Reviews and feature article
Vitamin D in allergic disease: Shedding light on a complex problem

https://doi.org/10.1016/j.jaci.2012.12.1562Get rights and content

Vitamin D is unique among nutritional factors because the intake of this special vitamin represents the sum of vitamin D obtained from diet, nutritional supplements, and endogenous production after exposure to sunlight. The current recommended nutritional intake requirements reflect needs based on its established role in calcium absorption and bone health. However, recent studies have revealed that vitamin D has important functions in the immune system and might influence the course of immune-mediated disorders, including atopic dermatitis and asthma. This review discusses the scientific rationale for a role for vitamin D in immune function, gives an update on allergic disease associations with lower vitamin D serum levels, and discusses recent observations relating to vitamin D in immune function.

Section snippets

Molecular mechanisms for the immunologic effects of vitamin D

Vitamin D target genes typically contain vitamin D response elements in their promoters, to which heterodimers of the vitamin D receptor (VDR) and retinoid X receptors can bind to transactivate expression of the target genes.3 Coactivators of the VDR, such as SRC3 and DRIP205, further regulate transcription of vitamin D–dependent innate immune target genes.4, 5 Insight into how vitamin D can participate in rapid and local immune responses was gained by understanding that the final activation

Cellular effects of vitamin D on innate and adaptive immunity

Laboratory models of the effects of vitamin D on immune function have shown a wide range of effects. Part of the difficulty in attributing a clear physiologic role for vitamin D in immune disorders stems from the many diverse and at times contradictory observations (Fig 1). In the innate immune system vitamin D appears to improve antimicrobial defenses in general. As mentioned earlier, vitamin D induces endogenous expression of the antimicrobial peptide cathelicidin. This can be seen in the

Associations of vitamin D with allergic diseases

Several groups have investigated whether 25OH-D3 serum values correlate with the risk of allergic disease. Dependent on the threshold value used to define vitamin D insufficiency, it is very common to identify large segments of the population that have inadequate vitamin D intake. A Danish study that measured the distribution of serum 25OH-D3 in 182 participants in January showed that 67% were vitamin D insufficient, as defined by 25OH-D3 values of less than 50 nmol/L, and 18% were vitamin D

Concluding remarks

Taken together, it is not yet possible to definitively assign an absolute strategy for using vitamin D in the therapy of immunologic disorders. Many confounding and unidentified variables appear to be present in exiting studies that lead to inconclusive or inconsistent results. There is overwhelming experimental evidence that vitamin D acts on immune cell functions, but the complexity of this system as it applies to the general population has not yet made clear how to translate this information

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    Disclosure of potential conflict of interest: B. Muehleisen has received a grant for Advanced Researchers from the Swiss National Science Foundation. R. L. Gallo declares that he has no conflicts of interest.

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