Vitamin D in the quantity of 50,000 IU / weak for 2 weeks followed by 5,000 IU / day for 2.5 months completely eliminated symptomatic case from COVID-19 to 0.0% vs. 22.5% in the control group, according to the clinical study disclosed in Tatiana L. Karonova et al., “Vitamin D intake may reduce SARS-CoV-2 infection morbidity in health care workers,” Nutrients, 24 January 2022, 14, 505, https://doi.org/10.3390/nu14030505, JIF 6.707 (top 17% journals in Nutrition & Dietetics).
Vitamin D in the quantity of 266 μg on day 3 and 7, and then weekly until discharge or ICU admission completely eliminated deaths from COVID-19 to 0.0% vs. 7.7% in the control group, according to the clinical study disclosed in Marta Entrenas Castillo 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,” Journal of Steroid Biochemistry and Molecular Biology, 29 August 2020, 203, https://doi.org/10.1016/j.jsbmb.2020.105751, JIF 5.011 (top 33% journals in Endocrinology & Metabolism and top 37% journals in Biochemistry & Molecular Biology).
Vitamin D in the quantity of 0.5 μg per day for 14 days or hospital discharge completely eliminated deaths from COVID-19 to 0.0% vs. 12.0% in the control group, and completely eliminated risk of mechanical ventilation from COVID-19 to 0.0% vs. 8.0% in the control group, according to the clinical study disclosed in Yasmine M. Elamir et al., “A randomized pilot study using calcitriol in hospitalized patients,” Bone, 8 September 2021, 154, 116175, https://doi.org/10.1016/j.bone.2021.116175, JIF 4.626 (top 41% journals in Endocrinology & Metabolism).
Vitamin D in the quantity of 200,000 IU once completely eliminated symptomatic cases from COVID-19 to 0.0% vs. 20.0% in the control group in the following 2 months, according to the clinical study disclosed in Sidra Jabeen et al., “Protective effect of vitamin-D supplementation in patients of acute coronary syndrome during COVID-19 pandemic,” Pakistan Journal of Medical and Health Sciences, 11 May 2022, 16(03), https://doi.org/10.53350/pjmhs221631053, JIF N/A.
Vitamin D has long been recognized as essential to the skeletal system. Newer evidence suggests that it also plays a major role regulating the immune system, perhaps including immune responses to viral infection. Interventional and observational epidemiological studies provide evidence that vitamin D deficiency may confer increased risk of influenza and respiratory tract infection. Vitamin D deficiency is also prevalent among patients with HIV infection. Cell culture experiments support the thesis that vitamin D has direct anti-viral effects particularly against enveloped viruses. Though vitamin D's anti-viral mechanism has not been fully established, it may be linked to vitamin D's ability to up-regulate the anti-microbial peptides LL-37 and human beta defensin 2, according to Jeremy A. Beard et al., “Vitamin D and the anti-viral state,” Journal of Clinical Virology 2011 Mar, 50(3):194-200, https://doi.org/10.1016/j.jcv.2010.12.006, JIF 14.481 (top 8% journals in Virology).
Vitamin D3 improves circulation and may prove to be beneficial in the treatment of hypertension and other cardiovascular diseases, including heart failure, myocardial infarction, vasculopathy, stroke and diabetes, according to Alamzeb Khan et al., “Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases,” International Journal of Nanomedicine, 19 January 2018, 13, 455-466, https://doi.org/10.2147/IJN.S152822, JIF 7.033 (top 12% journals in Pharmacology & Pharmacy).
Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines, according to William B. Grant et al., “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths,” Nutrients, 2020, 12, 988; https://doi.org/10.3390/nu12040988, JIF 6.706 (top 17% journals in Nutrition & Dietetics).
Non-classical actions of vitamin D were first suggested over 30 years ago when receptors for the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), were detected in various tissues and cells that are not associated with the regulation of calcium homeostasis, including activated human inflammatory cells. The question that remained was the biological significance of the presence of vitamin D receptors in the different tissues and cells and, with regard to the immune system, whether or not vitamin D plays a role in the normal immune response and in modifying immune mediated diseases. In this article findings indicating that vitamin D is a key factor regulating both innate and adaptive immunity are reviewed with a focus on the molecular mechanisms involved. In addition, the physiological significance of vitamin D action, as suggested by in vivo studies in mouse models is discussed. Together, the findings indicate the importance of 1,25(OH)2D3 as a regulator of key components of the immune system, according to Ran Wei et al., “Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D,” Nutrients 2015, 7(10), 8251–8260, https://doi.org/10.3390/nu7105392, JIF 6.706 (top 17% journals in Nutrition & Dietetics).
Vitamin D insufficiency and deficiency affect approximately half of the US population, with increased rates in people with darker skin, reduced sun exposure, people living in higher latitudes in the winter, nursing home residents, and healthcare workers. Populations with low levels of Vitamin D have also experienced higher rates of COVID-19, according to Jason B. Gibbons et al., “Association between vitamin D supplementation and COVID-19 infection and mortality,” Scientific Reports (2022) 12:19397, https://doi.org/10.1038/s41598-022-24053-4, JIF 4.997 (top 26% journals in Multidisciplinary Sciences).
Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage, according to Mariaelena Filippelli et al., “Anti-inflammatory effect of curcumin, homotaurine, and vitamin D3 on human vitreous in patients with diabetic retinopathy,” Frontiers in Neurology, 2021, 11, 592274, https://doi.org/10.3389/fneur.2020.592274, JIF 4.086 (top 42% journals in Clinical neurology and top 45% journals in Neurosciences).
In the last 5 years, there has been a remarkable change in our understanding of the health benefits of vitamin D. The classical actions of vitamin D as a determinant of mineral metabolism and rachitic bone disease have been expanded to include a broader role in skeletal homoeostasis and prevalent bone disorders such as osteoporosis. However, it is the nonskeletal function of vitamin D that has attracted most attention. Although pluripotent responses to vitamin D have been recognized for many years, our new perspective on nonclassical vitamin D function stems from two more recent concepts. The first is that impaired, vitamin D status is common to many populations across the globe. This has prompted studies to explore the health impact of suboptimal circulating levels of vitamin D, with association studies linking vitamin D 'insufficiency' to several chronic health problems including autoimmune and cardiovascular disease, hypertension and common cancers. In support of a broader role for vitamin D in human health, studies in vitro and using animal models have highlighted immunomodulatory and anticancer effects of vitamin D that appear to depend on localized activation of vitamin D. The conclusion from these reports is that many nonclassical actions of vitamin D are independent of conventional vitamin D endocrinology and are therefore more sensitive to variations in vitamin D status. The current review summarizes these developments, with specific reference to the newly identified effects of vitamin D on the immune system, but also highlights the challenges in translating these observations to clinical practice, according to Martin Hewison, “An update on vitamin D and human immunity,” Clinical Endocrinology 2012, 76, 315–325, https://doi.org/10.1111/j.1365-2265.2011.04261.x, JIF 3.523 (top 64% journals in Endocrinology & Metabolism).