Vitamin D as a modifiable risk factor in critical illness: questions and answers provided by observational studies

McNally, James Dayre

doi:10.1016/j.jped.2013.12.002

Cited by 14 publications

(11 citation statements)

References 19 publications

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“…It is clear that the daily recommended low-dose administration of vitamin D (400 to 4000 IU daily) cannot rapidly restore 25 hydroxyvitamin D (25(OH)D) levels in acutely ill patients [14]. Several studies have adopted higher bolus dose supplementation (single loading dose from 50,000 to 600,000 IU) to rapidly restore vitamin D levels [15–19].…”

Section: Introductionmentioning

confidence: 99%

Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths

et al. 2019

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Background Vitamin D supplementation has shown promise for reducing mortality in the intensive care setting. As a steroid prohormone with pleiotropic effects, there may be a lag between administration and observing clinical benefit. This secondary analysis of the VITdAL-ICU study sought to explore whether the effect size of vitamin D on mortality was different when study participants who died or were discharged early were excluded. Methods The VITdAL-ICU study was a randomized, placebo-controlled trial in critically ill adults who received placebo or 540,000 IU cholecalciferol followed by monthly supplementation. The effect of vitamin D on 28-day mortality was evaluated after exclusion of participants who died or were discharged within 7 days from study drug administration, according to vitamin D concentrations on day 3, using a bivariate analysis adjusted for confounders and in a stepwise multiple analysis. Results Of 475 study participants, 65 died or were discharged within the first 7 days. In the remaining 410 patients, vitamin D supplementation was associated with a reduction in 28-day mortality [OR 0.58 (95% CI 0.35–0.97) p value = 0.035]. The effect on mortality was not significant after adjusting for age, severity scores, female gender, chronic liver and kidney disease, COPD, diagnosis of the tumor, mechanical ventilation, and vasopressors at enrollment (all p > 0.05). In a multiple model, the mortality reduction by vitamin D supplementation did not remain independently significant [OR 0.61 (95% CI 0.35–1.05) p = 0.075]. Vitamin D metabolite response, in the treatment group, demonstrated that survivors at 28 days, had higher levels of 25-hydroxyvitamin D (34.4 vs 25.4 ng/ml, p = 0.010) and 1,25-dihydroxyvitamin D (107.6 vs 70.3 pg/ml, p = 0.049) on day 3. The increase of plasma metabolites after vitamin D oral supplementation, independent of the baseline value, was associated with lower odds of death [OR 0.48 (95% CI 0.27–0.87) p value = 0.016]. Conclusions High-dose vitamin D3 supplementation was associated with a reduction of 28-day mortality in a mixed population of critically ill adults with vitamin D deficiency when excluding patients who died or were discharged within 7 days after study inclusion. However, this survival benefit was not independently confirmed when adjusted for other factors strongly associated with mortality. Electronic supplementary material The online version of this article (10.1186/s13054-019-2472-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths

et al. 2019

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“…However, clinical recommendations concerning the optimal dose and frequency of administration of vitamin D supplements to achieve and maintain sufficient vitamin D levels are lacking. To date, many vitamin D intervention trials have been performed, and it has been suggested that the daily administration of low-dose vitamin D (400 to 1000 IU/d) does not increase the circulating 25(OH)D3 levels in a beneficial time frame [5] . A high-dose vitamin D intervention (50 000 to 600 000 IU) has been recommended as a more effective and safe method to increase blood 25(OH)D3 levels [5] .…”

Section: Introductionmentioning

confidence: 99%

“…To date, many vitamin D intervention trials have been performed, and it has been suggested that the daily administration of low-dose vitamin D (400 to 1000 IU/d) does not increase the circulating 25(OH)D3 levels in a beneficial time frame [5] . A high-dose vitamin D intervention (50 000 to 600 000 IU) has been recommended as a more effective and safe method to increase blood 25(OH)D3 levels [5] . A doubleblind, placebo-controlled trial has found that a dose of 250 000 IU of vitamin D3 leads to a significant increase in plasma 25(OH)D3 levels but has no significant effect on the plasma levels of calcium and PTH [6] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3

Chen

Duan

et al. 2016

Acta Pharmacol Sin

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Aim: To examine the biological consequences and demographic factors that might affect the pharmacokinetics of vitamin D3 after a single high dose intervention in a young Chinese population with vitamin D insufficiency status. Methods: A total of 28 young subjects (25 to 35 years old) with vitamin D insufficiency status [serum 25(OH)D <30 ng/mL] was recruited in Shanghai, China. The subjects were orally administered a single high dose of vitamin D3 (300 000 IU). Baseline characteristics and blood samples were collected at d 0, 1, 2, 3, 7, 28, 56, 84 and 112 after the intervention. The blood biomarker levels were determined with standardized methods. Results: The intervention markedly increased the blood 25(OH)D3 levels within the first five days (mean T max =5.1±2.1 d) and sustained an optimal circulating level of 25(OH)D3 (≥30 ng/mL) for 56 d. After the intervention, body weight and baseline 25(OH)D3 levels were significantly correlated with circulating 25(OH)D3 levels. No adverse events and no consistently significant changes in serum calcium, creatinine, glucose, parathyroid hormone, vitamin D binding protein, or the urinary calcium/creatinine ratio were observed. However, there was a significant increase in phosphorus after the vitamin D3 intervention. Total cholesterol and triglyceride levels were decreased at the end of the trial. Conclusion: The pharmacokinetics of vitamin D after intervention were influenced by baseline 25(OH)D3 levels and the body weight of the subjects. The results suggest that a single high oral vitamin D3 intervention is safe and efficient for improving the vitamin D status of young Chinese people with vitamin D insufficiency.

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“…However, observational studies, meta-analyses and RCTs suggest the presence of a U-shaped relationship between glutamine levels and outcome, as both glutamine deficiency and excess levels are associated with worse outcomes. [18,38,39] Therefore, it is pertinent to determine the influence of vitamin D on glutamine metabolism and ultimately serum glutamine levels, as this would further assist in clarifying any potential role of glutamine in critically ill patients. Despite the lack of an association between glutamine and vitamin D levels in this cohort of ICU patients, further studies are needed to clarify this potential interaction.…”

Section: Researchmentioning

confidence: 99%

Vitamin D levels in patients admitted to the intensive care unit and the association with organ dysfunction and glutamine levels

Seedat

Schleicher

Gaylard³

et al. 2020

S Afr Med J

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The prohormone vitamin D is best known for its key role in the metabolism of calcium and phosphate. [1] In critically ill patients, the potential to influence outcome through its pleiotropic effects on bone, muscle, cardiac and immunological function (where it is stimulatory to the innate but immunomodulatory to the adaptive immune system) has created interest in the use of vitamin D in the intensive care unit (ICU) among intensivists. [2,3] Vitamin D deficiency is highly prevalent in ICU patients, with a prevalence of 50-82%, and is associated with increased inflammatory markers, multi-organ dysfunction, immune dysregulation and poorer outcomes. [1,2,4-7] Elevated inflammatory markers, particularly C-reactive protein (CRP) and procalcitonin (PCT), occur with vitamin D deficiency. [8] A Brazilian cohort of critically ill patients with 25-hydroxyvitamin D (25(OH)D) levels <12 ng/mL had increased organ system dysfunction and a greater change in sequential organ failure assessment (SOFA) score. [9,10] Furthermore, observational studies have shown an independent association between vitamin D deficiency and mortality. [9,10] In meta-analyses examining vitamin D deficiency among critically ill patients, increased rates of infection, sepsis and mortality have been noted. [5,7] Randomised controlled trials (RCTs) that have investigated vita min D supplementation in deficient critically ill patients have shown little benefit. The VITdAL-ICU (Effect of High-Dose Vitamin D 3 on Hospital Length of Stay in Critically Ill Patients with Vitamin D Deficiency) RCT that assessed outcomes of critically ill vita min D-deficient patients following vitamin D supplementation did not demonstrate improvement in length of hospital stay, hospital mortality or 6-month mortality, except in severely vitamin D-deficient patients (25(OH)D <12 ng/mL), where mortality was reduced (hazard ratio (HR) 0.56 (95% confidence interval (CI) 0.35-0.90)). [11] Moreover, in patients supplemented with vitamin D, median inflammatory marker levels were reduced on day 28 compared with placebo (CRP 51 v. 32 mg/L (p=0.04); PCT 0.2 v. 0.1 ng/mL (p=0.05)). [11] In contrast, no improved 90-day mortality outcome was noted in the recent VIOLET (Early High-Dose Vitamin D 3 for Critically Ill, Vitamin D-Deficient Patients) double-blind, placebo-controlled RCT of early vitamin D 3 supplementation with a single enteral dose of 540 000 IU vitamin D 3 compared with placebo in vitamin D-deficient (25(OH)D <20 ng/mL) critically ill patients. [12] Recent data have illustrated that vitamin D deficiency (25(OH)D <15 ng/mL) during early critical illness is crucial in the regulation of glutathione and glutamate pathways. Both pathways influence glutamine metabolism and ultimately serum glutamine levels. [13] There is no consensus with regard to the data examining glutamine supplementation in critically ill patients. Some studies have shown reduced infection rates, ICU and hospital stay, and mortality This open-access article is distributed under Creative Commons licence CC-BY-NC 4...

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Vitamin D as a modifiable risk factor in critical illness: questions and answers provided by observational studies

Cited by 14 publications

References 19 publications

Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths

Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths

Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3

Vitamin D levels in patients admitted to the intensive care unit and the association with organ dysfunction and glutamine levels

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