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Vitamin D and covid-19

BMJ 2021; 372 doi: (Published 04 March 2021) Cite this as: BMJ 2021;372:n544

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Rapid Response:

Vitamin D and Covid-19: wishful thinking?

Dear Editor

In their editorial on vitamin D and covid-19, Vimaleswaran and colleagues repeat the claim that vitamin D has a modest protective effect against acute respiratory infection.[1] However, this claim does not withstand close scrutiny.

In the meta-analyses cited by the editorialists to support it,[2] the authors report risk estimates using odds ratios, which are misleading because the outcome is common.[3] In fact, using data from this meta-analysis, the relative risk reduction for vitamin D supplements in preventing acute respiratory infection is 0.97 (95%CI 0.95-1.00, P=0.049). Further, the authors of the meta-analysis noted the possibility of publication bias in favour of beneficial results for vitamin D and substantial heterogeneity in the results. In subgroup analyses exploring this heterogeneity, the purported benefits of vitamin D were confined to the trials conducted in children aged 1-16 years. In that subgroup, the relative risk was 0.91 (95%CI 0.84-0.98), with 2/15 trials reporting statistically significant reductions in risk. However, the trial with the most positive result[4] had a cluster design which was not accounted for in the meta-analysis;[3] its removal produces a pooled risk reduction that is no longer statistically significant. By contrast, in children aged 0-1 years, and in adults 16-64 and 65+ years, the relative risks were 0.96 to 0.99, the CIs included 1, and only 1/42 trials reported a statistically significant reduction in risk.

Even if vitamin D does have a very small protective benefit for respiratory infections, it is unwise to generalise results from a subgroup analysis in children to the broader population. While people can hope that benefits will emerge in trials of vitamin D in Covid-19 currently being undertaken, based on current evidence that hope is largely based on wishful thinking.

1. Vimaleswaran KS, Forouhi NG, Khunti K. Vitamin D and covid-19. BMJ 2021;372:n544.
2. Jolliffe DA, Camargo CA, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials. medRxiv 2020.
3. Bolland MJ, Avenell A. Incorrect and Misleading Claims Regarding Vitamin D. Ir Med J 2020;113(7):P145.
4. Camargo CA, Jr., Ganmaa D, Frazier AL, et al. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics 2012;130(3):e561-7.

Competing interests: We have conducted systematic reviews of the effect of vitamin D, and have critically reviewed the evidence for effects of vitamin D on non-skeletal outcomes in several articles.

09 March 2021
Mark J Bolland
Alison Avenell, Andrew Grey
University of Auckland
Auckland, New Zealand