研究发现维生素D可降低儿童孤独症风险

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一个在线发表在同行评审期刊《Dermato-Endocrinology》的研究发现额外的证据：维生素D降低孤独症发展风险（2012年Grant和Cannell）。该项研究调查了州内年龄6~17岁孤独症在2010年患病率的变化。发现太阳中波紫外线（夏季或冬季的中波紫外线）更高的州孤独症患病率是太阳中波紫外线辐射最低州的一半。该项研究也发现了，在低太阳中波紫外线的州，黑种美国人的孤独症患病率比白种美国人的要高出40%。由于肤色较黑及UVB对于大多数美国人来说是维生素D主源的原因，黑种美国人体内的维生素D含量或者血清25-羟基维生素[25(OH)D]浓度较低。

人们已经注意到，美国15种癌症的发病率和死亡率存在类似地理差异（2006年Grant 和 Garland）。基于结肠癌死亡率的变化和现今得到的观察性研究、作用机制的实验室研究的强烈支持及随机对照试验的有限支持，UVB-维生素D-癌症的假说于1980年被提出了。研究者发现，血清25(OH)D浓度较低者乳腺癌和结直肠癌的发展风险更高。此外，血清25(OH)D浓度较低者，时有至少七种类型癌症的诊断存活率较低。

20世纪30年代中期，也有对12~14岁白种男孩中蛀牙的类似地理差异的报道，说与阳光的照射量有关。另外，男性牙科问题的排名纳入第一次和第二次世界大战的武装部队，也表明了一个关于太阳UVB的类似差异。维生素D通过抗菌肽的诱导反应降低蛀牙风险，这种抗菌肽有抑菌作用。（2011年Grant WB）

因此，关于太阳UVB剂量的地理差异性疾病的研究，是鉴定维生素D在预防一种疾病方面扮演着一个潜在角色的很重要的方法。没有其他的因素像维生素D的产物一样，能够解释太阳UVB和癌症或者是蛀牙之间呈负相关的研究结果。从而，维生素D对孤独症似乎也会有相同的结论。

这个发现引出了关于孤独症这样一个问题：母体孕期维生素D的缺乏或新生儿维生素D的缺乏是否会与孤独症的发展有关。

至于母体维生素D的缺乏，其他研究已经发现，孕晚期胎儿大脑发展的不利与维生素D的缺乏有关，这种不利影响包括增加精神分裂症和交际困难的风险。并且，在一些研究中已有报道，孤独症风险的增加与春季出生有关。

维生素D的一个作用机制可能是通过减少影响胎儿发育的DNA散在突变风险来降低孤独症的风险。另一个是通过减少妊娠期间流感和其他感染性疾病的风险，这可能会与减少精神分裂症风险有关。并且，维生素D通过改变细胞因子向炎症因子的产生以减少炎症反应。

如果孕期维生素D缺乏是孤独症的一个风险因素，那么妊娠女性可以通过使用4000IU/d维生素D3而降低该风险，且能够提高血清25(OH)D浓度至40ng/ml(100 nmol/l)。已有研究证明这个剂量在降低维生素D的活性代谢产物——1,25-二羟维生素D（骨化三醇）浓度上是安全和必需的，1,25-二羟维生素D的浓度在南卡罗来纳医科大学Bruce Hollis博士、Carol Wagner和同事们进行的一项随机对照试验中保持了最佳水平。骨化三醇通过与维生素D受体的相互作用，可以控制超过200个基因的表达，这对胎儿发育期间是非常重要的。

新生儿维生素D缺乏可能会是孤独症的一个风险因素，尽管这还有待证实。维生素D可减少新生儿孤独症风险的方式是：强化机体先天免疫系统及减少炎症的发生。维生素D通过减少抗菌肽和防御素的生成来强化机体先天免疫系统，这能够抵抗细菌和病毒感染。维生素D同时也改变了炎症因子的产生：Th1（辅助性T细胞的类型）促炎细胞向Th2促炎因子的转变。近期研究也表明，维生素D能够增加神经营养因子、上调谷胱甘肽、增加DNA修复酶及防止线粒体损伤。

一旦孤独症恶化，症状可以通过治疗孤独症儿童维生素D的缺乏而减少，尽管这只是在随机对照试验中得到证实。这些声明的阐述是来自一些近期的研究，证明孤独症儿童普遍存在维生素D缺乏，且来自《Neurodevelopment》日报的一项近期研究证明维生素D水平是反比例和稳定的。

如果维生素D是孤独症的一个风险因素，那么孤独症儿童应该使他们的血清25(OH)D浓度提升至30~40ng/ml以上，这可以通过使用1000~2000IU/d维生素D3，或更多地依赖一些因素，如：遗传学、体重和呆在太阳底下的次数来实现。

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Study finds new evidence that vitamin D decreases risk of autism in children
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 (UVBlack Eye 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>

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.