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News — A study just published online in the peer-reviewed journal Dermato-Endocrinology found additional evidence that vitamin D reduces the risk of developing autism (Grant and Cannell, 2012). The study examined the variation of autism prevalence by state for those aged 6-17 years in 2010. It found that states with higher solar ultraviolet-B (UVB) doses in summer or autumn had half the rate of autism as states with the lowest doses. The study also found that in the states with the least solar UVB, black-Americans had a 40% higher rate of autism than white-Americans. Black-Americans have lower vitamin D or serum 25-hydroxyvitamin D [25(OH)D] concentrations due to their darker skin and since solar UVB is the primary source of vitamin D for most Americans.

Similar geographical variations have been noted for incidence and mortality rates for about 15 types of cancer in the United States (Grant and Garland, 2006). The UVB-vitamin D-cancer hypothesis was proposed in 1980 based on variations in colon cancer mortality rates in the United States and now has strong support from observational studies, laboratory studies of mechanisms, and limited support from randomized controlled trials. Those who have lower serum 25(OH)D concentrations have been found to have a greater risk of developing breast and colorectal cancer. In addition, those who have lower 25(OH)D concentrations at time of cancer diagnosis have a much lower survival rate for at least seven types of cancer.

Similar geographical variations in dental caries among white boys aged 12-14 years were also reported in the mid-1930s and linked to the amount of sunshine. Also, dental rank of men entering the Armed Forces for World War I and World War II also showed a similar variation with respect to solar UVB. Vitamin D reduces risk of dental caries through induction of cathelicidin, which has antibacterial effects. (Grant WB. 2011)

Thus, studies of geographical variation of disease with respect to solar UVB doses are important ways to identify a potential role of vitamin D in preventing a disease. No factor other than vitamin D production has been proposed to explain the findings for the inverse correlations between solar UVB and cancer or dental caries. Thus, the same conclusion seems very likely for autism.

This finding regarding autism leads to the question whether maternal vitamin D deficiency during pregnancy or vitamin D deficiency in early life is related to development of autism.

Regarding maternal vitamin D deficiency, other studies have found adverse effects on fetal brain development during the third trimester of pregnancy related to vitamin D deficiency, including increased risk of schizophrenia and language difficulties. Also, increased risk of autism related to springtime births has been reported in several studies.

One of the mechanisms whereby vitamin D might reduce the risk of autism is through reducing the risk of sporadic DNA mutations from influencing fetal development. Another is through reducing the risk of influenza and other infectious diseases during pregnancy, which have been linked to increased risk of schizophrenia. Also, vitamin D reduces inflammation by shifting cytokine production towards less inflammatory cytokines.

If vitamin D deficiency during pregnancy is a risk factor for autism, then risk could be reduced by having pregnant women take 4000 IU/d vitamin D3 and raising serum 25(OH)D concentrations to above 40 ng/ml (100 nmol/l). This amount has been shown to be both safe and necessary to increase concentrations of 1,25-dihydroxyvitamin D (calcitriol), the active metabolite of vitamin D, to optimal levels in a randomized controlled trial by Drs. Bruce Hollis, Carol Wagner and colleagues at the Medical University of South Carolina. Calcitriol can control the expression of more than 200 genes through interacting with vitamin D receptors, which would be very important during fetal development. Vitamin D deficiency in early life could be a risk factor for autism, although this remains to be proved. The ways that vitamin D might reduce the risk of autism in early life are by strengthening the body’s innate immune system and reducing inflammation. Vitamin D strengthens the body’s innate immune system by inducing production of cathelicidin and defensins, which can combat bacterial and viral infections. Vitamin D also shifts cytokine production away from T-helper 1 (Th1) proinflammatory ones toward Th2 cytokines. Recent studies also show vitamin D increases neurotrophins, upregulates glutathione, increases DNA repair enzymes, and protects against mitochondrial damage.

Once autism develops, symptoms may be reduced by treating vitamin D deficiency in autistic children, although this remains to be shown in randomized controlled trials. The rationale for such a statement comes from several recent studies showing vitamin D deficiency is common among autistic children and from a recent study in the Journal of Neurodevelopment that showed vitamin D levels are inversely and strongly (R=-0.86) associated with both severity on autism rating scales and serum levels of an anti-neural antibody found in autistic children.

If vitamin D is a risk factor for autism, then autistic children should have their serum 25(OH)D concentration raised to above 30-40 ng/ml, which could take 1000-2000 IU/d vitamin D3, or more depending on such factors as genetics, weight and amount of time spent in the sun.

ReferencesGrant WB. A review of the role of solar ultraviolet-B irradiance and vitamin D in reducing risk of dental caries. Dermatoendocrinol. 2011;3(3):193-198. Open access

Grant WB, Cannell JJ. Autism prevalence in the United States with respect to solar ultraviolet-B doses: An ecological study. Dermatoendocrinol. 2012;4(4): epub December 2012 (open access)

Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006 Jul-Aug;26(4A):2687-99.

Autism prevalence in the United States with respect to solar UV-B doses: An ecological study Volume 4, Issue 4 October/November/December 2012Authors: William B. Grant and John J. Cannell

Abstract: Evidence is mounting that vitamin D deficiency is intimately involved in autism. We report on autism prevalence by US state for those aged 6–17 y in 2010 with respect to indices of solar UV-B (UVB) doses. We calculated autism prevalence rates for white, black and Asian Americans by using total prevalence and relative populations of minors for each ethnic group by state. Analyses omit AK and HI (considered extreme cases), WY (no data), along with AZ and ND for black Americans (low numbers) and DC, ME, MT, ND and SD for Asian Americans (low numbers). For white Americans, the regression coefficient for solar UVB doses and autism prevalence ranged from -0.52 in January to -0.57 in October. For black Americans, the regression coefficient for latitude was 0.61, whereas those for solar UVB ranged from -0.55 to -0.61. For Asian Americans, the values for solar UVB ranged from -0.28 to -0.38. The inverse correlation between solar UVB and autism prevalence is similar to that for many types of cancer in the US. The journal literature indicates that adverse effects on fetal brain development during pregnancy due to vitamin D deficiency can explain these findings. However, we cannot rule out a role of vitamin D deficiency in early life. These results add to the evidence that vitamin D deficiency may be an important risk factor for autism and suggest that pregnant women and autistic individuals raise their serum 25-hydroxyvitamin D concentrations above 30 ng/ml.