Vitamin D: Physiology, clinical applications, dietary sources, and requirements

Vitamin D, the sunshine vitamin, is essential for bone health and reducing risk of acute and chronic diseases, including autoimmune diseases, cancers, heart disease, type II diabetes, neurocognitive dysfunction and infectious diseases including COVID-19. Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Vitamin D status is determined by measuring 25-hydroxyvitamin D in the blood. To maintain a normal level of at least 30ngmL−1 (75nmolL−1) as recommended by the Endocrine Society Guidelines on Vitamin D, infants up to 1 year need 400–1000IUs, children 600IU–1000IU, adults 1500–2000IU of vitamin D daily. Obese adults require 2–3 times more vitamin D to satisfy their requirement because of the vitamin D being diluted in the body fat and not available. This can be accomplished by receiving sensible sun exposure in combination with ingesting foods that either naturally contain or are fortified with vitamin D along with a vitamin D supplement. © 2023 Elsevier Ltd. All rights reserved

Association between Vitamin D Status and Secondary Infections in Patients with Severe COVID-19 Admitted in the Intensive Care Unit of a Tertiary-Level Hospital in Turkey.

There are several studies showing that the vitamin D status can determine risk of COVID-19 infections, severity and mortality from coronavirus disease 2019 (COVID-19). However, the association between vitamin D (25(OH)D) and secondary infections in the prognosis of COVID-19 patients has not been reported yet. The aim was to investigate whether the vitamin D status affects the rates of secondary infections in patients with severe COVID-19 hospitalized in the intensive care unit (ICU) of a tertiary-level hospital in Turkey. The data of 194 patients with diagnosis of severe COVID-19 who were admitted to the ICU from March 2020 to June 2021 and older than 18 years were evaluated in this retrospective study. The patients were divided into two groups according to total serum 25(OH)D level as normal group (≥20 ng/mL) and low group (<20 ng/mL). The 25(OH)D level was low in 118 (60.8%) and normal in 76 (39.2%) patients. The mean age of the low group was significantly higher than that of the normal group (67.02 ± 14.47 vs. 61.70 ± 14.38; p = 0.013). The systolic and diastolic blood pressure as well as the Glasgow coma scale score of the low group were significantly lower than that of the normal group (p = 0.004, 0.002 and 0.001, respectively). The intubation rate and APACHE (Acute Physiology and Chronic Health Evaluation) score of the low group was significantly higher than that of the normal group (p = 0.001). The platelets number and blood pH decreased, and the neutrophil/lymphocyte ratio, procalcitonin, lactate, urea, creatinine and lactate dehydrogenase concentrations increased significantly in the low group (p < 0.05). The mortality rate was 79.7% in the low group and 22.4% in the normal group (p < 0.001). Microbiological growth was observed in 68.6% of the normal group and 52.6% of the normal group (p = 0.025). The number of cultures with resistant bacteria was significantly higher in the low group (25.9%) than that in the normal group (17.5%) (p = 0.035). The severe COVID-19 patients hospitalized with vitamin D deficiency may have increased risks of poor prognosis and mortality due to secondary infections in the ICU.

An Appraisal to Address Health Consequences of Vitamin D Deficiency With Food Fortification and Supplements: Time to Act!

A symposium entitled "Vitamin D in Prevention and Therapy" was held on May 4-5, 2022, in Homburg, Germany to discuss important new advances in the field, including identification of new vitamin D signaling pathways, of new biologic effects of vitamin D-compounds (e.g., on the microbiome), and convincing proof of the relevance of vitamin D deficiency for the risk and outcome of many chronic diseases, including cancer, cardio-vascular, auto-immune, metabolic, and infectious diseases. Concerning the COVID-19-pandemic, an inverse association between 25(OH)D serum concentrations and SARS-CoV-2-infections, morbidity, and mortality was shown. In relation to cancer, several meta-analyses recently demonstrated an association of vitamin D-supplementation with significantly decreased mortality rates, which presumably would reduce health care costs. Considering the impressive body of evidence and the high safety of oral supplementation and food fortification with vitamin D, it was concluded that there is now an urgent need to act. In many countries worldwide, health care authorities need to increase efforts to address vitamin D deficiency, e.g., via food fortification and/or supplementation with vitamin D, and/or promoting moderate UV-exposure. It was estimated that in many countries, vitamin D intakes of the order of appr. 1,000 IE (25 µg)/day would be needed to bring and/or keep the vast majority of people over a serum 25(OH)D threshold of 20 ng/ml (50 nmol/l), which would be difficult to obtain alone from food fortification. New developments in personalized medicine may represent helpful tools to identify populations at risk for vitamin D deficiency and their responsiveness to vitamin D treatment.

Role of dietary supplement in viral infection with an outlook on corona virus disease-2019

For prevention and management of viral and bacterial infections, balanced nutrition which can help in maintaining immunity is essential. An outbreak of a novel coronavirus (COVID-19) infection in December 2019 in Wuhan, China has posed significant threats to international health and the economy. In the lack of treatment for this virus, there is an immediate need to find alternative methods to control the prevalence of the disease. In the present review, by using free search engines providing biomedical and clinical literature (Science Direct, PubMed, and Google Scholar) we have evaluated the possible benefits of some vitamins, trace elements and probiotics in viral infections. The immune response in various infections is very diverse. In conclusion, by examining the effect of micronutrients on the immune function, nutrition principles with vitamins, nutraceuticals and probiotics may be useful in possible prevention and management of viral infections and COVID-19. Copyright (C) 2021 Wolters Kluwer Health, Inc. All rights reserved.

The Association between Vitamin D and Zinc Status and the Progression of Clinical Symptoms among Outpatients Infected with SARS-CoV-2 and Potentially Non-Infected Participants: A Cross-Sectional Study.

Vitamin D and zinc are important components of nutritional immunity. This study compared the serum concentrations of 25-hydroxyvitamin D (25(OH)D) and zinc in COVID-19 outpatients with those of potentially non-infected participants. The association of clinical symptoms with vitamin D and zinc status was also examined. A checklist and laboratory examination were applied to collect data in a cross-sectional study conducted on 53 infected outpatients with COVID-19 and 53 potentially non-infected participants. Serum concentration of 25(OH)D were not significantly lower in patients with moderate illness (19 ± 12 ng/mL) than patients with asymptomatic or mild illness (29 ± 18 ng/mL), with a trend noted for a lower serum concentration of 25(OH)D in moderate than asymptomatic or mild illness patients (p = 0.054). Infected patients (101 ± 18 µg/dL) showed a lower serum concentration of zinc than potentially non-infected participants (114 ± 13 µg/dL) (p = 0.01). Patients with normal (odds ratio (OR), 0.19; p ≤ 0.001) and insufficient (OR, 0.3; p = 0.007) vitamin D status at the second to seventh days of disease had decreased OR of general symptoms compared to patients with vitamin D deficiency. This study revealed the importance of 25(OH)D measurement to predict the progression of general and pulmonary symptoms and showed that infected patients had significantly lower zinc concentrations than potentially non-infected participants.

Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach.

BACKGROUND: Vitamin D population status may have possible unappreciated consequences to the coronavirus disease 2019 (COVID-19) pandemic. Α significant association between vitamin D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease has recently been shown, while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Low serum 25-hydroxyvitamin-D [25(OH)D] was identified as an independent risk factor for COVID-19 infection and hospitalization, and administration of 0.532 mg (21280 IU) of calcifediol or 25(OH)D, followed by 0.266 mg on days 3 and 7 and then weekly until discharge or intensive care unit admission significantly reduced the need for intensive care unit treatment. AIM: To elucidate the role of vitamin D European population status in the COVID-19 pandemic, data from the Worldometer were analyzed. METHODS: Linear regression explored the correlation between published representative-standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19 for 26 European countries populated > 4 M (Worldometer). Life expectancy was analyzed with semi-parametric regression. Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status: Deficient < 50, insufficient: 50-62.5, mildly insufficient > 62.5-75 and sufficient > 75 nmol/L, while controlling for life expectancy for deaths/M. Statistical analyses were performed in XLSTAT LIFE SCIENCE and R (SemiPar Library). RESULTS: Linear regression found no correlation between population vitamin D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47%-64%-80% in serious-critical illnesses/M and of 61%-82%-102.4% in deaths/M further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L, sustained on August 15, 2020, indicating a truthful association. Weighted analysis of variance was performed to evaluate serious-critical/M (r 2 = 0.22) by the vitamin D population status and analysis of covariance the deaths/M (r 2 = 0.629) controlling for life expectancy (r 2 = 0.47). Serious-critical showed a decreasing trend (P < 0.001) from population status deficient (P < 0.001) to insufficient by 9.2% (P < 0.001), to mildly insufficient by 47.6% (P < 0.044) and to sufficient by 100% (reference, P < 0.001). For deaths/M the respective decreasing trend (P < 0.001) was 62.9% from deficient (P < 0.001) to insufficient (P < 0.001), 65.15% to mildly insufficient (P < 0.001) and 78.8% to sufficient (P = 0.041). CONCLUSION: Achieving serum 25(OH)D 100-150 nmol/L (40-60 ng/mL) (upper tolerable daily doses followed by maintenance proposed doses not requiring medical supervision, Endocrine Society) may protect from serious-critical illness/death from COVID-19 disease.

Low Vitamin D Status at Admission as a Risk Factor for Poor Survival in Hospitalized Patients With COVID-19: An Italian Retrospective Study.

OBJECTIVE: Preliminary findings suggest a relationship between lower serum 25-hydroxyvitamin D [25(OH)D] levels and incidence and severity of COVID-19. The aim of this study was to evaluate the relationship between vitamin D status at admission and different markers of inflammation, coagulation, and sepsis in hospitalized patients with COVID-19. METHOD: We conducted a retrospective study on 137 consecutive patients with SARS-CoV-2 infection and available data on serum 25(OH)D levels, who were admitted to our Institution between March 1 and April 30, 2020. Patients were divided into two groups: survivors (n = 78; 57%) and non-survivors (n = 59; 43%). RESULTS: At admission, all patients showed hypovitaminosis D. Median total serum 25(OH)D levels at admission were significantly higher in survivors than non-survivors (12 ng/mL vs 8 ng/mL; p < 0.01). Non-survivors exhibited significantly higher median levels of white blood cell (WBC) count, neutrophil-to-lymphocyte count ratio (NLR), high-sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6), D-dimer, fibrinogen, and procalcitonin (PCT) compared to survivors at three different time points during hospitalization. In a multivariate analysis performed by a logistic regression model, serum 25(OH)D levels were significantly inversely associated with risk of COVID-19-related in-hospital mortality (odds ratio, 0.91; 95% confidence interval, 0.85-0.98; p = 0.01). According to receiver operating characteristic curve analysis, hsCRP, NLR, ferritin, and D-dimer were the best predictive biomarkers for poor prognosis of COVID-19, whereas IL-6, PCT, fibrinogen, 25(OH)D, WBC count, and tumor necrosis factor alpha (TNF-α) may serve as supportive biomarkers for worse clinical course of the disease. CONCLUSIONS: We found a markedly high prevalence (100%) of hypovitaminosis D in patients admitted to hospital with COVID-19, suggesting a possible role of low vitamin D status in increasing the risk of SARS-CoV-2 infection and subsequent hospitalization. The inverse association between serum 25(OH)D levels and risk of in-hospital mortality observed in our cohort suggests that a lower vitamin D status upon admission may represent a modifiable and independent risk factor for poor prognosis in COVID-19.

Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis.

BACKGROUND: Observational studies suggest that the risk and clinical prognosis of coronavirus disease 2019 (COVID-19) are related to low vitamin D status; however, the data are inconsistent. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the association between low vitamin D status and COVID-19. METHODS: A systematic search was conducted with PubMed, Embase, and the Cochrane Library from database inception to September 25, 2020. The standardized mean difference (SMD) or odds ratio (OR) and corresponding 95% confidence interval (CI) was applied to estimate pooled results. Random - or fixed-effect models based on heterogeneity were used for the meta-analysis. Funnel plots and Egger regression tests were used to assess publication bias. RESULTS: A total of ten articles with 361,934 participants were selected for meta-analysis. Overall, the pooled OR in the fixed-effect model showed that vitamin D deficiency or insufficiency was associated with an increased risk of COVID-19 (OR = 1.43, 95% CI 1.00-2.05). In addition, COVID-19-positive individuals had lower vitamin D levels than COVID-19-negative individuals (SMD = -0.37, 95% CI = -0.52 to -0.21). Significant heterogeneity existed in both endpoints. Funnel plots and Egger regression tests revealed significant publication bias. CONCLUSIONS: This systematic review and meta-analysis indicated that low vitamin D status might be associated with an increased risk of COVID-19 infection. Further studies are needed to evaluate the impact of vitamin D supplementation on the clinical severity and prognosis in patients with COVID-19. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no: CRD42020216740.