Vitamin D to Prevent Acute Respiratory Infections?
April 1, 2017 4 minutes read
By Philip R. Fischer, MD, DTM&H
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
Dr. Fischer reports no financial relationships relevant to this field of study.
SYNOPSIS: Vitamin D supplementation is associated with a decreased risk of respiratory infections, especially in those who had low circulating levels of 25-hydroxyvitamin D.
SOURCE: Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583.
Acute respiratory infections are responsible for 10% of acute medical care visits in the United States and approximately 2.5 million deaths each year worldwide. Some studies have suggested that low circulating vitamin D levels are associated with increased risk of respiratory infections. However, previous meta-analyses of aggregates of studies provided conflicting results as to whether vitamin D supplementation reduces this risk of respiratory infection. Thus, Martineau and 24 coauthors from 13 countries conducted a systematic review and meta-analysis of individual participant data from previously conducted randomized trials of vitamin D supplementation.
Included participants had been involved in randomized, double-blind, placebo-controlled trials of any duration of vitamin D supplementation when acute respiratory infection was a pre-specified and prospectively followed outcome measure. Twenty-five eligible trials were identified, in which 11,321 subjects aged 0 to 95 years had participated. Individual subject data were available for 10,933 (97%) participants and formed the basis of this meta-analysis.
Overall, vitamin D supplementation reduced the risk of respiratory tract infection (adjusted odds ratio [OR] 0.88; 95% confidence interval [CI], 0.81-0.96; P < 0.001). On more detailed analysis, significant risk reduction was found with daily or weekly dosing, but not with less-frequent bolus doses. Protection from respiratory infection was significant in subjects with and without initial lower (< 25 nmol/L) 25-hydroxyvitamin D levels, but the protective effect was more notable in those with lower starting levels. Adverse outcomes did not differ between supplement and placebo recipients.
The authors concluded that vitamin D supplementation effectively reduces the risk of respiratory infection when given as regular doses. They noted that the protective effect is most significant in individuals who were initially vitamin D deficient.
COMMENTARY
In 1997, Muhe and colleagues found that rickets was a significant risk factor for development of pneumonia in pre-school-aged children in Ethiopia.1 They presumed that rickets in their patients was due to vitamin D deficiency even though there was emerging evidence that much of African rickets is due to calcium insufficiency.2 The mechanism by which rickets increased the risk of pneumonia was not known but was postulated to involve both immunologic mechanisms and alterations in chest wall mechanics with rickets-induced rib changes and vitamin D deficiency-induced myopathy.1 Since Muhe’s study, there has been further evidence, as reviewed by Martineau and colleagues, that vitamin D is important in inducing antimicrobial peptides and in inducing synthesis of reactive nitrogen and oxygen intermediates.
Comparison of various trials of vitamin D supplementation to prevent respiratory infections has yielded conflicting results. Wisely, Martineau and colleagues combined individual participant data for many studies to better determine the effects of supplementation. While the overall confidence interval of their findings approached 1.00 (0.81-0.96), the large size of the study allowed for statistical significance. However, this combined cohort included a wide variety of subjects with varied age, size, initial vitamin D status, and underlying respiratory conditions who were treated with different vitamin D formulations, doses, and durations (seven weeks to one and a half years).
In subgroup analysis, this new study provides direction as to who might benefit from vitamin D supplementation. Reduction in respiratory infections was most significant in vitamin D-deficient individuals and in children aged 1 to 15 years; the effect was minimal or inconsequential in vitamin D-replete subjects and in infants, older adolescents, and adults.
The outcomes data from Martineau’s study included subjects with both upper and lower respiratory tract infections. A previous, less-rigorous review focusing on lower respiratory tract infections in children concluded that supplementation was only indicated if the child was vitamin D deficient.3
Is vitamin D supplementation safe? Martineau’s careful study did not identify any statistically significant increased risk of serious adverse effects in supplemented vs. placebo-treated subjects. However, with more prevalent supplementation with vitamin D for lots of reasons in the United States, there is evidence that high blood levels of vitamin D are identified increasingly even though serious adverse effects are uncommon.4 Nonetheless, case reports of severe vitamin D toxicity in infants illustrate the life-threatening dangers of administration of inadvertently high doses of vitamin D.5 Especially when using liquid preparations of vitamin D for pediatric patients, careful attention to formulation and appropriate dosing is essential.
Thus, these new data provide support to the identification and correction of vitamin D deficiency, especially in children. At least for vitamin D-deficient children, restoration of normal vitamin D status can decrease the risk of subsequent respiratory infections.
REFERENCES
- Muhe L, Lulseged S, Mason KE, Simoes EA. Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet 1997;349:1801-1804.
- Thacher TD, Fischer PR, Pettifor JM, et al. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. N Engl J Med 1999;341:563-568.
- Ali SR, McDevitt H. Question 1: Does vitamin D supplementation prevent acute lower respiratory tract infections in children? Arch Dis Child 2015;100:892-895.
- Dudenkov DV, Yawn BP, Oberhelman SS, et al. Changing incidence of serum 25-hydroxyitamin D values above 50 ng/mL: A 10-year population-based study. Mayo Clin Proc 2015;90:577-586.
- Ketha H, Wadams H, Lteif A, Singh RJ. Iatrogenic vitamin D toxicity in an infant – a case report and review of literature. J Steroid Biochem Mol Biol 2015;148:14-18.
Vitamin D supplementation is associated with a decreased risk of respiratory infections, especially in those who had low circulating levels of 25-hydroxyvitamin D.
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