Vitamin D3 Supplementation at 5000 IU Daily for the Prevention of Influenza-Like Illness in Healthcare Workers: A Randomized Clinical Trial
Authors: van Helmond Noud , Brobyn Tracy L. , LaRiccia Patrick J. , Cafaro Teresa , Hunter Krystal , Roy Satyajeet , Bandomer Brigid , Ng Kevin Q. , Goldstein Helen , Mitrev Ludmil V. , Tsai Alan , Thwing Denise , Maag Mary Ann , Chung Myung K. 
Published: September 2022

ABSTRACTImportanceVitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers.ObjectiveThe aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers.DesignWe conducted an open label, randomized clinical trial wherein a random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare workers served as passive controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved.SettingThe trial was conducted at a tertiary university hospital.ParticipantsOut of 7,600 healthcare workers, two groups of 4,708 and 2,892 subjects were pre-randomized to the vitamin D3 intervention and passive control groups, respectively. Out of 4,708 intervention subjects approached, 299 with no history of hypercalcemia or nephrolithiasis were enrolled. Subjects who completed at least 2 months of supplementation to ensure adequate vitamin D levels were included in the analysis (n=255).InterventionDaily oral vitamin D3 gel capsules at 5000 IU for 9 months.Main Outcome and MeasureThe primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Incidence rates were compared between the vitamin D and control groups.ResultsBetween October 2020 and November 2021, 255 healthcare workers (age 47±12 years, 199 women) completed at least two months of vitamin D3 supplementation. Five subjects were withdrawn due to adverse effects. The control group consisted of 2,827 workers. Vitamin D3 5000 IU supplementation was associated with lower risk of ILI (incidence rate difference: - 1.7×10-4/person-day, 95%-CI: -3.0×10-4 to -3.3×10-5/person-day, P = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3×10-4/person-day, 95%-CI - 2.5×10-4 to -7.1×10-6 /person-day, P = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2×10-5/person-day, 95%-CI: -10.0×10-5 to 1.5×10-5/person-day, P = 0.152). An intention-to-treat analysis could not be performed due to low enrollment in the pre-randomized intervention group.Conclusion and RelevanceDaily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.Trial RegistrationClinicaltrials.gov, NCT04596657Key PointsQuestionCan 5,000 IU of daily vitamin D3 prevent influenza-like illness in healthcare workers?FindingsIn this randomized controlled trial, 5,000 IU of once daily vitamin D3 over a 9-month period revealed that vitamin D3 supplementation was associated with a statistically significant lower risk of influenza-like illness (incidence rate difference -1.7 × 10-4 / person-day, 95%-CI - 3.0 × 10-4 to -3.3 × 10-5 / person-day, P = 0.0147).MeaningDaily supplementation with 5,000 IU vitamin D3 reduces influenza-like illness in healthcare workers.