To date, there remains a significant lack of information available on what health measures might elicit protective effects against coronavirus disease 2019 (COVID-19). Supplementation with vitamin D has recently been studied for its potential to reduce the risk of infection by COVID-19.
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An overview of vitamin D
Vitamin D is an endogenously produced steroid hormone that can be absorbed from exposure to sunlight, during which the protein 7-dehydrocholesterol (7-DHC) in our skin interacts with ultraviolet B (UVB) rays and subsequently gets converted into the active form of vitamin D, which is vitamin D3.
Vitamin D can also get absorbed through various dietary sources including oily fish like salmon and sardines to red meats and egg yolks.
Once vitamin D enters the bloodstream, it can be used to assist the body in absorbing calcium, which helps to strengthen bones, allow for muscle movement, provide nerves with the ability to transmit messages between the brain and other parts of the body, as well as work with the immune system to fight off invading pathogens like bacteria and viruses.
Vitamin D and viral infections
Vitamin D plays a modulatory role in the immune system, as it increases the secretion of numerous antiviral peptides to support innate immunity and can also induce autophagy in response to viral substances.
Additionally, vitamin D has been shown to reduce the risk of microbial infections and mortality through various pathways. When an individual acquires the common cold, for example, vitamin D can act as a physical barrier against the infection, or act through cellular natural and/or adaptive immunity mechanisms to reduce the risk of infection.
Between the years 2007 and 2020, several meta-analyses of randomized controlled trials supported the hypothesis that vitamin D exerts protective effects against acute respiratory infections and that a deficiency of vitamin D within the serum can in fact increase the risk of community-acquired pneumonia.
Evidence linking vitamin D to COVID-19
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus that is responsible for the COVID-19 disease, has, as of December 16, 2020, been responsible for the deaths of over 1.6 million people worldwide.
As this virus continues to spread at a rapid rate throughout the world, there remains an immediate need to discover health measures capable of reducing the risk of infection by SARS-CoV-2, as well as limit its progression and severity.
Some of the most common mild symptoms that patients with COVID-19 experience include fever, marked asthenia and dry cough, whereas severe manifestations of disease can lead to lethal acute respiratory disease syndrome (ARDS).
The SARS-CoV-2 virus appears to infect individuals through an immune evasion process that can lead to the development of ARDS by a subsequent hyper reaction process and cytokine storm.
Prior to the COVID-19 pandemic, several in vitro studies demonstrated that vitamin D plays an important role in local respiratory homeostasis through either its ability to promote the secretion of antimicrobial peptides or by directly interfering with the replication of respiratory viruses.
In addition, the deficiency of vitamin D has also been found to promote the renin-angiotensin system (RAS), which can cause chronic cardiovascular disease (CVD) and reduce lung function. ARDS and heart failure, both of which are severe manifestations of COVID-19 patients, can therefore be linked to insufficient vitamin D levels, thus supporting the potential utility of vitamin D supplementation in COVID-19 patients.
Vitamin D mechanisms against COVID-19
Little is currently known about the potential role of vitamin D in its ability to prevent COVID-19 infection and/or fatalities; however, several studies have evaluated the possible correlations that might exist between this nutrient and the SARS-CoV-2 infection pathway.
Some of the first COVID-19 reports found that up to 85% of infected patients exhibited hypovitaminosis D and that serum levels of 25-hydroxyvitamin D (25(OH)D) concentrations were also lower in infected patients as compared to controls.
Although most older individuals, as well as those with pre-existing conditions, often have lower vitamin D levels, both of whom are most susceptible to COVID-19, physicians remained interested in determining the potential correlation that exists between vitamin D levels and COVID-19.
One of the first studies to correlate vitamin D and SARS-CoV-2 was a genetic study looking to identify repressors and activators of the ACE2 and FURIN genes, both of which have been found to be necessary for the entry of this virus into human cells.
In this study, the researchers inferred that vitamin D and quercetin could potentially serve as putative COVID-19 mitigation agents. Since these initial results have been published, several additional studies have evaluated the possible role of vitamin D in reducing the effects upon infection by SARS-CoV-2.
These studies concluded that by maintaining the rigidity of bot cell and gap junctions, as well as by reducing the effects of cytokine storm by acting on interferon g tumor necrosis factor alpha (TNF-α), vitamin D can improve cellular immunity and thus decrease the severity of COVID-19.
Additional data suggests that vitamin D may reduce some of the unfavorable downstream immunological responses to COVID-19 that are associated with severe manifestations through the disease. Some of these downstream pathways that vitamin D may be involved in include preventing the rise of interleukin 6 (IL-6) levels and delaying the interferon-gamma response.
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Has vitamin D supplementation helped COVID-19 patients?
Several randomized control trials throughout the world have investigated whether vitamin D supplementation might reduce the severity of COVID-19 patients and/or mortality rates. To date, these studies have determined that prophylactic vitamin D supplementation successfully reduced the risk of acute respiratory tract infections in COVID-19 patients.
In addition to assessing its influence on COVID-19 severity, vitamin D serum concentrations and the number of COVID-19 deaths in 20 countries throughout Europe were studied.
In their work, a significant correlation was observed between the number of COVID-19 cases and mean vitamin D concentrations, thus confirming previous studies that have identified a correlation between these two factors. While this may be true, the current study did not find the relationship between vitamin D levels and COVID-19 deaths to be significant.
In December 2020, the UK’s National Institute for Health and Care Excellence (NICE) in collaboration with Public Health England (PHE) issued a guideline about vitamin D.
It advised that individuals should consider taking vitamin D supplements during winter months, particularly due to enforced lockdown resulting in people being inside more than usual. However, it was concluded that there is currently not enough evidence to support vitamin D to solely treat or prevent COVID-19, and that more research with high-quality randomized and controlled trials is needed to obtain more information on this.
Research and trials are ongoing, with recent results from a study at the University of Chicago Medicine suggesting that vitamin D levels which are higher than what is usually considered sufficient may lower the risk of infection, particularly in Black individuals.
Conclusion
Despite a growing amount of information that has been published on the correlation between vitamin D levels and COVID-19, a definitive conclusion has not yet been made on whether this nutrient does in fact help infected patients.
While this may be true, the general consensus among clinicians is that it does not appear to be controversial to encourage the intake of vitamin D to the global population, which ranges from 400 IU/day in the United Kingdom to up to 800 IU/day in the United States.
References
- Ali, N. (2020). Role of vitamin D in preventing of COVID-19 infection, progression and severity. Journal of Infection and Public Health 13(10); 1373-1380. doi:10.1016/j.jiph.2020.06.021.
- Annweiler, C., Cao, Z., & Sabatier, J. (2020). Point of view: Should COVID-19 patients be supplemented with vitamin D? Maturitas 140; 24-26. doi:10.1016/j.maturitas.2020.06.003.
- COVID-19 rapid guideline: vitamin D. NICE (2020). [Online]. Available from: https://www.nice.org.uk/guidance/ng187/chapter/Recommendations
- Glinsky, Gennadi (2020). Vitamin D, Quercetin, and Estradiol manifest properties of candidate medicinal agents for mitigation of the severity of pandemic COVID-19 defined by genomics-guided tracing of SARS-CoV-2 targets in human cells. ChemRxiv. Preprint. doi:26434/chemrxiv.12052512.v7
- Martineau, A. R., & Forouhi, N. G. (2020). Vitamin D for COVID-19: a case to answer? The Lancet Diabetes & Endocrinology 8(9); 735-736. doi:10.1016/S2213-8587(20)30268-0.
- Meltzer, D. O., et al. (2021). Association of vitamin D levels, race/ethnicity, and clinical characteristics With COVID-19 test results. JAMA Netw Open, 4(3):e214117. doi:10.1001/jamanetworkopen.2021.4117
- Sun Protection and Vitamin D [Online]. Available from: https://www.skincancer.org/blog/sun-protection-and-vitamin-d/.
- Vitamin D [Online]. Available from: https://ods.od.nih.gov/factsheets/VitaminD-Consumer/.
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