Effect of Intravenous 25OHD Supplementation on Bone Turnover and Inflammation in Prolonged Critically Ill Patients

Abstract

Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 μg 25OHD followed by daily infusion of 15 μg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 –16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness.

Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19

“…However, no preventive effect of vitamin D supplementation on pneumonia was observed in three independent case-control studies [99], but the interpretation of these results should take into account the apparent lack of pre-existing vitamin D deficiency. Furthermore, the benefit of vitamin D replacement in an advanced stage of critical illness is controversial, as some studies do not show a benefit when it is administered late in the critical disease [100].…”

The Effect of Vitamin D Supplementation on Clinical Outcomes for Critically Ill Patients: A Systemic Review and Meta-Analysis of Randomized Clinical Trials

“…The sample size ranged from 25 to 1,078, including 10 small sample studies (number of included patients <100) ( 17 – 19 , 24 – 27 , 29 – 32 ). The analyzed population included patients with various disorders, including medical patients ( 21 , 30 , 32 ), neurological or surgical patients ( 18 , 20 , 24 – 26 , 28 , 29 ), and both medical and surgical patients ( 17 , 19 , 27 , 31 ). In 10 trials, all the participants had vitamin D deficiency (≤20 ng/ml) ( 18 , 20 , 21 , 25 – 30 , 32 ).…”

“…The analyzed population included patients with various disorders, including medical patients (21,30,32), neurological or surgical patients (18, 20, 24-26, 28, 29), and both medical and surgical patients (17,19,27,31). In 10 trials, all the participants had vitamin D deficiency (≤20 ng/ml) (18,20,21,(25)(26)(27)(28)(29)(30)32). In the trial conducted by Naguib et al (24), about 60% of the participants had vitamin D deficiency.…”

“…Furthermore, there was no significant difference between these two subgroups regarding length of ICU or hospital stay and duration of MV (Supplementary Figures 7-9). In 10 of the included studies, vitamin D was administered by enteral route (17-21, 24, 25, 28, 29, 32) while five studies by parenteral (18,26,27,30,31). The enteral subgroup showed no improvement in mortality reduction (OR, 0.91; 95% CI, 0.67-1.23; I 2 = 13%; Figure 4B).…”

Data_Sheet_2.PDF

“…Overall mortality was screened with different measures in all studies. Six studies (17,18,(24)(25)(26)32) reported in-hospital mortality, four studies (19,27,28,30) reported 28-/30-day mortality, and four studies (20,21,29,31) reported multiple results; we chose 28-/30-day mortality in the analysis. The pooled result indicated that vitamin D supplementation did not reduce overall mortality rate for critically ill patients (OR, 0.73; 95% CI, 0.52-1.03; I 2 = 28%, Figure 2).…”