Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial

Arch Med Res. 2022 Jun;53(4):423-430. doi: 10.1016/j.arcmed.2022.04.003. Epub 2022 Apr 18.


Background: Associations between vitamin D (VD) deficiency and the risk of SARS-CoV-2 infection have been documented in cross-sectional population studies. Intervention studies in patients with moderate to severe COVID-19 have failed to consistently document a beneficial effect.

Objective: To determine the efficacy and safety of VD-supplementation in the prevention of SARS-CoV-2 infection in highly exposed individuals.

Methods: A double-blind, parallel, randomized trial was conducted. Frontline healthcare workers from four hospitals in Mexico City, who tested negative for SARS-CoV-2 infection, were enrolled between July 15 and December 30, 2020. Participants were randomly assigned to receive 4,000 IU VD (VDG) or placebo (PG) daily for 30 d. RT-PCR tests were taken at baseline and repeated if COVID-19 manifestations appeared during follow-up. Serum 25-hydroxyvitamin D3 and antibody tests were measured at baseline and at day 45. Per-protocol and intention-to-treat analysis were conducted.

Results: Of 321 recruited subjects, 94 VDG and 98 PG completed follow-up. SARS-CoV-2 infection rate was lower in VDG than in PG (6.4 vs. 24.5%, p <0.001). The risk of acquiring SARS-CoV-2 infection was lower in the VDG than in the PG (RR: 0.23; 95% CI: 0.09-0.55) and was associated with an increment in serum levels of 25-hydroxyvitamin D3 (RR: 0.87; 95% CI: 0.82-0.93), independently of VD deficiency. No significant adverse events were identified.

Conclusions: Our results suggest that VD-supplementation in highly exposed individuals prevents SARS-CoV-2 infection without serious AEs and regardless of VD status.

Trial registration: ClinicalTrials.gov NCT04535791.

Keywords: 25-hydroxyvitamin D3; COVID-19; Healthcare workers; SARS-CoV-2; Vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / prevention & control
  • Calcifediol
  • Cross-Sectional Studies
  • Dietary Supplements
  • Health Personnel
  • Humans
  • SARS-CoV-2
  • Treatment Outcome
  • Vitamin D


  • Vitamin D
  • Calcifediol

Associated data

  • ClinicalTrials.gov/NCT04535791