[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
Purchase Options:
[Skip to Content Landing]
Original Investigation
July 18, 2017

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children

Author Affiliations
  • 1Department of Pediatrics, St Michael’s Hospital, Pediatric Research, Toronto, Ontario, Canada
  • 2Pediatric Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, the Hospital for Sick Children, Toronto, Ontario, Canada
  • 3Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 4Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  • 5Child Health Evaluative Sciences, Sick Kids Research Institute, Toronto, Ontario, Canada
  • 6Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • 7Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
  • 8The La Ka Shing Knowledge Institute of St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
  • 9Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  • 10Institute for Clinical Evaluative Sciences, Toronto, Canada
  • 11Faculty of Medicine, University of Toronto, Toronto, Canada
  • 12Department of Public Health Sciences, University of California, Davis, California
  • 13Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada
  • 14Department of Laboratory Medicine & Pathobiology, University of Toronto, Ontario, Canada
JAMA. 2017;318(3):245-254. doi:10.1001/jama.2017.8708
Key Points

Question  Does high-dose vitamin D supplementation (2000 IU/d) help to prevent wintertime viral upper respiratory tract infections compared with standard-dose vitamin D supplementation (400 IU/d) among preschool children?

Findings  In this multisite randomized clinical trial that included 703 children, the number of wintertime laboratory-confirmed viral upper respiratory tract infections was higher in the high-dose group than the standard-dose group, not a statistically significant difference.

Meaning  Vitamin D dosing higher than 400 IU/d may not be indicated for preventing wintertime viral upper respiratory tract infections in children.


Importance  Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown.

Objective  To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children.

Design, Setting, and Participants  A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice–based research network in Toronto, Ontario, Canada.

Interventions  Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May.

Main Outcome Measures  The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination.

Results  Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, −0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months (95% CI, 3.02-5.95 months) for the high-dose group vs 3.29 months (95% CI, 2.66-4.14 months) for the standard-dose group, or number of parent-reported upper respiratory tract illnesses between groups (625 for high-dose vs 600 for standard-dose groups, incidence RR, 1.01; 95% CI, 0.88-1.16). At study termination, serum 25-hydroxyvitamin D levels were 48.7 ng/mL (95% CI, 46.9-50.5 ng/mL) in the high-dose group and 36.8 ng/mL (95% CI, 35.4-38.2 ng/mL) in the standard-dose group.

Conclusions and Relevance  Among healthy children aged 1 to 5 years, daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections. These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections.

Trial Registration  clinicaltrials.gov Identifier: NCT01419262