Vitamin D in Moderation Reduces Risk of Acute Respiratory Infections

Sarfaroj Khan 


April 07, 2021


  • This meta-analysis found a small but significant protective effect of vitamin D supplementation on the risk of having ≥1 acute respiratory infections (ARIs) vs placebo, but there was evidence of significant heterogeneity of effect across trials.

  • Protection was associated with administration of daily doses of 400-1000 international units (IU) for up to 12 months and age at enrolment of 1.00-15.99 years.

Why this matters

  • A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of ARIs showed a protective effect of this intervention.

  • The relevance of these findings to COVID-19 is not known and requires further investigation.

Study design

  • Meta-analysis of 43 RCTs including 49,419 participants.

  • Funding: None.

Key results

  • A significantly lower proportion of participants in the vitamin D supplementation group had ≥1 ARIs vs placebo group (61.3% vs 62.3%; OR, 0.92; 95% CI, 0.86-0.99; 37 studies; I²=35.6%; Pheterogeneity=.018).

  • No significant effect of vitamin D supplementation on the risk of having ≥1 ARIs was seen for any of the subgroups defined by baseline 25(OH)D concentration.

  • A significant protective effect of vitamin D supplementation was seen in trials in which vitamin D was given (OR; 95% CI):

    • in a daily dosing regimen (0.78; 0.65-0.94; 19 studies; I²=53.5%, Pheterogeneity=.003);

    • at daily dose equivalents of 400-1000 IU (0.70; 0.55-0.89; 10 studies; I²=31.2%, Pheterogeneity=.16);

    • for a duration of ≤12 months (0.82; 0.72-0.93; 29 studies; I²=38.1%; Pheterogeneity=.021); and

    • to participants aged 1.00-15.99 years at enrolment (0.71; 0.57-0.90; 15 studies; I²=46.0%; Pheterogeneity=.027).

  • No significant interaction was seen between allocation to the vitamin D
    supplementation group vs the placebo group and dose, dose frequency, study duration, or age.


  • Heterogeneity across trials.

  • Risk of bias.


Jolliffe DA, Camargo CA, Sluyter JD, Aglipay M, Aloia JF, Ganmaa D, Bergman P, Bischoff-Ferrari HA, Borzutzky A, Damsgaard CT, Dubnov-Raz G, Esposito S, Gilham C, Ginde AA, Golan-Tripto I, Goodall EC, Grant CC, Griffiths CJ, Hibbs AM, Janssens W, Khadilkar AV, Laaksi I, Lee MT, Loeb M, Maguire JL, Majak P, Mauger DT, Manaseki-Holland S, Murdoch DR, Nakashima A, Neale RE, Pham H, Rake C, Rees JR, Rosendahl J, Scragg R, Shah D, Shimizu Y, Simpson-Yap S, Trilok-Kumar G, Urashima M, Martineau AR. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021 Mar 30 [Epub ahead of print]. doi: 10.1016/S2213-8587(21)00051-6. PMID: 33798465.  View full text 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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