Current advice on vitamin D relates to the protection of musculoskeletal health. The issue of vitamin D supplementation to reduce acute respiratory tract infections has been extensively debated, with strong arguments in favour and against, and the interest has increased since the emergence of the COVID-19 pandemic when media reports and some academic publications have suggested that vitamin D supplementation (particularly high doses) could reduce the risk of COVID-19.
Laboratory studies have shown that vitamin D metabolites support innate immune responses to respiratory viruses, other observational studies have reported independent associations between low circulating levels of vitamin D and increased risk of respiratory infections.
Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. Some recent studies have found that vitamin D level is markedly low in severe COVID-19 patients and that the inflammatory response is high in vitamin D deficient COVID-19 patients. This all translates into increased mortality in vitamin D deficient COVID-19 patients.
It is known that groups that traditionally exhibit vitamin D deficiency or insufficiency, such as older adults and nursing home residents, and people who are obese or with dark skin are the same groups that have also been disproportionately impacted by COVID-19. Additionally, increased time spent indoors due to strict lockdowns and shielding triggered concerns that some people might not obtain the necessary physiological levels of vitamin D from sunlight.
One important step towards providing more clarification on the protective effect of vitamin D has been a meta-analysis of 25 randomized controlled trials including 10,933 participants that studied the impact of vitamin D supplementation on risk of respiratory viral infections.1 Rigorously conducted meta-analyses are useful tools in evidence-based medicine, whose benefits include a consolidated and quantitative review of a large, and often complex, sometimes apparently conflicting, body of literature. This study showed a protective overall effect that was stronger in those with lower baseline vitamin D levels, and in trials where vitamin D was administered daily or weekly rather than in more widely spaced bolus doses.
Jolliffe and colleagues have updated this meta-analysis in November 2020 — currently published as a non-peer-reviewed pre-print – where they confirm that “vitamin D supplementation was safe and reduced risk of acute respiratory infections, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months”.
Various mechanisms have been suggested for explaining the protective action of vitamin D. One of them attributes the protective action of vitamin D to intracellular receptors (VDR) expressed by most immune cells including activated T cells, B cells, dendritic cells and macrophages. For example, it is known that vitamin D is important for the killing of phagocytized bacteria by macrophages (for example, it is known to play a role in tuberculosis).
One other plausible mechanism supporting the above evidences links vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of COVID-19 infection, such as the acute respiratory distress syndrome. Consistent suppression of the inflammatory cytokine response to pathogens has been shown by vitamin D in various animal models of pneumonia and pneumonitis. Some authors have also shown that the modulation of cytokine response by vitamin D consists of suppressing pro-inflammatory cytokines and interferon gamma and increasing the production of the anti-inflammatory cytokine by T cells. This has to be considered together with the finding that severe COVID-19 is accompanied by exacerbated T cells responses, which are suspected to contribute towards pathogenic hyper-inflammation .
Moreover, cardiovascular features of COVID-19 disease deserve attention as they may also be related to vitamin D.The biomedical research on this topic is still ongoing and, despite all the above, the current clinical data associating vitamin D with COVID-19 infection at this time must still be considered hypothetical.
- 1.Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. Published online February 15, 2017:i6583. doi:10.1136/bmj.i6583
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