Vitamin D in the News
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COVID-19 and Vitamin D Deficiency
Vitamin D is essential not only for healthy bones, but also for the body’s defense against infections.,,, Numerous studies have shown that insufficient vitamin D intakes are associated with an enhanced risk and severity of respiratory tract infections.,,
In a large population-based study in Germany, the mortality from respiratory diseases (including influenza and pneumonia) over a 15-year period was found to be three-fold higher in adults with vitamin D deficiency compared to those with a healthy vitamin D level. Based on statistics, 41% of the mortality due to respiratory diseases was attributable to inadequate vitamin D levels.
In 2020, studies investigating the importance of adequate vitamin D levels for a healthy immune response to the new coronavirus, SARS-CoV-2, and the disease associated with it, COVID-19, began to appear. These studies point towards vitamin D deficiency as a factor that contributes to infection with the virus and the severity of disease that occurs when one becomes infected, as discussed below.
The demographics of vitamin D deficiency
The global patterns of COVID-19 mortality reflect those of vitamin D status.
Vitamin D is known as the sunshine vitamin because it is generated within the skin upon exposure to ultraviolet B (UVB) rays, the rays responsible for suntans. Many variables affect UVB exposure (which is different from just being outside in the sun) and therefore influence vitamin D levels in the body.
Latitude strongly influences UVB exposure and vitamin D status., At northern latitudes, very little, if any, vitamin D is produced in the skin during the winter, and vitamin D levels drop unless vitamin D is supplemented., One study showed that young adults living in Pennsylvania, a northern state, had a 3.3-fold higher risk of vitamin D deficiency as compared to those living in Florida, a southern state. States with a substantial portion of their population living at approximately the same latitude as Pennsylvania include Ohio, Missouri, Utah and Nebraska; thus, similar findings would be anticipated in these regions, while the risk is even greater further north.
Scientists have observed that the global patterns of COVID-19 mortality reflect those of vitamin D status. In the winter of 2019-2020, countries in the Northern Hemisphere exhibited higher COVID-19 mortality rates compared to countries in the Southern Hemisphere. In fact, there was an estimated 4.4% increase in COVID-19 mortality for each 1 degree latitude north of 28 degrees North (a parallel that passes through south Texas).
The effect of latitude, and by inference vitamin D status, applies not only to COVID-19 but also to seasonal and pandemic influenza outbreaks., In a retrospective analysis of the 1918-1919 influenza pandemic, there was a substantial correlation between UVB intensity and case fatality rates in 12 different regions of the U.S. Among the states included in the study, the lowest case fatality rates occurred in Texas, which had the highest UVB irradiance and lowest latitude, while the highest rates were in Connecticut, which had the lowest UVB irradiance and highest latitude.
Age is also a factor, since aging can decrease by more than twofold the capacity of the skin to produce vitamin D. Vitamin D deficiency is extremely common in the elderly for this and other reasons, such as reduced sun exposure, digestive problems, diet inadequacies, comorbidities, and the use of medications. As a result, vitamin D levels tend to be severely low in aging populations.,, This may be one factor contributing to the fact that some countries with large elderly populations, such as Italy, had such severe COVID-19 outbreaks., Older adults were found to have higher viral loads and, especially those with comorbidities, had higher COVID-19-related fatality rates than younger adults.
Melanin in the skin blocks UVB light, so individuals with darker skin tend to synthesize less vitamin D than those with lighter skin., This may explain, in part, the disparities between infection rates between lighter and darker skin populations. Data from the UK showed that ethnic groups having darker skin were approximately two to four times more likely to die from COVID-19 than were those of white ethnicity., In addition to latitude, age, and skin melanin content, genetic variations play a role in COVID-19 susceptibility among different populations and ethnic groups.,,
Vitamin D deficiency is common in COVID-19 patients
Low vitamin D levels were found to be an independent risk factor for COVID‐19 infection and hospitalization.
Growing evidence suggests that the majority of COVID-19 patients are deficient or insufficient in vitamin D.,,, In one study, researchers found that 81% of the patients admitted to a hospital ICU had inadequate vitamin D levels. Another study found that low vitamin D levels were an independent risk factor for COVID‐19 infection and hospitalization.
In one of the largest population studies to date, which is currently published as a preprint, scientists assessed the relationship between the prevalence of vitamin D deficiency and a positive coronavirus test result. The study encompassed 4.6 million individuals, spanning across 200 localities in Israel. They found a significant association between low vitamin D levels and the risk of infection, with the highest risk observed for those with severe vitamin D deficiency, defined as 25(OH)D levels lower than 30 nmol/L.
These researchers also found that vitamin D deficiency was more prevalent among ultra-orthodox and Arab communities, reflecting the use of religious clothing that covers most of the skin and blocks UVB light. These population sub-groups had a two- to three-fold increased risk of COVID-19 infection.
The greatest risks of infection were observed among individuals with severe vitamin D deficiency who lived in regions where much of the population was low in vitamin D. The authors suggest that, in areas where vitamin D deficiency is widely prevalent, neighbors are more likely to spread the virus to each other. Conversely, a sort of “herd immunity” may occur in communities with greater average vitamin D levels, not because of any actual antibody-based immunity, but because adequate vitamin D levels reduce the risk of infection and hence the risk of passing the virus along to neighbors.
Adults who are obese are three times more likely to be vitamin D deficient as compared to those with normal body weights., Obesity is associated with cardiovascular metabolic diseases, including diabetes and hypertension, which are conditions that increase the risk and severity of COVID-19 infections.,, A meta-analysis of 75 studies concluded that obese individuals who had COVID-19 were more than twice as likely to require hospitalization as those with normal body weights.
Multiple studies have found that vitamin D deficiency is associated with the severity of COVID-19 infections as well., Low vitamin D levels contribute to excessive cytokine production and lung inflammation, which increases the risk of hospitalization.,,,, In one study of hundreds of individuals with COVID-19, scientists observed that inadequate plasma vitamin D levels raised the odds of hospitalization by 95%, even after adjusting for comorbidities. “Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization,” the authors concluded.
Calcifediol improves outcomes
A groundbreaking study published in August 2020 found a direct effect of vitamin D status on COVID-19 outcomes. In the controlled trial, hospitalized patients were treated with calcifediol, a prescription formulation of 25(OH)D, which is the major circulating form of vitamin D in the body.,, Calcifediol has been shown to raise blood levels of 25(OH)D more rapidly than vitamin D3.
In a study of COVID-19 patients being admitted to the hospital for their condition, a portion of them received a high dose of oral calcifediol in addition to indicated treatment established by hospital protocols. Outcomes were significantly better in the group receiving calcifediol: only 1 out of 50 patients (2%) required ICU admission, and none of them died, while in the no-calcifediol group, 13 out of 26 patients (50%) required ICU admission, and two died. Consequently, the administration of calcifediol reduced the odds of ICU admission by 93%.
While this study was small, it was the first to show that calcifediol administration could influence outcomes. According to the authors, “Our pilot study demonstrated that administration of a high dose of calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19.”
Clearly, there is much we are continuing to learn as we deal with this global pandemic. Research on vitamin D and other nutritional factors that may play a role in COVID-19 is coming out at rapid pace, exceeding that related to any other medical condition affecting humankind. As we look to modern medicine for a solution, it is important to remember that proper nutrition is the foundation for all aspects of good health.Click here to see References
 Holick MF, et al. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017 Jun;18(2):153-65.
 Cashman KD, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016 Apr;103(4):1033-44.
 Kroner Jde C, et al. Vitamin D every day to keep the infection away? Nutrients. 2015 May 29;7(6):4170-88.
 Zitterman A, et al. Vitamin D and airway infections: a European perspective. Eur J Med Res. 2016 Mar 24;21:14.
 Aranow C. Vitamin D and the immune system. J Investig Med. 2011 Aug;59(6):881-6.
 Martineau AR, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583.
 Gunville CF, et al. The role of vitamin D in prevention and treatment of infection. Inflamm Allergy Drug Targets. 2013 Aug;12(4):239-45.
 Ginde AA, et al. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23;169(4):384-90.
 Pham H, et al. Acute respiratory tract infection and 25-hydroxyvitamin D concentration: a systematic review and meta-analysis. Int J Environ Res Public Health. 2019 Aug 21;16(17):3020.
 Brenner H, et al. Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 pandemic? Nutrients. 2020 Aug 18;12(8):E2488.
 Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108.
 Poskitt EM, et al. Diet, sunlight, and 25-hydroxy vitamin D in healthy children and adults. Br Med J. 1979 Jan 27;1(6158):221-3.
 Religi A, et al. Estimation of exposure durations for vitamin D production and sunburn risk in Switzerland. J Expo Sci Environ Epidemiol. 2019 Oct;29(6):742-52.
 Webb AR, et al. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988 Aug;67(2):373-8.
 Leary PF, et al. Effect of latitude on vitamin D levels. J Am Osteopath Assoc. 2017 Jul 1;117(7):433-9.
 Rhodes JM, et al. Perspective: vitamin D deficiency and COVID-19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis. J Intern Med. 2020 Jul [online ahead of print]
 Juzeniene A, et al. The seasonality of pandemic and non-pandemic influenzas: the roles of solar radiation and vitamin D. Int J Infect Dis. 2010 Dec;14(12):e1099-105.
 Grant WB, et al. Seasonal variations of U.S. mortality rates: roles of solar ultraviolet-B doses, vitamin D, gene expression, and infections. J Steroid Biochem Mol Biol. 2017 Oct;173:5-12.
 MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985 Oct;76(4):1536-8.
 Wyskida M, et al. Prevalence and factors promoting the occurrence of vitamin D deficiency in the elderly. Postepy Hig Med Dosw (Online). 2017 Mar 13;71(0):198-204.
 Elliott ME, et al. Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D. Pharmacotherapy. 2003 Jun;23(6):702-10.
 Kennel KA, et al. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010 Aug;85(8):752-7.
 Ilie PC, et al. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. 2020 Jul;32(7):1195-8.
 Vellas C, et al. COVID-19, virology and geroscience: a perspective. J Nutr Health Aging. 2020;24(7):685-91.
 Murphy AB, et al. Predictors of serum vitamin D levels in African American and European American men in Chicago. Am J Mens Health. 2012 Sep;6(5):420-6.
 Cyrus E, et al. The impact of COVID-19 on African American communities in the United States. medRxiv. 2020 May 19 [preprint]
 Mitchell F. Vitamin-D and COVID-19: do deficient risk a poorer outcome? Lancet Diabetes Endocrinol. 2020 Jul;8(7):570.
 White C, Nafilyan V. Coronavirus (COVID-19) related deaths by ethnic group, England and Wales: 2 March 2020 to 10 April 2020 [Internet]. Newport (UK): Office for National Statistics; 2020 [cited 2020 Jun 16]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/coronavirusrelateddeathsbyethnicgroupenglandandwales/2march2020to10april2020
 Bunyavanich S, et al. Racial/ethnic variation in nasal gene expression of transmembrane serine protease 2 (TMPRSS2). JAMA. 2020 Sep 10.
 Hou Y, et al. New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC medicine. 2020 Dec;18(1):1-8.
 Ellinghaus D, et al. Genomewide association study of severe Covid-19 with respiratory failure. NEJM. 2020 Jun 17.
 Panagiotou G, et al. Low serum 25‐hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID‐19 are associated with greater disease severity. Clin Endocrinol. 2020 Jul 3.
 Meltzer DO, et al. Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA. 2020 Sep 3.
 Merzon E, et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study. FEBS J. 2020 Sep;287(17):3693-702.
 Munshi R, et al. Vitamin D insufficiency as a potential culprit in critical COVID‐19 patients. J Med Virol. 2020 Jul 27.
 Israel A, et al. The link between vitamin D deficiency and Covid-19 in a large population. medRxiv. 2020 Jan 1 [preprint]
 Liu X, et al. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. Br J Nutr. 2018 Apr;119(8):928-36.
 Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015 May;74(2):115-24.
 Li B, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109:531-8.
 Gao F, et al. Obesity is a risk factor for greater COVID-19 severity. Diabetes Care. 2020 May 12.
 Popkin BM, et al. Individuals with obesity and COVID-19: a global perspective on the epidemiology and biological relationships. Obes Rev. 2020 Aug 26.
 Daneshkhah A, et al. Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients. Aging Clin Exp Res. 2020 Sep 2.
 Orrù B, et al. Inhibitory effects of Vitamin D on inflammation and IL-6 release. A further support for COVID-19 management? Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):8187-93.
 Mardani R, et al. Association of vitamin D with the modulation of the disease severity in COVID-19. Virus Res. 2020 Nov;289:198148.
 Castillo ME, et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. J Steroid Biochem Mol Biol. 2020;203:105751.
 Heaney RP, et al. 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr. 2008 Jun;87(6):1738-42.
 Vaes AMM, et al. Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: a randomized controlled trial in older adults. Clin Nutr. 2018 Jun;37(3):808-14.
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Marina MacDonald, MS, PhD
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