The Relationship Between Vitamin D Levels and COVID-19
High vitamin D levels are associated with reduced risk of COVID-19 infection and decreased severity of disease outcomes, and vitamin D supplementation should be recommended for all individuals during the COVID-19 pandemic, particularly those at high risk of deficiency.
Evidence on Vitamin D and COVID-19
The relationship between vitamin D and COVID-19 has been investigated in multiple observational studies, with evidence suggesting several important connections:
Infection Risk
- Individuals with vitamin D deficiency (levels <20 ng/mL or 50 nmol/L) are 1.64 times more likely to contract COVID-19 compared to those with sufficient levels 1
- A large retrospective study of 191,779 individuals showed that SARS-CoV-2 positivity rates were significantly higher (12.5%) in subjects with vitamin D levels <20 ng/mL compared to those with sufficient levels (8.1%) 2
Disease Severity
- People with serum vitamin D levels below 20 ng/mL are 2.42 times more likely to develop severe COVID-19 1
- Individuals with vitamin D levels <30 nmol/L have 1.513 times higher risk for COVID-19 severity when infected 2
Biological Mechanisms
Vitamin D may reduce COVID-19 risk through several mechanisms:
- Reducing viral replication
- Decreasing inflammatory cytokine production
- Increasing angiotensin-converting enzyme 2 concentrations
- Maintaining endothelial integrity 3
Recommendations for Vitamin D Supplementation
Based on the available evidence, the following recommendations can be made:
General Population
- Supplementation with 800-1000 IU/day of vitamin D for all individuals during the pandemic 4
- Target blood level of at least 50 nmol/L (20 ng/mL) as recommended by the US National Academy of Medicine and European Food Safety Authority 4
High-Risk Groups
- Adults likely to be deficient should consider taking a higher initial dose of 4000 IU/day for the first four weeks before reducing to 800-1000 IU/day 4
- Mandatory supplementation should be considered for those in care homes, prisons, and other institutions where people are likely to have been indoors for extended periods 4
Hospitalized COVID-19 Patients
- Vitamin D status should be checked in patients admitted to the hospital with COVID-19 4
- Supplementation should be provided as appropriate based on measured levels
Clinical Considerations and Caveats
Interpretation of Evidence
- While observational studies show a correlation between vitamin D levels and COVID-19 outcomes, randomized controlled trials are still needed to establish causality 3
- The evidence generally satisfies Hill's criteria for causality (strength of association, consistency, temporality, biological gradient, plausibility, and coherence) 3
Testing Considerations
- D-dimer levels are frequently elevated in COVID-19 patients, which can affect interpretation of results 5
- When measuring vitamin D levels, standardized measuring units should be used (FEU, as either "μg/L" or "mg/L") 6
Safety Profile
- Vitamin D supplementation is very safe and inexpensive 4
- The therapeutic window is wide, making it appropriate for general recommendation during the pandemic 3
Practical Implementation
Assessment: Consider vitamin D testing for individuals at high risk of deficiency (elderly, institutionalized, darker skin tones, obese individuals)
Supplementation Strategy:
- General population: 800-1000 IU/day
- Known deficiency: 4000 IU/day for 4 weeks, then 800-1000 IU/day
- Hospitalized patients: Consider testing and appropriate supplementation
Monitoring: For those on higher doses, periodic monitoring of serum levels may be appropriate to ensure target levels of at least 50 nmol/L are achieved
Integration with Other Measures: Vitamin D supplementation should complement, not replace, other preventive measures such as vaccination, masking, and social distancing
While more definitive randomized controlled trials are still needed, the safety profile and potential benefits of vitamin D supplementation make it a reasonable recommendation during the ongoing COVID-19 pandemic, particularly as we approach winter months when vitamin D levels naturally decline.