDs. Listed below are some of the links between Vitamin D and ASD:
- County-level autism prevalence rates in three US states were greatest in areas with more rain and clouds . Notably, clouds and rain antagonize UVB’s Vitamin D-producing action in the skin.
- The prevalence of autism is less among those living in rural areas than in urban areas, where tall buildings and more pollution impede UVB exposure, and thereby, reduce Vitamin D production .
- Prevalence rate of ASD appears to be greater among children of mothers with darker skin pigmentation or melanin, which effectively reduces UVB production of Vitamin D [38, 39]. In another epidemiological study, the rate of ASD was shown to be higher among infants from immigrant mothers with dark skin than with lighter skin [40, 41].
- ASD prevalence increases among children born at higher latitudes  where the sun’s UVB radiation is less, and therefore, Vitamin D production is less.
- High seafood consumption has been linked with fewer cases of ASDs despite the fact that it is polluted with mercury and other toxins [43, 44]. Furthermore, fatty fish contains significant quantities of Vitamin D, and Vitamin D may protect the genome against damage from environmental toxins .
- Autism has been reported to be more common among mothers who took antiepileptic drugs during their pregnancy [46, 47]. This class of medications is one of the few drug classes that have been shown to reduce Vitamin D concentrations.
Although these findings are promising, the Vitamin D hypothesis isn’t supported by all research data [48, 49]. The problem is that most studies that have been completed at the time of this writing are not prospectively designed, randomized, blinded, and of sufficient size to conclude one way or another about the role of Vitamin D in ASDs. Although Vitamin D deficiency is unlikely to be the sole contributing factor to development of ASD, data from the sources cited above (along with others) are suggestive that Vitamin D deficiency may contribute to some of the medical problems observed in individuals with ASD, including immune system imbalances [50, 51], neurocognition delays , language delays , and reduced bone mineral density [53, 54].
The good news is that two active clinical studies are currently investigating the role of Vitamin D in ASDs:
- The first study is entitled: “Vitamin D to Prevent Autism in Newborn Siblings.” In this study, researchers from the Oregon Health and Science University are investigating whether administering Vitamin D3 to approximately 40 mothers who already have at least one child with autism and who are pregnant will prevent the recurrence of autism in the newborn sibling. Mothers will be given 4000 IU/day Vitamin D3 during their pregnancy and 6000 IU/day while breastfeeding. If the mothers are not breastfeeding, infants will be given 400 IU/day up until 1 year and then 1000 IU/day after 1 year up until 3 years of age. In this study, treatment with Vitamin D3 is being given in an “open-label” fashion during the pregnancy and while breastfeeding. In other words, all participants in the study will receive Vitamin D and know that they are being given Vitamin D; and the researchers will also know that their subjects are being given Vitamin D. The study has not yet started recruiting and is expected to be completed by the end October 2017. ClinicalTrials.gov Identifier: NCT01366885 (http://www.clinicaltrials.gov/ct2/show/NCT01366885?term=autism+AND+Vitamin+D&rank=1).
- The second active study is entitled “Open Label Clinical Trial of Vitamin D in Children With Autism.” This is another open-label study (see description in paragraph above); it is being conducted by researchers from the University of California, San Francisco. In this study, increasing doses of Vitamin D3 (up to a maximum of 10,000 IU/day) will be administered to 20 male and female 3 to 8-year-old subjects with ASD and Vitamin D deficiency. The dose of Vitamin D will be titrated to achieve blood concentrations of Vitamin D near the high range of normal. This study is currently recruiting and is expected to be completed by December 2013. This exploratory study will give preliminary information with respect to the safety and effectiveness of Vitamin D3 in children with ASD. Clinical Trials.gov identifier: NCT01535508 (http://www.clinicaltrials.gov/ct2/show/NCT01535508?term=autism+AND+Vitamin+D&rank=2).
Unfortunately, these two studies are not sufficient to prove or disprove the role of Vitamin D as an intervention to prevent ASD or to improve ASD symptomology. But, they are a start. Because both of these studies are rather small and “open-label”, the results won’t hold a significant weight of evidence among mainstream clinicians to support its use as a prevention or treatment of ASDs. However, if results are promising, these studies could lead to the design of randomized, blinded, placebo-controlled studies, which are considered the gold standard for establishing evidence among mainstream physicians and scientists.
The Vitamin D hypothesis resonates with me because only my oldest boy (1 of 4 children) has been diagnosed with ASD. Notably, during my pregnancy with him, I spent much of my time indoors while working long hours in an office setting. With my three subsequent pregnancies, I spent more time outdoors as I had reduced my working hours from full-time to part-time status. My son with ASD had documented failure to thrive between ages 4 to 6 years, along with bowed legs. At age 6, his Vitamin D levels were below normal (and this was the first time that a physician had measured his circulating Vitamin D concentrations). My son now takes approximately 5000 IU/day Vitamin D3 in the winter, which has increased his blood concentrations to a mid-to-high blood concentration. Since starting Vitamin D supplements, he rarely is sick. He is also growing at an average rate for males his same age. These anecdotal observations are not direct evidence that Vitamin D caused my son’s development of autism, but I think providing extra Vitamin D to achieve high-normal blood concentrations has certainly improved his health, and as a result, improved his day-to-day functioning and concentration. Until data shows otherwise, my son will continue taking his Vitamin D.
- Webb, A.R., L. Kline, and M.F. Holick, Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab, 1988. 67(2): p. 373-8.
- Humayun, Q. and R. Iqbal, The impact of atmospheric pollution on vitamin D status. J Pak Med Assoc, 2011. 61(2): p. 197-8.
- Agarwal, K.S., et al., The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child, 2002. 87(2): p. 111-3.
- Engelsen, O., et al., Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem Photobiol, 2005. 81(6): p. 1287-90.
- Kyriakidou-Himonas, M., J.F. Aloia, and J.K. Yeh, Vitamin D supplementation in postmenopausal black women. J Clin Endocrinol Metab, 1999. 84(11): p. 3988-90.
- MacLaughlin, J. and M.F. Holick, Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest, 1985. 76(4): p. 1536-8.
- Wortsman, J., et al., Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr, 2000. 72(3): p. 690-3.
- Matsuoka, L.Y., et al., Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab, 1987. 64(6): p. 1165-8.
- Zhou, C., et al., Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest, 2006. 116(6): p. 1703-12.
- Moore, C., et al., Vitamin D intake in the United States. J Am Diet Assoc, 2004. 104(6): p. 980-3.
- Moore, C.E., M.M. Murphy, and M.F. Holick, Vitamin D intakes by children and adults in the United States differ among ethnic groups. J Nutr, 2005. 135(10): p. 2478-85.
- Holick, M.F., The vitamin D epidemic and its health consequences. J Nutr, 2005. 135(11): p. 2739S-48S.
- Holick, M.F. and T.C. Chen, Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr, 2008. 87(4): p. 1080S-6S.
- Gutierrez, O.M., et al., Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int, 2011. 22(6): p. 1745-53.
- Collins-Fulea, C., K. Klima, and G.R. Wegienka, Prevalence of low vitamin D levels in an urban midwestern obstetric practice. J Midwifery Womens Health, 2012. 57(5): p. 439-44.
- Ganji, V., et al., Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey. Int Arch Med, 2010. 3: p. 29.
- John, E.M., et al., Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev, 1999. 8(5): p. 399-406.
- Judd, S.E., et al., Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr, 2008. 87(1): p. 136-41.
- Kositsawat, J., et al., Association of A1C levels with vitamin D status in U.S. adults: data from the National Health and Nutrition Examination Survey. Diabetes Care, 2010. 33(6): p. 1236-8.
- Sharief, S., et al., Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol, 2011. 127(5): p. 1195-202.
- Vaughan, C.P., et al., Vitamin D and lower urinary tract symptoms among US men: results from the 2005-2006 National Health and Nutrition Examination Survey. Urology, 2011. 78(6): p. 1292-7.
- Cantorna, M.T., J. Zhao, and L. Yang, Vitamin D, invariant natural killer T-cells and experimental autoimmune disease. Proc Nutr Soc, 2012. 71(1): p. 62-6.
- Deluca, H.F. and M.T. Cantorna, Vitamin D: its role and uses in immunology. FASEB J, 2001. 15(14): p. 2579-85.
- Hewison, M., Vitamin D and immune function: an overview. Proc Nutr Soc, 2012. 71(1): p. 50-61.
- Eyles, D.W., T.H. Burne, and J.J. McGrath, Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol, 2012.
- Kesby, J.P., et al., The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol, 2011. 347(1-2): p. 121-7.
- Eyles, D.W., et al., Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology, 2009. 34 Suppl 1: p. S247-57.
- Kesby, J.P., et al., Developmental vitamin D deficiency alters dopamine turnover in neonatal rat forebrain. Neurosci Lett, 2009. 461(2): p. 155-8.
- Norman, A.W., et al., 1,25(OH)2-vitamin D3, a steroid hormone that produces biologic effects via both genomic and nongenomic pathways. J Steroid Biochem Mol Biol, 1992. 41(3-8): p. 231-40.
- Holick, M.F., Evidence-based D-bate on health benefits of vitamin D revisited. Dermatoendocrinol, 2012. 4(2): p. 183-90.
- Holick, M.F., et al., Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab, 2012. 97(4): p. 1153-8.
- Heaney, R.P. and M.F. Holick, Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res, 2011. 26(3): p. 455-7.
- Maxmen, A., Nutrition advice: the vitamin D-lemma. Nature, 2011. 475(7354): p. 23-5.
- Cannell, J.J., Autism and vitamin D. Med Hypotheses, 2008. 70(4): p. 750-9.
- Cannell, J.J., On the aetiology of autism. Acta Paediatr, 2010. 99(8): p. 1128-30.
- Waldman, M., et al., Autism prevalence and precipitation rates in California, Oregon, and Washington counties. Arch Pediatr Adolesc Med, 2008. 162(11): p. 1026-34.
- Williams, J.G., J.P. Higgins, and C.E. Brayne, Systematic review of prevalence studies of autism spectrum disorders. Arch Dis Child, 2006. 91(1): p. 8-15.
- Bakare, M.O., K.M. Munir, and D.K. Kinney, Association of hypomelanotic skin disorders with autism: links to possible etiologic role of vitamin-D levels in autism? Hypothesis (Tor), 2011. 9(1).
- Matsuoka, L.Y., et al., Skin types and epidermal photosynthesis of vitamin D3. J Am Acad Dermatol, 1990. 23(3 Pt 1): p. 525-6.
- Dealberto, M.J., Prevalence of autism according to maternal immigrant status and ethnic origin. Acta Psychiatr Scand, 2011. 123(5): p. 339-48.
- Barnevik-Olsson, M., C. Gillberg, and E. Fernell, Prevalence of autism in children of Somali origin living in Stockholm: brief report of an at-risk population. Dev Med Child Neurol, 2010. 52(12): p. 1167-8.
- Grant, W.B. and C.M. Soles, Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermatoendocrinol, 2009. 1(4): p. 223-8.
- Rahbar, M.H., et al., Seafood Consumption and Blood Mercury Concentrations in Jamaican Children With and Without Autism Spectrum Disorders. Neurotox Res, 2012.
- Hibbeln, J.R., et al., Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet, 2007. 369(9561): p. 578-85.
- Kinney, D.K., et al., Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder? Med Hypotheses, 2010. 74(1): p. 102-6.
- Bromley, R.L., et al., Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology, 2008. 71(23): p. 1923-4.
- Evatt, M.L., et al., Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology, 2009. 73(12): p. 997.
- Whitehouse, A.J., et al., Maternal Vitamin D Levels and the Autism Phenotype Among Offspring. J Autism Dev Disord, 2012.
- Molloy, C.A., et al., Plasma 25(OH)D concentration in children with autism spectrum disorder. Dev Med Child Neurol, 2010. 52(10): p. 969-71.
- Becker, K.G., Autism, immune dysfunction and Vitamin D. Acta Psychiatr Scand, 2011. 124(1): p. 74; author reply 74-5.
- Mostafa, G.A. and L.Y. Al-Ayadhi, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation, 2012. 9: p. 201.
- Whitehouse, A.J., et al., Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics, 2012. 129(3): p. 485-93.
- Neumeyer, A.M., et al., Bone Density in Peripubertal Boys with Autism Spectrum Disorders. J Autism Dev Disord, 2012.
- Hediger, M.L., et al., Reduced bone cortical thickness in boys with autism or autism spectrum disorder. J Autism Dev Disord, 2008. 38(5): p. 848-56.