Vitamin D

Our Findings and Opinion

Vitamin D is a hormone, produced in the skin via U.V. (sun) light exposure. It is also ingested through numerous foods.

The majority of studies we found and reviewed showed a positive correlation between blood vitamin D levels and Covid-19 recovery, and potentially prevention. In numerous studies the recommendation of the authors was that further research be conducted. In most studies supplementation with vitamin D is recommended as a beneficial step in dealing with Covid-19 infection and symptoms. Vitamin D should not be considered a “cure”, and no studies suggested it is. The takeaway from the research done so far is that no harm is likely from correct levels of vitamin D supplementation, and yet there is a high probability of benefit both for Covid-19 recovery, and for the many other health benefits of having adequate blood serum vitamin D levels.

Studies showing positive effects of vitamin D in relation to Covid-19

1. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study — 12 November 2020
   “CONCLUSION: Greater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation.”
2. The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies — 23 September 2021
3. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study — 28 August 2020
4. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data — 15 February 2017 — Related to respiratory tract infections in general. Positive results.
5. Exploring links between vitamin D deficiency and COVID-19 — 16 September 2020
   Generally positive results, yet undecided in the ramifications. Recommends larger more robust studies.
6. Is there a link between vitamin D status, SARS-CoV-2 infection risk and COVID-19 severity? — 2 November 2020
   “Based on the available reports, supplementation with vitamin D has been proven to be protective against respiratory tract infections. Moreover, some retrospective studies suggested the existence of a correlation between a poor vitamin D status and SARS-CoV-2 infection and COVID-19outcomes, while other studies did not. In a research published on fifth October 2020 emerged that besides the lower levels of vitamin D in COVID-19 patients, compared to controls (13.14 vs 34.81 μg/L, on average), these patients also had lower serum phosphorus (4.09 ± 0.73 U/L vs 5.06 ± 0.93 U/L). Furthermore, the symptomatology (fever) was worst in vitamin D insufficient COVID-19 patients than in vitamin D sufficient COVID-19 patients, with a statistically significant negative correlation. Nonetheless, a major confounding factor in establishing the actual existence of an association between vitamin D concentrations and COVID-19 is that most of COVID-19 patients are elderly who generally also experience hypovitaminosis D. Thus, large-scale randomized controlled trials are needed to better inquire into this topic. Meanwhile, we suggest that people who are at risk of vitamin D deficiency/insufficiency should consider taking vitamin D supplements to maintain the circulating 25(OH)D above the deficiency/insufficiency thresholds during this global pandemic.”
7. COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis — 14 October 2021
   “The datasets provide strong evidence that low D3 is a predictor rather than just a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/mL to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.”
8. Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients — 9 January 2021
   CONCLUSION: “Among patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation. Further observational studies are needed to confirm these findings, and randomized clinical trials must be conducted to assess the role of vitamin D administration in improving the morbidity and mortality of COVID-19.”
9. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes — 22 December 2021
   CONCLUSION: “Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.”
10. The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis — 5 March 2021
    CONCLUSION: “In conclusion, low serum 25 (OH) Vitamin-D level was significantly associated with a higher risk of COVID-19 infection. The limited currently available data suggest that sufficient Vitamin D level in serum is associated with a significantly decreased risk of COVID-19 infection.”
11. Vitamin D and COVID-19: evidence and recommendations for supplementation — 1 December 2020 — Royal Society Open Science (UK)
    
    

Studies showing no significant benefit of vitamin D

1. Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study
   Conclusion
   In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.
   However, researchers noted that their study had some important limitations. It did not account for truly vitamin D deficient patients, consequently it remains possible that they may benefit from supplementation for COVID-19 related protection and outcomes. Additionally, the study only analyzed genetic variants from individuals of European ancestry. Future studies are needed to explore the relationship with vitamin D and COVID-19 outcomes in other populations, say the researchers.

Science Articles on Vitamin D and Covid-19

1. Nature Portfolio — Can Vitamin D Help Protect Against COVID-19? — 24 June 2021
   CONCLUSION: “Some studies suggest an impact, particularly for those who are vitamin-deficient. But for now, the jury is out.” “Given the results of Neale’s large-scale study and the modest benefits found in Martineau’s latest meta-analysis, it seems unlikely that vitamin D will prove to be a critical ingredient in fending off COVID-19 or modulating its severity. But these and other new trials may find it is useful in certain doses for certain populations. As Neale points out, “there is data that is suggestive” and enough smoke to indicate that you don’t want to be vitamin-D-deficient in a pandemic.”
2. University of Chicago Medicine — Study suggests high vitamin D levels may protect against COVID-19, especially for Black people — 19 March 2021
3. Purdue University — Researchers study the link between vitamin D and inflammation — 18 November 2021
   CONCLUSION: “We found that vitamin D – a specialized form of it, not the form you can get at the drugstore — has the potential to reduce inflammation in the test tube, and we figured out how and why it does that,” Kazemian said. However, it’s important to understand that we did not carry out a clinical study, and the results of our experiments in the test tube need to be tested in clinical trials in actual patients.”

Studies on the prevalence of Vitamin D deficiency

Some of the studies on Vitamin D in relation to Covid-19 suggest it may only be beneficial in those with a Vitamin D deficiency. If this is the case, and Vitamin D supplementation is generally considered beneficial or potentially beneficial to those with Vitamin D deficiency, it is worth noting that a significant proportion of people are deficient in Vitamin D. This is especially the case in dark skinned and hispanic populations (two demographics identified as being at a higher risk for SARS-CoV-2 infection and complications).

1. Prevalence and correlates of vitamin D deficiency in US adults — PubMed — January 2011
   “In summary, vitamin D deficiency was common in the US population, especially among blacks and Hispanics. Given that vitamin D deficiency is linked to some of the important risk factors of leading causes of death in the United States, it is important that health professionals are aware of this connection and offer dietary and other intervention strategies to correct vitamin D deficiency, especially in minority groups.”
2. Vitamin D deficiency 2.0: an update on the current status worldwide — Nature.com — 20 January 2020
   “Prevalence rates of severe vitamin D deficiency, defined as 25(OH)D <30 nmol/L (or 12 ng/ml), of 5.9% (US) [18], 7.4% (Canada) [19], and 13% (Europe) [2] have been reported. Estimates of the prevalence of 25(OH)D levels <50 nmol/L (or 20 ng/ml) have been reported as 24% (US), 37% (Canada), and 40% (Europe) [2, 17, 18, 19]. This may vary by age, with lower levels in childhood and the elderly [17], and also ethnicity in different regions, for example, European Caucasians show lower rates of vitamin D deficiency compared with nonwhite individuals [2, 17]. Worldwide, many countries report very high prevalences of low vitamin D status. 25(OH)D levels <30 nmol/L (or 12 ng/ml) in >20% of the population are common in India, Tunisia, Pakistan, and Afghanistan. For example, it has been estimated that 490 million individuals are vitamin D deficient in India [2, 17].”
3. Prevalence of Vitamin D Deficiency among Adult Population of Isfahan City, Iran — April 2011
   “The prevalence of mild, moderate and severe vitamin D deficiencies among the adult population was 19.6%, 23.9%, and 26.9% respectively. However, according to the second classification, the prevalence of vitamin D deficiency (combination of moderate and severe vitamin D deficiencies or 25-OHD <20 ng/mL) and vitamin D insufficiency (mild vitamin D deficiency or 25-OHD 20-30 ng/mL) was 50.8% and 19.6% respectively.”