By William Grant and John Cannell
There is a law called Occam’s razor, which is a principle of parsimony, economy, or succinctness used in logic and problem-solving. To quote Isaac Newton,
“We are to admit no more causes of natural things than such as are both true and sufficient to explain their appearances. Therefore, to the same natural effects we must, so far as possible, assign the same causes.”
Sometimes researchers don’t use Occam’s razor. Take the recent study finding that increasing maternal CRP levels are significantly associated with autism in the offspring.
The authors suggested that CRP levels were elevated due to immune response to maternal infections triggering the autism. In this blog, we outline the evidence that maternal vitamin D deficiency may explain the elevated CRP levels, the maternal infections, and the autism.
In adults, CRP is inversely correlated with serum 25-hydroxyvitamin D [25(OH)D] for 25(OH)D levels <21 ng/ml.1 An analysis of data from NHANES III found that the mean serum 25(OH)D level for pregnant women during the first trimester of pregnancy in the United States was 23 ng/ml.2 Thus, many pregnant women have serum 25(OH)D levels <21 ng/ml.
As far as evidence that vitamin D deficiency is a risk factor for autism, the evidence is mounting. For example, there are generally excess birth rates for autism around March in the northern hemisphere3, a time when serum 25(OH)D levels are lowest. In addition, a recent ecological study of autism prevalence in the United States found significant inverse correlations with respect to solar UVB doses.4
Recently, Mostafa and colleagues found that autistic children had much lower vitamin D levels than healthy children (P<0.001), 14 ng/ml/L versus 33 ng/ml.5 Eighty percent of the typically developing children had levels above 30 ng/ml while only 12% of the autistic children had such levels. Second, they found that 25(OH)D levels were very highly negatively correlated with autism severity as measured by the Clinical Autism Rating Scale (R = -0.84). Finally, they found that 70% of autistic children had antibodies against their own brain tissue (anti-MAG autoantibodies), which were negatively correlated with vitamin D levels, the R value in this case was an amazing -0.86. CRP, a marker of inflammation, is elevated in many autoimmune disorders.
There are also recent reports of adverse neurological birth outcomes associated with low maternal 25(OH)D levels during pregnancy. One study in Australia found that maternal vitamin D deficiency (<18 ng/ml) during pregnancy was significantly correlated with language impairment in the offspring.6 A second study by the same group found that the offspring of mothers with serum 25(OH)D levels <20 ng/ml at the 18th week of pregnancy tested high on an Attention Switching subscale.7
As far as infection and vitamin D deficiency, two recent reviews made the case why a number of infectious diseases will be higher in the vitamin D deficient.8, 9 A study during the first trimester of pregnancy found that, compared with a serum 25(OH)D level of 30 ng/ml, there is a 1.65-fold increase in the prevalence of bacterial vaginosis associated with a maternal serum 25(OH)D level of 10 ng/ml.10
If Brown and colleagues could look at the data again and do 25(OH)D levels on the stored blood, they may likely demonstrate that maternal vitamin D deficiency is a risk factor for autism in the offspring. Pregnant women looking to avoid autistic offspring are well advised to take at least 4,000 IU/day of vitamin D3 or more and raise serum 25(OH)D levels above 40 ng/ml based on a randomized controlled trial with pregnant and nursing women in South Carolina. This study found beneficial effects during pregnancy and no adverse effects associated with 4000 IU/d vitamin D3.11 The 25(OH)D levels >40 ng/ml are required for full maternal ability to raise gestational serum 1,25-dihydroxyvitamin D to optimal levels.
Again, Occam’s razor dictates that among competing hypotheses, the one that makes the fewest assumptions should be selected. In medicine, diagnostic parsimony insists that when diagnosing a given disease a doctor should strive to look for the fewest possible causes that will account for all the facts. Occam’s razor shouts out that maternal vitamin D deficiency explains the elevated CRP, the infections and the autism.
1. Amer M, Qayyum R. Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol. 2012;109:226-230.
2. Ginde AA, Sullivan AF, Mansbach JM, Camargo CA Jr. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol. 2010;202:436.e1-e8.
3. Grant WB, Soles CM. Epidemiologic evidence for supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermatoendocrinol. 2009;1:223-228. Erratum, 2009:1:315.
4. Grant WB, Cannell JJ. Autism prevalence in the United States with respect to solar ultraviolet-B doses: An ecological study. Dermatoendocrinol. 2012;5(1): epub December 2012
5. Mostafa GA, Al-Ayadhi LY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation. 2012;9:201.
6. Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics. 2012;129:485-493.
7. Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM. Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord. 2012 Oct 16. [Epub ahead of print]
8. Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: Systematic review of clinical studies. J Steroid Biochem Mol Biol. 2012 Dec 7.
9. Lang PO, Samaras N, Samaras D, Aspinall R. How important is vitamin D in preventing infections? Osteoporos Int. 2012 Nov 17.
10. Bodnar LM, Krohn MA, Simhan HN.Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. 2009;139:1157-1161.
11. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011;26:2341-2357.