What’s the Connection Between Vitamin D and COVID-19?

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Research linking vitamin D and SARS-CoV-2 (COVID-19) infection has been expanding. A recently published meta-analysis of 25 eligible trials featuring 8,128 participants published in the journal Clinical Nutrition intended to shed some light on this controversial topic.

“The meta-analysis of vitamin D supplementation on COVID-19 showed that vitamin D does not prevent infection, which makes sense because the only thing that can truly prevent infection is lack of exposure, usually by using masks or other barriers," explained immunologist Heather Zwickey, PhD. “Once someone is exposed, vitamin D appears to lessen the severity of infection with less admission to the ICU and less need for mechanical ventilation.”

Research indicates that low levels of vitamin D are associated with a higher risk of more severe COVID-19.

Most of the studies in this recent analysis were observational, and those types of studies have tended to show the benefit of vitamin D supplementation, whereas randomized controlled trials (RCTs) such as the 2022 CORONAVIT study published in BMJ showed no benefit. 

A 2017 analysis published in BMJ looking at acute respiratory tract infections showed that vitamin D supplementation provided protection, especially in patients who were vitamin D deficient. That analysis featured 25 eligible RCTs with 11,231 participants.

"Specific to respiratory infections, multiple meta-analyses have shown that vitamin D compared to placebo reduces the risk of upper respiratory infections when taken daily, even at low doses," explained Zwickey, an integrative medicine researcher and professor at the National University of Natural Medicine.

Additionally, the researchers of a 2023 review published in Cureus concluded, "Vitamin D levels affect the disease course in COVID-19 infection, and proper blood concentration can reduce the severity of the symptoms as well as post-COVID-19 complications."

A 2023 study featured in The Journal of Clinical Endocrinology & Metabolism also found that low vitamin D levels were associated with the development of long COVID syndrome in COVID-19 survivors.

Vitamin D and COVID-19 are logically linked because of vitamin D’s direct effects on the immune system.

Important Mechanisms

As the pandemic ensued, early research demonstrated the important role vitamin D could potentially play in both prevention and treatment. A 2021 mini-review published in SAGE Open Medicine described the numerous roles vitamin D plays in modulating the immune system, reducing inflammation, and reducing proinflammatory cytokines, which illustrates its ability to reduce the risk of COVID-19 severity in particular.

Almost all immune system cells have vitamin D receptors, which makes vitamin D important to both the innate and adaptive immune system.

“While vitamin D activity is complex, we know that it helps minimize damage caused by pathogens by decreasing the production of inflammatory cytokines,” explained Zwickey. “However, because the vitamin D receptor is inducible in many immune cells, it may have different effects during different phases of infection.”

With such significant mechanisms, why don’t the RCTs consistently show benefit? Zwickey has a theory.

"I tend to wonder whether it's because magnesium is needed for vitamin D metabolism, and none of the randomized controlled studies included magnesium with vitamin D," she said. "If vitamin D is given without magnesium, it can deplete magnesium. In addition to magnesium levels, vitamin D binding protein and vitamin D receptors may impact the absorption and utility of vitamin D.”

The Clinical Bottom Line

A 2023 systematic review published in Frontiers of Nutrition confirmed that vitamin D deficiency remains high globally. A 2021 review of 54 studies featured in the journal Frontiers in Public Health found that low vitamin D levels increase the risk of susceptibility and severity of COVID-19. 

Identifying and correcting vitamin D deficiency is always top of mind for integrative practitioners, with the research illustrating the importance of this clinical goal when it comes to COVID-19. Prevention and vitamin D supplementation in non-deficient patients is not as clear.

“Vitamin D is likely beneficial for prevention and treatment of severe COVID-19, but more research is necessary,” concluded Zwickey.