Original ArticleVitamin D for Treatment and Prevention of Infectious Diseases; A Systematic Review of Randomized Controlled Trials
Section snippets
INTRODUCTION
The link between vitamin D deficiency and susceptibility to infection has been suggested for longer than a century, with the early observation that children with nutritional rickets were more likely to experience infections of the respiratory system, leading to the coining of the phrase “rachitic lung” (1). The isolation of vitamin D3 from cod liver oil, which was used to treat tuberculosis (TB) in the 1930s, led to its widespread use in TB treatment and prevention, until the introduction of
Vitamin D and Bacterial Infections
The pioneering work by Rook et al (12) and Crowle et al (13) in the 1980s demonstrated that vitamin D enhanced bactericidal activity of human macrophages against Mycobacterium tuberculosis, the causative agent of TB. This discovery led to a new era of interest regarding the role of vitamin D in determining pathogenesis and the immune response to bacterial pathogens. Liu et al (11) provided a key mechanism to how vitamin D may enhance innate immunity. This group demonstrated that stimulation of
METHODS
We conducted a systematic review of randomized controlled clinical trials that investigated the relationship between vitamin D therapy and clinical outcomes related to infectious diseases in humans. We reviewed the medical literature in PubMed and Ovid MEDLINE from 1948 through 2009, using combinations of search terms including the following: “vitamin D2, ergocalciferol, vitamin D3, cholecalciferol, vitamin D analogue, vitamin D, rickets, infection, immunity, treatment, tuberculosis, upper
RESULTS
We found 13 controlled trials that met our search criteria 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47. (Table 1). Ten trials were placebo controlled 35., 36., 37., 40., 42., 43., 44., 45., 46., 47., and 9 of the 10 were conducted in a double-blind design. Five of the 13 trials 35., 36., 37., 38., 39. addressed vitamin D supplementation in patients with bacterial infection, with 4 of the 5 trials evaluating vitamin D as adjunctive therapy in patients with various forms of TB
CONCLUSION
Recent studies have described a high prevalence of vitamin D insufficiency and overt vitamin D deficiency in human populations worldwide (48). As our knowledge of the extraskeletal functions of vitamin D continues to grow, the clinical significance of maintaining vitamin D sufficiency becomes more apparent. Several of the studies reviewed in this report build on existing preclinical research in vitamin D immunology, which demonstrates a likely connection among vitamin D repletion,
DISCLOSURE
The authors have no conflicts of interest to disclose.
ACKNOWLEDGMENT
This work was supported by National Institutes of Health grants T32DK007298 (to A.V.Y.), K24 RR023356 (to T.R.Z.), and K23 AR054334 (to V.T.).
We thank Dr. Roberto Pacifici, principal investigator of National Institutes of Health grant T32DK007298, for his generous support of work related to this publication.
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Published as a Rapid Electronic Article in Press at http://www.endocrinepractice.org on June 2, 2009. DOI: 10.4158/EP09101.ORR.