Special Issue "COVID-19 and Other Pleiotropic Actions of Vitamin D: Proceedings from the 5th International Conference “Vitamin D—minimum, maximum, optimum”"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (1 June 2022) | Viewed by 29334

Special Issue Editor

Dr. Pawel Pludowski
E-Mail Website
Guest Editor
Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children's Memorial Health Institute, 04-730 Warsaw, Poland
Interests: disturbances of calcium-phosphate metabolism; disturbances of bone tissue metabolism; body composition and biological development; basics of statistics; GLP; research methodology
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Special Issue Information

Dear Colleagues,

It is a great pleasure and a special privilege to welcome you to this Special Issue of Nutrients related to the 5th International Conference “Vitamin D—Minimum, Maximum, Optimum”, under the auspices of the European Vitamin D Association (EVIDAS).

The conference and the forthcoming papers serve as an international forum for the presentation and discussion of current basic and clinical research in the field of vitamin D. Organizing this subsequent Special Issue of Nutrients on vitamin D is a real challenge, given that the vitamin has recently been shown by prestigious medical journals as an epiphenomenon that coincides with diseases and that the correction of vitamin D deficits has limited clinical meaning. On the other hand, it is recognized that vitamin D deficiency is a global health problem with potential negative consequences on health, welfare, and morbidity during growth and adulthood, therefore influencing health care services worldwide. Thus, due to mutually exclusive conclusions, it is essential to discuss vividly, and share scientific reports and evidence demonstrating both the benefits and lack thereof in relation to human health. COVID-19 emerged over the last and current year; therefore, COVID-19 and vitamin D are the major issues that will be presented and discussed in this Special Issue.

Dr. Pawel Pludowski
Guest Editor

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Keywords

  • cholecalciferol
  • calcifediol
  • pleiotropic action of vitamin D
  • COVID-19

Published Papers (11 papers)

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Research

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Article
Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study
Nutrients 2022, 14(13), 2602; https://doi.org/10.3390/nu14132602 - 23 Jun 2022
Viewed by 1891
Abstract
Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with [...] Read more.
Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = −0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19. Full article
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Article
Serum 25-hydroxyvitamin D Concentration Significantly Decreases in Patients with COVID-19 Pneumonia during the First 48 Hours after Hospital Admission
Nutrients 2022, 14(12), 2362; https://doi.org/10.3390/nu14122362 - 07 Jun 2022
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Abstract
It is unclear how ongoing inflammation in Coronavirus Disease 2019 (COVID-19) affects 25-hydroxyvitamin D (25[OH]D) concentration. The objective of our study was to examine serum 25(OH)D levels during COVID-19 pneumonia. Patients were admitted between 1 November and 31 December 2021. Blood samples were [...] Read more.
It is unclear how ongoing inflammation in Coronavirus Disease 2019 (COVID-19) affects 25-hydroxyvitamin D (25[OH]D) concentration. The objective of our study was to examine serum 25(OH)D levels during COVID-19 pneumonia. Patients were admitted between 1 November and 31 December 2021. Blood samples were taken on admission (day 0) and every 24 h for the subsequent four days (day 1–4). On admission, 59% of patients were 25(OH)D sufficient (>30 ng/mL), and 41% had 25(OH)D inadequacy (<30 ng/mL). A significant fall in mean 25(OH)D concentration from admission to day 2 (first 48 h) was observed (30.7 ng/mL vs. 26.4 ng/mL; p < 0.0001). No subsequent significant change in 25(OH)D concentration was observed between day 2 and 3 (26.4 ng/mL vs. 25.9 ng/mL; p = 0.230) and day 3 and day 4 (25.8 ng/mL vs. 25.9 ng/mL; p = 0.703). The absolute 25(OH)D change between hospital admission and day 4 was 16% (4.8 ng/mL; p < 0.0001). On day 4, the number of patients with 25(OH)D inadequacy increased by 18% (p = 0.018). Therefore, serum 25(OH)D concentration after hospital admission in acutely ill COVID-19 patients should be interpreted with caution. Whether low 25(OH)D in COVID-19 reflects tissue level vitamin D deficiency or represents only a laboratory phenomenon remains to be elucidated in further prospective trials of vitamin D supplementation. Full article
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Article
Prevalence of Vitamin D Deficiency in Patients Treated for Juvenile Idiopathic Arthritis and Potential Role of Methotrexate: A Preliminary Study
Nutrients 2022, 14(8), 1645; https://doi.org/10.3390/nu14081645 - 14 Apr 2022
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Abstract
Background: Vitamin D deficiency is reported in rheumatological diseases in adults. The aim was to evaluate the prevalence of vitamin D deficiency in children with juvenile idiopathic arthritis (JIA) and to investigate potential correlations between vitamin D status and clinical factors, laboratory traits, [...] Read more.
Background: Vitamin D deficiency is reported in rheumatological diseases in adults. The aim was to evaluate the prevalence of vitamin D deficiency in children with juvenile idiopathic arthritis (JIA) and to investigate potential correlations between vitamin D status and clinical factors, laboratory traits, and medical treatment, including methotrexate (MTX) and glucocorticoids (GCs). Methods: In 189 patients aged 3–17.7 years, with JIA in the stable stage of the disease, anthropometry, clinical status, serum 25-hydroxyvitamin D [25(OH)D], calcium (Ca), phosphate (PO4), total alkaline phosphatase (ALP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. Results: Median 25(OH)D level was 15.00 ng/mL, interquartile range (IQR) 12.00 ng/mL. Vitamin D deficiency was found in 67.2% and was independent of sex, disease manifestation, and CRP, ESR, ALP, or PO4 levels. Higher doses of MTX corresponded with lower 25(OH)D levels using both univariate and multivariate models (p < 0.05). No such trend was found for GCs treatment. Serum Ca was lower in patients treated with GCs (p = 0.004), MTX (p = 0.03), and combined GCs/MTX (p = 0.034). Conclusions: JIA patients are vitamin D depleted independently of disease activity or inflammatory markers. MTX therapy may be an iatrogenic factor leading to inadequate 25(OH)D levels. Vitamin D supplementation should be considered in all children with JIA, particularly those receiving long-term MTX therapy. Full article
Article
Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial
Nutrients 2022, 14(7), 1360; https://doi.org/10.3390/nu14071360 - 24 Mar 2022
Cited by 2 | Viewed by 904
Abstract
Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis [...] Read more.
Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency. Full article
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Article
Vitamin D Deficiency and Its Associated Factors among Female Migrants in the United Arab Emirates
Nutrients 2022, 14(5), 1074; https://doi.org/10.3390/nu14051074 - 03 Mar 2022
Cited by 1 | Viewed by 1220
Abstract
Vitamin D is important for bone health, and vitamin D deficiency could be linked to noncommunicable diseases, including cardiovascular disease. The purpose of this study was to determine the prevalence of vitamin D deficiency and its associated risk factors among female migrants from [...] Read more.
Vitamin D is important for bone health, and vitamin D deficiency could be linked to noncommunicable diseases, including cardiovascular disease. The purpose of this study was to determine the prevalence of vitamin D deficiency and its associated risk factors among female migrants from Philippines, Arab, and South Asian countries residing in the United Arab Emirates (UAE). We used a cross-sectional study to recruit a random sample (N = 550) of female migrants aged 18 years and over in the city of Al Ain, UAE. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentrations ≤20 ng/mL (50 nmol/L). We used multivariable logistic regression analysis to identify risk factors associated with vitamin D deficiency. The mean age of participants was 35 years (SD ± 10). The overall prevalence rate of vitamin D deficiency was 67% (95% CI 60–73%), with the highest rate seen in Arabs (87%), followed by South Asians (83%) and the lowest in Filipinas (15%). Multivariate analyses showed that low physical activity (adjusted odds ratio (aOR) = 4.59; 95% CI 1.98, 10.63), having more than 5 years duration of residence in the UAE (aOR = 4.65; 95% CI: 1.31, 16.53) and being obese (aOR = 3.56; 95% CI 1.04, 12.20) were independently associated with vitamin D deficiency, after controlling for age and nationality. In summary, vitamin D deficiency was highly prevalent among female migrants, especially Arabs and South Asians. It is crucial that health professionals in the UAE become aware of this situation among this vulnerable subpopulation and provide intervention strategies aiming to rectify vitamin D deficiency by focusing more on sun exposure, physical activity, and supplementation. Full article
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Review

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Review
Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature
Nutrients 2022, 14(12), 2518; https://doi.org/10.3390/nu14122518 - 17 Jun 2022
Viewed by 639
Abstract
Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by [...] Read more.
Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy. Full article
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Review
Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement
Nutrients 2022, 14(7), 1483; https://doi.org/10.3390/nu14071483 - 02 Apr 2022
Cited by 7 | Viewed by 1911
Abstract
Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address [...] Read more.
Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L). Full article
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Review
A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health
Nutrients 2022, 14(3), 639; https://doi.org/10.3390/nu14030639 - 02 Feb 2022
Cited by 11 | Viewed by 9519
Abstract
Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world’s population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative [...] Read more.
Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world’s population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered the strongest form of evidence for pharmaceutical drugs, the study designs and the conduct of RCTs performed for vitamin D have mostly been flawed for the following reasons: they have been based on vitamin D dose rather than on baseline and achieved 25(OH)D concentrations; they have involved participants with 25(OH)D concentrations above the population mean; they have given low vitamin D doses; and they have permitted other sources of vitamin D. Thus, the strongest evidence generally comes from the other types of studies. The general finding is that optimal 25(OH)D concentrations to support health and wellbeing are above 30 ng/mL (75 nmol/L) for cardiovascular disease and all-cause mortality rate, whereas the thresholds for several other outcomes appear to range up to 40 or 50 ng/mL. The most efficient way to achieve these concentrations is through vitamin D supplementation. Although additional studies are warranted, raising serum 25(OH)D concentrations to optimal concentrations will result in a significant reduction in preventable illness and death. Full article
Review
Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19
Nutrients 2022, 14(3), 464; https://doi.org/10.3390/nu14030464 - 21 Jan 2022
Cited by 2 | Viewed by 1901
Abstract
Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious [...] Read more.
Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium. Full article
Review
Critical Appraisal of Large Vitamin D Randomized Controlled Trials
Nutrients 2022, 14(2), 303; https://doi.org/10.3390/nu14020303 - 12 Jan 2022
Cited by 11 | Viewed by 1990
Abstract
As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few [...] Read more.
As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches. Full article
Review
Vitamin D Dosing: Basic Principles and a Brief Algorithm (2021 Update)
Nutrients 2021, 13(12), 4415; https://doi.org/10.3390/nu13124415 - 10 Dec 2021
Cited by 4 | Viewed by 6115
Abstract
Nowadays, in modern societies, many people can be at high risk to have low vitamin D levels. Therefore, testing of serum 25-hydroxy-vitamin D (25OH-D) levels should be performed before prescribing them vitamin D supplementation. However, in some cases the 25OH-D level assessment is [...] Read more.
Nowadays, in modern societies, many people can be at high risk to have low vitamin D levels. Therefore, testing of serum 25-hydroxy-vitamin D (25OH-D) levels should be performed before prescribing them vitamin D supplementation. However, in some cases the 25OH-D level assessment is not available at the right moment, e.g., due to mandatory quarantine of COVID-19 outpatients. Therefore, such patients could be advised to start taking moderate vitamin D doses (e.g., 4000 IU/day for adults), and their 25-OH-D levels could be checked later. The proposed algorithm also comprises vitamin D dosing principles when baseline 25OH-D levels are known. Full article
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