Does vitamin D have protective role against COVID-19?

By Tarun Sai LomteReviewed by Lily Ramsey, LLMMar 1 2024

In a recent study published in Nutrients, researchers investigated whether vitamin D supplementation before the onset of coronavirus disease 2019 (COVID-19) could provide benefits.

Study: Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis. Image Credit: FotoHelin/Shutterstock.com

Background

Vitamin D is fat-soluble and synthesized in the epidermis; metabolic processes are required for its activation. 1,25-hydroxyvitamin D is the primary end product of these processes.

It binds to the vitamin D receptor (VDR) that mediates a majority of the vitamin’s effects, promoting the expression of genes with specific sequences.

The interplay between VDR, vitamin D, and repressor/promoter proteins has a crucial impact on bone mineral density.

Around 3% of the human genome is controlled by 1,25-dihydroxyvitamin D; as such, vitamin D is speculated to regulate muscle function, metabolism, immune responses, and oncogenesis, among others. The effects of vitamin D in disease, including COVID-19, are under scrutiny.

Available data support that adequate vitamin serum levels may be protective against COVID-19 incidence and mortality; however, this has not been validated.

About the study

The present study examined whether prophylactic vitamin D supplementation pre-COVID-19 could yield beneficial outcomes.

They searched the MEDLINE/PubMed, Scopus, Google Scholar, and Cochrane databases for randomized controlled trials (RCTs) and quasi-experimental, case-control, cross-sectional, and cohort studies with relevant quantitative data on vitamin D supplementation before COVID-19 diagnosis and its role against the disease.

The study population comprised patients or healthcare workers (HCWs). The primary outcome was COVID-19 incidence; secondary outcomes were COVID-19-related admission to the intensive care unit (ICU) and mortality.

The researchers excluded studies with insufficient data and those that did not meet the population, intervention, comparison, outcome, and study design (PICOS) criteria. There were no restrictions on the language or year of publication.

Two authors screened the literature, and studies were included after a full-text review. Data on relevant parameters were extracted. The team computed odds ratios and corresponding 95% confidence intervals as effect measures.

Study quality and bias were evaluated using distinct assessment tools specific to the type of study. Statistical heterogeneity was assessed using χ² and I² statistics. Publication bias was assessed using funnel plots and Egger’s linear regression.

Findings

Overall, the team selected 16 publications for analysis. Seven studies were RCTs, and eight were analytical studies. Five RCTs included HCWs, and two included patients. RCTs compared vitamin D supplementation with no treatment or high- vs. low-dose regimens.

COVID-19 incidence was assessed in 13 studies, ICU admission in three, and mortality in 11. The frequency of supplementation varied across studies.

Fifteen studies reported the precise dose of vitamin D. Controls received a placebo, low-dose vitamin D, or none. In RCTs, vitamin D supplementation was associated with a lower risk of infection despite the substantial degree of heterogeneity.

In RCTs on HCWs, the risk reduction with supplementation was approximately 80%, with negligible heterogeneity. The prevalence of vitamin D insufficiency and deficiency was consistent across these studies.

In RCTs on non-HCW populations, vitamin D supplementation did not affect the COVID-19 infection rate. Notably, the treatment group received a lower-dose regimen compared to other studies.

The researchers speculate that the low dose and low prevalence of vitamin D deficiency might have contributed to the lack of an effect. There was a protective role of supplementation among analytical studies, albeit the heterogeneity was high.

Only one RCT evaluated COVID-19 mortality and reported that vitamin D recipients had significantly reduced mortality.

Further, no association was observed between vitamin D supplementation and COVID-19 mortality in analytical studies. Moreover, vitamin D supplementation was protective against COVID-19-related ICU admission.

Conclusions

The study assessed the protective effects of vitamin D supplemented before COVID-19 onset on disease incidence, ICU admission, and mortality.

RCTs and analytical studies reported a decline in COVID-19 in vitamin D recipients, especially in populations with increased incidence of vitamin D insufficiency and deficiency. Notably, the number of studies analyzed was smaller than prior meta-analyses.

However, unlike the current study, they focused on other aspects, viz., supplementation during COVID-19. Besides, several studies in this analysis lacked data on the prevalence of vitamin D insufficiency and deficiency and the vitamin D formulation, i.e., calcitriol, cholecalciferol, etc.

Overall, the findings support the use of vitamin D in preventing COVID-19 and associated complications, particularly in individuals with vitamin D deficiencies.