By: Sahil Sheth of Brown University, Vimala Alagappan, Krish Sheth, and Ripal Shah, MD, MPH of Stanford University School of Medicine
Vitamin D is a fat-soluble vitamin associated with regulating bone health and gene regulation.1 After the production of Vitamin D3 in the skin by a thermal reaction, it is stored in the body as 25-hydroxyvitamin D (25(OH)D3 before being converted in the liver and kidneys to Vitamin D2 (also known as calcitriol).2 Recent studies have indicated that Vitamin D has significant antiviral effects, making Vitamin D deficiencies (VDDs) especially important in combating COVID-19.4 This is especially relevant when attempting to understand why certain ethnicities and population groups may be considered more at-risk, especially those who have higher rates of Vitamin D deficiencies as a result of increased melanin concentrations in skin.
Vitamin D and Ethnicity
The relative levels of Vitamin D synthesis have long been associated with skin color. This relationship is mainly attributed to increased melanin production in darker-skinned populations
preventing the absorption of sunlight and thus preventing the same level of Vitamin D synthesis as more fair-skinned populations.1New studies have corroborated this finding, providing evidence as to why certain racial minority groups (specifically those with darker skin) have overall lower Vitamin D levels. In addition to darker skin, obesity has emerged as another significant risk factor5 and data indicate that non-white racial groups have significantly higher rates of obesity in their populations.5 Individuals with a higher body weight require more Vitamin D to be considered at a “healthy” level.1
Vitamin D and COVID-19 Risk
With the onset of the COVID-19 pandemic, there has been a large effort to identify at-risk populations. One such population is the VDD population. Vitamin D has previously been shown to fight viral infections through three main mechanisms: maintenance of the tight junctions of respiratory organs, enacting cathelicidins and defensins and acting as an inflammatory agonist through the release of anti-inflammatory cytokines.7 There have been many studies conducted in a short amount of time since the pandemic began, and most suggest that deficiencies in Vitamin D are a potential risk factor for morbidity from COVID-192,5-10 when Vitamin D deficiency is defined as 25(OH)D being less than 50 nnmol/L of blood.8 Studies have indicated that having a low Vitamin D level, whether from diet, skin color, or other factors, greatly increases the probability of contracting COVID-19 but there is no significant data supporting a higher mortality rate from COVID-19.11
There is not yet an established method for dealing with VDD to treat or prevent COVID-19, and the literature suggests approaching this on a case-by-case basis. However, older studies have hypothesized that 40-60 μg of Vitamin D daily (1600-2400 IU) can help prevent viral infections.7 Some public health agencies recommend Vitamin D supplementation on a regular basis of 400- 1000 IU daily, and suggest that megadoses of 100,000-300,000 IU weekly may have efficacy in reducing risk of infection and severity of COVID-19.4 Capsules of 50,000 IU are now available OTC for Vitamin D3 form (50,000 IU of Vitamin D2 still requires a prescription), and we may begin to see more patients taking it at this dose weekly rather than daily. Persons with high sun exposure (living at longitudes near the equator) may already have increased melanin which serves to better protect the skin from harmful UV radiation, while providing the anti-viral benefits of Vitamin D absorption. This is one of the reasons that ethnic minority groups in the U.S. are at higher risk of COVID-19 infection (living at elevated longitudes), while lighter-skinned populations near the equator are more susceptible to UV radiation.3
Since the beginning of the COVID-19 outbreak, there have been many attempts to identify which factors may make subsets of the population at increased risk of acquiring, spreading, maintaining, suffering, or passing from the infection. Vitamin D deficiency is distinct in that it can be affected by both biological and sociocultural differences. To further understand the mechanisms behind the link between Vitamin D deficiencies and at-risk groups for COVID-19, further research is necessary to identify how Vitamin D is able to mitigate the multi-organ effects of COVID-19 infection, and whether Vitamin D deficiency itself is a main contributor to increases in COVID-19 morbidity, or whether the deficiency is simply a confounding factor for increased comorbidity or mortality in patients already suffering from other risk factors due to socioeconomic factors or issues of health disparities.
- Weishaar T, Rajan S, Keller B. Probability of Vitamin D Deficiency by Body Weight and Race/Ethnicity. J Am Board FamMed. 2016 Mar-Apr;29(2):226-32. doi: 10.3122/jabfm.2016.02.150251. PMID: 26957379.
- Grant, William B et al. “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths.” Nutrients vol. 12,4 988. 2 Apr. 2020, doi:10.3390/nu12040988
- Merchant RA, van Dam RM, Tan LWL, Lim MY, Low JL, Morley JE. Vitamin D Binding Protein and Vitamin D Levels in Multi-Ethnic Population. J Nutr Health Aging. 2018;22(9):1060-1065. doi: 10.1007/s12603-018-1114-5. PMID: 30379303.
- Vyas N, Kurian SJ, Bagchi D, Manu MK, Saravu K, Unnikrishnan MK, Mukhopadhyay C, Rao M, Miraj SS. Vitamin D in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects. J Am Coll Nutr. 2020 Sep 1:1-14. Doi: 10.1080/07315724.2020.1806758. Epub ahead of print. PMID: 32870735.
- Townsend MJ, Kyle TK, Stanford FC. Outcomes of COVID-19: disparities in obesity and by ethnicity/race. Int J Obes (Lond). 2020 Sep;44(9):1807-1809. doi: 10.1038/s41366-020-0635-2. Epub 2020 Jul PMID: 32647359; PMCID: PMC7347050.
- Brown M. In response to: Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity. Clin Endocrinol (Oxf). 2020 Jul 16:10.1111/cen.14285. Doi: 10.1111/cen.14285. Epub ahead of print. PMID: 32671847; PMCID: PMC7405162.
- Martín Giménez VM, Inserra F, Ferder L, García J, Manucha W. Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2. J Hum Hypertens. 2020 Aug 13:1–3. doi: 10.1038/s41371-020-00398-z. Epub ahead of print. PMID: 32792611; PMCID: PMC7425793.
- Jain SK, Parsanathan R. Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans? J Am Coll Nutr. 2020 Jul 13:1-6. Doi: 10.1080/07315724.2020.1789518. Epub ahead of print. PMID: 32659175.
- Mendy A, Apewokin S, Wells AA, Morrow AL. Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients. medRxiv [Preprint]. 2020 Jun 27:2020.06.25.20137323. Doi: 10.1101/2020.06.25.20137323. PMID: 32607513; PMCID: PMC7325178.
- Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open. 2020 Sep 1;3(9):e2019722. Doi: 10.1001/jamanetworkopen.2020.19722. PMID: 32880651.
- Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O’Donnell CA, Gill JM, Sattar N, Pell JP. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020 Jul-Aug;14(4):561-565. doi: 10.1016/j.dsx.2020.04.050. Epub 2020 May 7. Erratumin: Diabetes Metab Syndr. 2020 Sep – Oct;14(5):1315-1316. PMID: 32413819; PMCID: PMC7204679.