Can vitamin D3 supplementation reduce COVID-19 severity?

By Vijay Kumar MalesuReviewed by Lily Ramsey, LLMMay 10 2024

In a recent study published in the Nutrients, a group of researchers assessed the effectiveness of Vitamin D3 supplementation in reducing intensive care unit (ICU) admissions and coronavirus disease 2019 (COVID-19)-related mortality through a meta-analysis of 13 randomized clinical trials.

Study: Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials. Image Credit: Oldesign/Shutterstock.com

Background 

At the end of 2019, COVID-19, caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, quickly escalated into a global pandemic, impacting healthcare systems worldwide. By February 2024, over 7 million deaths had been reported.

COVID-19 can cause severe respiratory issues, including acute respiratory distress syndrome (ARDS), particularly in older patients with comorbidities like cardiovascular disease. Vitamin D, known for its immunomodulatory effects, has been suggested to reduce severe COVID-19 outcomes by regulating immune responses and reducing inflammation.

Further research is needed to establish the efficacy of Vitamin D3 supplementation in improving clinical outcomes for COVID-19 patients across diverse populations and variants.

About the study 

The present analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials as of 15 February 2024 using keywords related to Vitamin D and COVID-19, focusing on severe cases.

The inclusion criteria were restricted to control-compared randomized clinical trials (RCTs) that examined the impact of vitamin D3 supplementation on patients with severe COVID-19. Studies not in English or lacking relevant endpoints like hospitalization length, ICU admissions, or mortality rates were excluded.

For data extraction, continuous data presented as medians or percentages were converted into means or whole numbers using established statistical methods to ensure uniformity across studies.

The quality of the studies was rigorously assessed using the Cochrane Collaboration’s tool, which evaluates aspects like randomization, blinding, and bias, categorizing them into low, high, or unclear risk.

Statistical analysis was performed using R, calculating relative risks and mean differences with 95% confidence intervals to determine the effects of vitamin D3 supplementation. The heterogeneity of results was assessed with I² statistics, interpreting various levels of heterogeneity and its impact on the meta-analysis.

Potential publication bias was evaluated through funnel plots and regression tests, ensuring the robustness of the findings. The significance level was set at p < 0.05, emphasizing the precision of the statistical evaluation.

Study results 

The search for relevant literature on the impact of Vitamin D3 supplementation on COVID-19 outcomes initially yielded 1,222 articles, which were narrowed down after removing duplicates and irrelevant studies such as meta-analyses, systematic reviews, and non-human studies.

The selection was further refined to include only RCTs written in English that focused on severe COVID-19 cases, resulting in 13 articles that qualified for in-depth analysis.

These studies varied in their control group setups: five included a placebo, four had no supplementation, and four used a standard dose of Vitamin D3. The studies included diverse demographics and were conducted across several countries, including Spain, Brazil, Switzerland, Mexico, Egypt, Russia, France, Argentina, Belgium, Iran, and Croatia.

The risk of bias in these studies was thoroughly assessed, and four were found to have a high risk of bias, while the others showed relatively low risk. This risk assessment was crucial for ensuring the reliability of the meta-analysis results.

The analysis of the effect of Vitamin D3 supplementation revealed mixed results. While there was no significant difference in the length of hospitalization for COVID-19 patients between the supplementation and control groups, the supplementation did show a 27% reduction in ICU admissions. However, it did not significantly affect the length of ICU stays.

Regarding respiratory support, Vitamin D3 supplementation did not significantly alter the number of cases requiring supplemental oxygenation or the duration of such oxygenation.

In terms of mortality, the supplementation did not significantly affect overall mortality rates. Still, it was associated with a 44% reduction in deaths related to COVID-19, suggesting a potential benefit in the most severe cases.

Finally, the publication bias analysis using funnel plots and regression tests generally indicated an absence of bias across most outcomes. However, there was a notable exception for the number of ICU admissions, where publication bias was detected. 

Conclusions 

To summarize, the meta-analysis of 13 randomized clinical trials found that Vitamin D3 potentially reduces ICU admissions and COVID-19-related mortality but does not significantly impact hospitalization length, ICU stay, supplemental oxygen requirements, or overall mortality.

These results align with some studies highlighting Vitamin D’s benefits against severe COVID-19, though others report no substantial effects. The analysis revealed publication bias, suggesting the underrepresentation of smaller studies with negative outcomes.