The immunoregulatory functions
of Vitamin D have become prominent in the current medical literature.
With respect to infectious diseases, there is growing evidence for
vitamin D enhancing innate immunity [1,2]. In vitro studies have shown
that 1,25-dihydroxyvitamine D3,
the active metabolite of vitamin D, is important for promoting and
regulating immune responses [3,4], induces expression of the TLR
co-receptor CD14 [5] and antimicrobial gene expression (CAMP and
defensin B2 expression). The
increased expression of anti-microbial cathelicidin by macrophages and
epithelial cells in response to exposure to microbes depends upon the
presence of vitamin D [1,2]. However, there is no clinical trial
evidence for the effectiveness of vitamin D supplementation for
improving treatment outcomes during infectious disease episodes.
Observational studies have demonstrated important links between rickets
or vitamin D deficiency and higher rates of infectious diseases that
have significant burden of disease, such as pneumonia and tuberculosis.
In pediatrics, two hospital-based case-control studies from Ethiopia [6]
and India [7] suggest that vitamin D deficiency may substantially
increase the risk of severe pneumonia among children. Only one other
published study, prior to Choudhary and Gupta [8] in this volume of
Indian Pediatrics, investigated the effect of vitamin D
supplementation upon the treatment of pneumonia in children. A
randomized placebo controlled trial of Cholecalciferol (Vitamin D3)
(100,000 IU) supplementation along with antibiotic treatment to 1-3 year
old children with clinically diagnosed pneumonia found no difference in
the time to recovery between the vitamin D and placebo groups [9]. The
study in this issue resembles the 2006 study [9]. However, due to the
totally different dosage regime of vitamin D, comparison of results
becomes difficult. The trial by Choudhary and Gupta has strengths such
as effective randomisation and looking at the most vulnerable category
of pneumonia patients with more reliable clinical diagnosis, namely
severe pneumonia patients. However, as acknowledged by the authors, its
major weakness is the low dosage which together with no blood levels of
vitamin D, makes adequate supplementation questionable and the study
difficult to interpret. It is not clear if the lack of positive effect
of supplementation was due to inadequate dosage or actual no effect from
adequate supplementation.
An optimal vitamin D supplementation regime, for
skeletal or immunological functions of vitamin D remains controversial,
as does the fully sufficient serum levels for immunological function
[10]. Nevertheless, it is important that numerous researchers in a range
of settings investigate the effect of vitamin D supplementation upon
pneumonia. Other infectious diseases should be explored, too. For
example, in vitro studies indicate that diarrhea infections could
be affected by vitamin D deficiency through the role of vitamin D on
cethelicidin and a-defensin
in gastrointestinal defence and IgA in adaptive immunity. As yet, this
area remains unexplored.
Importance of further research is due to the public
health significance of the topic. Vitamin D supplementation is
affordable and pragmatic from the programmatic point of view. There is
widespread evidence for vitamin D deficiency in low, middle and high
income countries, and diarrhea and pneumonia are responsible for the
highest burden of childhood mortality and morbidity, globally.
Therefore, if alleviating deficiency is possible with supplementation
and has an effect upon pneumonia or diarrhea rates or prognosis, this
could be linked with significant reductions in childhood mortality. More
research is needed in a range of settings, using different dosing
regimes in order to establish whether and how any benefit can be
demonstrated from vitamin D supplementation.
Competing interest: None stated; Funding:
None.
References
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