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A number of cross-sectional studies have confirmed the protective role of vitamin D. In cross-sectional studies (CSS), researchers stratify subjects according to their levels of vitamin D and then they assess differences between these groups. For example, in CSS of 800 finish recruits, they found that recruits with vitamin D deficiency spend significantly more days out of duty because of upper respiratory infections than recruits with higher vitamin D levels (above 40nmol). In another CSS
These data are backed by a meta-analysis published in The British Journal of Medicine. Here, they analysed 25 studies with 11321 total participants and vitamin D supplementation was shown to reduce the risk of acute respiratory tract infection.
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review
Our immune system is powerful but needs to be kept in check. There is a direct correlation between the severity of influenza and levels of released cytokines. In avian influenza, high levels of cytokines are reflective of fatal outcomes. This phenomenon is called “cytokine storm”. The pathological storm is probably caused by immune cells being infected, breaking regulatory cascades and dysregulating inflammatory response which can irreversibly damage lung tissue.
These cytokines are released among others by cells called macrophages. As reported in a study published in Molecular and Cellular Endocrinology, Vitamin D was found to modulate macrophages’ response and prevents them from releasing too many cytokines.
Furthermore, a study published in Cellular Immunology, also reported that Vitamin D deficiency is dysregulating maturation of macrophages in bone marrow, the primary site of immune cell production. These unmatured macrophages cannot produce anti-microbial compounds like hydrogen peroxide (H202) or acid phosphate which serves as a hydrolysing (degrading) enzyme in lysosomes.
H202 and acid phosphate are not the only antimicrobial agents. Antimicrobial peptides (AMP) are released by monocytes and neutrophils. These peptides are endogenous antibiotics and some of them like defensins directly destroy invading microorganism. As reported in the Journal of Immunology, vitamin D can stimulate the expression of these peptides. Indeed, AMPs were reported to be crucial in the fight against influenza.
A study published in Science, reported that upon triggering of toll-like receptors by pathogens, the expression of genes coding for vitamin D receptor and vitamin D1 is stimulated. The higher density of vitamin D receptor and a higher concentration of vitamin D then enhanced the production of antimicrobial peptides as described in the previous paragraph.
Cells fighting intracellular pathogen need autophagy to “clean up the mess” connected with the infection. Many proteins might be misfolded due to the dysregulated intracellular pH and other cytosolic components might be damaged by the entry of the pathogen. Autophagy is the mechanism through which dysfunctional cellular components are degraded. In a study published in Cell Host & Microbe, it was reported that vitamin D can induce autophagy in monocytes and macrophages.
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