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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) Cite this as: BMJ 2017;356:i6583

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Author's second response to Prof Hemilä

Patently, our paper does not state that vitamin D reduces the risk of respiratory infections by 12%, either in the abstract or in the main body of the text (1). The only place that this figure appears in the BMJ is in the editorial by Avenell and Bolland (2); I am not responsible for the content of this piece. Neither does our abstract imply ‘that the benefits of vitamin D supplementation are universal and apply to all people.’ On the contrary, we highlight that the magnitude of protective effects of vitamin D against acute respiratory infection vary according to baseline vitamin D status.

It is statistically invalid to calculate relative risk reduction by halving the difference between the adjusted odds ratio and 1, as Prof Hemilä appears to do.

I questioned Prof Hemilä’s sensitivity analysis primarily on the basis that he excluded one trial from Afghanistan, seemingly because it was conducted in a ‘less developed country’, but retained another study that was conducted in the same country. This seemed inconsistent to me. I am struck by further inconsistencies in his latest response: why, for example, are findings from a trial conducted in university students more ‘relevant for ordinary people’ than findings of a trial conducted in young men undergoing military training?

I agree with Prof Hemilä that the overall estimate of the protective effect of vitamin D against acute respiratory infection is unlikely to apply to all populations similarly. This in fact was the basis for undertaking individual participant data meta-analysis in the first place. Rather than overlooking the ‘apples and oranges problem’, our paper specifically addresses it, for example by showing that protective effects of vitamin D against ARI are stronger in individuals with baseline 25(OH)D levels <25 nmol/L vs. ≥25 nmol/L.

1. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. Epub 2017/02/17.
2. Bolland MJ, Avenell A. Do vitamin D supplements help prevent respiratory tract infections? BMJ. 2017;356:j456. Epub 2017/02/17.

Competing interests: I am corresponding author for the paper on which Prof Hemila has commented.

01 March 2017
Adrian Martineau
Professor of Respiratory Infection and Immunity
Queen Mary University of London
58 Turner St