By Martina M. McGrath, MD
August 30, 2017
As the cooler weather descends and the school year starts, we are again entering the season of viruses, colds, flu, and miscellaneous sniffles. Aside from vaccination and good hand hygiene, what else can we recommend to our patients to reduce their risk of upper respiratory tract infection?
A large meta-analysis of 25 randomized controlled trials of vitamin D supplementation and respiratory tract infections was published in the BMJ earlier this year.1 The researchers accessed patient-level data on 10,933 trial participants treated with supplemental vitamin D versus placebo. The trials included all age ranges, from birth to adults in their 70s , and had varied dosing regimens for vitamin D supplementation.
Incorporating the results from all participants, vitamin D supplementation reduced the risk of experiencing at least one upper respiratory tract infection (URTI), with an adjusted odds ratio of 0.88 (95% CI 0.81-0.96; number needed to treat (NNT) = 33). However, more detailed analyses of subgroups and the approach to supplementation were revealing. As might be expected, patients with low baseline vitamin D levels experienced the greatest benefit. In patients with 25-hydroxyvitamin D level <25nmol/L, supplementation was associated with an OR of 0.58 of URTI (95% CI 0.40-0.82; NNT = 8).
A significant protective effect was observed in patients aged between 1 and 65 years, with less benefit in older age group. However, most participants over 65 years in this analysis came from a single trial of vitamin D-sufficient nursing home residents, treated with bolus versus oral vitamin D supplementation. Based on the results of the remaining analysis, this lack of benefit might be expected.
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To this end, the vast majority of the benefit was seen in patients treated with daily or weekly vitamin D, and bolus dosing (defined as monthly or 3-monthly) did not show a protective effect. The cause for this is unclear, but in their discussion, the authors quote some prior data suggesting that high-circulating vitamin D levels associated with bolus treatment could dysregulate the enzymes involved in vitamin D metabolism, and paradoxically lead to reduced tissue concentrations of active vitamin D.2
Other secondary end points including protection from lower respiratory tract infections, need for antimicrobial therapy, absences from school or work, hospitalization or death were all negative. No significant adverse events were noted with similar incidences of renal calculi and hypercalcemia in treated versus untreated participants.
Low levels of vitamin D have been associated with increased risk of many diseases including malignancy, multiple sclerosis, autoimmune disease, and infections such as tuberculosis,3-5 but few trials have shown hard evidence of benefit to supplementation.
This study is a broad, robust analysis of data on a large number of patients. However, the effects are small overall and unfortunately, this study had limited power to detect many of the secondary end points, including the effect of vitamin D on lower respiratory tract infection. The results of the study are in keeping with a Cochrane review, carried out by the same group, which found that vitamin D supplementation reduced the risk of severe asthma exacerbations,6 lending some weight to the plausibility. Based on their results, the authors recommend regular vitamin D intake, either as daily/weekly supplementation, and consideration for food fortification, particularly in areas of endemic vitamin D deficiency.
- 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. The BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583.
- Vieth R. How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology. Anticancer Res 2009;29:3675-84.
- Miragliotta G, Miragliotta L. Vitamin D and infectious diseases. Endocr Metab Immune Disord Drug Targets. 2014;14(4):267-71.
- Charan J, Goyal JP, Saxena D, Yadav P. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. Journal of Pharmacology & Pharmacotherapeutics. 2012;3(4):300-303.
- Basit S. Vitamin D in health and disease: a literature review. Br J Biomed Sci. 2013;70(4):161-72.
- Martineau AR, Cates CJ, Urashima M, et al. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2016;9:CD011511
Dr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.