New study suggests vitamin D supplementation may lower ICU and intubation rates in COVID-19 patients, with greater benefits seen in older and severe cases.

Study: The Effect of Vitamin D Supplementation Post COVID-19 Infection and Related Outcomes: A Systematic Review and Meta-Analysis. Image Credit: yurok/Shutterstock.com

The impact of vitamin D on the progression of COVID-19 remains uncertain. A recent meta-analysis in Nutrients reviewed studies on vitamin D supplementation in COVID-19 patients to assess its effectiveness in reducing disease severity across various health metrics.

Why is vitamin D important?

Vitamin D is essential for bone health, but its influence extends far beyond, as its receptor is present in all nucleated human cells. This receptor regulates nearly 4% of human genes, impacting many physiological processes, including cancer development, muscle function, cardiovascular health, glucose balance, and immune response to infections and autoimmune reactions.

With the onset of the SARS-CoV-2 pandemic, there was significant interest in whether vitamin D could reduce the severity or spread of COVID-19. Vitamin D plays a role in immunity by lowering the release of pro-inflammatory cytokines, boosting antimicrobial peptides, supporting epithelial barriers, and modulating T-cell activity—mechanisms that may help prevent the severe hyperinflammation associated with critical COVID-19 cases and high mortality.

This study investigates the protective effects of vitamin D supplementation during COVID-19, used alongside standard treatments like glucocorticoids, anticoagulants, and antivirals, as recommended in current care guidelines.

About the study

The researchers included 21 randomized controlled trials (RCTs) and eight analytical studies in the meta-analysis. Of these, mortality rates were examined in 19 RCTs and seven analytical studies, intensive care unit (ICU) admissions in 14 and five, respectively, intubation rates in nine and three, respectively, and the length of hospital stay (LOS) only in RCTs.

Vitamin D dosage varied considerably between studies, both in intervention and control groups.

Vitamin D and ICU admissions

In the randomized controlled trials (RCTs), vitamin D supplementation demonstrated a stronger protective effect at higher doses compared to lower doses. Specifically, higher doses were associated with a 63% reduction in ICU admission rates compared to lower doses.

ICU admissions decreased by 57% among patients aged 65 or older and by 44% among those under 65. Patients with severe disease did not show a significant response to vitamin D, while those with non-severe disease experienced 33% fewer ICU admissions.

Intubation rates

Intubation rates fell by 50% in RCTs. The lack of effect in analytical studies may have been because they were carried out only in non-severe older COVID-19 patients and were limited in number.

The tendency towards significance strengthens the hypothesis of the benefit of vitamin D in reducing the need for intubation during COVID-19.

Mortality rates

Mortality rates showed significant differences in the vitamin D supplementation group but only in analytical studies, with a fall of 55%. This might indicate a tendency to bias in analytical studies.

Despite the overall lack of significance, age-stratified analysis of the RCTs showed a 42% reduction in mortality in older patients but not those

Another interesting effect was that vitamin D supplementation had a more marked mortality-reducing impact in the early months of the pandemic, up to May 2020, than later on.

Finally, the most ill patients had a 50% mortality reduction benefit, but not the less severely ill patients. Thus, mortality analyses in the RCTs present a complex picture, with significant protective effects observable in some subgroups but not in the overall analysis.

LOS

Among non-severe COVID-19 patients, vitamin D supplementation was associated with a -0.95-day difference in hospital length of stay. Potential benefits could exist in other groups, but this awaits validation from future research.

The variations between studies should be interpreted as accounting for the forms of vitamin D in use, such as calcifediol or cholecalciferol.

The latter is faster-acting than the former, which may make a difference in acute severe COVID-19, especially as evidence indicates that active vitamin D is used up in the acute response to the infection.

However, broad differences were noted across the studies, including baseline vitamin D levels, dosages, and duration of symptoms before vitamin D supplementation. Still, the findings agree with some previous analyses, with a more nuanced conclusion.

Conclusions

The findings do indicate that vitamin D supplementation could be of benefit in COVID-19 treatment, reducing ICU admissions, mortality, and intubation requirements.  All studies showed fewer ICU admissions in the intervention group.

“The differing effects based on age, disease severity, and possibly baseline vitamin D status highlight the need for a nuanced approach to vitamin D supplementation in COVID-19 management.”

The greatest effect seems to be in reducing ICU admissions. Still, with differences in the evidence across various patient subgroups and for different outcomes, there is a need for larger trials with a better design that adjusts for baseline vitamin D levels and uses standardized dosages and regimens, as well as compensating for patient characteristics.