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

Abstract

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.

Vitamin D deficiency 2.0: an update on the current status worldwide

“…Similarly, critically ill patients have a very high prevalence of vitamin D deficiency, and low vitamin D levels are clearly associated with greater illness severity, morbidity, and mortality in both adult and pediatric intensive care unit (ICU) patients, as well as medical and surgical ICUs [23]. However, as in most other populations, the most important question remains unanswered: whether low vitamin D is an innocent bystander, simply reflecting greater disease severity, or represents an independent and modifiable risk factor amenable to rapid normalization through loading dose supplementation [24,25].…”

Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes

“…Several large studies and meta-analyses have found that vitamin D deficiency is associated with greater illness severity, morbidity and mortality in both critically ill adult and geriatric patients, but there is a lack of clinical data demonstrating the efficacy of normalising levels as an effective therapy and trials are being designed to this end [53].…”

Prevalence of Vitamin D Deficiency among Adult Patients in A Tertiary Care Hospital

“…5 Early finding of vitamin D deficiency and supplement can decrease the risk of many diseases and mortality rate. 6 Free Full Text Articles are Available at www.jnma.com.np Level of vitamin D is tested by quantitative method, chemiluminescent immunoassay (CLIA) methods. Blood sample (5 mL) was taken in gel tube for each subject and serum was separated by centrifuge to estimate vitamin D [25(OH)D].…”