Acute respiratory tract infections prevented by vitamin D (even when ignoring the dose size – Meta-analysis Feb 2017

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6583 (Published 15 February 2017)
Plot of data by GrassrootsHeatlh

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Adrian R Martineau, professor of respiratory infection and immunity1 2, David A Jolliffe, postdoctoral research fellow1, Richard L Hooper, reader in medical statistics1, Lauren Greenberg, medical statistician1, John F Aloia, professor of medicine3, Peter Bergman, associate professor4, Gal Dubnov-Raz, consultant paediatrician5, Susanna Esposito, professor of paediatrics6, Davaasambuu Ganmaa, assistant professor7, Adit A Ginde, professor of emergency medicine8, Emma C Goodall, assistant professor9, Cameron C Grant, associate professor10, Christopher J Griffiths, professor of primary care1 2 11, Wim Janssens, professor of pneumonology12, Ilkka Laaksi, chief administrative medical officer13, Semira Manaseki-Holland, senior clinical lecturer14, David Mauger, professor of public health sciences and statistics15, David R Murdoch, professor of pathology16, Rachel Neale, associate professor17, Judy R Rees, assistant professor18, Steve Simpson Jr, postdoctoral research fellow19, Iwona Stelmach, professor of paediatric allergy20, Geeta Trilok Kumar, associate professor21, Mitsuyoshi Urashima, professor of molecular epidemiology22, Carlos A Camargo Jr, professor of emergency medicine, medicine, and epidemiology23
Correspondence to: A R Martineau a.martineau at qmul.ac.uk

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.

Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.

Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.

Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.

Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants.
Vitamin D supplementation [ ignoring dose size] reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05).
Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.

Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.

Systematic review registration PROSPERO CRD42014013953.

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Review of the above study: Vitamin D supplementation to prevent acute respiratory tract infections - July 2017

Journal of Paediatics and Child Health, DOI: 10.1111/jpc.13624, First published: 2 July 2017
Professor Craig Mellis, craig.mellis at sydney.edu.au

Vitamin D deficiency, and the role of vitamin D supplementation, is controversial. However, it is hard to ignore the recent systematic review suggesting that, at last, we may have a magic bullet for reducing the rate of respiratory tract infections in children.[1] This systematic review was unusual in that the authors obtained the individual data from all 10 933 participants in the 25 randomised trials included in their review. Such non-aggregated data enable a far more reliable assessment of response in pre-specified subgroups. The quality of the evidence was rated as high, and the overall result was protective, with an adjusted odds ratio (OR) of 0.88; 95% confidence interval (CI) 0.81, 0.96; P = 0.001; number needed to treat (NNT) = 33 (to prevent one respiratory tract infection).

• Twelve randomised controlled trials were in children <16 years;
• four in infants <1 year (n = 5571) and
• eight in 1.1–15.9 years (n = 1079).

No significant benefit was seen in infants; adjusted OR = 0.94 (95% CI 0.83, 1.06; P = 0.33).
However, in the 1.1–15.9 year age group, the adjusted OR was 0.60 (95% CI 0.46, 0.77; P < 0.001), with an NNT of 8. Subgroup analysis found, unsurprisingly, a better response in those with low baseline vitamin D levels (i.e. 25-hydroxyvitamin D < 25 nmol/L). Surprisingly, daily or weekly supplementation was more effective than bolus injections. Influenza vaccine status had no significant effect on response. The generalisability of these findings is unclear.

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Another review of the study: Can vitamin D prevent acute respiratory infections? - Feb 2020

"Reduce acute respiratory tract infections in those with significant vitamin D deficiency (circulating 25-hydroxyvitamin D levels < 10 ng/mL) with daily or weekly vitamin D supplementation—not bolus vitamin D treatment."
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short UR: = is.gd/RTIVITD