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



. 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.


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


. 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.


. 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.


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

Key Words

Vitamin D
Healthcare workers
25-hydroxyvitamin D3


SARS-CoV-2, the cause of COVID-19, has led to more than 338 million cases and over 5.71 million deaths worldwide as for February 4, 2022. Mexico is one of the most affected countries, with more than 5.03 million infections and more than 307,000 deaths (1). COVID-19 pandemic coexists with vitamin D (VD) deficiency, which is also a major public health problem, both globally ([2][3][4]) and in Mexico (5). This is relevant because of the well-known immunomodulatory role of VD as it attenuates Th1 cell and stimulates Th2 cell proliferation, favoring the synthesis and secretion of anti-inflammatory cytokines, and limiting the production of pro-inflammatory mediators (6). Therefore, it is expected that VD deficiency increases the susceptibility to bacterial and viral infections, including SARS-CoV-2.

Very active research regarding VD and COVID-19 has been conducted in the last two years. Cross sectional, as well as large population-based studies have found an inverse correlation between serum 25-hydroxyvitamin D3 concentrations and SARS-Cov-2 positivity rate, severity, and mortality ([7][8][9][10][11][12]). Furthermore, meta-analyses of case-control and cohort studies conclude that individuals with lower 25-hydroxyvitamin D3 concentrations not only have an increased risk of SARS-CoV-2 positivity but are also more likely to require admission to intensive care units and to dye from the disease. However, most of these meta-analyses report a high degree of heterogeneity, and low precision or certainty of the analyzed studies ([13][14][15]).

You can download the study via this link: https://www.sciencedirect.com/science/article/pii/S0188440922000455/pdfft?md5=5ae465b58c7d2c44a70afd68b42f9e5c&pid=1-s2.0-S0188440922000455-main.pdf

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