Vitamin D levels not linked to asthma or dermatitis

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Vitamin D supplementation is unlikely to reduce the risk of asthma in children or adults, atopic dermatitis, or allergies according to a study from McGill University, Canada, and the Lady Davis Institute at the Jewish General Hospital – Canada .

Some previous epidemiological studies have suggested that low vitamin D levels are associated with increased rates of asthma, atopic dermatitis—an itchy inflammation of the skin – and elevated levels of IgE, an immune molecule linked to atopic disease (allergies). In the new work, researchers looked at genetic and health data on more than 100,000 individuals from previous large studies to determine whether genetic alterations that are associated with vitamin D levels predispose people to asthma, dermatitis, or high IgE levels.

The researchers found no statistically significant difference between rates of asthma (including childhood-onset asthma), atopic dermatitis, or IgE levels in people with or without any of the four genetic changes associated with lower levels of 25-hydroxyvitamin D. However, the results do not exclude an association between the outcomes and levels of 1,25-dihydroxyvitamin D, the active form of the vitamin, and more work will be needed to determine if the results hold true in non-European populations and in people with vitamin D deficiency.

“Our findings suggest that previous associations between low vitamin D and atopic disease could be due to spurious associations with other factors,” said Despoina Manousaki, the lead author and a PhD student at the Lady Davis Institute. “Efforts to increase vitamin D levels will probably not result in decreased risk of adult and pediatric asthma, atopic dermatitis, or elevated IgE levels.”

These findings contrast with a recent study from the same group which used similar methods to provide evidence supporting a causal role for vitamin D in the risk of multiple sclerosis, a common neurological disorder. “Our previous findings suggest that low vitamin D levels increase risk for some inflammatory diseases like multiple sclerosis, but these effects do not translate to other inflammatory diseases like asthma and atopic dermatitis”, said Richards. Risk of multiple sclerosis is elevated in some population groups, including white people of European descent and women, and these findings suggest that people at risk for multiple sclerosis should ensure that they have adequate vitamin D levels, but that efforts to increase vitamin D would not be expected to protect against asthma.

Background: Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable.
Methods and findings: We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90–1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69–1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92–1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was −0.40 (95% CI −1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia.
Conclusions: In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.

Despoina Manousaki, Lavinia Paternoster, Marie Standl, Miriam F Moffatt, Martin Farrall, Emmanuelle Bouzigon, David P Strachan, Florence Demenais, Mark Lathrop, William OCM Cookson, J Brent Richards

PLOS Journals
PLOS Medicine abstract

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