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Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.
Murai, IH, Fernandes, AL, Sales, LP, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, Macedo, MB, Dalmolin, HHH, et al
JAMA. 2021;(11):1053-1060
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Abstract
IMPORTANCE The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. INTERVENTIONS Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURES The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. RESULTS Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. CONCLUSIONS AND RELEVANCE Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04449718.
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Vitamin D supplementation and improvement of pneumonic children at a tertiary pediatric hospital in Egypt: A randomized controlled trial.
Labib, JR, Ibrahem, SK, Ismail, MM, Fatah, SAMAE, Sedrak, AS, Attia, MAS, El-Hanafi, HM, Kamel, MH
Medicine. 2021;(13):e25011
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BACKGROUND Despite the well-recognized effect of vitamin D in metabolism and homeostasis, there is now growing interest in its probable association with pneumonia. This study aims to supply vitamin D3 (Cholecalciferol) (100,000 IU) to pneumonic children to minimize the duration of illness and improve their outcome. METHODS A double-blinded, randomized, placebo-controlled trial was conducted in a Pediatric Cairo University affiliated hospital. An intervention arm (93 children) and a control arm (98 children), who had pneumonia with an insufficient or deficient level of vitamin D and whose parental permission was obtained, were enrolled in the trial. All children were treated with antibiotics according to WHO guidelines. Children were given a single injection of 1 mL of 100,000 IU of vitamin D3 or placebo. Clinical data were recorded every eight hours for all children. Outcomes were assessed 7 days after vitamin D injection.The primary outcome variable was the change in serum level of 25(OH)D, while the secondary outcomes were the medical state of the assigned cases (improvement or death) and duration between enrollment and hospital discharge for improved cases. RESULTS In the supplementation group, the percentage of patients who suffered either deficient (38.7%) or insufficient levels (61.3%) of 25 (OH)D at day one had significantly decreased in the seventh day to (11.8%) and (52.7%), respectively. Kaplan--Meier plots highlighted that the median time to recover of the placebo group was significantly longer than that of the supplementation group (Log Rank P value < .001). CONCLUSION VDD was detected in pediatric critical care children. In pneumonic children with high VDD, it is illustrated that Vitamin D supplementation is accompanied by lowered mortality risk and pSOFA scores, reduced time to recover, and improved PaO2/FiO2. TRIAL REGISTRATION Trial Identifier number: NCT04244474. Registered on 27 January 2020- Retrospectively registered at ClinicalTrials.gov https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009JXO&selectaction=Edit&uid=U0004UO8&ts=152&cx=9cceq6.
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Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.
Han, JH, Ginde, AA, Brown, SM, Baughman, A, Collar, EM, Ely, EW, Gong, MN, Hope, AA, Hou, PC, Hough, CL, et al
Chest. 2021;(3):909-918
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BACKGROUND Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.
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Phosphate Concentrations and Modifying Factors in Healthy Children From 12 to 24 Months of Age.
Koljonen, L, Enlund-Cerullo, M, Hauta-Alus, H, Holmlund-Suila, E, Valkama, S, Rosendahl, J, Andersson, S, Pekkinen, M, Mäkitie, O
The Journal of clinical endocrinology and metabolism. 2021;(10):2865-2875
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CONTEXT Phosphate homeostasis and its modifiers in early childhood are inadequately characterized. OBJECTIVE To determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age. DESIGN This study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age 2 weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months. MAIN OUTCOME MEASURES Plasma phosphate concentrations at 12 and 24 months of age. RESULTS Mean (SD) phosphate concentration decreased from 12 months (1.9 ± 0.15 mmol/L) to 24 months (1.6 ± 0.17 mmol/L) of age (P < 0.001 for repeated measurements). When adjusted by covariates, such as body size, creatinine, serum 25-hydroxyvitamin D, intact and C-terminal fibroblast growth factor 23, mean plasma phosphate was higher in boys than girls during follow-up (P = 0.019). Phosphate concentrations were similar in the vitamin D intervention groups (P > 0.472 for all). Plasma iron was associated positively with plasma phosphate at both time points (B, 0.006 and 0.005; 95% CI, 0.004-0.009 and 0.002-0.008; P < 0.001 at both time points, respectively). At 24 months of age, the main modifier of phosphate concentration was plasma creatinine (B, 0.007; 95% CI 0.003-0.011, P < 0.001). CONCLUSION Plasma phosphate concentration decreased from age 12 to 24 months. In infants and toddlers, the strongest plasma phosphate modifiers were sex, iron, and creatinine, whereas vitamin D supplementation did not modify phosphate concentrations.
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Effects of Combined Vitamin K2 and Vitamin D3 Supplementation on Na[18F]F PET/MRI in Patients with Carotid Artery Disease: The INTRICATE Rationale and Trial Design.
Florea, A, Kooi, ME, Mess, W, Schurgers, LJ, Bucerius, J, Mottaghy, FM
Nutrients. 2021;(3)
Abstract
INTRICATE is a prospective double-blind placebo-controlled feasibility study, assessing the influence of combined vitamin K2 and vitamin D3 supplementation on micro-calcification in carotid artery disease as imaged by hybrid Sodium [18F]Fluoride (Na[18F]F) positron emission tomography (PET)/ magnetic resonance imaging (MRI). Arterial calcification is an actively regulated process and results from the imbalance between calcification promoting and inhibiting factors. Considering the recent advancements in medical imaging, ultrasound (US), PET/MRI, and computed tomography (CT) can be used for the selection and stratification of patients with atherosclerosis. Fifty-two subjects with asymptomatic carotid artery disease on at least one side of the neck will be included in the study. At baseline, an Na[18F]F PET/MRI and CT examination will be performed. Afterwards, subjects will be randomized (1:1) to a vitamin K (400 µg MK-7/day) and vitamin D3 (80 µg/day) or to placebo. At the 3-month follow-up, subjects will undergo a second Na[18F]F PET/MRI and CT scan. The primary endpoint is the change in Na[18F]F PET/MRI (baseline vs. after 3 months) in the treatment group as compared to the placebo arm. Secondary endpoints are changes in plaque composition and in blood-biomarkers. The INTRICATE trial bears the potential to open novel avenues for future large scale randomized controlled trials to intervene in the plaque development and micro-calcification progression.
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Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited.
Brenner, H, Kuznia, S, Laetsch, C, Niedermaier, T, Schöttker, B
Nutrients. 2021;(5)
Abstract
Meta-analyses of randomized controlled trials (RCTs) have demonstrated a protective effect of vitamin D3 (cholecalciferol) supplementation against cancer mortality. In the VITAL study, a RCT including 25,871 men ≥ 50 years and women ≥ 55 years, protective effects of vitamin D3 supplementation (2000 IU/day over a median of 5.3 years) with respect to incidence of any cancer and of advanced cancer (metastatic cancer or cancer death) were seen for normal-weight participants but not for overweight or obese participants. We aimed to explore potential reasons for this apparent variation of vitamin D effects by body mass index. We conducted complementary analyses of published data from the VITAL study on the association of body weight with cancer outcomes, stratified by vitamin D3 supplementation. Significantly increased risks of any cancer and of advanced cancer were seen among normal-weight participants compared to obese participants in the control group (relative risk (RR), 1.27; 95% confidence interval (CI), 1.07-1.52, and RR, 1.44; 95% CI, 1.04-1.97, respectively). No such patterns were seen in the intervention group. Among those with incident cancer, vitamin D3 supplementation was associated with a significantly reduced risk of advanced cancer (RR, 0.86; 95% CI, 0.74-0.99). The observed patterns point to pre-diagnostic weight loss of cancer patients and preventive effects of vitamin D3 supplementation from cancer progression as plausible explanations for the body mass index (BMI)-intervention interactions. Further research, including RCTs more comprehensively exploring the potential of adjuvant vitamin D therapy for cancer patients, should be pursued with priority.
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Effectiveness of eight-week zinc supplementation on vitamin D3 status and leptin levels in a population of postmenopausal women: a double-blind randomized trial.
Vázquez-Lorente, H, Molina-López, J, Herrera-Quintana, L, Gamarra-Morales, Y, López-González, B, Planells, E
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2021;:126730
Abstract
BACKGROUND The menopausal period is characterized by hormonal imbalance related to the alteration of parameters involved in lipid metabolism. In addition, menopause increases the risk of deficiencies of key vitamins and minerals such as vitamin D and zinc in such women. The present study investigates the influence of zinc supplementation on the status of vitamin D3 and other lipid parameters in postmenopausal women. METHODS Fifty-one healthy postmenopausal women aged 44-76 years from the province of Granada (Spain) were divided into two groups (placebo and zinc) of 25 and 26 women, respectively. The zinc group was supplemented with 50 mg/day of zinc for 8 weeks. Nutrient intake assessment was performed by means of a 24 -h reminder. Zinc was determined by flame atomic absorption spectrophotometry. Vitamin D was analyzed by liquid chromatography - tandem mass spectrometry. Leptin was determined by enzyme immunoassay. RESULTS Zinc supplementation improved the initial vitamin D3 status of the postmenopausal population (p = 0.049). Plasma levels of 25-OH-D3 increased significantly after Zn supplementation in women with lower age at menopause (p = 0.045). Both intake and plasma zinc levels were inversely correlated to serum leptin levels (p = 0.044 and p = 0.033, respectively), being significantly lower in lower age at menopause (p < 0.001). CONCLUSION Zinc supplementation improved vitamin D3 status and was associated to low leptin levels in the postmenopausal women of the study.
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Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection during Military Training.
Harrison, SE, Oliver, SJ, Kashi, DS, Carswell, AT, Edwards, JP, Wentz, LM, Roberts, R, Tang, JCY, Izard, RM, Jackson, S, et al
Medicine and science in sports and exercise. 2021;(7):1505-1516
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PURPOSE This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2). METHODS In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d-1 for 4 wk and then 400 IU·d-1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography-mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay. RESULTS In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D-sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L-1 (OR = 0.6, 95% confidence interval = 0.4-0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin. CONCLUSION Vitamin D sufficiency reduced the URTI burden during military training.
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Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?
Ames, BN, Grant, WB, Willett, WC
Nutrients. 2021;(2)
Abstract
African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.
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COVID-19 in age-related neurodegenerative diseases: is there a role for vitamin D3 as a possible therapeutic strategy?
de Barros Viana, M, Rosário, BDA, de Fátima Santana de Nazaré, M, Estadella, D, Ribeiro, DA, Socorro de Barros Viana, G
Reviews in the neurosciences. 2021;(2):235-247
Abstract
The coronavirus disease (COVID-19), identified in Wuhan, China, on December 2019, was declared a pandemic by the World Health Organization, on March, 2020. Since then, efforts have been gathered to describe its clinical course and to determine preventive measures and treatment strategies. Adults older than 65 years of age are more susceptible to serious clinical symptoms and present higher mortality rates. Angiotensin-converting enzyme 2 (ACE2) is a major receptor for some coronavirus infection, including SARS-COV-2, but is also a crucial determinant in anti-inflammation processes during the renin-angiotensin system (RAS) functioning - converting angiotensin II to angiotensin 1-7. The decline in ACE2 expression that occurs with aging has been associated to the higher morbidity and mortality rates in older adults. These observations highlight the importance of investigating the association between COVID-19 and age-related neurodegenerative disorders, i.e., Parkinson's and Alzheimer's diseases. A possible option to reduce the risk of COVID-19 is vitamin D supplementation, due to its anti-inflammatory and immune-system-modulating effects. It has also been suggested that vitamin D supplementation plays a role in slowing progression of Parkinson and Alzheimer. The present study is a literature review of articles published on the theme COVID-19, Parkinson and Alzheimer's diseases, and the role played by vitamin D. PUBMED, MEDLINE, and EMBASE databases were consulted. Results confirm neurodegenerative and neuroinflammatory effects of COVID-19, aggravated in Parkinson's and Alzheimer's patients, and the important role of vitamin D as a possible therapeutic strategy. Nevertheless, randomized controlled trials and large population studies are still warranted.