Allergic asthma is a disease of chronic inflammation due to a hypersensitive immune reaction to an allergen such as pet dander, pollen, or dust mite excretions. It is characterized by airway hyperresponsiveness (AHR), an increased tendency for airways to constrict, and airway remodeling. The disease is more common in developed countries than developing countries.
Researchers are interested in vitamin D and asthma because of vitamin D’s ability to influence the immune system. It is well-established that vitamin D is an immunomodulator. An immunomodulator is a substance that balances the immune system, with the ability to stimulate a weak immune response and dampen an overactive response.
However, the effect of vitamin D on allergic asthma is under debate. Previous studies have shown no effect of vitamin D supplementation on inflammatory markers in the lungs, while other studies have shown reduced vitamin D levels are associated with impaired lung function and AHR.
To help clarify vitamin D’s role in allergic asthma, researchers in the Department of Biomedical Sciences and Center for Clinical and Translational Science at Creighton University School of Medicine recently studied the effect of vitamin D supplementation in an animal model of allergic asthma.
In this study, the researchers measured inflammatory and allergic markers, such as ARH, airway remodeling, nuclear factor-κB (NF- κB), cytokines, and regulatory T cells (Tregs) in six different groups of female mice. Cytokines are chemical messengers released by immune cells, such as Tregs, and they can be either pro-inflammatory or anti-inflammatory. Tregs are immune cells that suppress the immune response of other cells. Nf-κB is what is called a transcriptional factor, and it essentially “tells” the cell to produce these cytokines. It is therefore dubbed “the central mediator of human immune response” and is implicated in chronic inflammatory diseases.
The researchers divided mice into six groups. To induce allergic asthma into three of the groups, the researchers sensitized the groups with an allergenic protein found in egg whites called ovalbumin and then exposed them to a compound called methacholine, which constricts airways. These three groups were separated by their dietary vitamin D intake:
- OVA-vitamin D deficient (0 IU/kg)
- OVA-vitamin D sufficient (2000 IU/kg)
- OVA-vitamin D supplemented (10,000 IU/kg)
And to setup control groups, the researchers administered corresponding amounts of vitamin D to three groups of mice not sensitized or administered a methacholine challenge test:
- Control-vitamin D deficient (0 IU/kg)
- Control-vitamin D sufficient (2000 IU/kg)
- Control-vitamin D supplemented (10,000 IU/kg)
In response to the methacholine challenge test, OVA-sensitized mice exhibited significantly elevated AHR compared to the control mice. Of the OVA-sensitized mice, the mice that received 10,000 IU/kg showed a lesser degree of AHR compared to the other two OVA groups.
Furthermore, in the OVA-vitamin D deficient group, there was drastic thickening and narrowing of the airways due to growth of muscle surrounding airways, as well as collagen being deposited in the airways. The other two OVA groups that received some or a lot of vitamin D showed similar airway remodeling, but to a lesser degree (although the remodeling was still more pronounced than in the control groups).
OVA-vitamin D deficient mice also showed the highest levels of NF-κB and inflammatory cytokines, while OVA-vitamin D supplemented mice showed the lowest levels of either. Still, the OVA-vitamin D supplemented mice showed higher levels than the control groups.
Higher levels of vitamin D in the diet were also associated with higher number of Tregs, which released an anti-inflammatory cytokine called IL-10, resulting in a decrease of pro-inflammatory cytokines.
The researchers concluded that the changes in levels of NF-κB, cytokines, and Tregs were likely in part responsible for the AHR and airway remodeling described above.
What’s the takeaway from all this?
Although vitamin D sufficiency shows some promise in some areas of allergic asthma, the results need to be replicated in randomized controlled trials in humans. Since the study was carried out with an animal model of allergic asthma, the findings in the current study may not translate well in humans.
If vitamin D proves effective in human study, the results of this animal study imply that vitamin D supplementation can alleviate allergic airway inflammation and hyperresponsiveness (but not completely reverse the condition), and be used as a complimentary treatment in the management of asthma.
Agrawal, T., Gupta, G. K., & Agrawal, D. K. (2013). Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 43(6), 672–683. doi:10.1111/cea.12102